WorldWideScience

Sample records for camptothecin induces escape

  1. Phenylbutyrate inhibits homologous recombination induced by camptothecin and methyl methanesulfonate

    DEFF Research Database (Denmark)

    Kaiser, Gitte Schalck; Germann, Susanne Manuela; Westergaard, Tine;

    2011-01-01

    Homologous recombination is accompanied by extensive changes to chromatin organization at the site of DNA damage. Some of these changes are mediated through acetylation/deacetylation of histones. Here, we show that recombinational repair of DNA damage induced by the anti-cancer drug camptothecin...

  2. Camptothecin resistance

    DEFF Research Database (Denmark)

    Brangi, M; Litman, Thomas; Ciotti, M; Nishiyama, K; Kohlhagen, G; Takimoto, C; Robey, R; Pommier, Y; Fojo, T; Bates, S E

    1999-01-01

    after camptothecin treatment. In addition to topotecan and SN-38, MXR-overexpressing cells are highly resistant to mitoxantrone and epirubicin. Because these compounds are susceptible to glucuronidation, we examined UDP-glucurono-syltransferase (UGT) activity in parental and resistant cells by TLC...

  3. Protein kinase Cη activates NF-κB in response to camptothecin-induced DNA damage

    International Nuclear Information System (INIS)

    Highlights: → Protein kinase C-eta (PKCη) is an upstream regulator of the NF-κB signaling pathway. → PKCη activates NF-κB in non-stressed conditions and in response to DNA damage. → PKCη regulates NF-κB by activating IκB kinase (IKK) and inducing IκB degradation. -- Abstract: The nuclear factor κB (NF-κB) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-κB in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-κB regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKCη) regulates NF-κB upstream signaling by activating the IκB kinase (IKK) and the degradation of IκB. Furthermore, PKCη enhances the nuclear translocation and transactivation of NF-κB under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKCη confers protection against DNA damage-induced apoptosis. Our present study suggests that PKCη is involved in NF-κB signaling leading to drug resistance.

  4. High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation

    International Nuclear Information System (INIS)

    Although most of pharmacological therapies for cancer utilize the apoptotic machinery of the cells, the available anti-cancer drugs are limited due to the ability of prostate cancer cells to escape from the anti-cancer drug-induced apoptosis. A human prostate cancer cell line PC3 is resistant to camptothecin (CPT). To elucidate the mechanism of this resistance, we have examined the involvement of sphingosine kinase (SPHK) and sphingosine 1-phosphate (S1P) receptor in CPT-resistant PC3 and -sensitive LNCaP cells. PC3 cells exhibited higher activity accompanied with higher expression levels of protein and mRNA of SPHK1, and also elevated expression of S1P receptors, S1P1 and S1P3, as compared with those of LNCaP cells. The knockdown of SPHK1 by small interfering RNA and inhibition of S1P receptor signaling by pertussis toxin in PC3 cells induced significant inhibition of cell growth, suggesting implication of SPHK1 and S1P receptors in cell proliferation in PC3 cells. Furthermore, the treatment of PC3 cells with CPT was found to induce up-regulation of the SPHK1/S1P signaling by induction of both SPHK1 enzyme and S1P1/S1P3 receptors. These findings strongly suggest that high expression and up-regulation of SPHK1 and S1P receptors protect PC3 cells from the apoptosis induced by CPT

  5. Wind-Induced Atmospheric Escape: Titan

    Science.gov (United States)

    Hartle, Richard; Johnson, Robert; Sittler, Edward, Jr.; Sarantos, Menelaos; Simpson, David

    2012-01-01

    Rapid thermospheric flows can significantly enhance the estimates of the atmospheric loss rate and the structure of the atmospheric corona of a planetary body. In particular, rapid horizontal flow at the exobase can increase the corresponding constituent escape rate. Here we show that such corrections, for both thermal and non-thermal escape, cannot be ignored when calculating the escape of methane from Titan, for which drastically different rates have been proposed. Such enhancements are also relevant to Pluto and exoplanets.

  6. Protein kinase C{eta} activates NF-{kappa}B in response to camptothecin-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Raveh-Amit, Hadas; Hai, Naama; Rotem-Dai, Noa; Shahaf, Galit [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel); Gopas, Jacob [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel); The Department of Oncology, Soroka University Medical Center, Beer-Sheva 84105 (Israel); Livneh, Etta, E-mail: etta@bgu.ac.il [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel)

    2011-08-26

    Highlights: {yields} Protein kinase C-eta (PKC{eta}) is an upstream regulator of the NF-{kappa}B signaling pathway. {yields} PKC{eta} activates NF-{kappa}B in non-stressed conditions and in response to DNA damage. {yields} PKC{eta} regulates NF-{kappa}B by activating I{kappa}B kinase (IKK) and inducing I{kappa}B degradation. -- Abstract: The nuclear factor {kappa}B (NF-{kappa}B) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-{kappa}B in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-{kappa}B regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKC{eta}) regulates NF-{kappa}B upstream signaling by activating the I{kappa}B kinase (IKK) and the degradation of I{kappa}B. Furthermore, PKC{eta} enhances the nuclear translocation and transactivation of NF-{kappa}B under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKC{eta} confers protection against DNA damage-induced apoptosis. Our present study suggests that PKC{eta} is involved in NF-{kappa}B signaling leading to drug resistance.

  7. Camptothecin and khat (Catha edulis Forsk. induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines

    Directory of Open Access Journals (Sweden)

    Fossan Kjell O

    2009-11-01

    Full Text Available Abstract Background An organic extract of the recreational herb khat (Catha edulis Forsk. triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity. Results Khat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation. Conclusion Khat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.

  8. Plasma-induced Escape and Alterations of Planetary Atmospheres

    Science.gov (United States)

    Johnson, R. E.; Tucker, O. J.; Ewrin, J.; Cassidy, T. A.; Leblanc, F.

    2009-12-01

    The atmospheres of planets and planetary satellites are typically imbedded in space plasmas. Depending on the interaction with the induced or intrinsic fields energetic ions can have access to the thermosphere and the corona affecting their composition and thermal structure and causing loss to space. These processes are often lumped together as ‘atmospheric sputtering’ (Johnson 1994). In this talk I will review the results of simulations of the plasma bombardment at a number of solar system bodies and use those data to describe the effect on the upper atmosphere and on escape. Of considerable recent interest is the modeling of escape from Titan. Prior to Cassini’s tour of the Saturnian system, plasma-induced escape was suggested to be the dominant loss process, but recent models of enhanced thermal escape, often referred to as ‘slow hydrodynamic’ escape, have been suggested to lead to much larger Titan atmospheric loss rates (Strobel 2008; Cui et al. 2008). Such a process has been suggested to be active at some point in time on a number of solar system bodies. I will present hybrid fluid/ kinetic models of the upper atmosphere of certain bodies in order to test both the plasma-induced and thermal escape processes. Preliminary results suggest that the loss rates estimated using the ‘slow hydrodynamic’ escape process can be orders of magnitude too large. The implications for Mars, Titan and Pluto will be discussed. Background for this talk is contained in the following papers (Johnson 2004; 2009; Chaufray et al. 2007; Johnson et al. 2008; 2009; Tucker and Johnson 2009). References: Chaufray, J.Y., R. Modolo, F. Leblanc, G. Chanteur, R.E. Johnson, and J.G. Luhmann, Mars Solar Wind interaction: formation of the Martian corona and atmosphric loss to space, JGR 112, E09009, doi:10.1029/2007JE002915 (2007) Cui, J., Yelle, R. V., Volk, K. Distribution and escape of molecular hydrogen in Titan's thermosphere and exosphere. J. Geophys. Res. 113, doi:10

  9. Brain targeting effect of camptothecin-loaded solid lipid nanoparticles in rat after intravenous administration

    DEFF Research Database (Denmark)

    Martins, S. M.; Sarmento, B.; Nunes, C.; Lucio, M.; Reis, S.; Ferreira, D. C.

    This study intended to investigate the ability of solid lipid nanoparticles (SLN) to deliver camptothecin into the brain parenchyma after crossing the blood-brain barrier. For that purpose, camptothecin-loaded SLN with mean size below 200 nm, low polydispersity index (94%) were produced...... studies against glioma and macrophage human cell lines revealed that camptothecin-loaded SLN induced cell death with the lowest maximal inhibitory concentration (IC50) values, revealing higher antitumour activity of camptothecin-loaded SLN against gliomas. Furthermore, in vivo biodistribution studies of...... intravenous camptothecin-loaded SLN performed in rats proved the positive role of SLN on the brain targeting since significant higher brain accumulation of camptothecin was observed, compared to non-encapsulated drug. Pharmacokinetic studies further demonstrated lower deposition of camptothecin in peripheral...

  10. Knockdown of autophagy-related protein 5, ATG5, decreases oxidative stress and has an opposing effect on camptothecin-induced cytotoxicity in osteosarcoma cells

    International Nuclear Information System (INIS)

    Autophagy induction can increase or decrease anticancer drug efficacy. Anticancer drug-induced autophagy induction is poorly characterized in osteosarcoma (OS). In this study, we investigated the impact of autophagy inhibition on camptothecin (CPT)-induced cytotoxicity in OS. Autophagy-inhibited DLM8 and K7M3 metastatic murine OS cell lines were generated by infection with lentiviral shRNA directed against the essential autophagy protein ATG5. Knockdown of ATG5 protein expression and inhibition of autophagy was confirmed by immunoblot of ATG5 and LC3II proteins, respectively. Metabolic activity was determined by MTT assay and cell viability was determined by trypan blue exclusion. Acridine orange staining and immunoblotting for LC3II protein expression were used to determine autophagy induction. Oxidative stress was assessed by staining cells with HE and DCFH-DA followed by flow cytometry analysis. Mitochondrial membrane potential was determined by staining cells with TMRE followed by flow cytometry analysis. Immunoblotting was used to detect caspase activation, Parp cleavage and p53 phosphorylation. Autophagy inhibition caused a greater deficit in metabolic activity and cell growth in K7M3 cells compared to DLM8 cells. K7M3 cells exhibited higher basal autophagy levels than DLM8 cells and non-transformed murine MCT3 osteoblasts. Autophagy inhibition did not affect CPT-induced DNA damage. Autophagy inhibition decreased CPT-induced cell death in DLM8 cells while increasing CPT-induced cell death in K7M3 cells. Autophagy inhibition reduced CPT-induced mitochondrial damage and CPT-induced caspase activation in DLM8 cells. Buthionine sulfoximine (BSO)-induced cell death was greater in autophagy-competent DLM8 cells and was reversed by antioxidant pretreatment. Camptothecin-induced and BSO-induced autophagy induction was also reversed by antioxidant pretreatment. Significantly, autophagy inhibition not only reduced CPT-induced oxidative stress but also reduced basal

  11. Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Shibakura M

    2002-10-01

    Full Text Available We previously reported that anthracyclines, which could generate reactive oxygen species (ROS, could induce the urokinase-type plasminogen activator (uPA gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC, an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.

  12. Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines

    OpenAIRE

    Fossan Kjell O; Skavland Jørn; Wergeland Line; Hagland Hanne R; Dimba Elizabeth AO; Bredholt Therese; Tronstad Karl J; Johannessen Anne C; Vintermyr Olav K; Gjertsen Bjørn T

    2009-01-01

    Abstract Background An organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity. Results Khat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. ...

  13. Structured noise induced non-recross barrier escaping

    CERN Document Server

    Wang, Chun-Yang

    2015-01-01

    The time-dependent barrier passage of a particle driven by the structured noise is studied in the field of a metastable potential. Quantities such as the probability of passing over the saddle point and transmission coefficient of the escaping rate are calculated for a thimbleful of insight into the diffusion dynamical properties. Results show that the barrier recrossing behavior is greatly reduced by the structured noisy environment. Particles diffusion in such an dissipative environment tends to successfully escape from the potential well without any embarrassments.

  14. Noise induced escape from a nonhyperbolic chaotic attractor of a periodically driven nonlinear oscillator

    Science.gov (United States)

    Chen, Zhen; Li, Yang; Liu, Xianbin

    2016-06-01

    Noise induced escape from the domain of attraction of a nonhyperbolic chaotic attractor in a periodically excited nonlinear oscillator is investigated. The general mechanism of the escape in the weak noise limit is studied in the continuous case, and the fluctuational path is obtained by statistical analysis. Selecting the primary homoclinic tangency as the initial condition, the action plot is presented by parametrizing the set of escape trajectories and the global minimum gives rise to the optimal path. Results of both methods show good agreements. The entire process of escape is discussed in detail step by step using the fluctuational force. A structure of hierarchical heteroclinic crossings of stable and unstable manifolds of saddle cycles is found, and the escape is observed to take place through successive jumps through this deterministic hierarchical structure.

  15. Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape?

    International Nuclear Information System (INIS)

    According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed “cure” following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma

  16. Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape?

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, William W. [Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, Room S-321, San Francisco, CA 94143 (United States); Fadaki, Niloofar; Leong, Stanley P., E-mail: leongsx@cpmcri.org [Department of Surgery and Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, 2340 Clay Street, 2nd floor, San Francisco, CA 94115 (United States)

    2011-02-21

    According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed “cure” following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

  17. Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape?

    Directory of Open Access Journals (Sweden)

    William W. Tseng

    2011-02-01

    Full Text Available According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed “cure” following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

  18. Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Seok [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kang, Shin-il [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Yoo, Kyu-dong [Hazardous Substances Analysis Division, Gwangju Regional Food and Drug Administration, Gwangju (Korea, Republic of); Lee, Mi-Yea [Department of Nursing Kyungbok University, Pocheon (Korea, Republic of); Yoo, Hwan-Soo; Hong, Jin-Tae [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Shin, Hwa-Sup [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kim, Bokyung [Department of Physiology, Konkuk Medical School, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Yun, Yeo-Pyo, E-mail: ypyun@chungbuk.ac.kr [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of)

    2013-04-15

    The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 μM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5–2 μM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway. - Highlights: ► CPT inhibits proliferation of PDGF-BB-induced VSMC without cytotoxicity. ► CPT arrests the cell cycle in G0/G1 phase by downregulation of cyclin D1 and CDK2. ► CPT significantly attenuates Akt phosphorylation in PDGF-BB signaling pathway. ► LY294002 enhanced the inhibitory effect of CPT on VSMC proliferation. ► Thus, CPT is mediated by downregulating the PI3K/Akt signaling pathway.

  19. The diurnal and solar cycle variation of the charge exchange induced hydrogen escape flux

    Science.gov (United States)

    Maher, L. J.; Tinsley, B. A.

    1978-01-01

    On the basis of ion temperature and density data at specific points and times in June 1969 provided by the OGO 6 satellite, and altitude profiles of the ion and electron temperature and concentration provided by the Arecibo radar facility over the period February 1972-April 1974, the diurnal and solar cycle variation of the charge-exchange-induced hydrogen escape flux was investigated. It was calculated that for low to moderate solar activity at Arecibo, the diurnal ratio of the maximum-to-minimum charge-exchange-induced hydrogen escape flux was approximately 6 with a peak around noon and a minimum somewhere between 0100 and 0300 h LT. This study of a limited amount of OGO 6 and Arecibo data seems to indicate that the charge-exchange-induced hydrogen escape flux increases as the F(10.7) flux increases for low to moderate solar activity.

  20. Precipitation of Energetic Neutral Atoms and Induced Non-Thermal Escape Fluxes from the Martian Atmosphere

    CERN Document Server

    Lewkow, Nicholas

    2014-01-01

    The precipitation of energetic neutral atoms (ENAs), produced through charge exchange (CX) collisions between solar wind (SW) ions and thermal atmospheric gases, is investigated. Subsequent induced non-thermal escape fluxes have been carried out for the Martian atmosphere. Detailed modeling of the ENA energy input and determination of connections between parameters of precipitating ENAs and resulting escape fluxes, reflection coefficients of fast atoms from the Mars atmosphere, and altitude dependent ENA energy distributions are established using Monte Carlo (MC) simulations of the precipitation process with accurate quantum mechanical (QM) cross sections. Detailed descriptions of secondary hot (SH) atoms and molecules induced by ENAs have been obtained for a better understanding of the mechanisms responsible for atmospheric escape and evolution. The effects of using isotropic hard sphere (HS) cross sections as compared to realistic, anisotropic quantum cross sections are examined for energy-deposition profil...

  1. Derepression of hTERT gene expression promotes escape from oncogene-induced cellular senescence.

    Science.gov (United States)

    Patel, Priyanka L; Suram, Anitha; Mirani, Neena; Bischof, Oliver; Herbig, Utz

    2016-08-23

    Oncogene-induced senescence (OIS) is a critical tumor-suppressing mechanism that restrains cancer progression at premalignant stages, in part by causing telomere dysfunction. Currently it is unknown whether this proliferative arrest presents a stable and therefore irreversible barrier to cancer progression. Here we demonstrate that cells frequently escape OIS induced by oncogenic H-Ras and B-Raf, after a prolonged period in the senescence arrested state. Cells that had escaped senescence displayed high oncogene expression levels, retained functional DNA damage responses, and acquired chromatin changes that promoted c-Myc-dependent expression of the human telomerase reverse transcriptase gene (hTERT). Telomerase was able to resolve existing telomeric DNA damage response foci and suppressed formation of new ones that were generated as a consequence of DNA replication stress and oncogenic signals. Inhibition of MAP kinase signaling, suppressing c-Myc expression, or inhibiting telomerase activity, caused telomere dysfunction and proliferative defects in cells that had escaped senescence, whereas ectopic expression of hTERT facilitated OIS escape. In human early neoplastic skin and breast tissue, hTERT expression was detected in cells that displayed features of senescence, suggesting that reactivation of telomerase expression in senescent cells is an early event during cancer progression in humans. Together, our data demonstrate that cells arrested in OIS retain the potential to escape senescence by mechanisms that involve derepression of hTERT expression. PMID:27503890

  2. Predator-induced morphology enhances escape locomotion in crucian carp

    OpenAIRE

    Domenici, Paolo; Turesson, Håkan; Brodersen, Jakob; Brönmark, Christer

    2007-01-01

    Fishes show a remarkable diversity of shapes which have been associated with their swimming abilities and anti-predator adaptations. The crucian carp (Carassius carassius) provides an extreme example of phenotypic plasticity in body shape which makes it a unique model organism for evaluating the relationship between body form and function in fishes. In crucian carp, a deep body is induced by the presence of pike (Esox lucius), and this results in lower vulnerability to gape-limited predators,...

  3. IMF-induced escape of molecular ions from the Martian ionosphere

    Directory of Open Access Journals (Sweden)

    Y. Kubota

    2013-08-01

    Full Text Available Since Mars does not possess a significant global intrinsic magnetic field, the solar wind interacts directly with the Martian ionosphere and can induce ion escapes from it. Phobos-2 and recent Mars Express (MEX observations have shown that the escaping ions are O+ as well as molecular O2+ and CO2+. While O+ escape can be understood by the ion pick-up of non-thermal O corona extended around the planet, regarding the heavy molecular O2+ and CO2+, which are buried in the lower ionosphere, a novel escape mechanism needs to considered. Here we attack this problem by global magnetohydrodynamic (MHD simulations. First, we clarify the global structure of the streamlines that result from the interaction with the solar wind. Then, by focusing on the streamlines that dip into the low-altitude part of the dayside ionosphere, we investigate the escape path of the molecular ions. The effects of the interplanetary magnetic field (IMF on the molecular ion escape process are investigated by comparing the results with and without IMF. IMF has little effect on O+ escape via ion pick-up mediated by solar wind electron impact ionization of the O corona. O2+ and CO2+ are shoveled from the low-altitude regions of the dayside ionosphere by magnetic tension in the presence of IMF. These ions are pulled by the U-shaped field lines to the north and south poles, and at the terminator, they are concentrated in the noon–midnight meridian plane. These ions remain confined to the noon–midnight plane as they are transported to the nightside to form the tail ray. Then they escape along the streamlines open to the interplanetary space. Under a typical solar wind and IMF condition expected at Mars, O+, O2+ and CO2+ escape fluxes are 8.0 × 1023, 3.5 × 1023 and 5.0 × 1022 ion s−1, respectively, which are in good agreement with the MEX observations.

  4. X-ray-induced photoemission yield for surface studies of solids beyond the photoelectron escape depth

    CERN Document Server

    Stoupin, Stanislav; Zhernenkov, Mikhail

    2016-01-01

    X-ray-induced photoemission in materials research is commonly acknowledged as a method with a probing depth limited by the escape depth of the photoelectrons. This general statement should be complemented with exceptions arising from the distribution of the X-ray wavefield in the material. Here we show that the integral hard-X-ray-induced photoemission yield is modulated by the Fresnel reflectivity of a multilayer structure with the signal originating well below the photoelectron escape depth. A simple electric self-detection of the integral photoemission yield and Fourier data analysis permit extraction of thicknesses of individual layers. The approach does not require detection of the reflected radiation and can be considered as a framework for non-invasive evaluation of buried layers with hard X-rays under grazing incidence.

  5. Mechanisms Of Hypoxia-Induced Immune Escape In Cancer And Their Regulation By Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Charles Graham

    2015-08-01

    Full Text Available The acquired ability of tumour cells to avoid destruction by immune effector mechanisms (immune escape is important for malignant progression. Also associated with malignant progression is tumour hypoxia, which induces aggressive phenotypes such as invasion, metastasis and drug resistance in cancer cells. Our studies revealed that hypoxia contributes to escape from innate immunity by increasing tumour cell expression of the metalloproteinase ADAM10 in a manner dependent on accumulation of the alpha subunit of the transcription factor hypoxia-inducible factor-1 (HIF-1α. Increased ADAM10 expression leads to shedding of the NK cell-activating ligand, MICA, from the surface of tumour cells, thereby resulting in resistance to NK cell-mediated lysis. Our more recent studies demonstrated that hypoxia, also via HIF-1α accumulation, increases the expression of the inhibitory co-stimulatory ligand PD-L1 on tumour cells. Elevated PD-L1 expression leads to escape from adaptive immunity via increased apoptosis of CD8+ cytotoxic T lymphocytes. Accumulating evidence indicates that hypoxia-induced acquisition of malignant phenotypes, including immune escape, is in part due to impaired nitric oxide (NO-mediated activation of cGMP signalling and that restoration of cGMP signalling prevents such hypoxic responses. We have shown that NO/cGMP signalling inhibits hypoxia-induced malignant phenotypes likely in part by interfering with HIF-1α accumulation via a mechanism involving calpain. These findings indicate that activation of NO/cGMP signalling may have useful applications in cancer therapy.

  6. Precipitation of energetic neutral atoms and induced non-thermal escape fluxes from the Martian atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Lewkow, N. R.; Kharchenko, V. [Department of Physics, University of Connecticut, Storrs, CT 06269 (United States)

    2014-08-01

    The precipitation of energetic neutral atoms, produced through charge exchange collisions between solar wind ions and thermal atmospheric gases, is investigated for the Martian atmosphere. Connections between parameters of precipitating fast ions and resulting escape fluxes, altitude-dependent energy distributions of fast atoms and their coefficients of reflection from the Mars atmosphere, are established using accurate cross sections in Monte Carlo (MC) simulations. Distributions of secondary hot (SH) atoms and molecules, induced by precipitating particles, have been obtained and applied for computations of the non-thermal escape fluxes. A new collisional database on accurate energy-angular-dependent cross sections, required for description of the energy-momentum transfer in collisions of precipitating particles and production of non-thermal atmospheric atoms and molecules, is reported with analytic fitting equations. Three-dimensional MC simulations with accurate energy-angular-dependent cross sections have been carried out to track large ensembles of energetic atoms in a time-dependent manner as they propagate into the Martian atmosphere and transfer their energy to the ambient atoms and molecules. Results of the MC simulations on the energy-deposition altitude profiles, reflection coefficients, and time-dependent atmospheric heating, obtained for the isotropic hard sphere and anisotropic quantum cross sections, are compared. Atmospheric heating rates, thermalization depths, altitude profiles of production rates, energy distributions of SH atoms and molecules, and induced escape fluxes have been determined.

  7. Camptothecin disrupts androgen receptor signaling and suppresses prostate cancer cell growth

    International Nuclear Information System (INIS)

    The androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers. The present study demonstrates that the topoisomerase I inhibitor camptothecin selectively inhibits androgen-responsive growth of prostate cancer cells. Camptothecin strikingly inhibited mutated and wild-type AR protein expression in LNCaP and PC-3/AR cells. This inhibition coincided with decreased androgen-mediated AR phosphorylation at Ser81 and reduced androgen-mediated AR transcriptional activity in a dose-dependent manner. Additionally, camptothecin disrupted the association between AR and heat shock protein 90 and impeded binding of the synthetic androgen [3H]R1881 to AR in LNCaP cells. Camptothecin also blocked androgen-induced AR nuclear translocation, leading to downregulation of the AR target gene PSA. In addition to decreasing the intracellular and secreted prostate-specific antigen (PSA) levels, camptothecin markedly inhibited androgen-stimulated PSA promoter activity. Collectively, our data reveal that camptothecin not only serves as a traditional genotoxic agent but, by virtue of its ability to target and disrupt AR, may also be a novel candidate for the treatment of prostate cancer.

  8. Camptothecin disrupts androgen receptor signaling and suppresses prostate cancer cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shicheng, E-mail: liusc59@yahoo.co.jp [Research and Development Department, Nipro Patch Co., Ltd., 8-1, Minamisakae-cho, Kasukabe, Saitama 344-0057 (Japan); Yuan, Yiming [Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041 (China); Okumura, Yutaka; Shinkai, Norihiro; Yamauchi, Hitoshi [Research and Development Department, Nipro Patch Co., Ltd., 8-1, Minamisakae-cho, Kasukabe, Saitama 344-0057 (Japan)

    2010-04-02

    The androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers. The present study demonstrates that the topoisomerase I inhibitor camptothecin selectively inhibits androgen-responsive growth of prostate cancer cells. Camptothecin strikingly inhibited mutated and wild-type AR protein expression in LNCaP and PC-3/AR cells. This inhibition coincided with decreased androgen-mediated AR phosphorylation at Ser{sup 81} and reduced androgen-mediated AR transcriptional activity in a dose-dependent manner. Additionally, camptothecin disrupted the association between AR and heat shock protein 90 and impeded binding of the synthetic androgen [{sup 3}H]R1881 to AR in LNCaP cells. Camptothecin also blocked androgen-induced AR nuclear translocation, leading to downregulation of the AR target gene PSA. In addition to decreasing the intracellular and secreted prostate-specific antigen (PSA) levels, camptothecin markedly inhibited androgen-stimulated PSA promoter activity. Collectively, our data reveal that camptothecin not only serves as a traditional genotoxic agent but, by virtue of its ability to target and disrupt AR, may also be a novel candidate for the treatment of prostate cancer.

  9. Role of renal aquaporins in escape from vasopressin-induced antidiuresis in rat.

    OpenAIRE

    Ecelbarger, C A; S. Nielsen; Olson, B R; Murase, T; Baker, E A; Knepper, M A; Verbalis, J G

    1997-01-01

    The purpose of this study was to investigate whether escape from vasopressin-induced antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day...

  10. Topoisomerase I inhibitors: camptothecins and beyond.

    Science.gov (United States)

    Pommier, Yves

    2006-10-01

    Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme. It is the only known target of the alkaloid camptothecin, from which the potent anticancer agents irinotecan and topotecan are derived. As camptothecins bind at the interface of the TOP1-DNA complex, they represent a paradigm for interfacial inhibitors that reversibly trap macromolecular complexes. Several camptothecin and non-camptothecin derivatives are being developed to further increase anti-tumour activity and reduce side effects. The mechanisms and molecular determinants of tumour response to TOP1 inhibitors are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage. PMID:16990856

  11. Parathyroid hormone and calcitonin interactions in bone: Irradiation-induced inhibition of escape in vitro

    International Nuclear Information System (INIS)

    Calcitonin (CT) inhibits hormonally stimulated bone resorption only transiently in vitro. This phenomenon has been termed ''escape,'' but the mechanism for the effect is not understood. One possible explanation is that bone cell differentiation and recruitment of specific precursor cells, in response to stimulators of resorption, lead to the appearance of osteoclasts that are unresponsive to CT. To test this hypothesis, cell proliferation in neonatal mouse calvaria in organ culture was inhibited by irradiation from a cobalt-60 source. At a dose of 6000 R, [3H]thymidine incorporation into intact calvaria was inhibited approximately 90%. Irradiation had no effect on the resorptive response to 0.1 U/ml parathyroid hormone (PTH). However, irradiation induced a dose-dependent inhibition of the escape response which was maximal at 6000 R. A dose of 6000 R did not affect the binding of 125I-salmon CT to calvaria and decreased PTH stimulation of cyclic AMP release from bone without affecting the cyclic AMP response to CT. Although irradiation caused a dose-dependent inhibition of DNA synthesis, the dose-response curves for that effect and inhibition of escape were not superimposable. A morphologic study of hormonally treated calvaria demonstrated that irradiation prevented the early increase in number of osteoclasts in PTH-treated calvaria that had been observed previously in unirradiated bones. Autoradiography showed that irradiation also prevented the PTH-stimulated recruitment of newly divided mononuclear cell precursors into osteoclasts. This may be correlated with the effect of irradiation to prevent the loss of responsiveness to CT in the presence of PTH. (orig.)

  12. Mutator suppression and escape from replication error-induced extinction in yeast.

    Directory of Open Access Journals (Sweden)

    Alan J Herr

    2011-10-01

    Full Text Available Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10⁻³ inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer.

  13. Synthesis of camptothecin-loaded gold nanomaterials

    International Nuclear Information System (INIS)

    Camptothecin-loaded gold nanomaterials have been synthesized by the sodium borohydride reduction method under a strong basic condition. The obtained gold nanomaterials have been characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM) and UV-vis absorption spectroscopy. The camptothecin-loaded gold colloidal solution was very stable and can be stored for more than two months at room temperature without obvious changes. The color of the colloidal solution can change from wine red to purple and blue during the acidifying process. It was revealed that the release of camptothecin and the aggregation of gold nanoparticles can be controlled by tuning the solution pH. The present study implied that the gold nanomaterials can be used as the potential carrier for CPT delivery.

  14. Quantitation of camptothecin and related compounds.

    Science.gov (United States)

    Palumbo, M; Sissi, C; Gatto, B; Moro, S; Zagotto, G

    2001-11-25

    Camptothecin and congeners represent a clinically very useful class of anticancer agents. Proper identification and quantitation of the original compounds and their metabolites in biological fluids is fundamental to assess drug metabolism and distribution in animals and in man. In this paper we will review the recent literature available on the methods used for separation and quantitative determination of the camptothecin family of drugs. Complications arise from the fact that they are chemically labile, and the pharmacologically active lactone structure can undergo ring opening at physiological conditions. In addition, a number of metabolic changes usually occur, producing a variety of active or inactive metabolites. Hence, the conditions of extraction, pre-treatment and quantitative analysis are to be carefully calibrated in order to provide meaningful results. PMID:11817024

  15. The effect of transportation suit induced heat stress on helicopter underwater escape preparation and task performance.

    Science.gov (United States)

    Taber, Michael J; Dies, Natalie F; Cheung, Stephen S

    2011-11-01

    Although essential in an emergency such as a helicopter ditching, mandatory survival suits worn by civilian personnel may lead to heat strain during a normal flight. To explore the possibility that wearing a helicopter transportation suit impairs emergency performance, 11 individuals completed underwater escape procedures immediately following a pre-recorded emergency announcement (randomly played between 50 and 90 min) in two ambient temperature conditions (Thermoneutral = 21 °C and Hot = 34 °C). Mean skin and rectal temperatures were recorded throughout the trials, while situation awareness and thermal sensation/comfort were recorded on completion of trials. Results indicate that although mean skin and rectal temperatures were significantly higher at the end of both trials, escape procedures were not impaired. It can therefore be concluded that although conditions inside an offshore transport helicopter are perceived as being hot and uncomfortable, no deficits in escape performance should be expected in the first 90 min of flight. PMID:21439548

  16. Escape Velocity

    OpenAIRE

    Nikola Vlacic

    2010-01-01

    In this project, we investigated if it is feasible for a single staged rocket with constant thrust to attain escape velocity. We derived an equation for the velocity and position of a single staged rocket that launches vertically. From this equation, we determined if an ideal model of a rocket is able to reach escape velocity.

  17. Exploring the Cellular Activity of Camptothecin-Triple-Helix-Forming Oligonucleotide Conjugates†

    OpenAIRE

    Arimondo, Paola B.; Thomas, Craig J.; Oussedik, Kahina; Baldeyrou, Brigitte; Mahieu, Christine; Halby, Ludovic; Guianvarc'h, Dominique; Lansiaux, Amélie; Hecht, Sidney M.; Bailly, Christian; Giovannangeli, Carine

    2006-01-01

    Topoisomerase I is a ubiquitous DNA-cleaving enzyme and an important therapeutic target in cancer chemotherapy for camptothecins (CPTs). These drugs stimulate DNA cleavage by topoisomerase I but exhibit little sequence preference, inducing toxicity and side effects. A convenient strategy to confer sequence specificity consists of the linkage of topoisomerase poisons to DNA sequence recognition elements. In this context, triple-helix-forming oligonucleotides (TFOs) covalently linked to CPTs we...

  18. Effect of P-glycoprotein modulators on the pharmacokinetics of camptothecin using microdialysis

    OpenAIRE

    Tsai, T H; Lee, C. H.; Yeh, P H

    2001-01-01

    By performing microdialysis, this study investigated the pharmacokinetics of unbound camptothecin in rat blood, brain and bile in the presence of P-glycoprotein mediated transport modulators (cyclosporin A, berberine, quercetin, naringin and naringenin). Pharmacokinetic parameters of camptothecin were assessed using a non-compartmental model.Camptothecin rapidly crosses the blood-brain barrier (BBB) within 20 min after camptothecin administration. The disposition of camptothecin in rat bile a...

  19. The self-assembly of a camptothecin-lysine nanotube.

    Science.gov (United States)

    Sun, Yuan; Shieh, Aileen; Kim, Se Hye; King, Samantha; Kim, Anne; Sun, Hui-Lung; Croce, Carlo M; Parquette, Jon R

    2016-06-15

    A simple, low molecular weight camptothecin-lysine conjugate is reported to self-assemble into nanotubes with diameters of 70-100nm and a drug loading level of 60.5%. The nanotubes exhibited promising in vitro cytotoxicity against cancer cell lines A549, NCI-H460 and NCI-H23. The release of active camptothecin was highly dependent on conjugate concentration, temperature and pH of the solution. PMID:27156772

  20. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Neng [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Yin, Huabing, E-mail: huabing.yin@glasgow.ac.uk [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Ji, Bozhi; Klauke, Norbert; Glidle, Andrew [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Zhang, Yongkui; Song, Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Cai, Lulu; Ma, Liang; Wang, Guangcheng [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Chen, Lijuan, E-mail: lijuan17@hotmail.com [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Wang, Wenwen [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)

    2012-12-01

    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: Black-Right-Pointing-Pointer BSA-doped calcium carbonate microspheres with porous structure were prepared. Black-Right-Pointing-Pointer Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. Black-Right-Pointing-Pointer The release of encapsulated camptothecin is pH dependent Black-Right-Pointing-Pointer In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  1. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    International Nuclear Information System (INIS)

    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: ► BSA-doped calcium carbonate microspheres with porous structure were prepared. ► Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. ► The release of encapsulated camptothecin is pH dependent ► In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  2. Marine dinoflagellates show induced life-history shifts to escape parasite infection in response to water-borne signals.

    Science.gov (United States)

    Toth, Gunilla B; Norén, Fredrik; Selander, Erik; Pavia, Henrik

    2004-04-01

    Many dinoflagellate species form dormant resting cysts as a part of their life cycle, and in some freshwater species, hatching of these cysts can be delayed by the presence of water-borne signals from grazing zooplankton. Some marine dinoflagellates can form temporary cysts, which may function to resist unfavourable short-term environmental conditions. We investigated whether the marine dinoflagellate Alexandrium ostenfeldii is able to induce an increased resistance to the parasitic flagellate Parvilucifera infectans by forming temporary cysts. We performed several laboratory experiments where dinoflagellates were exposed either to direct contact with parasites or to filtered water from cultures of parasite-infected conspecifics (parasite-derived signals). Infection by P. infectans is lethal to motile A. ostenfeldii cells, but temporary cysts were more resistant to parasite infection. Furthermore, A. ostenfeldii induced a shift in life-history stage (from motile cells to temporary cysts) when exposed to parasite-derived water-borne signals. The response was relaxed within a couple of hours, indicating that A. ostenfeldii may use this behaviour as a short-term escape mechanism to avoid parasite infection. The results suggest that intraspecies chemical communication evoked by biotic interactions can be an important mechanism controlling life-history shifts in marine dinoflagellates, which may have implications for the development of toxic algal blooms. PMID:15209107

  3. Induced resistance enzymes in wild plants-do `early birds' escape from pathogen attack?

    Science.gov (United States)

    Heil, Martin; Ploss, Kerstin

    2006-09-01

    Systemic acquired resistance (SAR) of plants to pathogens is a well-defined phenomenon. The underlying signalling pathways and its application in crop protection are intensively studied. However, most studies are conducted on crop plants or on Arabidopsis as a model plant. The taxonomic distribution of this phenomenon and its dependence on life history are thus largely unknown. We quantified activities of three classes of resistance-related enzymes in 18 plant species to investigate whether plants with varying life histories differ in their investment in disease resistance. Enzyme activities were quantified in untreated plants, and in plants induced with BION, a chemical resistance elicitor. All species showed constitutive activities of chitinase, peroxidase, or glucanase. However, constitutive chitinase activities varied by 30 times, and peroxidase by 50 times, among species. Several species did not respond to the induction treatment, while enzyme activities in other species increased more than threefold after BION application. Plant species differ dramatically in the presence and inducibility of resistance enzymes. This variation could be related to life history: While all resistance enzymes were significantly induced in larger perennial plants that flower during summer, spring geophytes hardly showed inducible resistance. These plants grow in an environment that is characterised by a low-pathogen pressure, and thus may simply ‘escape’ from infection. Our study presents the first comparative data set on resistance-related enzymes in noncultivated plants. The current view on SAR—narrowed by the concentration on cultivated crops—is not sufficient to understand the ecological and evolutionary relevance of this widespread plant trait.

  4. Sequence-specific targeting of IGF-I and IGF-IR genes by camptothecins

    OpenAIRE

    Oussedik, Kahina; François, Jean-Christophe; Halby, Ludovic; Senamaud-Beaufort, Catherine; Toutirais, Géraldine; Dallavalle, Sabrina; Pommier, Yves; Pisano, Claudio; Arimondo, Paola B.

    2010-01-01

    We and others have clearly demonstrated that a topoisomerase I (Top1) inhibitor, such as camptothecin (CPT), coupled to a triplex-forming oligonucleotide (TFO) through a suitable linker can be used to cause site-specific cleavage of the targeted DNA sequence in in vitro models. Here we evaluated whether these molecular tools induce sequence-specific DNA damage in a genome context. We targeted the insulin-like growth factor (IGF)-I axis and in particular promoter 1 of IGF-I and intron 2 of typ...

  5. Sequence-specific targeting of IGF-I and IGF-IR genes by camptothecins.

    Science.gov (United States)

    Oussedik, Kahina; François, Jean-Christophe; Halby, Ludovic; Senamaud-Beaufort, Catherine; Toutirais, Géraldine; Dallavalle, Sabrina; Pommier, Yves; Pisano, Claudio; Arimondo, Paola B

    2010-07-01

    We and others have clearly demonstrated that a topoisomerase I (Top1) inhibitor, such as camptothecin (CPT), coupled to a triplex-forming oligonucleotide (TFO) through a suitable linker can be used to cause site-specific cleavage of the targeted DNA sequence in in vitro models. Here we evaluated whether these molecular tools induce sequence-specific DNA damage in a genome context. We targeted the insulin-like growth factor (IGF)-I axis and in particular promoter 1 of IGF-I and intron 2 of type 1 insulin-like growth factor receptor (IGF-IR) in cancer cells. The IGF axis molecules represent important targets for anticancer strategies, because of their central role in oncogenic maintenance and metastasis processes. We chemically attached 2 CPT derivatives to 2 TFOs. Both conjugates efficiently blocked gene expression in cells, reducing the quantity of mRNA transcribed by 70-80%, as measured by quantitative RT-PCR. We confirmed that the inhibitory mechanism of these TFO conjugates was mediated by Top1-induced cleavage through the use of RNA interference experiments and a camptothecin-resistant cell line. In addition, induction of phospho-H2AX foci supports the DNA-damaging activity of TFO-CPT conjugates at specific sites. The evaluated conjugates induce a specific DNA damage at the target gene mediated by Top1. PMID:20179147

  6. Recent advances in topoisomerase I-targeting agents, camptothecin analogues.

    Science.gov (United States)

    Kim, Dae-Kee; Lee, Namkyu

    2002-12-01

    The present review concentrates on camptothecin (CPT) analogues, the most extensively studied topoisomerase I (topo I) inhibitors, and provides concise information on the structural features of human topo I enzyme, mechanisms of interaction of CPT with topo I, structure-activity relationship study of CPT analogues including the influence of lactone stability on antitumor activity, and recent updates of valuable CPT analogues. PMID:12370044

  7. Thymidine selectively enhances growth suppressive effects of camptothecin/irinotecan in MSI+ cells and tumors containing a mutation of MRE11

    DEFF Research Database (Denmark)

    Rodriguez, Rene; Hansen, Lasse Tengbjerg; Phear, Geraldine; Scorah, Jennifer; Spang-Thomsen, Mogens; Cox, Angela; Helleday, Thomas; Meuth, Mark

    2008-01-01

    PURPOSE: DNA synthesis inhibitors and damaging agents are widely used in cancer therapy; however, sensitivity of tumors to such agents is highly variable. The response of tumor cells in culture to these agents is strongly influenced by the status of DNA damage response pathways. Here, we attempt ...... exploit the altered response of mismatch repair (MMR)-deficient colon cancer cells and tumors to camptothecin or irinotecan and thymidine by combining them to improve therapeutic response. EXPERIMENTAL DESIGN: A panel of colon cancer cell lines was assayed for response to camptothecin...... in nude mice. RESULTS: Camptothecin-thymidine combinations suppress colony formation of MMR-deficient tumor cells 10- to 3,000-fold relative to that obtained with camptothecin alone and significantly reduce the concentrations of the agents required to induce late S/G(2) arrest and senescence....... Sensitivity is not a direct result of MMR, p53, or p21 status. However MMR-deficient cell lines containing an intronic frameshift mutation of MRE11 show greatest sensitivity to these agents. Increased sensitivity to this combination is also evident in vivo as thymidine enhances irinotecan-induced growth...

  8. Synthesis and cytotoxic activity of 7-alkynyl camptothecin derivatives

    Institute of Scientific and Technical Information of China (English)

    Feng Xiao; Yadong Xue; Yu Luo; Bo Zhang; Wei Lu; Bo Yang

    2009-01-01

    Several 7-alkynyl camptothecin derivatives were prepared via Sonogashira coupling.And anti-tumor activities of these compounds were evaluated against human esophageal cancer cell line (Eca-109),human chronic myeloid leukaemia cell line (K562),bladder cancer cell line (5637) and gastric cell line (SGC7901).Compounds 9a-d and 10a exhibited remarkable in vitro cytotoxic activity,compared with topotecan.

  9. Polylactide Conjugates of Camptothecin with Different Drug Release Abilities

    OpenAIRE

    Ewa Oledzka; Paweł Horeglad; Zuzanna Gruszczyńska; Andrzej Plichta; Grzegorz Nałęcz-Jawecki; Marcin Sobczak

    2014-01-01

    Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled ...

  10. Sequence dependent modulating effect of camptothecin on the DNA-cleaving activity of the calf thymus type I topoisomerase.

    OpenAIRE

    Gromova, I I; Buchman, V L; Abagyan, R A; Ulyanov, A V; Bronstein, I B

    1990-01-01

    High-resolution mapping of topol cleavages in the regions of human DNA including the oncogene c-Ha-ras and p53, has revealed three kinds of topol cleavage sites: cleavage sites not affected by camptothecin; cleavage sites reinforced only in the presence of camptothecin, and cleavage sites which weaken in the presence of camptothecin. Statistical analysis of sequences revealed certain nucleotide or dinucleotide preferences for three groups studied. The preferences in camptothecin-reduced sites...

  11. Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants

    OpenAIRE

    Sirikantaramas, Supaart; Yamazaki, Mami; Saito, Kazuki

    2008-01-01

    Plants produce a variety of toxic compounds, which are often used as anticancer drugs. The self-resistance mechanism to these toxic metabolites in the producing plants, however, remains unclear. The plant-derived anticancer alkaloid camptothecin (CPT) induces cell death by targeting DNA topoisomerase I (Top1), the enzyme that catalyzes changes in DNA topology. We found that CPT-producing plants, including Camptotheca acuminata, Ophiorrhiza pumila, and Ophiorrhiza liukiuensis, have Top1s with ...

  12. Effects of camptothecin, etoposide and Ca2+ on caspase-3 activity and myofibrillar disruption of chicken during postmortem ageing.

    Science.gov (United States)

    Chen, Lin; Feng, Xian Chao; Lu, Feng; Xu, Xing Lian; Zhou, Guang Hong; Li, Qing Yun; Guo, Xiang Ying

    2011-03-01

    Recently, a novel consideration has focused on the potential relationship of apoptosis and the protease caspases and the underlying mechanism for meat postmortem tenderization. In this study, apoptosis inducers, camptothecin and etoposide as well as Ca(2+) were used to treat chicken muscle immediately after slaughter and follow the changes in caspase-3 activities and changes in the myofibrillar structures during 7 days of ageing. All three treatments resulted in significantly higher caspase-3 activities during storage (p<0.05), with the natural substrates, whereas Western blotting analysis of the α-spectrin cleavage product, 120 kDa peptide (SBDP 120), showed that Ca(2+) was more effective than either camptothecin or etopside, and all were most active up to day 3 (p<0.01). According to SDS-PAGE, each treatment enhanced the accumulation of the 30 kD Troponin-T degradation product, especially during the first 3 days (p<0.05), and this was supported by the degradation of myofibrils observed by electron microscopy (TEM). TEM images showed the treatments resulted in enlargement of the I-bands and shrinkage of A-bands; however Z-lines were only slightly affected, even at day 7. The findings revealed that the three apoptosis inducers could increase myofibrillar dissociation and proteolysis during the first 3 days of chicken meat ageing. Because of the high activity of caspase-3 during the early postmortem period, it is possible that caspase-3 contributes to the conversion of muscle into meat. PMID:21055882

  13. Semisynthesis, cytotoxic activity, and oral availability of new lipophilic 9-substituted camptothecin derivatives.

    Science.gov (United States)

    Rodriguez-Berna, Guillermo; Cabañas, Maria Jose Díaz; Mangas-Sanjuán, Victor; Gonzalez-Alvarez, Marta; Gonzalez-Alvarez, Isabel; Abasolo, Ibane; Schwartz, Simó; Bermejo, Marival; Corma, Avelino

    2013-07-11

    Despite that 9-substituted camptothecins are promising candidates in cancer therapy, the limited accessibility to this position has reduced the studies of these derivatives to a few standard modifications. We report herein a novel semisynthetic route based on the Tscherniac-Einhorn reaction to synthesize new lipophilic camptothecin derivatives with amidomethyl and imidomethyl substitutions in position 9. Compounds were evaluated for their antiproliferative activity, topoisomerase I inhibition, and oral availability. Preliminary data demonstrated that bulky imidomethyl modification is an appropriate lipophilic substitution for an effective oral administration relative to topotecan. In addition, this general procedure paves the way for obtaining new camptothecin derivatives. PMID:24900725

  14. Polylactide Conjugates of Camptothecin with Different Drug Release Abilities

    Directory of Open Access Journals (Sweden)

    Ewa Oledzka

    2014-11-01

    Full Text Available Camptothecin-polylactide conjugates (CMPT-PLA were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79 via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems—important delivery systems for anti-cancer agents.

  15. Mild oxidative stress induced by a low dose of cisplatin contributes to the escape of TRAIL-mediated apoptosis in the ovarian cancer SKOV3 cell line.

    Science.gov (United States)

    Lu, Jinzhi; Zhang, Lei; Xie, Fang; Zhu, Liya; Li, Xiaolan; Ouyang, Jingping; He, Xiaohua; Han, Song; Yi, Cunjian

    2016-06-01

    Tumor necrosis factor (TNF)-related apoptosis‑inducing ligand (TRAIL) is expressed in ovarian tissue and is widely thought to exhibit strong antitumor activity in a variety of tumor cell types. Therefore, we hypothesized that the cisplatin resistance of ovarian cancer is linked to the ability to escape from TRAIL-mediated apoptosis. We demonstrated that cisplatin-resistant ovarian cancer cell line SKOV3/DDP tolerated treatment with TRAIL, in contrast to the cisplatin‑sensitive ovarian cancer cell line SKOV3. SKOV3/DDP cells exhibited a much higher cell viability and a lower apoptosis rate than SKOV3 cells after treatment with TRAIL. To determine whether cisplatin induced the tolerance of TRAIL, we pretreated the SKOV3 cells with cisplatin in the presence of TRAIL. This revealed that a low dose of cisplatin (1 µM) increased the TRAIL tolerance of SKOV3 cells. Furthermore, cisplatin induced oxidative stress in both the SKOV3/DDP and SKOV3 cells, although the oxidative stress level of the SKOV3/DDP cells was generally much higher than that noted in the SKOV3 cells. Similarly, a low dose of hydrogen peroxide increased the TRAIL tolerance in SKOV3 cells. Notably, the TRAIL tolerance in the SKOV3 and SKOV3/DDP cells could be abrogated by the oxidative stress scavenger N-acetyl-cysteine. These results suggest that a low dose of cisplatin induces the tolerance of TRAIL in SKOV3 cells at least partly, depending on the oxidative stress signaling pathway. PMID:27035109

  16. Estimation of camptothecin and pharmacological evaluation of Ophiorrhiza prostrata D. Don and Ophiorrhiza mungos L.

    Institute of Scientific and Technical Information of China (English)

    Krishnakumar G; Rameshkumar KB; Priya Srinivas; Satheeshkumar K; Krishnan PN

    2012-01-01

    Objective: To carry out the qualitative and quantitative evaluation of camptothecin, estimation of total phenolic compounds and evaluation of in vitro antioxidant activity and cytotoxic activity of Ophiorrhiza prostrata and Ophiorrhiza mungos. Methods: Direct Analysis in Real Time- Mass Spectrometry (DART-MS) was employed for the detection of camptothecin in the Ophiorrhiza species, while high performance thin layer chromatography (HPTLC) was used for the estimation of camptothecin. Total phenolic compounds were estimated by modified Folins-Ciocalteu’s reagent method. Antioxidant activity was evaluated through DPPH radical, hydroxyl radical, superoxide radical scavenging assays and reducing power assay. The cytotoxicity evaluation was performed using MTT assay on MCF-7 cell lines. Results: The presence of camptothecin was confirmed in both the species by the [M++H] peak at 349 by DART-MS analysis. Camptothecin content was estimated as 1.47 μg/gm (dry wt) in O. prostrata and 188.60 μg/gm (dry wt) in O.mungos using HPTLC method. The moderate in vitro antioxidant activities of the methanol extracts corroborates with the low content of phenolic compounds in O. prostrata (9.88 GAE mg/g) and O. mungos (12.73 GAE mg/g). The methanol extract of O. prostrata exhibited remarkable cytotoxicity on human breast cancer cell lines (MCF-7), with IC50 value 1.10μg/mL compared to O. mungos (3.48μg/mL) and standard camptothecin (3.51μg/mL). Conclusions: The application of DART-MS proved to be a simple and rapid technique for the detection of camptothecin in Ophiorrhiza species. The higher cytotoxicity for O. prostrata, despite the low content of camptothecin suggests the presence of other potential cytotoxic compounds in O. prostrata.

  17. Characterization of DNA topoisomerase-1 in Spodoptera exigua for toxicity evaluation of camptothecin and hydoxy-camptothecin.

    Directory of Open Access Journals (Sweden)

    Lan Zhang

    Full Text Available Camptothecin (CPT, a plant alkaloid originally isolated from the native Chinese tree, Camptotheca acuminate, exerts the toxic effect by targeting eukaryotic DNA topoisomerase 1 (DNA Topo1. Besides as potent anti-cancer agents, CPT and its derivatives are now being explored as potential pesticides for insect control. In this study, we assessed their toxicity to an insect homolog, the Topo1 protein from beet armyworms (Spodoptera exigua Hübner, a worldwide pest of many important crops. The S. exigua Topo1 gene contains an ORF of 2790 base pairs that is predicted to encode a polypeptide of 930 amino acids. The deduced polypeptide exhibits polymorphism at residue sites V420, L530, A653 and T729 (numbered according to human Topo1 among insect species, which are predicted to confer sensitivity to CPT. The DNA relaxation activity of this protein was subsequently examined using a truncated form that contained the residues 337-930 and was expressed in bacteria BL21 cells. The purified protein retained the ability to relax double-stranded DNA and was susceptible to CPT and its derivative hydroxy-camptothecin (HCPT in a dose-dependent manner. The same inhibitory effect was also found on the native Topo1 extracted from IOZCAS-Spex-II cells, a cell line established from beet armyworms. Additionally, CPT and HCPT treatment reduced the steady accumulation of Topo1 protein despite the increased mRNA expression in response to the treatment. Our studies provide information of the S. exigua Topo1 gene and its amino acid polymorphism in insects and uncover some clues about potential mechanisms of CPT toxicity against insect pests. These results also are useful for development of more effective Topo1-targeted CPT insecticides in the future.

  18. Self-assembling nanomicelles of a novel camptothecin prodrug engineered with a redox-responsive release mechanism.

    Science.gov (United States)

    Li, Xue-Quan; Wen, Hui-Yun; Dong, Hai-Qing; Xue, Wei-Ming; Pauletti, Giovanni M; Cai, Xiao-Jun; Xia, Wen-Juan; Shi, Donglu; Li, Yong-Yong

    2011-08-14

    A novel amphiphilic camptothecin prodrug that spontaneously arranges into nanomicelles which preferentially release the cytotoxic drug under tumor-relevant reductive conditions is designed. PMID:21725532

  19. Escaping from MOND

    OpenAIRE

    Famaey, Benoit; Bruneton, Jean-Philippe; Zhao, HongSheng

    2007-01-01

    We present a new test of modified Newtonian dynamics (MOND) on galactic scales, based on the escape speed in the solar neighbourhood. This test is independent from other empirical successes of MOND at reproducing the phenomenology of galactic rotation curves. The galactic escape speed in MOND is entirely determined by the baryonic content of the Galaxy and the external field in which it is embedded. We estimate that the external field in which the Milky Way must be embedded to produce the obs...

  20. Isoeugenol is a selective potentiator of camptothecin cytotoxicity in vertebrate cells lacking TDP1.

    Science.gov (United States)

    Elsayed, Waheba; El-Shafie, Lamia; Hassan, Mohamed K; Farag, Mohamed A; El-Khamisy, Sherif F

    2016-01-01

    Camptothecin (CPT), a topoisomerase I (TOP1) inhibitor, exhibits anti-tumor activity against a wide range of tumors. Redundancy of TOP1-mediated repair mechanisms is a major challenge facing the efficiency of TOP1-targetting therapies. This study aims to uncover new TOP1 targeting approaches utilising a selection of natural compounds in the presence or absence of tyrosyl DNA phosphodiesterase I (TDP1); a key TOP1-mediated protein-linked DNA break (PDB) repair enzyme. We identify, isoeugenol, a phenolic ether found in plant essential oils, as a potentiator of CPT cytotoxicity in Tdp1 deficient but not proficient cells. Consistent with our cellular data, isoeugenol did not inhibit Tdp1 enzymatic activity in vitro nor it sensitized cells to the PARP1 inhibitor olaparib. However, biochemical analyses suggest that isoeugenol inhibits TDP2 catalytic activity; a pathway that can compensate for the absence of TDP1. Consistent with this, isoeugenol exacerbated etoposide-induced cytotoxicity, which generates TOP2-mediated PDBs for which TDP2 is required for processing. Together, these findings identify isoeugenol as a potential lead compound for developing TDP2 inhibitors and encourage structure-activity relationship studies to shed more light on its utility in drug discovery programs. PMID:27220325

  1. Isoeugenol is a selective potentiator of camptothecin cytotoxicity in vertebrate cells lacking TDP1

    Science.gov (United States)

    Elsayed, Waheba; El-Shafie, Lamia; Hassan, Mohamed K.; Farag, Mohamed A.; El-Khamisy, Sherif F.

    2016-01-01

    Camptothecin (CPT), a topoisomerase I (TOP1) inhibitor, exhibits anti-tumor activity against a wide range of tumors. Redundancy of TOP1-mediated repair mechanisms is a major challenge facing the efficiency of TOP1-targetting therapies. This study aims to uncover new TOP1 targeting approaches utilising a selection of natural compounds in the presence or absence of tyrosyl DNA phosphodiesterase I (TDP1); a key TOP1-mediated protein-linked DNA break (PDB) repair enzyme. We identify, isoeugenol, a phenolic ether found in plant essential oils, as a potentiator of CPT cytotoxicity in Tdp1 deficient but not proficient cells. Consistent with our cellular data, isoeugenol did not inhibit Tdp1 enzymatic activity in vitro nor it sensitized cells to the PARP1 inhibitor olaparib. However, biochemical analyses suggest that isoeugenol inhibits TDP2 catalytic activity; a pathway that can compensate for the absence of TDP1. Consistent with this, isoeugenol exacerbated etoposide-induced cytotoxicity, which generates TOP2-mediated PDBs for which TDP2 is required for processing. Together, these findings identify isoeugenol as a potential lead compound for developing TDP2 inhibitors and encourage structure-activity relationship studies to shed more light on its utility in drug discovery programs. PMID:27220325

  2. DNA damaging and cell cycle effects of the topoisomerase I poison camptothecin in irradiated human cells

    International Nuclear Information System (INIS)

    This study addressed the potential radiosensitizing and DNA-damaging actions of the DNA topoisomerase I poison camptothecin (CPT) on SV40 transformed normal (MRC5CVI) and ataxia-telangiectasia (AT5BIVA) fibroblast cell lines. In both cell lines CPT induced a dose-dependent delay of cells in S phase, followed by a dose-dependent trapping in G2/M phase. Acute X-irradiation produced patterns of G2/M arrest and S-phase delay similar to those observed for CPT in the MRC5CVI cell line, but no S phase delay was observed in the AT5BIVA cell line consistent with the ataxia-telangiectasia phenotype of this cell line. X-irradiation of CPT-treated cells resulted in additive prolongation of S phase delay in MRC5CVI cultures and additive effects for cell killing in both cell lines. The potential for topoisomerase I-DNA cross-linking by CPT was not altered by 24 h pretreatment with CPT, or by acute X-irradiation. Hypersensitivity of AT5BIVA to CPT was not attributable to elevated levels of complex trapping. (author)

  3. Thermosensitive PNIPAM-b-HTPB block copolymer micelles: molecular architectures and camptothecin drug release.

    Science.gov (United States)

    Luo, Yan-Ling; Yang, Xiao-Li; Xu, Feng; Chen, Ya-Shao; Zhang, Bin

    2014-02-01

    Two kinds of thermo-sensitive poly(N-isoproplacrylamide) (PNIPAM) block copolymers, AB4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with hydroxyl-terminated polybutadiene (HTPB) as central blocks, and characterization was performed by (1)H NMR, FT-IR and SEC. The multiblock copolymers could spontaneously assemble into more regular spherical core-shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension technique, nano particle analyzer, TEM, DLS and UV-vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature about 33-35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles. PMID:24184534

  4. Escape behaviors in insects.

    Science.gov (United States)

    Card, Gwyneth M

    2012-04-01

    Escape behaviors are, by necessity, fast and robust, making them excellent systems with which to study the neural basis of behavior. This is especially true in insects, which have comparatively tractable nervous systems and members who are amenable to manipulation with genetic tools. Recent technical developments in high-speed video reveal that, despite their short duration, insect escape behaviors are more complex than previously appreciated. For example, before initiating an escape jump, a fly performs sophisticated posture and stimulus-dependent preparatory leg movements that enable it to jump away from a looming threat. This newfound flexibility raises the question of how the nervous system generates a behavior that is both rapid and flexible. Recordings from the cricket nervous system suggest that synchrony between the activity of specific interneuron pairs may provide a rapid cue for the cricket to detect the direction of an approaching predator and thus which direction it should run. Technical advances make possible wireless recording from neurons while locusts escape from a looming threat, enabling, for the first time, a direct correlation between the activity of multiple neurons and the time-course of an insect escape behavior. PMID:22226514

  5. Enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, Fusarium solani.

    Science.gov (United States)

    Venugopalan, Aarthi; Srivastava, Smita

    2015-01-01

    Ethanolic extract of a non-camptothecin producing plant, Catharanthus roseus when added in the suspension culture of the endophyte Fusarium solani known to produce camptothecin, resulted in enhanced production of camptothecin by 10.6-fold in comparison to that in control (2.8 μg/L). Interestingly, addition of pure ethanol (up to 5% v/v) in the suspension culture of F. solani resulted in maximum enhancement in camptothecin production (up to 15.5-fold) from that obtained in control. In the presence of ethanol, a reduced glucose uptake (by ∼ 40%) and simultaneous ethanol consumption (up to 9.43 g/L) was observed during the cultivation period (14 days). Also, the total NAD level and the protein content in the biomass increased by 3.7- and 1.9-fold, respectively, in comparison to that in control. The study indicates a dual role of ethanol, presumably as an elicitor and also as a carbon/energy source, leading to enhanced biomass and camptothecin production. PMID:25603728

  6. Targeted gene correction using psoralen, chlorambucil and camptothecin conjugates of triplex forming peptide nucleic acid (PNA)

    DEFF Research Database (Denmark)

    Birkedal, Henrik; Nielsen, Peter E

    2011-01-01

    Gene correction activation effects of a small series of triplex forming peptide nucleic acid (PNA) covalently conjugated to the DNA interacting ligands psoralen, chlorambucil and camptothecin targeted proximal to a stop codon mutation in an EGFP reporter gene were studied. A 15-mer homopyrimidine....... Consistent with the extract experiments, treatment with adduct forming PNA conjugates (psoralen and chlorambucil) resulted in a decrease in background correction frequencies in transiently transfected cells, whereas unmodified PNA or the PNA-camptothecin conjugate had little or no effect. These results...... suggest that simple triplex forming PNAs have little effect on proximal gene correctional events whereas PNA conjugates capable of forming DNA adducts and interstrand crosslinks are strong inhibitors. Most interestingly the PNA conjugated to the topoisomerase inhibitor, camptothecin enhanced repair in...

  7. Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation, identification, and fermentation conditions optimization for camptothecin production.

    Science.gov (United States)

    Pu, Xiang; Qu, Xixing; Chen, Fei; Bao, Jinku; Zhang, Guolin; Luo, Yinggang

    2013-11-01

    Camptothecin (CPT), the third largest anticancer drug, is produced mainly by Camptotheca acuminata and Nothapodytes foetida. CPT itself is the starting material for clinical CPT-type drugs, but the plant-derived CPT cannot support the heavy demand from the global market. Research efforts have been made to identify novel sources for CPT. In this study, three CPT-producing endophytic fungi, Aspergillus sp. LY341, Aspergillus sp. LY355, and Trichoderma atroviride LY357, were isolated and identified from C. acuminata. Most CPT produced by these fungi was found in the fermentation broth, and their corresponding CPT yields were 7.93, 42.92, and 197.82 μg l(-1), respectively. The CPT-producing capability of LY341 and LY355 was completely lost after repeat subculturing. A substantial decrease of CPT production was also observed in the second generation of LY357. However, a stable and sustainable production of CPT was found from the second generation through the eighth generation of LY357. The fermentation medium, time, pH, temperature, and agitation rate were optimized for CPT production. Methyl jasmonate and XAD16 were proven to be an optimum elicitor and adsorbent resin, respectively, in view of that CPT yield was increased 3.4- and 11-fold through their use. A 50- to 75-fold increase of CPT yield was obtained when the optimized fermentation conditions, elicitor, and adsorbent resin were combined and applied to the culture of the seventh and eighth generations of LY357, and the highest CPT yield was 142.15 μg l(-1). The CPT-producing T. atroviride LY357 paves a potential to uncover the mysteries of CPT biosynthesis. PMID:23949997

  8. Effect of fermentation parameters, elicitors and precursors on camptothecin production from the endophyte Fusarium solani.

    Science.gov (United States)

    Venugopalan, Aarthi; Potunuru, Uma Rani; Dixit, Madhulika; Srivastava, Smita

    2016-04-01

    Volumetric productivity of camptothecin from the suspension culture of the endophyte Fusarium solani was enhanced up to ∼152 fold (from 0.19 μg l(-1) d(-1) to 28.9 μg l(-1) d(-1)) under optimized fermentation conditions including initial pH (6.0), temperature (32 °C) and agitation speed (80 rpm) with (5% (v/v)) ethanol as medium component. Among various elicitors and precursors studied, tryptamine (0.5 mM) as precursor and bovine serum albumin (BSA) (0.075 mM) as an elicitor added on day 6 of the cultivation period resulted in maximum enhancement of camptothecin concentration (up to 4.5 and 3.4-fold, respectively). These leads provide immense scope for further enhancement in camptothecin productivity at bioreactor level. The cytotoxicity analysis of the crude camptothecin extract from the fungal biomass revealed its high effectiveness against colon and mammary gland cancer cell lines. PMID:26851893

  9. Hydrogen Escape from early Earth and Mars

    Science.gov (United States)

    Zugger, M. E.; Ramirez, R. M.; Kasting, J. F.

    2012-12-01

    A controversy regarding hydrodynamic escape rates arose when Tian et al. (2005) published transonic escape rates for an atmosphere composed of pure H2. Tian et al. concluded that the hydrogen escape rate from early Earth would have been a factor of 20 or more slower than the diffusion limit, even if the solar EUV (extreme ultraviolet) flux was enhanced by a factor of 5 relative to today. This conclusion was challenged by Catling (2006), who pointed out that solar EUV fluxes could have been much higher than this so that plenty of energy should have been available to power escape. This controversy has remained unresolved to date. Hydrogen escape from early Mars is also of interest. As discussed in this session in a complementary paper by Ramirez et al., collision-induced absorption by molecular hydrogen could have helped to warm early Mars, perhaps explaining the formation of valleys and valley networks. Ramirez et al. have shown that a mixture of 90% CO2 and 10% H2 is capable raising early Mars' surface temperature above the freezing point of water, for surface pressures exceeding ~3 bar. However, we need to understand whether H2 mixing ratios of 10% are physically plausible. The H2 partial pressure in Mars' early atmosphere would have been determined by the balance between volcanic outgassing and escape to space. The 10% mixing ratio is high compared to the value of ~10-3 typically assumed for early Earth. But Mars' early atmosphere may have been more reduced than Earth's (Wadwha, 2001); if the hydrogen escape rate on Mars was also slower than on Earth, then additional increases in atmospheric hydrogen concentration are possible. To answer these questions about the early atmospheres of Earth and Mars, we have modified an existing model of hydrodynamic escape, developed by F. Tian, J. Kasting, and others, to converge for atmospheres with a wide range of hydrogen mixing ratios. The model finds subsonic solutions to the hydrodynamic equations; these can be shown to

  10. Escape Performance Following Exposure to Inescapable Shock: Deficits in Motor Response Maintenance

    Science.gov (United States)

    Anisman, Hymie; And Others

    1978-01-01

    A series of 13 experiments employing mice systematically investigated shock-elicited activity in a circular field and escape performance in a shuttle box following exposure to either escapable or inescapable shock. Results show that escape interference induced by inescapable shock may be comfortably interpreted in terms of a decreased tendency for…

  11. Reconstructing the Alcatraz escape

    Science.gov (United States)

    Baart, F.; Hoes, O.; Hut, R.; Donchyts, G.; van Leeuwen, E.

    2014-12-01

    In the night of June 12, 1962 three inmates used a raft made of raincoatsto escaped the ultimate maximum security prison island Alcatraz in SanFrancisco, United States. History is unclear about what happened tothe escapees. At what time did they step into the water, did theysurvive, if so, where did they reach land? The fate of the escapees has been the subject of much debate: did theymake landfall on Angel Island, or did the current sweep them out ofthe bay and into the cold pacific ocean? In this presentation, we try to shed light on this historic case using avisualization of a high-resolution hydrodynamic simulation of the San Francisco Bay, combined with historical tidal records. By reconstructing the hydrodynamic conditions and using a particle based simulation of the escapees we show possible scenarios. The interactive model is visualized using both a 3D photorealistic and web based visualization. The "Escape from Alcatraz" scenario demonstrates the capabilities of the 3Di platform. This platform is normally used for overland flooding (1D/2D). The model engine uses a quad tree structure, resulting in an order of magnitude speedup. The subgrid approach takes detailed bathymetry information into account. The inter-model variability is tested by comparing the results with the DFlow Flexible Mesh (DFlowFM) San Francisco Bay model. Interactivity is implemented by converting the models from static programs to interactive libraries, adhering to the Basic ModelInterface (BMI). Interactive models are more suitable for answeringexploratory research questions such as this reconstruction effort. Although these hydrodynamic simulations only provide circumstantialevidence for solving the mystery of what happened during the foggy darknight of June 12, 1962, it can be used as a guidance and provides aninteresting testcase to apply interactive modelling.

  12. Effects of submarine escape training on the pulmonary function and carbon dioxide retention in the escape

    Institute of Scientific and Technical Information of China (English)

    CHEN Rui-yong; WANG Wen-bo; FANG Yi-qun; XU Ji; XU Lin-jun

    2011-01-01

    Objective Fast buoyancy ascent escape used in submarine escape is the most probable choice of survival in case of a submarine accident.Rate of success for escape depends very much on the extent of training,in spite of the fact that rapid compression and decompression pose great challenges to the human body in terms of enormous stresses.To minimize stresses experienced during sub escape training has always been a research subject for us.Lungs are susceptible to rapid change in pressure during escape.Dynamic pulmonary function and the end-tidal PCO2 ( PETCO2 ) might be the best indicator for its effect on the pulmonary function of the submarine escapee.Methods Five male navy divers received submarine escape trainings,at different depths from 3-60 m.They were compressed at different rates (with pressure doubled every 20 s or 30 s),in the simulated submarine escape tower located in the Naval Medical Research Institute.The gas of end-expiration was collected immediately after escape,respiratory rate (RR) and dynamic pulmonary function were closely monitored,and PETCO2 was determined with the mass spectrometer.Results Experimental results showed that forced expiratory volume in 1 second (FEV1.0) tended to increase with increasing depth,and that it increased significantly at 50 m and 60 m,when compared with the basic data (P < 0.05 ),and it was coupled with a decrease in forced expiratory flow at 25 % ( FEF25% ),indicating that it had certain effect on the function of small airways.PETCO2 and RR all elevated markedly following escapes.No significant differences could be seen in RR following escapes at various depths.PETCO2 and depth ( r =0.387,P < 0.01 ) were positively correlated with compression rate ( r =0.459,P < 0.01 ) and RR ( r =0.467,P < 0.01 ).CO2 retention might be attributed to pulmonary ventilation disorder induced by rapid changes in pressure.PETCO2 was within normal range,following escapes at various depths,suggesting that increased RR might be

  13. Escape from a Riddled-Like Basin

    Institute of Scientific and Technical Information of China (English)

    CHAO Xiao-Gang; DAI Jun; WANG Wen-Xiu; HE Da-Ren

    2005-01-01

    @@ We investigate a system described by a conservative and a dissipative map concatenation. A fat fractal forbidden net, induced by interaction between discontinuous and noninvertible properties, introduces rippled-like attraction basins of two periodic attractors. Small areas, which serve as escaping holes of a new type of crisis, are dominated by conventional strong dissipation and are bounded by the forbidden region, but only in the vicinity of each periodic point.

  14. PVA engineered microcapsules for targeted delivery of camptothecin to HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Galbiati, Alice; Rocca, Blasco Morozzo della; Tabolacci, Claudio; Beninati, Simone; Desideri, Alessandro [Dipartimento di Biologia, Universita di Roma Tor Vergata, Via della Ricerca Scientifica, 00133 Rome (Italy); Paradossi, Gaio, E-mail: paradossi@stc.uniroma2.it [Dipartimento di Scienze e Tecnologie Chimiche, Universita di Roma Tor Vergata, Via della Ricerca Scientifica, 00133 Rome (Italy)

    2011-12-01

    Capsular microvectors are an important tool in the recent research field of nanomedicine to address a drug cargo for the therapeutic treatment of several pathologies. In this study we describe how the product of the conjugation of the polysaccharide chitosan with folate can be used as a coating of poly (vinyl alcohol), PVA, based microcapsules for an efficient targeting of HeLa cells. The influence of the coating on the bioadhesive properties of the vector and on its cargo capacity was also considered using camptothecin as an anticancer drug model. The coating strategy was finalized to exploit the good chemical versatility of PVA, used to form the shell of the vector. This study is a follow up of an investigation activity aiming to show the potentialities of PVA-shelled microcapsules or microbubbles as injectable microdevices supporting a theranostic approach for different types of tumour. Highlights: {yields}Coating of PVA-shelled microcapsules with chitosan-folate. {yields} Selective bioadhesion of microcapsules to HeLa Cells. {yields} Effective loading and release of camptothecin. {yields} In vitro anti-proliferative action of camptothecin loaded microcapsules.

  15. Synthesis and Insecticidal Activity of Novel Camptothecin Derivatives Containing Analogs of Chrysanthemic Acid Moieties

    Institute of Scientific and Technical Information of China (English)

    DENG Li; ZHANG Lan; CAO Li-dong; XIE Ru-liang; ZHANG Yan-ning; HE Wei-zhi; JIANG Hong-yun

    2014-01-01

    Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin (CPT) and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin (1) and 10-hydroxycamptothecin (2) derivatives (1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e) were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua Hübner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.

  16. Escape from Vela X

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, J.; /Leicester U.; Funk, S.; /KIPAC, Menlo Park; Parsons, R.D.; /Leeds U.; Ohm, S.; /Leicester U. /Leeds U.

    2012-02-15

    While the Vela pulsar and its associated nebula are often considered as the archetype of a system powered by a {approx} 10{sup 4} year old isolated neutron star, many features of the spectral energy distribution of this pulsar wind nebula are both puzzling and unusual. Here we develop a model that for the first time relates the main structures in the system, the extended radio nebula (ERN) and the X-ray cocoon through continuous injection of particles with a fixed spectral shape. We argue that diffusive escape of particles from the ERN can explain the steep Fermi-LAT spectrum. In this scenario Vela X should produce a distinct feature in the locally-measured cosmic ray electron spectrum at very high energies. This prediction can be tested in the future using the Cherenkov Telescope Array (CTA). If particles are indeed released early in the evolution of PWNe and can avoid severe adiabatic losses, PWN provide a natural explanation for the rising positron fraction in the local CR spectrum.

  17. Enhanced sensitivity to camptothecin in ataxia-telangiectasia cells and its relationship with the expression of DNA topoisomerase I

    International Nuclear Information System (INIS)

    The drug Camptothecin induced a marked cell cycle block in G2 phase, the magnitude of the block being closely related to cell kill xeroderma pigmentosum (XP) group A cells showed normal sensitivity to CPT, whereas ataxia-telangiectasis (A-T) derived cells were consistently hypersensitive (3-5 fold) in a manner which could not be related to a primary deficiency in topoisomerase I activity, abnormal capacity for complex formation or anomalies in the intracellular generation of DNA strand breaks. A CPT-resistant A-T subline had reduced topoisomerase I activity but retained the characteristic of hypersensitivity to X-radiation. The subline lost resistance upon in vitro passage with evidence that resistance was initially an unstable feature of a subpopulation of cells. The findings have implications for the role of topoisomerase I in the in vitro phenotype of A-T cells, and the contribution made by topoisomerase I-dependent damage to the cytotoxic action of CPT. (author)

  18. Thermosensitive AB4 four-armed star PNIPAM-b-HTPB multiblock copolymer micelles for camptothecin drug release.

    Science.gov (United States)

    Luo, Yan-Ling; Fu, Jing-Yu; Xu, Feng; Chen, Ya-Shao; Zhang, Bin

    2014-01-01

    Thermo-sensitive poly(N-isoproplacrylamide)m-block-hydroxyl-terminated polybutadiene-block-poly(N-isoproplacrylamide)m (PNIPAMm-b-HTPB-b-PNIPAMm, m = 1 or 2) block copolymers, AB4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with HTPB as central blocks, and characterization was performed by (1)H NMR, Fourier transform infrared, and size exclusion chromatography. The multiblock copolymers could spontaneously assemble into more regular spherical core-shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension, nanoparticle analyzer, transmission electron microscope (TEM), dynamic light scattering, and UV-vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm, and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature of about 33-35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks, and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles. PMID:24236748

  19. Novel 20(S)-sulfonylamidine derivatives of camptothecin and the use thereof as a potent antitumor agent: a patent evaluation of WO2015048365 (A1).

    Science.gov (United States)

    Beretta, Giovanni Luca; Zaffaroni, Nadia; Varchi, Greta

    2016-05-01

    A series of camptothecin (CPT) derivatives featuring acyl-esterification of the 20(S)-hydroxyl group with a residue containing a sulfonylamidine moiety is synthesized via a Cu catalyzed three-component reaction. The compounds show remarkable cytotoxicity against a panel of tumor cells, including a cell line exhibiting Multi-Drug Resistant (MDR) phenotype. The patent develops 9a, the best derivative of the series, that i) selectively poisons DNA Topoisomerase I (TopoI); ii) induces cell-cycle S-phase arrest with activation of the DNA damage response pathway and apoptosis induction and iii) shows considerable in vivo antitumor potency. We envision that the peculiar modification of the 20(S)-hydroxyl group of CPT with a sulfonylamidine residue will play a continuing role in affording new TopoI poison drug candidates for therapeutic applications. PMID:26814056

  20. Suicide as Escape from Self.

    Science.gov (United States)

    Baumeister, Roy F.

    1990-01-01

    Suicide is analyzed as a motivation to escape from adversive self-awareness. The causal chain is traced from initial failures that are attributed internally because of a cognitively deconstructed state. (SLD)

  1. 15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPAR{gamma} pathways

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Yasuhiro [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan); Fujita, Megumi [Faculty of Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien-kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Koma, Hiromi [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan); Yamamori, Motohiro [Faculty of Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien-kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Nakamura, Tsutomu [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan); Okamura, Noboru [Faculty of Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien-kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Yagami, Tatsurou, E-mail: yagami@himeji-du.ac.jp [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan)

    2011-07-08

    Highlights: {yields} A topoisomerase-I inhibitor, camptothecin, exhibited synergistically toxicity with 15d-PGJ{sub 2}. {yields} The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. {yields} A PPAR{gamma} antagonist did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. {yields} The treatment of camptothecin combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. -- Abstract: Renal cell carcinoma (RCC) is chemoresistant cancer. Although several clinical trials were conducted to explore effective medications, the chemoresistance of RCC has not yet been conquered. An endogenous ligand for peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), 15-deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ{sub 2} in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ{sub 2}, but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. The synergistic effect of topoisomerase-I and II inhibitors was not also detected. A PPAR{gamma} antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ{sub 2} exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPAR{gamma}.

  2. Scrunching: a novel escape gait in planarians.

    Science.gov (United States)

    Cochet-Escartin, Olivier; Mickolajczyk, Keith J; Collins, Eva-Maria S

    2015-10-01

    The ability to escape a predator or other life-threatening situations is central to animal survival. Different species have evolved unique strategies under anatomical and environmental constraints. In this study, we describe a novel musculature-driven escape gait in planarians, 'scrunching', which is quantitatively different from other planarian gaits, such as gliding and peristalsis. We show that scrunching is a conserved gait among different flatworm species, underlying its importance as an escape mechanism. We further demonstrate that it can be induced by a variety of physical stimuli, including amputation, high temperature, electric shock and low pH. We discuss the functional basis for scrunching as the preferential gait when gliding is impaired due to a disruption of mucus production. Finally, we show that the key mechanical features of scrunching are adequately captured by a simple biomechanical model that is solely based on experimental data from traction force microscopy and tissue rheology without fit parameters. Together, our results form a complete description of this novel form of planarian locomotion. Because scrunching has distinct dynamics, this gait can serve as a robust behavioral readout for studies of motor neuron and muscular functions in planarians and in particular the restoration of these functions during regeneration. PMID:26356147

  3. Scrunching: a novel escape gait in planarians

    Science.gov (United States)

    Cochet-Escartin, Olivier; Mickolajczyk, Keith J.; Collins, Eva-Maria S.

    2015-10-01

    The ability to escape a predator or other life-threatening situations is central to animal survival. Different species have evolved unique strategies under anatomical and environmental constraints. In this study, we describe a novel musculature-driven escape gait in planarians, ‘scrunching’, which is quantitatively different from other planarian gaits, such as gliding and peristalsis. We show that scrunching is a conserved gait among different flatworm species, underlying its importance as an escape mechanism. We further demonstrate that it can be induced by a variety of physical stimuli, including amputation, high temperature, electric shock and low pH. We discuss the functional basis for scrunching as the preferential gait when gliding is impaired due to a disruption of mucus production. Finally, we show that the key mechanical features of scrunching are adequately captured by a simple biomechanical model that is solely based on experimental data from traction force microscopy and tissue rheology without fit parameters. Together, our results form a complete description of this novel form of planarian locomotion. Because scrunching has distinct dynamics, this gait can serve as a robust behavioral readout for studies of motor neuron and muscular functions in planarians and in particular the restoration of these functions during regeneration.

  4. Amplitude modulation control of escape from a potential well

    Energy Technology Data Exchange (ETDEWEB)

    Chacón, R. [Departamento de Física Aplicada, Escuela de Ingenierías Industriales, Universidad de Extremadura, Apartado Postal 382, E-06006 Badajoz (Spain); Martínez García-Hoz, A. [Departamento de Física Aplicada, Escuela Universitaria Politécnica, Universidad de Castilla-La Mancha, E-13400 Almadén (Ciudad Real) (Spain); Miralles, J.J. [Departamento de Física Aplicada, Escuela de Ingenieros Industriales, Universidad de Castilla-La Mancha, E-02071 Albacete (Spain); Martínez, P.J. [Departamento de Física Aplicada, E.I.N.A., Universidad de Zaragoza, E-50018 Zaragoza (Spain); Instituto de Ciencia de Materiales de Aragón, CSIC – Universidad de Zaragoza, E-50009 Zaragoza (Spain)

    2014-03-01

    We demonstrate the effectiveness of periodic amplitude modulations in controlling (suppressing and enhancing) escape from a potential well through the universal model of a damped Helmholtz oscillator subjected to an external periodic excitation (the escape-inducing excitation) whose amplitude is periodically modulated (the escape-controlling excitation). Analytical and numerical results show that this multiplicative control works reliably for different subharmonic resonances between the two periodic excitations involved, and that its effectiveness is comparable to those of different methods of additive control. Additionally, we demonstrate the robustness of the multiplicative control against the presence of low-intensity Gaussian noise. -- Highlights: •Multiplicative control of escape from a potential well has been demonstrated. •Theoretical predictions are obtained from a Melnikov analysis. •It has been shown the robustness of the multiplicative control against noise.

  5. Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents

    OpenAIRE

    Zhao, Xiao-Bo; Goto, Masuo; Song, Zi-Long; Morris-Natschke, Susan L.; Zhao, Yu; Wu, Dan; Yang, Liu; Li, Shu-Gang; Liu, Ying-Qian; Zhu, Gao-Xiang; Wu, Xiao-Bing; Lee, Kuo-Hsiung

    2014-01-01

    A series of novel 7-(N-substituted-methyl)-camptothecin derivatives was designed, synthesized, and evaluated for in vitro cytotoxicity against four human tumor cell lines, A-549, MDA-MB-231, KB, and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, with IC50 values ranging from 0.0023 to 1.11 μM, and were as or more potent than topotecan. Compounds 9d, 9e, and 9r exhibited the highest antiproliferative activity among all prepared d...

  6. Has the UAE Escaped the Oil Curse?

    OpenAIRE

    Ilham Haouas; Raimundo Soto

    2012-01-01

    The UAE is blessed with vast deposits of oil and gas. Contrary to other oil-rich economies, the UAE seems to have escaped from the so-called “oil curse”. We study how the UAE used resource rents to achieve economic development and provide higher welfare for the local population. We identify, nevertheless, symptoms of the resource curse in three areas: very low growth in labor productivity, government policies unable to counteract economic cycles induced by oil-price volatility, and massive ov...

  7. Energy-limited escape revised

    OpenAIRE

    Salz, M.; Schneider, P. C.; Czesla, S.; Schmitt, J. H. M. M.

    2015-01-01

    Gas planets in close proximity to their host stars experience photoevaporative mass loss. The energy-limited escape concept is generally used to derive estimates for the planetary mass-loss rates. Our photoionization hydrodynamics simulations of the thermospheres of hot gas planets show that the energy-limited escape concept is valid only for planets with a gravitational potential lower than $\\log_\\mathrm{10}\\left( -\\Phi_{\\mathrm{G}}\\right) < 13.11~$erg$\\,$g$^{-1}$ because in these planets th...

  8. Self-defensive nano-assemblies from camptothecin-based antitumor drugs.

    Science.gov (United States)

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Li, Bin; Wang, Shi-Bo; Cheng, Si-Xue; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2015-09-01

    Camptothecin (CPT)-based drugs always undergo the reversible, pH-dependent lactone ring-opening reaction, yielding the inactive but toxic carboxylate form. Self-assembly strategy provides an effective route for preserving their bio-stability. In this article, nano-sized self-assemblies from CPT-based antitumor drugs were simply built up by directly diluting the stock dimethylsulfoxide solutions of (S)-(+)-CPT, (S)-10-hydroxyl camptothecin and carboxylic CPT with water/phosphate-buffered saline solution. Because of their different molecular structures in A-ring or modification on the 20-OH group, CPT self-assembled into helical nano-ribbons, whereas 10-hydroxycamptothecin and carboxylic CPT self-aggregated into flat nano-ribbons and cylindric nano-rods, respectively. Attractively, the self-assembly of CPT-based drugs could occur within 1 min at a low concentration of 1 × 10(-5 )M. Adopting the J-type self-aggregation, self-assemblies were stable in aqueous solution and could effectively protect the CPT-based drugs from hydrolysis, which thereby kept their bioactivity for tumor therapy. PMID:26816639

  9. Reprint of: Effect of fermentation parameters, elicitors and precursors on camptothecin production from the endophyte Fusarium solani.

    Science.gov (United States)

    Venugopalan, Aarthi; Potunuru, Uma Rani; Dixit, Madhulika; Srivastava, Smita

    2016-08-01

    Volumetric productivity of camptothecin from the suspension culture of the endophyte Fusarium solani was enhanced up to ∼152 fold (from 0.19μgl(-1)d(-1) to 28.9μgl(-1)d(-1)) under optimized fermentation conditions including initial pH (6.0), temperature (32°C) and agitation speed (80rpm) with (5% (v/v)) ethanol as medium component. Among various elicitors and precursors studied, tryptamine (0.5mM) as precursor and bovine serum albumin (BSA) (0.075mM) as an elicitor added on day 6 of the cultivation period resulted in maximum enhancement of camptothecin concentration (up to 4.5 and 3.4-fold, respectively). These leads provide immense scope for further enhancement in camptothecin productivity at bioreactor level. The cytotoxicity analysis of the crude camptothecin extract from the fungal biomass revealed its high effectiveness against colon and mammary gland cancer cell lines. PMID:27189536

  10. Sharks modulate their escape behavior in response to predator size, speed and approach orientation.

    Science.gov (United States)

    Seamone, Scott; Blaine, Tristan; Higham, Timothy E

    2014-12-01

    Escape responses are often critical for surviving predator-prey interactions. Nevertheless, little is known about how predator size, speed and approach orientation impact escape performance, especially in larger prey that are primarily viewed as predators. We used realistic shark models to examine how altering predatory behavior and morphology (size, speed and approach orientation) influences escape behavior and performance in Squalus acanthias, a shark that is preyed upon by apex marine predators. Predator models induced C-start escape responses, and increasing the size and speed of the models triggered a more intense response (increased escape turning rate and acceleration). In addition, increased predator size resulted in greater responsiveness from the sharks. Among the responses, predator approach orientation had the most significant impact on escapes, such that the head-on approach, as compared to the tail-on approach, induced greater reaction distances and increased escape turning rate, speed and acceleration. Thus, the anterior binocular vision in sharks renders them less effective at detecting predators approaching from behind. However, it appears that sharks compensate by performing high-intensity escapes, likely induced by the lateral line system, or by a sudden visual flash of the predator entering their field of view. Our study reveals key aspects of escape behavior in sharks, highlighting the modulation of performance in response to predator approach. PMID:25041843

  11. Escaping carbon lock-in

    Energy Technology Data Exchange (ETDEWEB)

    Unruh, G.C. [Instituto de Empresa, Madrid (Spain)

    2002-03-01

    This article explores the climate policy implications of the arguments made in ''Understanding carbon lock-in'' (Unruh, 2000), which posited that industrial countries have become locked-into fossil fuel-based energy systems through path dependent processes driven by increasing returns to scale. Carbon lock-in arises through technological, organizational, social and institutional co-evolution, ''culminating'' in what was termed as techno-institutional complex (TIC). In order to resolve the climate problem, an escape from the lock-in condition is required. However, due to the self-referential nature of TIC, escape conditions are unlikely to be generated internally and it is argued here that erogenous forces are probably required. (author)

  12. Molecular Dications in Planetary Atmospheric Escape

    Directory of Open Access Journals (Sweden)

    Stefano Falcinelli

    2016-08-01

    Full Text Available Fundamental properties of multiply charged molecular ions, such as energetics, structure, stability, lifetime and fragmentation dynamics, are relevant to understand and model the behavior of gaseous plasmas as well as ionosphere and astrophysical environments. Experimental determinations of the Kinetic Energy Released (KER for ions originating from dissociations reactions, induced by Coulomb explosion of doubly charged molecular ions (molecular dications produced by double photoionization of CO2, N2O and C2H2 molecules of interest in planetary atmospheres, are reported. The KER measurement as a function of the ultraviolet (UV photon energy in the range of 28–65 eV was extracted from the electron-ion-ion coincidence spectra obtained by using tunable synchrotron radiation coupled with ion imaging techniques at the ELETTRA Synchrotron Light Laboratory Trieste, Italy. These experiments, coupled with a computational analysis based on a Monte Carlo trajectory simulation, allow assessing the probability of escape for simple ionic species in the upper atmosphere of Mars, Venus and Titan. The measured KER in the case of H+, C+, CH+, CH2+, N+, O+, CO+, N2+ and NO+ fragment ions range between 1.0 and 5.5 eV, being large enough to allow these ionic species to participate in the atmospheric escape from such planets into space. In the case of Mars, we suggest a possible explanation for the observed behavior of the O+ and CO22+ ion density profiles.

  13. How some T cells escape tolerance induction.

    Science.gov (United States)

    Gammon, G; Sercarz, E

    1989-11-01

    A feature common to many animal models of autoimmune disease, for example, experimental allergic encephalomyelitis, experimental autoimmune myasthenia gravis and collagen-induced arthritis, is the presence of self-reactive T cells in healthy animals, which are activated to produce disease by immunization with exogenous antigen. It is unclear why these T cells are not deleted during ontogeny in the thymus and, having escaped tolerance induction, why they are not spontaneously activated by self-antigen. To investigate these questions, we have examined an experimental model in which mice are tolerant to an antigen despite the presence of antigen-reactive T cells. We find that the T cells that escape tolerance induction are specific for minor determinants on the antigen. We propose that these T cells evade tolerance induction because some minor determinants are only available in relatively low amounts after in vivo processing of the whole antigen. For the same reason, these T cells are not normally activated but can be stimulated under special circumstances to circumvent tolerance. PMID:2478888

  14. Increased synthesis and release of atrial peptide during DOCA escape in conscious dogs

    International Nuclear Information System (INIS)

    The escape from the sodium-retaining effects of prolonged mineralocorticoid treatment in animals and humans was first noted over 40 yr ago, but despite intense study the mechanisms responsible for the escape phenomenon have not been identified. Putative natriuretic hormones have been proposed to account for the escape phenomenon. To determine whether atrial natriuretic peptides (ANP) could participate in the escape phenomenon, the mineralocorticoid deoxycorticosterone acetate (DOCA) was administered to conscious dogs for 14 days. Escape was accompanied by a doubling of plasma ANP concentration, determined by radioimmunoassay, and four- to sevenfold increases in caridac ANP messenger RNA. There were also significant increases in mean arterial blood pressure during the last 8 days of DOCA treatment. Thus increases in the synthesis and secretion of ANP and increases in atrial pressure may represent mechanisms that contribute to the escape from mineralocorticoid-induced sodium retention

  15. Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

    KAUST Repository

    Kieler-Ferguson, Heidi M.

    2013-01-17

    For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery. WIREs Nanomed Nanobiotechnol 2013, 5:130-138. doi: 10.1002/wnan.1209 For further resources related to this article, please visit the WIREs website. Conflict of interest: Drs Kieler-Ferguson and Fréchet declare no conflicts of interest. Dr Szoka is the founder of a liposome drug delivery company that is not working on any of the compounds mentioned in this article. © 2013 Wiley Periodicals, Inc.

  16. Antifungal activity of camptothecin, trifolin, and hyperoside isolated from Camptotheca acuminata.

    Science.gov (United States)

    Li, Shiyou; Zhang, Zhizhen; Cain, Abigail; Wang, Bo; Long, Melissa; Taylor, Josephine

    2005-01-12

    Leaf spots and root rots are major fungal diseases in Camptotheca acuminata that limit cultivation of the plant for camptothecin (CPT), a promising anticancer and antiviral alkaloid. Bioassays showed that pure CPT and flavonoids (trifolin and hyperoside) isolated from Camptotheca effectively control fungal pathogens in vitro, including Alternaria alternata, Epicoccum nigrum, Pestalotia guepinii, Drechslera sp., and Fusarium avenaceum, although antifungal activity of these compounds in the plant is limited. CPT inhibited mycelial growth by approximately 50% (EC50) at 10-30 microg/mL and fully inhibited growth at 75-125 microg/mL. The flavonoids were less effective than CPT at 50 microg/mL, particularly within 20 days after treatment, but more effective at 100 or 150 microg/mL. CPT, trifolin, and hyperoside may serve as leads for the development of fungicides. PMID:15631505

  17. Homogenate extraction technology of camptothecine and hydroxycamptothecin from Camptotheca acuminata leaves

    Institute of Scientific and Technical Information of China (English)

    SHI Wei-guo; ZU Yuan-gang; ZHAO Chun-jian; YANG Lei

    2009-01-01

    Camptothecine (CPT) and hydroxycamptothecin (HCPT), two kinds of anti-cancer alkaloids, were extracted from Camptotheca acuminata leaves using homogenate extraction technology under different conditions such as the ratio of material to liquid, ethanol concentration, and homogenate time. The optimum technology parameters for homogenate extraction of CPT and HCPT from C. acuminata leaves were determined as homogenate time at 8 min, ethanol concentration at 55% and the ratio of material to liquid at 1:15 (g:mL). By using the optimized parameters, we obtained 0.639‰ extraction rate for CPT and 0.437‰ for HCPT. The extraction yields of CPT and HCPT extracted by homogenating technology were higher than those by other extractive methods, such as ultrasonic, reflux, shaking in water bath. It is concluded that the homogenate extraction technology was an efficient method for extracting CPT and HCPT from C. acuminata leaves, with characteristics of less extraction time and high yield.

  18. On UV-Vis spectra and structure of the anticancer drug camptothecin in solutions

    Science.gov (United States)

    Dvoranová, Dana; Bobeničová, Miroslava; Šoralová, Stanislava; Breza, Martin

    2013-08-01

    UV-Vis spectra of camptothecin (CPT) in toluene, acetone, ethanol, acetonitrile, dimethylsulfoxide and aqueous solutions are investigated by UV-Vis spectroscopy and DFT calculations. The structures of CPT and its π-dimer have been optimized using B3LYP and B97D functionals with cc-pVDZ basis sets. Solvent effects were estimated using the Integral Equation Formalism Polarizable Continuum Model. Electron transitions in the studied systems were evaluated by TD-DFT treatment. Whereas the strong peak at the highest wavelength corresponds to the CPT monomer, the existence of the blue shifted one may be explained by its π-dimers formation instead of CPT hydrogen bonding with water molecules.

  19. Selection of Natural and Base-Modified DNA Aptamers for a Camptothecin Derivative.

    Science.gov (United States)

    Fujita, Hiroto; Kuwahara, Masayasu

    2016-01-01

    Nucleic acid aptamers for small molecules are currently being developed and have a potential role in diverse applications including biosensing, diagnostics, and therapeutics involving low-molecular-weight biomarkers and drugs. To enhance and broaden their functions through chemical modification, systematic evolution of ligands by exponential enrichment (SELEX) selection has been attempted with modified DNA/RNA libraries. Recently, we demonstrated the superior efficacy of base modification for affinity enhancement and the usefulness of unnatural nucleic acid libraries for development of small-molecule aptamers. In this unit, we describe construction of a modified DNA library that includes (E)-5-(2-(N-(2-(N(6) -adeninyl)ethyl))carbamylvinyl)uracil bases and acquisition of high-affinity camptothecin-binding DNA aptamers, in addition to those of the corresponding natural DNA library and aptamers, using the SELEX method. © 2016 by John Wiley & Sons, Inc. PMID:27248786

  20. Non-thermal escape of molecular hydrogen from Mars

    CERN Document Server

    Gacesa, Marko; Kharchenko, Vasili

    2012-01-01

    We present a detailed theoretical analysis of a non-thermal escape of molecular hydrogen from Mars induced by collisions with hot atomic oxygen from martian corona. To accurately describe the energy transfer in O + H$_2(v,j)$ collisions, we performed extensive quantum-mechanical calculations of state-to-state elastic, inelastic, and reactive cross sections. The escape flux of H$_2$ molecules was evaluated using a simplified 1D column model of the martian atmosphere with realistic densities of atmospheric gases and hot oxygen production rates for the low solar activity conditions. An average density of the non-thermal escape flux of H$_2$ of $1.9\\times10^5$ cm$^{-2}$s$^{-1}$ was obtained considering energetic O atoms produced in dissociative recombinations of O$_{2}^{+}$ ions. Predicted rovibrational distribution of the escaping H$_2$ was found to contain a significant fraction of higher rotational states. While the non-thermal escape rate was found to be lower than Jeans flux for H$_2$ molecules, the non-ther...

  1. Photochemical Escape of Oxygen from Early Mars

    CERN Document Server

    Zhao, Jinjin

    2015-01-01

    Photochemical escape is an important process for oxygen escape from present Mars. In this work, a 1-D Monte-Carlo Model is developed to calculate escape rates of energetic oxygen atoms produced from O2+ dissociative recombination reactions (DR) under 1, 3, 10, and 20 times present solar XUV fluxes. We found that although the overall DR rates increase with solar XUV flux almost linearly, oxygen escape rate increases from 1 to 10 times present solar XUV conditions but decreases when increasing solar XUV flux further. Analysis shows that atomic species in the upper thermosphere of early Mars increases more rapidly than O2+ when increasing XUV fluxes. While the latter is the source of energetic O atoms, the former increases the collision probability and thus decreases the escape probability of energetic O. Our results suggest that photochemical escape be a less important escape mechanism than previously thought for the loss of water and/or CO2 from early Mars.

  2. Gated narrow escape time for molecular signaling.

    Science.gov (United States)

    Reingruber, Jürgen; Holcman, David

    2009-10-01

    The mean time for a diffusing ligand to activate a target protein located on the surface of a microdomain can regulate cellular signaling. When the ligand switches between various states induced by chemical interactions or conformational changes, while target activation occurs in only one state, this activation time is affected. We investigate this dynamics using new equations for the sojourn times spent in each state. For two states, we obtain exact solutions in dimension one, and asymptotic ones confirmed by Brownian simulations in dimension 3. We find that the activation time is quite sensitive to changes of the switching rates, which can be used to modulate signaling. Interestingly, our analysis reveals that activation can be fast although the ligand spends most of the time "hidden" in the nonactivating state. Finally, we obtain a new formula for the narrow escape time in the presence of switching. PMID:19905605

  3. Formation of nanoparticles by cooperative inclusion between (S-camptothecin-modified dextrans and β-cyclodextrin polymers

    Directory of Open Access Journals (Sweden)

    Thorbjørn Terndrup Nielsen

    2015-01-01

    Full Text Available Novel (S-camptothecin–dextran polymers were obtained by “click” grafting of azide-modified (S-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were prepared with a degree of substitution of (S-camptothecin between 3.1 and 10.2%. The binding properties with β-cyclodextrin and β-cyclodextrin polymers were measured by isothermal titration calorimetry and fluorescence spectroscopy, showing no binding with β-cyclodextrin but high binding with β-cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S-camptothecin–dextran polymers and the β-cyclodextrin polymers.

  4. Compound Specific Extraction of Camptothecin from Nothapodytes nimmoniana and Piperine from Piper nigrum Using Accelerated Solvent Extractor

    OpenAIRE

    Vinayak Upadhya; Pai, Sandeep R.; Sharma, Ajay K.; Hegde, Harsha V; Kholkute, Sanjiva D; Joshi, Rajesh K.

    2014-01-01

    Effects of varying temperatures with constant pressure of solvent on extraction efficiency of two chemically different alkaloids were studied. Camptothecin (CPT) from stem of Nothapodytes nimmoniana (Grah.) Mabb. and piperine from the fruits of Piper nigrum L. were extracted using Accelerated Solvent Extractor (ASE). Three cycles of extraction for a particular sample cell at a given temperature assured complete extraction. CPT and piperine were determined and quantified by using a simple and ...

  5. Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin

    OpenAIRE

    Cheetham, A.G.; Zhang, P.; Lin, Y.-A; Lin, R; Cui, H

    2014-01-01

    Self-assembly of anticancer therapeutics into discrete nanostructures provides an innovative way to develop a self-delivering nanomedicine with a high, quantitative drug loading. We report here the synthesis and assembly of a mikto-arm star dual drug amphiphile (DA) containing both a bulky paclitaxel (PTX) and a planar camptothecin (CPT). The two anti-cancer drugs of interest were stochastically conjugated to a β-sheet forming peptide (Sup35) and under physiologically-relevant conditions the ...

  6. Endophytic fungi harbored in Camptotheca acuminata, Hypericum perforatum and Juniperus communis plants as promising sources of camptothecin, hypericin and deoxypodophyllotoxin

    OpenAIRE

    Kusari, Souvik

    2010-01-01

    Endophytic microorganisms are a diverse group of microbes that colonize living, internal tissues of plants without causing any immediate, overt negative effects within the hosts. A number of novel endophytic microorganisms are capable of producing host plant-specific secondary metabolites with therapeutic potential. The main objective of this study was isolation, identification, biological and biochemical characterization of endophytic fungi capable of indigenously producing camptothecin (CPT...

  7. Energy-limited escape revised

    CERN Document Server

    Salz, M; Czesla, S; Schmitt, J H M M

    2016-01-01

    Gas planets in close proximity to their host stars experience photoevaporative mass loss. The energy-limited escape concept is generally used to derive estimates for the planetary mass-loss rates. Our photoionization hydrodynamics simulations of the thermospheres of hot gas planets show that the energy-limited escape concept is valid only for planets with a gravitational potential lower than $\\log_\\mathrm{10}\\left( -\\Phi_{\\mathrm{G}}\\right) < 13.11~$erg$\\,$g$^{-1}$ because in these planets the radiative energy input is efficiently used to drive the planetary wind. Massive and compact planets with $\\log_\\mathrm{10}\\left( -\\Phi_{\\mathrm{G}}\\right) \\gtrsim 13.6~$erg$\\,$g$^{-1}$ exhibit more tightly bound atmospheres in which the complete radiative energy input is re-emitted through hydrogen Ly$\\alpha$ and free-free emission. These planets therefore host hydrodynamically stable thermospheres. Between these two extremes the strength of the planetary winds rapidly declines as a result of a decreasing heating eff...

  8. Electronic Escape Trails for Firefighters

    Science.gov (United States)

    Jorgensen, Charles; Schipper, John; Betts, Bradley

    2008-01-01

    A proposed wireless-communication and data-processing system would exploit recent advances in radio-frequency identification devices (RFIDs) and software to establish information lifelines between firefighters in a burning building and a fire chief at a control station near but outside the building. The system would enable identification of trails that firefighters and others could follow to escape from the building, including identification of new trails should previously established trails become blocked. The system would include a transceiver unit and a computer at the control station, portable transceiver units carried by the firefighters in the building, and RFID tags that the firefighters would place at multiple locations as they move into and through the building (see figure). Each RFID tag, having a size of the order of a few centimeters, would include at least standard RFID circuitry and possibly sensors for measuring such other relevant environmental parameters as temperature, levels of light and sound, concentration of oxygen, concentrations of hazardous chemicals in smoke, and/or levels of nuclear radiation. The RFID tags would be activated and interrogated by the firefighters and control-station transceivers. Preferably, RFID tags would be configured to communicate with each other and with the firefighters units and the control station in an ordered sequence, with built-in redundancy. In a typical scenario, as firefighters moved through a building, they would scatter many RFID tags into smoke-obscured areas by use of a compressed-air gun. Alternatively or in addition, they would mark escape trails by dropping RFID tags at such points of interest as mantraps, hot spots, and trail waypoints. The RFID tags could be of different types, operating at different frequencies to identify their functions, and possibly responding by emitting audible beeps when activated by signals transmitted by transceiver units carried by nearby firefighters.

  9. Action of cocaine and chronic sympathetic denervation on vagal escape

    Science.gov (United States)

    Campos, H. A.; Urquilla, P. R.

    1969-01-01

    1. The effect of cocaine has been studied on vagal escape and on the tachycardia due to vagal stimulation in the atropinized dog. All the dogs were submitted to acute cervical section of the spinal cord and acute or chronic sympathetic denervation. 2. Cocaine, 5 mg/kg or 40 μg/kg/min, I.V., induces a significant enhancement of the ventricular escape. The effects of a continuous infusion of cocaine are more reproducible than those of a single injection of the drug. 3. Cocaine, 40 μg/kg/min, I.V., potentiates the tachycardia due to vagal stimulation in the atropinized dog. 4. Chronic thoracic sympathectomy markedly retards the recovery of the ventricular rate from the inhibitory action of the vagus. Under this condition, the infusion of cocaine does not significantly enhance the ventricular escape. 5. These findings suggest that an adrenergic mechanism located at the sympathetic nerves supplying the heart is substantially involved in the phenomenon of vagal escape. PMID:5249864

  10. Escape as Reinforcement and Escape Extinction in the Treatment of Feeding Problems

    Science.gov (United States)

    LaRue, Robert H.; Stewart, Victoria; Piazza, Cathleen C.; Volkert, Valerie M.; Patel, Meeta R.; Zeleny, Jason

    2011-01-01

    Given the effectiveness of putative escape extinction as treatment for feeding problems, it is surprising that little is known about the effects of escape as reinforcement for appropriate eating during treatment. In the current investigation, we examined the effectiveness of escape as reinforcement for mouth clean (a product measure of…

  11. Micropropagation and production of camptothecin form in vitro plants of Ophiorrhiza mungos

    Institute of Scientific and Technical Information of China (English)

    A. G. Namdeo; Priya T.; B. B. Bhosale

    2012-01-01

    Objective: To explore the biotechnological potential of Ophiorrhiza mungos for micropropagation and camptothecin (CPT) production from in vitro grown plants.Methods: Surface sterilized explants of O. mungos were transferred aseptically in MS media containing various combinations of phytohormones for callus initiation and multiple shoot proliferation. The content of CPT was quantified in the methanolic extract of O. mungos plants and in in vitro grown plants by using high performance liquid chromatography (HPLC). Results: Maximum fresh weight and dry weight biomass of O. mungos callus was obtained from MS medium supplemented with IAA (2 ppm)+ BAP (2 ppm) + GA (1 ppm). The maximum shoot proliferation (25) and elongation (6.5 cm) was found in MS medium supplemented with Picloram + Thidiazuron + Gibberellic Acid in 1:2:1 ratio after four weeks of incubation. The maximum content of CPT (0.0768 % w/w) was found in wholein vitro plants whereas the minimum CPT was observed in adventitious buds (0.0026 % w/w) as compared to the naturally grown O. mungos plants (0.0030% w/w).Conclusions: Present findings indicate that O. mungos plants respond favourably for in vitro propagation and also produce higher amount of CPT as compared to naturally grown plants.

  12. Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2.

    Science.gov (United States)

    Dong, Qiaolin; Luo, Ju; Qiu, Wen; Cai, Li; Anjum, Syed Ishtiaq; Li, Bin; Hou, Mingsheng; Xie, Guanlin; Sun, Guochang

    2016-01-01

    Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial brown stripe, by measuring cell growth, DNA damage, cell membrane integrity, the expression of secretion systems, and topoisomerase-related genes, as well as the secretion of effector protein Hcp. Results indicated that CPT solutions at 0.05, 0.25, and 0.50 mg/mL inhibited the growth of strain RS-2 in vitro, while the inhibitory efficiency increased with an increase in CPT concentration, pH, and incubation time. Furthermore, CPT treatment affected bacterial growth and replication by causing membrane damage, which was evidenced by transmission electron microscopic observation and live/dead cell staining. In addition, quantitative real-time PCR analysis indicated that CPT treatment caused differential expression of eight secretion system-related genes and one topoisomerase-related gene, while the up-regulated expression of hcp could be justified by the increased secretion of Hcp based on the ELISA test. Overall, this study indicated that CPT has the potential to control the bacterial brown stripe pathogen of rice. PMID:27472315

  13. Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yuuki Takashima

    2012-10-01

    Full Text Available The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT in solution and in methoxy poly(ethylene glycol (MPEG/poly(e-caprolactone (PCL amphiphilic block copolymers (MPEG-PCL and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL-Tat didn’t show any cytotoxicity, even at high concentrations (2 mmol/mL. CPT-loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats. These results indicate that intranasal delivery of anti-cancer drugs with cell penetrating peptide-modified nanomicelles might be an effective therapy for brain tumors.

  14. Synthesis and Characterization of Camptothecin Intercalated into Mg/AI Layered Double Hydroxide

    Institute of Scientific and Technical Information of China (English)

    LIU,Chun-Xia; HOU,Wan-Guo; LI,Yan; LI,Li-Fang

    2008-01-01

    The intercalation of camptothecin(CPT)into a layered inorganic host,Mg-Al layered double hydroxide(LDH),was carried out using a coprecipitation method tO obtain CPT-LDH nanohybrids.It Was found that the intercalated amounts(Ain)of CPrr-LDH nanohybrids were remarkably dependent on the molar ratios(Rc,M)of CPT tO metal ions in raw materials.The Ain value increases with the RC/M value increasing.According to the gallery heights of CPT-LDH and sizes of CPT molecule,a probably morphology of CPT molecules in the gallery of LDH was suggested that the horizontal-arranged monolayer and vertical-arranged bilayer of CPT molecules coexisted in the interlayer region of LDH.An interesting result was found that the gallery height corresponding to the bilayer of CPT-LDH sample with a high Ain value was remarkably Iower than that with low Ain value.111e/n vitro CPT release examinations from the nanohybrids showed that the CPT-LDH nanohybrids were a potential drug controlled release system.The kinetic analysis showed that the release kinetics of CPT from the nanohybrids obeyed the pseudo-first order kinetic model and the diffusion Of CPT through the LDH particle Of CPT played an important role in controlling the drug release rate.

  15. Effect of planting density on plant growth and camptothecin content of Camptotheca acuminata seedlings

    Institute of Scientific and Technical Information of China (English)

    WEIHuan-yong; WANGYang; WANGZhen-yue; YANXiu-feng

    2005-01-01

    C. acuminata seedlings cultivated in greenhouse were transplanted into the fields with 5 designed planting densities (11, 16, 25,44 and 100 plants·m-2) in May of 2004 and were harvested in the middle of September of 2004. The seedling growth indexes including plant height and crown width, biomass allocation, camptothecin (CPT) content and CPT yield of different organs (young leaf, old leaf, stem,and root) were studied. For the 5 selected planting densities, the plant biomass, height, crown width, and total leaf area of C. acuminata seedlings all showed highest values at the planting density of 25 plants ·m-2. CPT content in young leaves was higher than that in other organs of seedlings and presented an obvious change with the variation of planting densities and with the highest value at density of 100plants·m-2, while for other organs no significant variation in CPT content was found with change of planting density. The accumulation of CPT was enhanced significantly at the planting density of 25 plants·m-2. It is concluded that for the purpose to get raw materials with more CPT from C. acuminata, the optimal planting density of C. acuminata seedlings should be designed as 25 plants·m-2.

  16. 3D-QSAR study of 20 (S)-camptothecin analogs

    Institute of Scientific and Technical Information of China (English)

    Ai-jun LU; Zhen-shan ZHANG; Ming-yue ZHENG; Han-jun ZOU; Xiao-min LUO; Hua-liang JIANG

    2007-01-01

    Aim: To build up a quantitative structure-activity relationship (QSAR) model of20 (S)-camptothecin (CPT) analogs for the prediction of the activity of new CPT analogs for drug design. Methods: A training set of 43 structurally diverse CPT analogs which were inhibitors of topoisomerase Ⅰ were used to construct a quan-titative structure-activity relationship model with a comparative molecular field analysis (CoMFA). The QSAR model was optimized using partial least squares(PLS) analysis. A test set of 10 compounds was evaluated using the model. Results: The CoMFA model was constructed successfully, and a good cross-validated correlation was obtained in which q2 was 0.495. Then, the analysis of the non-cross-validated PLS model in which r2 was 0.935 was built and permitted demonstrations of high predictability for the activities of the 10 CPT analogs in the test set selected in random. Conclusion: The CoMFA model indicated that bulky negative-charged group at position 9, 10 and 11 of CPT would increase activity, but excessively increasing bulky group at position 10 is adverse to inhibi-tory activity; substituents that occupy position 7 with the bulky positive group will enhance the inhibitive activity. The model can be used to design new CPT analogs and understand the mechanism of action.

  17. Camptothecine production by mixed fermentation of two endophytic fungi from Nothapodytes nimmoniana.

    Science.gov (United States)

    Bhalkar, Bhumika N; Patil, Swapnil M; Govindwar, Sanjay P

    2016-01-01

    Two endophytic fungi isolated from the endangered plant Nothapodytes nimmoniana (Grah.) Mabb. were found to effectively synthesize CPT independent of their host plant under submerged fermentation conditions. Molecular characterization of fungi revealed their identity as Colletotrichum fructicola SUK1 (F1) and Corynespora cassiicola SUK2 (F2). Mixed fermentation experiments were carried out to study the effect of microbial signalling between the two fungal species on camptothecine production. Effect of culture parameters on CPT production was studied for both mono-cultures (F1 and F2) separately as well as for the mixed fermentation (F1 + F2). Further the most influencing ones were optimized statistically using response surface methodology. Statistical model based optimized parameters were whey (70 %), agitation rate (110 rpm), temperature (30 °C), and incubation period (7 d) for the mixed fermentation. Monocultures of the two fungal species F1 and F2 yielded CPT up to 33 ± 1.1 mg l(-1)and 69 ± 1.1 mg l(-1), respectively; while their mixed fermentation under the optimized conditions yielded up to 146 ± 0.2 mg l(-1). HPLC and LC-MS/MS techniques were used to analyze the products obtained. PMID:27268247

  18. Synthesis and biological evaluation of novel conjugates of camptothecin and 5-Flurouracil as cytotoxic agents

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Liu, E-mail: yqliu@lzu.edu.c [Lanzhou Jiaotong University (China). Environmental and Municipal Engineering School; Chun-Yan Zhaob; Ying-Qian Liu [Lanzhou University (China). School of Pharmacy

    2011-07-01

    A series of novel conjugates of camptothecin and 5-fluorouracil were first synthesized and their cytotoxic activities against two human tumor cell lines (SGC-7901 and A-549) as well as in vitro pharmacokinetic determination of lactone stability were studied. Among these compounds, most tested conjugates showed comparable or superior cytotoxic activities to 2, but less potent compared with 1. Particularly, conjugates 10b and 10d were highly active against A-549 with IC{sub 50} values of 0.45 and 0.38 {mu}mol L{sup -1}, respectively. Also, the in vitro pharmacokinetic determination of lactone levels of representative compound 10b showed that the biological life span of their lactone forms in human and mouse plasma significantly increased compared with their mother compound 1. Quantitative structure-activity relationship (QSAR) method was then applied for developing linear models to predict the cytotoxic activities of these derivatives that have not yet been synthesized or experimentally tested. In addition, molecular docking was used to clarify the binding mode of these derivatives to human DNA topoisomerase I. The important hydrogen-bonding interactions were observed between these derivatives and their receptor. The results from molecular modeling and QSAR study can guide the design of novel conjugates with higher antitumor activity. (author)

  19. Escape of atmospheric gases from the Moon

    Indian Academy of Sciences (India)

    Da Dao-an; Yang Ya-tian

    2005-12-01

    The escape rate of atmospheric molecules on the Moon is calculated.Based on the assumption that the rates of emission and escape of gases attain equilibrium, the ratio of molecular number densities during day and night, 0/0, can be explained. The plausible emission rate of helium and radioactive elements present in the Moon has also been calculated.

  20. Submarine 'safe to escape' studies in man.

    Science.gov (United States)

    Jurd, K M; Seddon, F M; Thacker, J C; Blogg, S L; Stansfield, M R D; White, M G; Loveman, G A M

    2014-01-01

    The Royal Navy requires reliable advice on the safe limits of escape from a distressed submarine (DISSUB). Flooding in a DISSUB may cause a rise in ambient pressure, increasing the risk of decompression sickness (DCS) and decreasing the maximum depth from which it is safe to escape. The aim of this study was to investigate the pressure/depth limits to escape following saturation at raised ambient pressure. Exposure to saturation pressures up to 1.6 bar (a) (160 kPa) (n = 38); escapes from depths down to 120 meters of sea water (msw) (n = 254) and a combination of saturation followed by escape (n = 90) was carried out in the QinetiQ Submarine Escape Simulator, Alverstoke, United Kingdom. Doppler ultrasound monitoring was used to judge the severity of decompression stress. The trials confirmed the previously untested advice, in the Guardbook, that if a DISSUB was lying at a depth of 90 msw, then it was safe to escape when the pressure in the DISSUB was 1.5 bar (a), but also indicated that this advice may be overly conservative. This study demonstrated that the upper DISSUB saturation pressure limit to safe escape from 90 msw was 1.6 bar (a), resulting in two cases of DCS. PMID:25109084

  1. Escaping Homelessness: Anticipated and Perceived Facilitators

    Science.gov (United States)

    Patterson, Allisha; Tweed, Roger

    2009-01-01

    One study with two distinct sections was conducted to identify factors facilitating escape from homelessness. In Section 1, 58 homeless individuals rated possible facilitators of escape (factors they believed would help them become more independent and self-sufficient). In Section 2, 80 participants who had already exited homelessness rated the…

  2. Effects of inescapable versus escapable social stress in Syrian hamsters: The importance of stressor duration versus escapability

    OpenAIRE

    McCann, Katharine E.; Bicknese, Corinne N.; Norvelle, Alisa; Huhman, Kim L.

    2014-01-01

    Social avoidance is a common characteristic of many clinical psychopathologies and is often triggered by social stress. Our lab uses Syrian hamsters to model stress-induced social avoidance, and we have previously established that both inescapable and escapable social defeat result in increased social avoidance when compared with no-defeat controls. Our previous work suggested, however, that social avoidance was significantly greater after inescapable defeat. The goal of this study was to det...

  3. Optimal escape theory predicts escape behaviors beyond flight initiation distance: risk assessment and escape by striped plateau lizards Sceloporus virgatus

    Institute of Scientific and Technical Information of China (English)

    William E.COOPER Jr

    2009-01-01

    Escape theory predicts that flight initiation distance (FID=distance between predator and prey when escape begins) is longer when risk is greater and shorter when escape is more costly. A few tests suggest that escape theory applies to distance fled. Escape models have not addressed stochastic variables, such as probability of fleeing and of entering refuge, but their economic logic might be applicable. Experiments on several risk factors in the lizard Sceloporus virgatus confirmed all predictions for the above escape variables. FID was greater when approach was faster and more direct, for lizards on ground than on trees, for lizards rarely exposed to humans, for the second of two approaches, and when the predator turned toward lizards rather than away. Lizards fled further during rapid and second consecutive approaches. They were more likely to flee when approached directly, when a predator turned toward them, and during second approaches. They were more likely to enter refuge when approached rapidly. A novel finding is that perch height in trees was unrelated to FID because lizards escaped by moving out of sight, then moving up or down unpredictably. These findings add to a growing body of evidence supporting predictions of escape theory for FID and distance fled. They show that two probabilistic aspects of escape are predictable based on relative predation risk levels. Because individuals differ in boldness, the assessed optimal FID and threshold risks for fleeing and entering refuge are exceeded for an increasing proportion of individuals as risk increases[Current Zoology 55(2):123-131,2009].

  4. Synergism of Cyclin-Dependent Kinase Inhibitors with Camptothecin Derivatives in Small Cell Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Gerhard Hamilton

    2014-02-01

    Full Text Available Advanced small cell lung cancer (SCLC has a dismal prognosis. Modulation of the camptothecin topotecan, approved for second-line therapy, may improve response. Our recent finding of synergistic enhancement of the cytotoxic activity of camptothecin (CPT by cyclin-dependent kinase 4 inhibitors is extended here to a panel of camptothecin analogs comprising 10-hydroxy-CPT (HOCPT, topotecan (TPT; 9-[(dimethylamino-methyl]-10-hydroxy-CPT, 9-amino-CPT (9AC, 9-nitrocamptothecin (rubitecan, SN38 (7-ethyl-10-hydroxycamptothecin and 10-hydroxy-9-nitrocamptothecin (CPT109 in combination with PD0332991, CDK4I, roscovitine and olomoucine. SCLC cell lines employed are chemoresistant NCI-H417 and DMS153 and the chemosensitive SCLC26A line established at our institution. The CPT analogs exhibiting highest cytotoxicity towards the three SCLC lines tested were SN38 and 9AC, followed by rubitecan, HOCPT, TPT and CPT109. NCI-H417 and DMS153 revealed an approximately 25-fold and 7-fold higher resistance compared to the chemosensitive SCLC26A cell line. Whereas the CDK4/6 inhibitor PD0332991 proved less effective to chemosensitize SCLC cells to CPT analogs, the CDK inhibitors CDK4I, roscovitine and olomoucine gave comparable chemosensitization effects in combination with 9AC, SN38, rubitecan and to a lesser extent with TPT and CPT109, not directly related with topoisomerase mRNA expression. In conclusion, small chemical modifications of the parent CPT structure result in differing cytotoxicities and chemomodulatory effects in combination with CDKIs of the resulting analogs.

  5. Escapes in Hamiltonian systems with multiple exit channels: Part II

    OpenAIRE

    Zotos, Euaggelos E.

    2015-01-01

    We explore the escape dynamics in open Hamiltonian systems with multiple channels of escape continuing the work initiated in Part I. A thorough numerical investigation is conducted distinguishing between trapped (ordered and chaotic) and escaping orbits. The determination of the location of the basins of escape towards the different escape channels and their correlations with the corresponding escape periods of the orbits is undoubtedly an issue of paramount importance. We consider four diffe...

  6. Karachi Commander Escapes Attack, 10 Dead

    Institute of Scientific and Technical Information of China (English)

    潘志强

    2004-01-01

    KARACHI: The army commander in the Pakistani city of Karachi narrowly① escaped assassination② yesterday when gunmen attacked his convoy③ with gunfire and a bomb, killing at least 10 and wounding his driver, officials said.

  7. Escape dynamics: a continuous-time approximation

    Czech Academy of Sciences Publication Activity Database

    Kolyuzhnov, D.; Bogomolova, A.; Slobodyan, Sergey

    2014-01-01

    Roč. 38, January (2014), s. 161-183. ISSN 0165-1889 Institutional support: RVO:67985998 Keywords : constant gain adaptive learning * escape dynamics * recursive least squares Subject RIV: AH - Economics Impact factor: 1.018, year: 2014

  8. Submarine tower escape decompression sickness risk estimation.

    Science.gov (United States)

    Loveman, G A M; Seddon, E M; Thacker, J C; Stansfield, M R; Jurd, K M

    2014-01-01

    Actions to enhance survival in a distressed submarine (DISSUB) scenario may be guided in part by knowledge of the likely risk of decompression sickness (DCS) should the crew attempt tower escape. A mathematical model for DCS risk estimation has been calibrated against DCS outcome data from 3,738 exposures of either men or goats to raised pressure. Body mass was used to scale DCS risk. The calibration data included more than 1,000 actual or simulated submarine escape exposures and no exposures with substantial staged decompression. Cases of pulmonary barotrauma were removed from the calibration data. The calibrated model was used to estimate the likelihood of DCS occurrence following submarine escape from the United Kingdom Royal Navy tower escape system. Where internal DISSUB pressure remains at - 0.1 MPa, escape from DISSUB depths 60% DCS risk predicted for a 200-meter escape from saturation at 0.21 MPa. Using the calibrated model to predict DCS for direct ascent from saturation gives similar risk estimates to other published models. PMID:25109085

  9. Alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance through altering the expression of Fas/FasL and tumor necrosis factor related apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells

    Institute of Scientific and Technical Information of China (English)

    Meng-Sen Li; Qiu-Ling Ma; Qian Chen; Xin-Hua Liu; Ping-Feng Li; Guo-Guang Du; Gang Li

    2005-01-01

    AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured human lymphoma Jurkat T cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor necrosis factor related apoptosisinducing ligand (TRAIL) and its receptor (TRAILR) mRNA were analyzed by Northern blot and Western blot wasused to detect the expression of Fas and Fas ligand (FasL)protein.RESULTS: AFP (20 mg/L) could promote the expression of FasL and TRAIL, and inhibit the expression of Fas and TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could abolish these functions of AFP.CONCLUSION: AFP is able to promote the expression of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells from the host's lymphocytes immune surveillance.

  10. Langmuir monolayers and Differential Scanning Calorimetry for the study of the interactions between camptothecin drugs and biomembrane models.

    Science.gov (United States)

    Casadó, Ana; Giuffrida, M Chiara; Sagristá, M Lluïsa; Castelli, Francesco; Pujol, Montserrat; Alsina, M Asunción; Mora, Margarita

    2016-02-01

    CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe side effects and the chemical instability of their lactone ring have questioned the usual forms for its administration and have focused the current research on the development of new suitable pharmaceutical formulations. This work presents a biophysical study of the interfacial interactions of CPT-11 and SN-38 with membrane mimetic models by using monolayer techniques and Differential Scanning Calorimetry. The aim is to get new insights for the understanding of the bilayer mechanics after drug incorporation and to optimize the design of drug delivery systems based on the formation of stable bilayer structures. Moreover, from our knowledge, the molecular interactions between camptothecins and phospholipids have not been investigated in detail, despite their importance in the context of drug action. The results show that neither CPT-11 nor SN-38 disturbs the structure of the complex liposome bilayers, despite their different solubility, that CPT-11, positively charged in its piperidine group, interacts electrostatically with DOPS, making stable the incorporation of a high percentage of CPT-11 into liposomes and that SN-38 establishes weak repulsive interactions with lipid molecules that modify the compressibility of the bilayer without affecting significantly neither the lipid collapse pressure nor the miscibility pattern of drug-lipid mixed monolayers. The suitability of a binary and a ternary lipid mixture for encapsulating SN-38 and CPT-11, respectively, has been demonstrated. PMID:26656185

  11. Bcmfs1, a novel major facilitator superfamily transporter from Botrytis cinerea, provides tolerance towards the natural toxic compounds camptothecin and cercosporin and towards fungicides

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, De M.A.

    2002-01-01

    Bcmfs1, a novel major facilitator superfamily gene from Botrytis cinerea, was cloned, and replacement and overexpression mutants were constructed to study its function. Replacement mutants showed increased sensitivity to the natural toxic compounds camptothecin and cercosporin, produced by the plant

  12. Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT on human leukemia HL-60 cells

    Directory of Open Access Journals (Sweden)

    Jiang Pingping

    2010-04-01

    Full Text Available Abstract Background Polysaccharopeptide (PSP from Coriolus versicolor (Yunzhi is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT. Methods We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI flow cytometry analysis to measure the relative movement (RM of the BrdUrd positively labeled cells and DNA synthesis time (Ts on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. Results PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. Conclusion The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.

  13. Pyrosequencing of the Camptotheca acuminata transcriptome reveals putative genes involved in camptothecin biosynthesis and transport

    Directory of Open Access Journals (Sweden)

    Sun Yongzhen

    2011-10-01

    Full Text Available Abstract Background Camptotheca acuminata is a Nyssaceae plant, often called the "happy tree", which is indigenous in Southern China. C. acuminata produces the terpenoid indole alkaloid, camptothecin (CPT, which exhibits clinical effects in various cancer treatments. Despite its importance, little is known about the transcriptome of C. acuminata and the mechanism of CPT biosynthesis, as only few nucleotide sequences are included in the GenBank database. Results From a constructed cDNA library of young C. acuminata leaves, a total of 30,358 unigenes, with an average length of 403 bp, were obtained after assembly of 74,858 high quality reads using GS De Novo assembler software. Through functional annotation, a total of 21,213 unigenes were annotated at least once against the NCBI nucleotide (Nt, non-redundant protein (Nr, Uniprot/SwissProt, Kyoto Encyclopedia of Genes and Genomes (KEGG, and Arabidopsis thaliana proteome (TAIR databases. Further analysis identified 521 ESTs representing 20 enzyme genes that are involved in the backbone of the CPT biosynthetic pathway in the library. Three putative genes in the upstream pathway, including genes for geraniol-10-hydroxylase (CaPG10H, secologanin synthase (CaPSCS, and strictosidine synthase (CaPSTR were cloned and analyzed. The expression level of the three genes was also detected using qRT-PCR in C. acuminata. With respect to the branch pathway of CPT synthesis, six cytochrome P450s transcripts were selected as candidate transcripts by detection of transcript expression in different tissues using qRT-PCR. In addition, one glucosidase gene was identified that might participate in CPT biosynthesis. For CPT transport, three of 21 transcripts for multidrug resistance protein (MDR transporters were also screened from the dataset by their annotation result and gene expression analysis. Conclusion This study produced a large amount of transcriptome data from C. acuminata by 454 pyrosequencing. According to

  14. On the escape of CH4 from Pluto's atmosphere

    OpenAIRE

    Koskinen, T. T.; Erwin, J. T.; Yelle, R. V.

    2015-01-01

    We adapted a multi-species escape model, developed for close-in extrasolar planets, to calculate the escape rates of CH4 and N2 from Pluto. In the absence of escape, CH4 should overtake N2 as the dominant species below the exobase. The CH4 profile depends strongly on the escape rate, however, and the typical escape rates predicted for Pluto lead to a nearly constant mixing ratio of less than 1 % below the exobase. In this case the CH4 escape rate is only 5-10 % of the N2 escape rate. Observat...

  15. Radiative equilibrium and escape of Pluto's atmosphere

    Science.gov (United States)

    Erwin, Justin; Koskinen, Tommi T.; Yelle, Roger V.

    2015-11-01

    Observations of Pluto’s extend atmosphere by the New Horizons spacecraft motivate an update to our modeling effort on Pluto’s atmosphere. New Horizons observations have already improved our constraints on planet radius and surface pressure, which are key to modeling the atmospheric structure. We model the radiative conductive equilibrium in the lower atmosphere combined with the UV driven escape model of the upper atmosphere. The non-LTE radiative transfer model in the lower atmosphere include heating and cooling by CH4, CO, and HCN. The escape model of the upper atmosphere is updated to include diffusion and escape of each molecular component. These results will be used to aid in the analysis and better understanding of the full atmospheric structure.

  16. Unexpected variability of Martian hydrogen escape

    OpenAIRE

    Chaffin, Michael S.; Chaufray, Jean-Yves; Stewart, Ian; Montmessin, Franck; Schneider, Nicholas M.; Bertaux, Jean-Loup

    2014-01-01

    International audience Mars today is much drier than the Earth, though they likely began with similar relative amounts of water. One potential cause for this discrepancy is hydrogen loss to space, which may have removed a large fraction of Mars' initial water. Here we demonstrate an order-of-magnitude change in the Martian hydrogen escape rate in 2007, inconsistent with established models for the source of escaping hydrogen. We analyze 121.6 nm (hydrogen Lyman-α) airglow observations made ...

  17. Martian Atmospheric and Ionospheric plasma Escape

    Science.gov (United States)

    Lundin, Rickard

    2016-04-01

    Solar forcing is responsible for the heating, ionization, photochemistry, and erosion processes in the upper atmosphere throughout the lifetime of the terrestrial planets. Of the four terrestrial planets, the Earth is the only one with a fully developed biosphere, while our kin Venus and Mars have evolved into arid inhabitable planets. As for Mars, there are ample evidences for an early Noachian, water rich period on Mars. The question is, what made Mars evolve so differently compared to the Earth? Various hydrosphere and atmospheric evolution scenarios for Mars have been forwarded based on surface morphology, chemical composition, simulations, semi-empiric (in-situ data) models, and the long-term evolution of the Sun. Progress has been made, but the case is still open regarding the changes that led to the present arid surface and tenuous atmosphere at Mars. This presentation addresses the long-term variability of the Sun, the solar forcing impact on the Martian atmosphere, and its interaction with the space environment - an electromagnetic wave and particle interaction with the upper atmosphere that has implications for its photochemistry, composition, and energization that governs thermal and non-thermal escape. Non-thermal escape implies an electromagnetic upward energization of planetary ions and molecules to velocities above escape velocity, a process governed by a combination of solar EUV radiation (ionization), and energy and momentum transfer by the solar wind. The ion escape issue dates back to the early Soviet and US-missions to Mars, but the first more accurate estimates of escape rates came with the Phobos-2 mission in 1989. Better-quality ion composition measurement results of atmospheric/ionospheric ion escape from Mars, obtained from ESA Mars Express (MEX) instruments, have improved our understanding of the ion escape mechanism. With the NASA MAVEN spacecraft orbiting Mars since Sept. 2014, dual in-situ measurement with plasma instruments are now

  18. Effects of Serotonergic and Opioidergic Drugs on Escape Behaviors and Social Status of Male Crickets

    Science.gov (United States)

    Dyakonova, V. E.; Schürmann, F.-W.; Sakharov, D. A.

    We examined the effects of selective serotonin depletion and opioid ligands on social rank and related escape behavior of the cricket Gryllus bimaculatus. Establishment of social rank in a pair of males affected their escape reactions. Losers showed a lower and dominants a higher percentage of jumps in response to tactile cercal stimulation than before a fight. The serotonin-depleting drug α-methyltryptophan (AMTP) caused an activation of the escape reactivity in socially naive crickets. AMTP-treated animals also showed a lower ability to become dominants. With an initial 51.6+/-3.6% of wins in the AMTP group, the percentage decreased to 26+/-1.6% on day 5 after injection. The opiate receptor antagonist naloxone affected fight and escape similarly as AMTP. In contrast to naloxone, the opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin decreased escape responsiveness to cercal stimulation in naive and subordinate crickets. We suggest that serotonergic and opioid systems are involved in the dominance induced depression of escape behavior.

  19. Escape rate of Brownian particles from a metastable potential well under time derivative Ornstein-Uhlenbeck noise

    Science.gov (United States)

    Bai, Zhan-Wu; Wang, Ping

    2016-03-01

    We investigate the escape rate of Brownian particles that move in a cubic metastable potential subjected to an internal time derivative Ornstein-Uhlenbeck noise (DOUN). This noise can induce the ballistic diffusion of force-free Brownian particles. Some new features are found. The escape rate for DOUN shows qualitative different dependence on potential well width compared with OUN which induces normal diffusion. As the potential barrier height decreases, the escape rate of DOUN deviates from Arrhenius law considerably earlier than that of Ornstein-Uhlenbeck noise (OUN). The Brownian particles escape faster under DOUN than that under OUN. A quasi-periodic oscillation occurs in transient state. A solvable case is presented to demonstrate the significant cancellation behavior in the barrier region that governs most of these phenomena. The physical mechanism of the findings can be clarified by the noise features. These characteristics should be common for internal noises that induce superdiffusion, especially the ballistic diffusion.

  20. On the escape of CH4 from Pluto's atmosphere

    CERN Document Server

    Koskinen, T T; Yelle, R V

    2015-01-01

    We adapted a multi-species escape model, developed for close-in extrasolar planets, to calculate the escape rates of CH4 and N2 from Pluto. In the absence of escape, CH4 should overtake N2 as the dominant species below the exobase. The CH4 profile depends strongly on the escape rate, however, and the typical escape rates predicted for Pluto lead to a nearly constant mixing ratio of less than 1 % below the exobase. In this case the CH4 escape rate is only 5-10 % of the N2 escape rate. Observations of the CH4 profile by the New Horizons/ALICE spectrograph can constrain the CH4 escape rate and provide a unique test for escape models.

  1. Pade approximant calculations for neutron escape probability

    International Nuclear Information System (INIS)

    The neutron escape probability from a non-multiplying slab containing internal source is defined in terms of a functional relation for the scattering function for the diffuse reflection problem. The Pade approximant technique is used to get numerical results which compare with exact results. (author)

  2. Centrifugally Stimulated Exospheric Ion Escape at Mercury

    Science.gov (United States)

    Delcourt, Dominique; Seki, K.; Terada, N.; Moore, Thomas E.

    2012-01-01

    We investigate the transport of ions in the low-altitude magnetosphere magnetosphere of Mercury. We show that, because of small spatial scales, the centrifugal effect due to curvature of the E B drift paths can lead to significant particle energization in the parallel direction. We demonstrate that because of this effect, ions with initial speed smaller than the escape speed such as those produced via thermal desorption can overcome gravity and escape into the magnetosphere. The escape route of this low-energy exosphere originating material is largely controlled by the magnetospheric convection rate. This escape route spreads over a narrower range of altitudes when the convection rate increases. Bulk transport of low-energy planetary material thus occurs within a limited region of space once moderate magnetospheric convection is established. These results suggest that, via release of material otherwise gravitationally trapped, the E B related centrifugal acceleration is an important mechanism for the net supply of plasma to the magnetosphere of Mercury.

  3. Net escapement of Antartic krill in trawls

    DEFF Research Database (Denmark)

    Krafft, B.A.; Krag, Ludvig Ahm; Herrmann, Bent; Engås, A.; Nordrum, S.; Iversen, S.

    This document describes the aims and methodology of a three year project (commenced in 2012) entitled Net Escapement of Antarctic krill in Trawls (NEAT). The study will include a morphology based mathematical modeling (FISHSELECT) of different sex and maturity groups of Antarctic krill (Euphausia...

  4. Escape dynamics: a continuous-time approximation

    Czech Academy of Sciences Publication Activity Database

    Kolyuzhnov, Dmitri; Bogomolova, Anna; Slobodyan, S.

    2014-01-01

    Roč. 38, January (2014), s. 161-183. ISSN 0165-1889 R&D Projects: GA ČR(CZ) GBP402/12/G097 Institutional support: PRVOUK-P23 Keywords : constant gain adaptive learning * escape dynamics * recursive least squares Subject RIV: AH - Economics Impact factor: 1.018, year: 2014

  5. Launch Pad Escape System Design (Human Spaceflight)

    Science.gov (United States)

    Maloney, Kelli

    2011-01-01

    A launch pad escape system for human spaceflight is one of those things that everyone hopes they will never need but is critical for every manned space program. Since men were first put into space in the early 1960s, the need for such an Emergency Escape System (EES) has become apparent. The National Aeronautics and Space Administration (NASA) has made use of various types of these EESs over the past 50 years. Early programs, like Mercury and Gemini, did not have an official launch pad escape system. Rather, they relied on a Launch Escape System (LES) of a separate solid rocket motor attached to the manned capsule that could pull the astronauts to safety in the event of an emergency. This could only occur after hatch closure at the launch pad or during the first stage of flight. A version of a LES, now called a Launch Abort System (LAS) is still used today for all manned capsule type launch vehicles. However, this system is very limited in that it can only be used after hatch closure and it is for flight crew only. In addition, the forces necessary for the LES/LAS to get the capsule away from a rocket during the first stage of flight are quite high and can cause injury to the crew. These shortcomings led to the development of a ground based EES for the flight crew and ground support personnel as well. This way, a much less dangerous mode of egress is available for any flight or ground personnel up to a few seconds before launch. The early EESs were fairly simple, gravity-powered systems to use when thing's go bad. And things can go bad very quickly and catastrophically when dealing with a flight vehicle fueled with millions of pounds of hazardous propellant. With this in mind, early EES designers saw such a passive/unpowered system as a must for last minute escapes. This and other design requirements had to be derived for an EES, and this section will take a look at the safety design requirements had to be derived for an EES, and this section will take a look at

  6. Induction of apoptosis in the human Leukemic U937 cell line by Kaempferia parviflora Wall.ex.Baker extract and effects of paclitaxel and camptothecin.

    Science.gov (United States)

    Banjerdpongchai, Ratana; Chanwikruy, Yupa; Rattanapanone, Viboon; Sripanidkulchai, Bungorn

    2009-01-01

    Kaempferia parviflora Wall.ex.Baker is a Thai medicinal herb that has high antioxidant and anti-inflammatory activities. Apoptotic effects of the herbal extract alone and in combination with chemotherapeutic drugs, paclitaxel and camptothecin, were here studied in the human promonocytic leukemic U937 cell line. K. parviflora extract suppressed cell proliferation and decreased cell viability in a dose- and time-dependent manner as assessed using the trypan blue exclusion assay. Staining of extract-treated cells with propidium iodide and examination under a fluorescence microscope showed condensed nuclei and apoptotic bodies. Mitochondrial transmembrane potential (MTP) decreased after treatment and the number of cells with decreased MTP also increased. Furthermore, activation of caspase-3 was found in herbal extract-treated cells. When the extract was combined with paclitaxel, an additive effect on U937 cell apoptosis was obtained, whereas camptothecin exerted an antagonistic effect. PMID:20192599

  7. Effects of camptothecin on double-strand break repair by non-homologous end-joining in DNA mismatch repair-deficient human colorectal cancer cell lines

    OpenAIRE

    Jacob, Sandrine; Miquel, Catherine; Sarasin, Alain; Praz, Françoise

    2005-01-01

    Loss of a functional mismatch repair (MMR) system in colorectal cancer (CRC) cells is associated with microsatellite instability and increased sensitivity to topoisomerase inhibitors. In this study, we have investigated whether a defect in double-strand break (DSB) repair by non-homologous end-joining (NHEJ) could explain why MMR-deficient CRC cells are hypersensitive to camptothecin (CPT), a topoisomerase I inhibitor. To evaluate the efficiency and the fidelity of DSB repair, we have transie...

  8. Mixed Micelles made of Poly(ethylene glycol)-Phosphatidylethanolamine Conjugate and D-α-tocopheryl Polyethylene Glycol 1000 Succinate as Pharmaceutical Nanocarriers for Camptothecin

    OpenAIRE

    Mu, L; Elbayoumi, T.A.; Torchilin, V.P.

    2005-01-01

    Micelles from the mixture of poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) and D-α-tocopheryl polyetheyene glycol 1000 succinate (TPGS) were prepared loaded with the poorly soluble anticancer drug camptothecin (CPT). The solubilization of CPT by the mixed micelles was more efficient than with earlier described micelles made of PEG-PE alone. CPT-loaded mixed micelles were stable upon storage and dilution and firmly retained the incorporated drug. The cytotoxicity of the CP...

  9. Measurement of the resonance escape probability

    International Nuclear Information System (INIS)

    The average cadmium ratio in natural uranium rods has been measured, using equal diameter natural uranium disks. These values correlated with independent measurements of the lattice buckling, enabled us to calculate values of the resonance escape probability for the G1 reactor with one or the other of two definitions. Measurements were performed on 26 mm and 32 mm rods, giving the following values for the resonance escape probability p: 0.8976 ± 0.005 and 0.912 ± 0.006 (d. 26 mm), 0.8627 ± 0.009 and 0.884 ± 0.01 (d. 32 mm). The influence of either definition on the lattice parameters is discussed, leading to values of the effective integral. Similar experiments have been performed with thorium rods. (author)

  10. [Escape mutants of hepatitis B virus].

    Science.gov (United States)

    Jaramillo, Carlos Mario; Navas, María-Cristina

    2015-04-01

    The hepatitis B virus (HBV) infection is a public health problem worldwide. Considering HBV morbidity and mortality and the economic consequences .of this infection, policies and strategies to control it have been implemented, especially in regions where HBV infection is endemic, with high rates of vertical and horizontal infection. One of these strategies is the development of the recombinant vaccine. A 92% of the countries in the world have implemented the vaccine with a global coverage of 69%. The escape variants of HBV correspond to isolates with mutations in the sequence coding for the "a" determinant; these mutations result in changes in the amino acid sequence of the surface antigen (HBsAg) that prevent neutralization of viral particles by antibodies generated in response to vaccination or infection. The escape variants can infect vaccinated individuals and have been identified in the population of countries with different epidemiological patterns. PMID:26065452

  11. Escape and Stand of the Pluto Atmosphere

    Institute of Scientific and Technical Information of China (English)

    GAO Chong-Yi

    2002-01-01

    Molar mass μmin of the lightest gas, which will exist "forever" in the atmosphere at the planet surface,can be evaluated by Jeans rule. The μmin of Pluto is 17.3 g@ mol-1. It is evident that both N2 and CO can be major atmospheric composition at the Pluto surface, and will exist "forever". CH4 can only be escaping slowly from Pluto atmosphere, and still holds quite a proportion in current Pluto atmosphere. However, it will not escape from Titan (or Jupiter, Saturn) atmosphere largely, and will exist "forever". Given the quantitylevelof partial pressure of CH4 in Pluto and Titan (or Jupiter, Saturn) original atmosphere is the same, it will be clear that the current partial pressure of CH4 in Pluto surface atmosphere is 10-3 Pa.

  12. Designing an escape room with the Experience Pyramid model

    OpenAIRE

    Heikkinen, Outi; Shumeyko, Julia

    2016-01-01

    The concept of real life room escape, although relatively new, has been constantly gaining popularity and spreading across countries and continents. Despite the ever-growing appeal and widespread appreciation, the phenomenon is highly underresearched. The authors of this paper, employed at InsideOut Escape Games – the first room escape company of Finland – decided to explore the question of applicability of available experience design tools in the context of room escape. The Experience Py...

  13. Dishabituation of the Tritonia Escape Swim

    OpenAIRE

    Mongeluzi, Donna L.; Frost, William N.

    2000-01-01

    When repeatedly elicited, the oscillatory escape swim of the marine mollusc Tritonia diomedea undergoes habituation of the number of cycles per swim. Although similar in most respects to habituation observed in vertebrates and other invertebrates, one key feature, dishabituation, has been surprisingly difficult to demonstrate. Here we evaluate the hypothesis that this is due to interference from short-term sensitization, which is manifested as a reduction in swim onset latency, that occurs si...

  14. The Escape Rate of a Molecule

    Energy Technology Data Exchange (ETDEWEB)

    Knauf, Andreas, E-mail: knauf@mi.uni-erlangen.de; Krapf, Markus [Universitaet Erlangen-Nuernberg, Department Mathematik (Germany)

    2010-06-15

    We show existence and give an implicit formula for the escape rate of the n-centre problem of celestial mechanics for high energies. Furthermore we give precise computable estimates of this rate. This exponential decay rate plays an important role especially in semiclassical scattering theory of n-atomic molecules. Our result shows that the diameter of a molecule is measurable in a (classical) high-energy scattering experiment.

  15. How inflation hawks escape expectations traps

    OpenAIRE

    Sylvain Leduc

    2003-01-01

    Why did inflation increase so dramatically from the 1960s to the 1970s? One possible theory is that once people started believing inflation would rise, the Fed was forced to validate those expectations by increasing the money supply. In "How Inflation Hawks Escape Expectations Traps," Sylvain Leduc discusses this "expectations trap" hypothesis and uses a direct measure of expectations to see if the theory is consistent with the data.

  16. Cold ion escape from the Martian ionosphere

    Science.gov (United States)

    Fränz, M.; Dubinin, E.; Andrews, D.; Barabash, S.; Nilsson, H.; Fedorov, A.

    2015-12-01

    We here report on new measurements of the escape flux of oxygen ions from Mars by combining the observations of the ASPERA-3 and MARSIS experiments on board the European Mars Express spacecraft. We show that in previous estimates of the total heavy ion escape flow the contribution of the cold ionospheric outflow with energies below 10 eV has been underestimated. Both case studies and the derived flow pattern indicate that the cold plasma observed by MARSIS and the superthermal plasma observed by ASPERA-3 move with the same bulk speed in most regions of the Martian tail. We determine maps of the tailside heavy ion flux distribution derived from mean ion velocity distributions sampled over 7 years. If we assume that the superthermal bulk speed derived from these long time averages of the ion distribution function represent the total plasma bulk speed we derive the total tailside plasma flux. Assuming cylindrical symmetry we determine the mean total escape rate for the years 2007-2014 at 2.8 ± 0.4 ×1025 atoms / s which is in good agreement with model estimates. A possible mechanism to generate this flux can be the ionospheric pressure gradient between dayside and nightside.

  17. Xenon Fractionation and Archean Hydrogen Escape

    Science.gov (United States)

    Zahnle, K. J.

    2015-01-01

    Xenon is the heaviest gas found in significant quantities in natural planetary atmospheres. It would seem the least likely to escape. Yet there is more evidence for xenon escape from Earth than for any element other than helium and perhaps neon. The most straightforward evidence is that most of the radiogenic Xe from the decay of (129)I (half-life 15.7 Myr) and (244)Pu (half-life 81 Myr) that is Earth's birthright is missing. The missing xenon is often attributed to the impact erosion of early atmospheres of Earth and its ancestors. It is obvious that if most of the radiogenic xenon were driven off by impacts, most of the rest of the atmophiles fared the same fate. The other line of evidence is in the nonradiogenic isotopes of xenon and its silent partner, krypton. Atmospheric xenon is strongly mass fractionated (at about 4% per amu) compared to any known solar system source (Figure 1). This is in stark contrast to krypton, which may not be fractionated at all: atmospheric Kr is slightly heavier than solar Kr (at about 0.5% per amu), but it is the same as in carbonaceous chondrites. Nonradiogenic xenon is also under abundant relative to krypton (the so-called "missing xenon" problem). Together these observations imply that xenon has been subject to fractionating escape and krypton not.

  18. The escape of natural satellites from Mercury and Venus

    International Nuclear Information System (INIS)

    Kumar's (1977) suggestion that the slow rotations of Mercury and Venus are in part due to natural satellites that subsequently escaped is discussed. A more useful criterion for the escape of such satellites than the previously proposed is derived, and it is shown that this distance is sufficiently small for Mercury and Venus to make the escape of satellites a likely possibility. (Auth.)

  19. 46 CFR 177.500 - Means of escape.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Means of escape. 177.500 Section 177.500 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) CONSTRUCTION AND ARRANGEMENT Escape Requirements § 177.500 Means of escape. (a) Except as otherwise provided...

  20. 30 CFR 75.382 - Mechanical escape facilities.

    Science.gov (United States)

    2010-07-01

    ... HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Ventilation § 75.382 Mechanical escape facilities. (a) Mechanical escape facilities shall be provided with overspeed, overwind, and automatic stop... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical escape facilities. 75.382 Section...

  1. Combined proteomics and pathways analysis of collecting duct reveals a protein regulatory network activated in vasopressin escape

    OpenAIRE

    Hoorn, Ewout J; Hoffert, Jason D.; Knepper, Mark A.

    2005-01-01

    Low sensitivity is characteristic of many proteomics methods. Here we present an approach that combines proteomics based on “Difference Gel Electrophoresis” (DIGE) with bioinformatic pathways analysis to identify both abundant and relatively non-abundant proteins in inner medullary collecting duct (IMCD) altered in abundance during escape from vasopressin-induced antidiuresis. Rats received the vasopressin analog dDAVP by osmotic minipump plus either a daily water load (vasopressin escape) or...

  2. RKIP phosphorylation and STAT3 activation is inhibited by oxaliplatin and camptothecin and are associated with poor prognosis in stage II colon cancer patients

    International Nuclear Information System (INIS)

    A major obstacle in treating colorectal cancer (CRC) is the acquired resistance to chemotherapeutic agents. An important protein in the regulation of cancer cell death and clinical outcome is Raf kinase inhibitor protein (RKIP). In contrast, activated signal transducer and activator of transcription 3 (STAT3) is a protein that promotes tumor cell survival by inhibiting apoptosis and has an important role in cancer progression in many of cancer types. The aim of this study was to evaluate the regulation of RKIP and STAT3 after treatment with clinically relevant chemotherapeutic agents (camptothecin (CPT) and oxaliplatin (OXP)) and the cytokine interleukin-6 (IL-6) in HCT116 colon cancer cells as well as evaluate the association between RKIP and STAT3 with clinical outcome of Stage II colon cancer patients. HCT-116 colon cancer cells were treated with CPT, OXP, and IL-6 separately or in combination in a time and dose-dependent manner and examined for phosphorylated and non-phosphorylated RKIP and STAT3 via Western blot analysis. STAT3 transcriptional activity was measured via a luciferase reporter assay in HCT116 cells treated with CPT, IL-6 or transfected with JAK 1, 2 separately or in combination. We extended these observations and determined STAT3 and RKIP/ pRKIP in tumor microarrays (TMA) in stage II colon cancer patients. We demonstrate IL-6-mediated activation of STAT3 occurs in conjunction with the phosphorylation of RKIP in vitro in human colon cancer cells. OXP and CPT block IL-6 mediated STAT3 activation and RKIP phosphorylation via the inhibition of the interaction of STAT3 with gp130. We determined that STAT3 and nuclear pRKIP are significantly associated with poor patient prognosis in stage II colon cancer patients. In the analysis of tumor samples from stage II colon cancer patients and the human colon carcinoma cell line HCT116, pRKIP and STAT3, 2 proteins potentially involved in the resistance to conventional treatments were detected. The

  3. Hydrodynamical Modeling of Hydrogen Escape from Rocky Planets

    Science.gov (United States)

    Barringer, Daniel; Zugger, M.; Kasting, J.

    2013-01-01

    Hydrogen escape affects both the composition of primitive atmospheres of terrestrial planets and the planet’s state of oxidation. On Mars, hydrogen escape played a critical role in how long the planet remained in a warm wet state amenable to life. For both solar and extrasolar planets, hydrogen-rich atmospheres are better candidates for originating life by way of Miller-Urey-type prebiotic synthesis. However, calculating the rate of atmospheric hydrogen escape is difficult, for a number of reasons. First, the escape can be controlled either by diffusion through the homopause or by conditions in the upper atmosphere, whichever is slower. Second, both thermal and non-thermal escape mechanisms are typically important. Third, thermal escape itself can be subdivided into Jeans escape (thin upper atmosphere), and hydrodynamic escape, and hydrodynamic escape can be further subdivided into transonic escape and slower subsonic escape, depending on whether the exobase occurs above or below the sonic point. Additionally, the rate of escape for real terrestrial planet atmospheres, which are not 100% hydrogen, depends upon the concentration of infrared coolants, and upon heating and photochemistry driven largely by extreme ultraviolet (EUV) radiation. We have modified an existing 1-D model of hydrodynamic escape (F. Tian et al., JGR, 2008) to work in the high- hydrogen regime. Calculations are underway to determine hydrogen escape rates as a function of atmospheric H2 mixing ratio and the solar EUV flux. We will compare these rates with the estimated upper limit on the escape rate based on diffusion. Initial results for early Earth and Mars will later be extended to rocky exoplanets.

  4. Risks incurred by hydrogen escaping from containers and conduits

    Energy Technology Data Exchange (ETDEWEB)

    Swain, M.R.; Grilliot, E.S. [Univ. of Miami, Coral Gables, FL (United States); Swain, M.N. [Analytical Technologies, Inc., Miami, FL (United States)

    1998-08-01

    This paper is a discussion of a method for hydrogen leak classification. Leaks are classified as; gas escapes into enclosed spaces, gas escapes into partially enclosed spaces (vented), and gas escapes into unenclosed spaces. Each of the three enclosure classifications is further divided into two subclasses; total volume of hydrogen escaped and flow rate of escaping hydrogen. A method to aid in risk assessment determination in partially enclosed spaces is proposed and verified for several enclosure geometries. Examples are discussed for additional enclosure geometries.

  5. The cost of the sword: escape performance in male swordtails.

    Directory of Open Access Journals (Sweden)

    Alex Baumgartner

    Full Text Available The handicap theory of sexual selection posits that male display traits that are favored in mate choice come at a significant cost to performance. We tested one facet of this hypothesis in the green swordtail (Xiphophorus helleri. In this species, the lower ray of male caudal fin is extended into a 'sword', which serves to attract potential mates. However, bearing a long sword may increase drag and thus compromise a male's ability to swim effectively. We tested escape performance in this species by eliciting C-start escape responses, an instinctive escape behavior, in males with various sword lengths. We then removed males' swords and retested escape performance. We found no relationship between escape performance and sword length and no effect of sword removal on escape performance. While having a large sword may attract a predator's attention, our results suggest that sword size does not compromise a male's escape performance.

  6. Arduino adventures escape from Gemini station

    CERN Document Server

    Kelly, James Floyd

    2013-01-01

    Arduino Adventures: Escape from Gemini Station provides a fun introduction to the Arduino microcontroller by putting you (the reader) into the action of a science fiction adventure story.  You'll find yourself following along as Cade and Elle explore Gemini Station-an orbiting museum dedicated to preserving and sharing technology throughout the centuries. Trouble ensues. The station is evacuated, including Cade and Elle's class that was visiting the station on a field trip. Cade and Elle don't make it aboard their shuttle and are trapped on the station along with a friendly artificial intellig

  7. Escape Artists of the X Chromosome.

    Science.gov (United States)

    Balaton, Bradley P; Brown, Carolyn J

    2016-06-01

    Inactivation of one X chromosome in mammalian females achieves dosage compensation between XX females and XY males; however, over 15% of human X-linked genes continue to be expressed from the inactive X chromosome. New genomic methodologies have improved our identification and characterization of these escape genes, revealing the importance of DNA sequence, chromatin structure, and chromosome ultrastructure in regulating expression from an otherwise inactive chromosome. Study of these exceptions to the rule of silencing highlights the interconnectedness of chromatin and chromosome structure in X-chromosome inactivation (XCI). Recent advances also demonstrate the importance of these genes in sexually dimorphic disease risk, particularly cancer. PMID:27103486

  8. Tectonically controlled methane escape in Lake Baikal

    OpenAIRE

    Klerkx, J.; De Batist, M.; J. Poort; Hus, R.; Van Rensbergen, P.; Khlystov, O.; Granin, N.

    2006-01-01

    Methane, which is at least partly stored in the bottom sediments of Lake Baikal as gas hydrates, is released on the lake floor in the deeper parts of the basin along major faults, forming venting structures similar to small mud volcanoes. The CH4 venting structures are considered to be the surface expression of escape pathways for excess CH4 generated by the dissociation of pre-existing hydrates. The existence of a local heat flow anomaly associated with the seep area is most likely due to a ...

  9. The utility of camptothecin as a synergist of Bacillus thuringiensis var. kurstaki and nucleopolyhedroviruses against Trichoplusia ni and Spodoptera exigua.

    Science.gov (United States)

    Sun, Shifeng; Cheng, Zhongshan; Fan, Jing; Cheng, Xinghu; Pang, Yi

    2012-08-01

    We studied the effect of combining microbial pesticides with camptothecin (CPT) on the mortality of two lepidopteran insects: Trichoplusia ni (Hübner) and Spodoptera exigua (Hübner). CPT is an alkaloid that is often used as an anticancer agent. Here, CPT was evaluated as a microbial pesticide synergist of Bacillus thuringiensis (Bt) and insect baculovirus. The toxicity of CPT and its synergistic effects on two microbial pesticides were studied using the diet overlay method. Bioassay results showed that CPT significantly enhances the toxicity of Bt variety kurstaki to S. exigua and T ni. In addition, CPT strongly enhanced the infectivity of Autographa californica (Speyer) multinucleocapsid nucleopolyhedrovirus (AcMNPV) and S. exigua nucleopolyhedrovirus (SeMNPV). Using light microscopy, we found that CPT disrupts the peritrophic membrane of T. ni larvae and severely affects the structure of the midgut, resulting in an abnormal gut lumen morphology. We speculate that CPT increases toxicity by affecting the permeability of the peritrophic membrane. PMID:22928294

  10. Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila.

    Science.gov (United States)

    Cui, Lijie; Ni, Xiaoling; Ji, Qian; Teng, Xiaojuan; Yang, Yanru; Wu, Chao; Zekria, David; Zhang, Dasheng; Kai, Guoyin

    2015-01-01

    Camptothecin (CPT) belongs to a group of monoterpenoidindole alkaloids (TIAs) and its derivatives such as irinothecan and topothecan have been widely used worldwide for the treatment of cancer, giving rise to rapidly increasing market demands. Genes from Catharanthus roseus encoding strictosidine synthase (STR) and geraniol 10-hydroxylase (G10H), were separately and simultaneously introduced into Ophiorrhiza pumila hairy roots. Overexpression of individual G10H (G lines) significantly improved CPT production with respect to non-transgenic hairy root cultures (NC line) and single STR overexpressing lines (S lines), indicating that G10H plays a more important role in stimulating CPT accumulation than STR in O. pumila. Furthermore, co-overexpression of G10H and STR genes (SG Lines) caused a 56% increase on the yields of CPT compared to NC line and single gene transgenic lines, showed that simultaneous introduction of G10H and STR can produce a synergistic effect on CPT biosynthesis in O. pumila. The MTT assay results indicated that CPT extracted from different lines showed similar anti-tumor activity, suggesting that transgenic O. pumila hairy root lines could be an alternative approach to obtain CPT. To our knowledge, this is the first report on the enhancement of CPT production in O. pumila employing a metabolic engineering strategy. PMID:25648209

  11. Design, Synthesis, and Biological Evaluation of New Cathepsin B-Sensitive Camptothecin Nanoparticles Equipped with a Novel Multifuctional Linker.

    Science.gov (United States)

    Zhang, Xuan; Tang, Kaiyong; Wang, Hong; Liu, Yaqian; Bao, Bin; Fang, Yanfen; Zhang, Xiongwen; Lu, Wei

    2016-05-18

    Traditional antitumor drugs such as camptothecin and paclitaxel derivatives are widely used in cancer chemotherapy. However, the major defects of those agents include severe toxicity and poor water solubility. With these in mind, a novel multifunctional linker was designed and two Cathepsin B (CTB) sensitive CPT conjugates (9a and 9b) were synthesized. Through click chemistry, additional functional group mPEG2000 can be easily introduced into these conjugates. The introduction of mPEG2000 fragment resulted in the formation of nanoparticles 1a and 1b (average particle sizes were 216.9 and 257.9 nm, respectively) with significantly increased water solubility (more than 19 000-fold). The release of therapeutic drug SN-38 in the presence of CTB was confirmed by HPLC and prodrug 1a showed potent in vitro cytotoxicity against all tested cell lines. Impressively, compared with irinotecan, CTB sensitive prodrug 1a displayed similar in vivo efficacy with remarkable decreased in vivo toxicity. PMID:27070848

  12. Electron paramagnetic resonance (EPR) study of spin-labeled camptothecin derivatives: a different look of the ternary complex.

    Science.gov (United States)

    Ricci, Antonio; Marinello, Jessica; Bortolus, Marco; Sánchez, Albert; Grandas, Anna; Pedroso, Enrique; Pommier, Yves; Capranico, Giovanni; Maniero, Anna Lisa; Zagotto, Giuseppe

    2011-02-24

    Camptothecin (CPT) derivatives are clinically effective poisons of DNA topoisomerase I (Top1) able to form a ternary complex with the Top1-DNA complex. The aim of this investigation was to examine the dynamic aspects of the ternary complex formation by means of site-directed spin labeling electron paramagnetic resonance (SDSL-EPR). Two semisynthetic CPT derivatives bearing the paramagnetic moiety were synthesized, and their biological activity was tested. A 22-mer DNA oligonucleotide sequence with high affinity cleavage site for Top1 was also synthesized. EPR experiments were carried out on modified CPT in the presence of DNA, of Top1, or of both. In the last case, a slow motion component in the EPR signal appeared, indicating the formation of the ternary complex. Deconvolution of the EPR spectrum allowed to obtain the relative drug amounts in the complex. It was also possible to demonstrate that the residence time of CPT "trapped" in the ternary complex is longer than hundreds of microseconds. PMID:21254781

  13. Compound Specific Extraction of Camptothecin from Nothapodytes nimmoniana and Piperine from Piper nigrum Using Accelerated Solvent Extractor.

    Science.gov (United States)

    Upadhya, Vinayak; Pai, Sandeep R; Sharma, Ajay K; Hegde, Harsha V; Kholkute, Sanjiva D; Joshi, Rajesh K

    2014-01-01

    Effects of varying temperatures with constant pressure of solvent on extraction efficiency of two chemically different alkaloids were studied. Camptothecin (CPT) from stem of Nothapodytes nimmoniana (Grah.) Mabb. and piperine from the fruits of Piper nigrum L. were extracted using Accelerated Solvent Extractor (ASE). Three cycles of extraction for a particular sample cell at a given temperature assured complete extraction. CPT and piperine were determined and quantified by using a simple and efficient UFLC-PDA (245 and 343 nm) method. Temperature increased efficiency of extraction to yield higher amount of CPT, whereas temperature had diminutive effect on yield of piperine. Maximum yield for CPT was achieved at 80°C and for piperine at 40°C. Thus, the study determines compound specific extraction of CPT from N. nimmoniana and piperine from P. nigrum using ASE method. The present study indicates the use of this method for simple, fast, and accurate extraction of the compound of interest. PMID:24527258

  14. Fabrication and optimization of camptothecin loaded Eudragit S 100 nanoparticles by Taguchi L4 orthogonal array design

    Science.gov (United States)

    Mahalingam, Manikandan; Krishnamoorthy, Kannan

    2015-01-01

    Introduction: The objective of this investigation was to design and optimize the experimental conditions for the fabrication of camptothecin (CPT) loaded Eudragit S 100. Nanoparticles, and to understand the effect of various process parameters on the average particles size, particle size uniformity and surface area of the prepared polymeric nanoparticles using Taguchi design. Materials and Methods: CPT loaded Eudragit S 100 nanoparticles were prepared by nanoprecipitation method and characterized by particles size analyzer. Taguchi orthogonal array design was implemented to study the influence of seven independent variables on three dependent variables. Eight experimental trials involving seven independent variables at higher and lower levels were generated by design expert. Results: Factorial design result has shown that (a) except, β-cyclodextrin concentration all other parameters do not significantly influenced the average particle size (R1); (b) except, sonication duration and aqueous phase volume, all other process parameters significantly influence the particle size uniformity; (c) all the process parameters does not significantly influence the surface area. Conclusion: The R1, particle size uniformity and surface area of the prepared drug-loaded polymeric nanoparticles were found to be 120 nm, 0.237 and 55.7 m2 /g and the results were good correlated with the data generated by the Taguchi design method. PMID:26258056

  15. Compound Specific Extraction of Camptothecin from Nothapodytes nimmoniana and Piperine from Piper nigrum Using Accelerated Solvent Extractor

    Directory of Open Access Journals (Sweden)

    Vinayak Upadhya

    2014-01-01

    Full Text Available Effects of varying temperatures with constant pressure of solvent on extraction efficiency of two chemically different alkaloids were studied. Camptothecin (CPT from stem of Nothapodytes nimmoniana (Grah. Mabb. and piperine from the fruits of Piper nigrum L. were extracted using Accelerated Solvent Extractor (ASE. Three cycles of extraction for a particular sample cell at a given temperature assured complete extraction. CPT and piperine were determined and quantified by using a simple and efficient UFLC-PDA (245 and 343 nm method. Temperature increased efficiency of extraction to yield higher amount of CPT, whereas temperature had diminutive effect on yield of piperine. Maximum yield for CPT was achieved at 80∘C and for piperine at 40∘C. Thus, the study determines compound specific extraction of CPT from N. nimmoniana and piperine from P. nigrum using ASE method. The present study indicates the use of this method for simple, fast, and accurate extraction of the compound of interest.

  16. The effects of steady swimming on fish escape performance.

    Science.gov (United States)

    Anwar, Sanam B; Cathcart, Kelsey; Darakananda, Karin; Gaing, Ashley N; Shin, Seo Yim; Vronay, Xena; Wright, Dania N; Ellerby, David J

    2016-06-01

    Escape maneuvers are essential to the survival and fitness of many animals. Escapes are frequently initiated when an animal is already in motion. This may introduce constraints that alter the escape performance. In fish, escape maneuvers and steady, body caudal fin (BCF) swimming are driven by distinct patterns of curvature of the body axis. Pre-existing muscle activity may therefore delay or diminish a response. To quantify the performance consequences of escaping in flow, escape behavior was examined in bluegill sunfish (Lepomis macrochirus) in both still-water and during steady swimming. Escapes executed during swimming were kinematically less variable than those made in still-water. Swimming escapes also had increased response latencies and lower peak velocities and accelerations than those made in still-water. Performance was also lower for escapes made up rather than down-stream, and a preference for down-stream escapes may be associated with maximizing performance. The constraints imposed by pre-existing motion and flow, therefore, have the potential to shape predator-prey interactions under field conditions by shifting the optimal strategies for both predators and prey. PMID:27161016

  17. Escape from X inactivation varies in mouse tissues.

    Directory of Open Access Journals (Sweden)

    Joel B Berletch

    2015-03-01

    Full Text Available X chromosome inactivation (XCI silences most genes on one X chromosome in female mammals, but some genes escape XCI. To identify escape genes in vivo and to explore molecular mechanisms that regulate this process we analyzed the allele-specific expression and chromatin structure of X-linked genes in mouse tissues and cells with skewed XCI and distinguishable alleles based on single nucleotide polymorphisms. Using a binomial model to assess allelic expression, we demonstrate a continuum between complete silencing and expression from the inactive X (Xi. The validity of the RNA-seq approach was verified using RT-PCR with species-specific primers or Sanger sequencing. Both common escape genes and genes with significant differences in XCI status between tissues were identified. Such genes may be candidates for tissue-specific sex differences. Overall, few genes (3-7% escape XCI in any of the mouse tissues examined, suggesting stringent silencing and escape controls. In contrast, an in vitro system represented by the embryonic-kidney-derived Patski cell line showed a higher density of escape genes (21%, representing both kidney-specific escape genes and cell-line specific escape genes. Allele-specific RNA polymerase II occupancy and DNase I hypersensitivity at the promoter of genes on the Xi correlated well with levels of escape, consistent with an open chromatin structure at escape genes. Allele-specific CTCF binding on the Xi clustered at escape genes and was denser in brain compared to the Patski cell line, possibly contributing to a more compartmentalized structure of the Xi and fewer escape genes in brain compared to the cell line where larger domains of escape were observed.

  18. Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism.

    Science.gov (United States)

    Krupka, C; Kufer, P; Kischel, R; Zugmaier, G; Lichtenegger, F S; Köhnke, T; Vick, B; Jeremias, I; Metzeler, K H; Altmann, T; Schneider, S; Fiegl, M; Spiekermann, K; Bauerle, P A; Hiddemann, W; Riethmüller, G; Subklewe, M

    2016-02-01

    Bispecific T-cell engagers (BiTEs) are very effective in recruiting and activating T cells. We tested the cytotoxicity of the CD33/CD3 BiTE antibody construct AMG 330 on primary acute myeloid leukemia (AML) cells ex vivo and characterized parameters contributing to antileukemic cytolytic activity. The E:T ratio and the CD33 expression level significantly influenced lysis kinetics in long-term cultures of primary AML cells (n=38). AMG 330 induced T-cell-mediated proinflammatory conditions, favoring the upregulation of immune checkpoints on target and effector cells. Although not constitutively expressed at the time of primary diagnosis (n=123), PD-L1 was strongly upregulated on primary AML cells upon AMG 330 addition to ex vivo cultures (n=27, Pcheckpoint molecules in upcoming clinical trials with AMG 330 to enhance BiTE antibody construct-mediated cytotoxicity. PMID:26239198

  19. Uremic escape of renal allograft rejection

    International Nuclear Information System (INIS)

    It is demonstrated in rats that, in the presence of early postoperative severe but transient uremia, the survival of first set Brown-Norway (BN) renal allografts in Lewis (LEW) recipients is at least three times prolonged when compared to non-uremic controls. This phenomenon is called 'uremic escape of renal allograft rejection'. By means of lethal X-irradiation of donors of BN kidneys transplanted into transiently uremic and non-uremic LEW recipients, the presence of passenger lymphocyte immunocompetence is demonstrated to be obilgatory for this phenomenon to occur. As a result of mobile passenger lymphocyte immunocompetence, a graft-versus-host (GVH) reaction is elicited in the spleens of LEW recipients of BN kidneys which amplifies the host response. The splenomegaly observed in LEW recipients of BN kidneys is caused not only by this GVH reaction, which is shown to be exquisitely sensitive to even mild uremia. It is also contributed to by a proliferative response of the host against the graft (which latter response is equated with an in vivo equivalent of a unilateral mixed lymphocyte reaction (MLR)), since the reduction in spleen weights caused by abrogation of mobile passenger lymphocyte immunocompetence brought about by lethal donor X-irradiation is increased significantly by early postoperative severe but transient uremia. It is concluded that in uremic escape of renal allograft rejection both reactions are suppressed by uremia during the early post-operative period. (Auth.)

  20. Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape.

    Directory of Open Access Journals (Sweden)

    Katharine J Bar

    Full Text Available Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, antibody adsorptions and virus-entry assays, we found evidence in three subjects of neutralizing antibody (Nab responses as early as 2 weeks post-seroconversion, with Nab titers as low as 1∶20 to 1∶50 (IC(50 selecting for virus escape. In each of the subjects, Nabs targeted different regions of the HIV-1 envelope (Env in a strain-specific, conformationally sensitive manner. In subject CH40, virus escape was first mediated by mutations in the V1 region of the Env, followed by V3. HIV-1 specific monoclonal antibodies from this subject mapped to an immunodominant region at the base of V3 and exhibited neutralizing patterns indistinguishable from polyclonal antibody responses, indicating V1-V3 interactions within the Env trimer. In subject CH77, escape mutations mapped to the V2 region of Env, several of which selected for alterations of glycosylation. And in subject CH58, escape mutations mapped to the Env outer domain. In all three subjects, initial Nab recognition was followed by sequential rounds of virus escape and Nab elicitation, with Nab escape variants exhibiting variable costs to replication fitness. Although delayed in comparison with autologous CD8 T-cell responses, our findings show that Nabs appear earlier in HIV-1 infection than previously recognized, target diverse sites on HIV-1 Env, and impede virus replication at surprisingly low titers. The unexpected in vivo sensitivity of early transmitted/founder virus to Nabs raises the possibility that similarly low concentrations of vaccine-induced Nabs could impair virus acquisition in natural HIV-1 transmission, where the risk of infection is low and the number of viruses responsible for transmission and productive clinical

  1. New Analysis of Hydrogen and Deuterium Escape from Venus

    Science.gov (United States)

    Donahue, Thomas M.

    1999-10-01

    This paper is concerned with the time required for escape of hydrogen and deuterium to produce the present D/ H ratio in Venus water, the sizes of the original hydrogen reservoirs and their sensitivity to the magnitude of the present escape fluxes, the characteristics of exogenous and endogenous hydrogen sources, and the D/ H ratio for primordial Venus hydrogen. The procedure followed allowed the H escape flux to vary over a large range, the ratio of input to escape flux to vary from 0 to 1, and the fractionation factor, which expresses the relative efficiency of D and H escape, to vary between 0.02 and 0.5. It was found that, unless deuterium escape is very efficient, the present H escape flux (averaged over a solar cycle) cannot be larger than about 10 7 cm -2 s -1 if today's water is to be the remnant of water deposited eons ago. On the other hand if the escape flux is as large as large as 3×10 7 cm -2 s -1, today's water would be the remnant of water outgassed only about 500 million years ago. These conclusions are relatively insensitive to factors other than the magnitude of the escape flux. Since recent analysis of escape fluxes indicates that the H escape fluxes may be in the neighborhood of 3×10 7 cm -2 s -1 and the fractionation factor may be 0.14 or larger, the suggestion of Grinspoon (1993, Nature 363, 1702-1704) that the water now on Venus was created during a recent massive resurfacing event is credible. However, since it is still possible that the average escape flux is as small as 7×10 6 cm -2 s -1, the choice between 4 and 0.5 Gyr must await a resolution of this conflict by reanalysis of Pioneer Venus Lyman α data (Paxton, L., D. E. Anderson, and A. I. F. Stewart 1988, J. Geophys. Res. 93, 1766-1772).

  2. The atmospheric escape at Mars: complementing the scenario

    Science.gov (United States)

    Lilensten, Jean; Simon, Cyril; Barthélémy, Mathieu; Thissen, Roland; Ehrenreich, David; Gronoff, Guillaume; Witasse, Olivier

    2013-04-01

    In the recent years, the presence of dications in the atmospheres of Mars, Venus, Earth and Titan has been modeled and assessed. These studies also suggested that these ions could participate to the escape of the planetary atmospheres because a large fraction of them is unstable and highly ener- getic. When they dissociate, their internal energy is transformed into kinetic energy which may be larger than the escape energy. This study assesses the impact of the doubly-charged ions in the escape of CO2-dominated planetary atmospheres and to compare it to the escape of thermal photo-ions.We solve a Boltzmann transport equation at daytime taking into account the dissociative states of CO++ for a simplified single constituent atmosphere of a 2 case-study planet. We compute the escape of fast ions using a Beer-Lambert approach. We study three test-cases. On a Mars-analog planet in today's conditions, we retrieve the measured electron escape flux. When comparing the two mechanisms (i.e. excluding solar wind effects, sputtering ...), the escape due to the fast ions issuing from the dissociation of dications may account for up to 6% of the total and the escape of thermal ions for the remaining. We show that these two mechanisms cannot explain the escape of the atmosphere since the magnetic field vanished but complement the other processes and allow writing the scenario of the Mars escape. We show that the atmosphere of a Mars analog planet would empty in another giga years and a half. At Venus orbit, the contribution of the dications in the escape rate is negligible.When simulating the hot Jupiter HD209458b, the two processes cannot explain the measured escape flux of C+.

  3. RpoS controls the Vibrio cholerae mucosal escape response.

    Directory of Open Access Journals (Sweden)

    Alex Toftgaard Nielsen

    2006-10-01

    Full Text Available Vibrio cholerae causes a severe diarrhoeal disease by secreting a toxin during colonization of the epithelium in the small intestine. Whereas the initial steps of the infectious process have been intensively studied, the last phases have received little attention. Confocal microscopy of V. cholerae O1-infected rabbit ileal loops captured a distinctive stage in the infectious process: 12 h post-inoculation, bacteria detach from the epithelial surface and move into the fluid-filled lumen. Designated the "mucosal escape response," this phenomenon requires RpoS, the stationary phase alternative sigma factor. Quantitative in vivo localization assays corroborated the rpoS phenotype and showed that it also requires HapR. Expression profiling of bacteria isolated from ileal loop fluid and mucus demonstrated a significant RpoS-dependent upregulation of many chemotaxis and motility genes coincident with the emigration of bacteria from the epithelial surface. In stationary phase cultures, RpoS was also required for upregulation of chemotaxis and motility genes, for production of flagella, and for movement of bacteria across low nutrient swarm plates. The hapR mutant produced near-normal numbers of flagellated cells, but was significantly less motile than the wild-type parent. During in vitro growth under virulence-inducing conditions, the rpoS mutant produced 10- to 100-fold more cholera toxin than the wild-type parent. Although the rpoS mutant caused only a small over-expression of the genes encoding cholera toxin in the ileal loop, it resulted in a 30% increase in fluid accumulation compared to the wild-type. Together, these results show that the mucosal escape response is orchestrated by an RpoS-dependent genetic program that activates chemotaxis and motility functions. This may furthermore coincide with reduced virulence gene expression, thus preparing the organism for the next stage in its life cycle.

  4. Chaotic Scattering and Escape Times of Marginally Trapped Ultracold Neutrons

    Science.gov (United States)

    Coakley, K. J.; Doyle, J. M.; Dzhosyuk, S. N.; Yang, L.; Huffman, P. R.

    2005-01-01

    We compute classical trajectories of Ultracold neutrons (UCNs) in a superconducting Ioffe-type magnetic trap using a symplectic integration method. We find that the computed escape time for a particular set of initial conditions (momentum and position) does not generally stabilize as the time step parameter is reduced unless the escape time is short (less than approximately 10 s). For energy intervals where more than half of the escape times computed for UCN realizations are numerically well determined, we predict the median escape time as a function of the midpoint of the interval.

  5. The Fastest Saccadic Responses Escape Visual Masking

    DEFF Research Database (Denmark)

    M. Crouzet, Sébastien; Overgaard, Morten; Busch, Niko A.

    2014-01-01

    Object-substitution masking (OSM) occurs when a briefly presented target in a search array is surrounded by small dots that remain visible after the target disappears. The reduction of target visibility occurring after OSM has been suggested to result from a specific interference with reentrant...... visual processing while the initial feedforward processing is thought to be left intact. We tested a prediction derived from this hypothesis: the fastest responses, being triggered before the beginning of reentrant processing, should escape the OSM interference. In a saccadic choice reaction time task......, which gives access to very early stages of visual processing, target visibility was reduced either by OSM, conventional backward masking, or low stimulus contrast. A general reduction of performance was observed in all three conditions. However, the fastest saccades did not show any sign of interference...

  6. Core–shell hybrid nanocapsules for oral delivery of camptothecin: formulation development, in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ünal, Hale, E-mail: unalhale@gmail.com [Hacettepe University, Division of Nanotechnology and Nanomedicine, Institute of Pure and Applied Science (Turkey); D’Angelo, Ivana [Second University of Napoli, Di.S.T.A.Bi.F. (Italy); Pagano, Ester; Borrelli, Francesca; Izzo, Angelo; Ungaro, Francesca; Quaglia, Fabiana [University of Naples Federico II, Department of Pharmacy (Italy); Bilensoy, Erem [Hacettepe University, Division of Nanotechnology and Nanomedicine, Institute of Pure and Applied Science (Turkey)

    2015-01-15

    The objective of this study was to design and in vitro–in vivo evaluate oral nanocapsules prepared from amphiphilic cyclodextrins (CDs) or poly-ε-caprolactone (PCL) for the effective oral delivery of an anticancer agent, camptothecin (CPT). CPT-loaded anionic and Chitosan (CS)-coated cationic nanocapsules were prepared and characterized in vitro. Morphological analysis was performed by scanning electron microscope (SEM). CPT release profile was evaluated using dialysis method under sink conditions. To determine the protective effect and drug stability provided by nanocapsules, all the formulations were incubated in simulated gastrointestinal media. Measurement of mucoadhesive tendency of CPT-loaded nanocapsules was realized by turbidimetric method. Penetration of nanocapsules was performed through an artificial mucus model. The permeability of CPT in solution form and bound to nanocapsule formulations were demonstrated across Caco-2 cell line. Finally, the intestinal uptake of nanocapsules was evaluated in vivo, in a mouse model. Both anionic and cationic formulations were in the range of 180–220 nm with a narrow size distribution and desired zeta potential values. CPT-loaded nanocapsules were found to be stable in simulated gastrointestinal media. Turbidimetric measurements confirmed the interaction between nanoparticles and mucin. Penetration of CPT through an artificial mucus gel layer was higher with CS-coated nanocapsules in accordance with the results obtained from permeability studies across Caco-2 cell line. In vivo animal studies confirmed that the intestinal uptake of nanocapsules was significantly higher with cationic nanocapsules. CPT-loaded positively charged CD nanocapsules might be an attractive and promising treatment for oral chemotherapy.

  7. Autophagy is preferred pathway of camptothecin-induced programmed cell death of v-myb-transformed monoblasts

    Czech Academy of Sciences Publication Activity Database

    Zahradníčková, Eva; Souček, Karel; Horváth, Viktor; Šmarda, Jan

    Budapest, 2005. P-251. [13th Euroconference on Apoptosis. 01.10.2005-04.10.2005, Budapest] R&D Projects: GA ČR(CZ) GA301/03/1055; GA MŠk(CZ) MSM0021622415 Institutional research plan: CEZ:AV0Z50040507 Keywords : autophagy * v-myb * BM2 cells Subject RIV: BO - Biophysics

  8. Co-lethality studied as an asset against viral drug escape: the HIV protease case

    Directory of Open Access Journals (Sweden)

    Ollivier Emmanuelle

    2010-06-01

    Full Text Available Abstract Background Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL or a co-lethal. Like invariant positions, SL sets (SL linked couples are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic lethality. Results From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap, 4 (in the cantilever and 5 (in the fulcrum amino acid positions were found. Conclusions These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. Reviewers This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.

  9. Teachers Offering Healthy Escape Options for Teenagers in Pain

    Science.gov (United States)

    Kaywell, Joan F.

    2005-01-01

    "[T]wenty-five percent of today's teenagers have inordinate emotional baggage beyond the normal angst of adolescence." This burden can lead to unhealthy escapes, including substance abuse, sexual activity, violence, eating disorders, and suicide. One healthy escape, however, lies in books, where students can read about teenagers living in painful…

  10. Escape response of planktonic protists to fluid mechanical signals

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2001-01-01

    The escape response to fluid mechanical signals was examined in 6 protists, 4 ciliates and 2 dinoflagellates. When exposed to a siphon flow. 3 species of ciliates, Balanion comatum, Strobilidium sp., and Mesodinium pulex, responded with escape jumps. The threshold deformation rates required to...

  11. Split-second escape decisions in blue tits (Parus caeruleus)

    Science.gov (United States)

    Lind, Johan; Kaby, Ulrika; Jakobsson, Sven

    2002-07-01

    Bird mortality is heavily affected by birds of prey. Under attack, take-off is crucial for survival and even minor mistakes in initial escape response can have devastating consequences. Birds may respond differently depending on the character of the predator's attack and these split-second decisions were studied using a model merlin (Falco columbarius) that attacked feeding blue tits (Parus caeruleus) from two different attack angles in two different speeds. When attacked from a low attack angle they took off more steeply than when attacked from a high angle. This is the first study to show that escape behaviour also depends on predator attack speed. The blue tits responded to a high-speed attack by dodging sideways more often than when attacked at a low speed. Escape speed was not significantly affected by the different treatments. Although they have only a split-second before escaping an attack, blue tits do adjust their escape strategy to the prevailing attack conditions.

  12. Escaping in couples facilitates evacuation: Experimental study and modeling

    CERN Document Server

    Guo, Ning; Hu, Mao-Bin; Ding, Jian-Xun; Ding, Zhong-Jun

    2015-01-01

    In this paper, the impact of escaping in couples on the evacuation dynamics has been investigated via experiments and modeling. Two sets of experiments have been implemented, in which pedestrians are asked to escape either in individual or in couples. The experiments show that escaping in couples can decrease the average evacuation time. Moreover, it is found that the average evacuation time gap is essentially constant, which means that the evacuation speed essentially does not depend on the number of pedestrians that have not yet escaped. To model the evacuation dynamics, an improved social force model has been proposed, in which it is assumed that the driving force of a pedestrian cannot be fulfilled when the composition of physical forces exceeds a threshold because the pedestrian cannot keep his/her body balance under this circumstance. To model the effect of escaping in couples, attraction force has been introduced between the partners. Simulation results are in good agreement with the experimental ones.

  13. UV-vis spectra of the anticancer camptothecin family drugs in aqueous solution: specific spectroscopic signatures unraveled by a combined computational and experimental study.

    Science.gov (United States)

    Sanna, Nico; Chillemi, Giovanni; Gontrani, Lorenzo; Grandi, Andrea; Mancini, Giordano; Castelli, Silvia; Zagotto, Giuseppe; Zazza, Costantino; Barone, Vincenzo; Desideri, Alessandro

    2009-04-23

    The ultraviolet-visible absorption spectrum of camptothecin (CPT) has been been recorded in aqueous solution at pH 5.3, where the equilibrium among the different CPT forms is shifted toward the lactonic one. Time-dependent density functional theory (TD-DFT) computations lead to a remarkable reproduction of the experimental spectrum only upon addition of explicit water molecules in interaction with specific moieties of the camptothecin molecule. Molecular dynamics (MD) simulations enforcing boundary periodic conditions for CPT embedded with 865 water molecules, with a force field derived from DFT computations, show that the experimental spectrum is due to the contributions of CPT molecules with different solvation patterns. A similar solvent effect is observed for several CPT derivatives, including the clinically relevant SN-38 and topotecan drugs. The quantitative agreement between TD-DFT/MD computations and experimental data allow us to identify specific spectroscopic signatures diagnostic of the drug environment and to develop procedures that can be used to monitor the drug-DNA/protein interaction. PMID:19334673

  14. Mission Impossible (Escape from the Lyman Limit)

    CERN Document Server

    Fernández-Soto, A; Chen, H W

    2003-01-01

    We investigate the intrinsic opacity of high-redshift galaxies to outgoing ionising photons using high-quality photometry of a sample of 27 spectroscopically-identified galaxies of redshift 1.9escape galaxies of redshift 1.9

  15. Pregabalin attenuates place escape/avoidance behavior in a rat model of spinal cord injury.

    Science.gov (United States)

    Baastrup, Cathrine; Jensen, Troels Staehelin; Finnerup, Nanna Brix

    2011-01-25

    Spinal cord injury (SCI) pain in humans is difficult to treat, and the lack of valid methods to measure behavior comparable to the complex human pain experience preclinically represents an important obstacle to finding better treatments for this type of central pain. The place escape/avoidance paradigm (PEAP) relies on the active choice of an animal between its natural preference for a dark environment or pain relief, and it has been suggested to measure the affective-motivational component of pain. We have modified the method to a T10 spinal cord contusion model (SCC) of at-level central neuropathic pain in Sprague-Dawley rats. In order to demonstrate sensitivity to change in escape/avoidance behavior and thus the applicability of the PEAP method to predict drug efficacy, we investigated the effect of pregabalin (30 mg/kg) treatment in a randomized design. SCC animals displayed increased escape/avoidance behavior postinjury, indicating at-level mechanical hypersensitivity. Second, we found no correlation between state anxiety levels in SCC animals (elevated plus maze) and PEAP behavior, suggesting that the PEAP measurement is not biased by differences in anxiety levels. Third, we demonstrated a decrease in escape/avoidance behavior in response to treatment with the analgesic drug pregabalin. Thus, the PEAP may be applicable as a surrogate correlate of human pain. In conclusion, the primary finding in this study was a sensitivity to change in escape/avoidance behavior induced by pharmacological modulation with analgesics, supporting the use of the PEAP as a central outcome measure in preclinical SCI pain research. PMID:21070753

  16. Dications and thermal ions in planetary atmospheric escape

    Science.gov (United States)

    Lilensten, J.; Simon Wedlund, C.; Barthélémy, M.; Thissen, R.; Ehrenreich, D.; Gronoff, G.; Witasse, O.

    2013-01-01

    In the recent years, the presence of dications in the atmospheres of Mars, Venus, Earth and Titan has been modeled and assessed. These studies also suggested that these ions could participate to the escape of the planetary atmospheres because a large fraction of them is unstable and highly energetic. When they dissociate, their internal energy is transformed into kinetic energy which may be larger than the escape energy. The goal of this study is to assess the impact of the doubly-charged ions in the escape of CO2-dominated planetary atmospheres and to compare it to the escape of thermal photo-ions. We solve a Boltzmann transport equation at daytime taking into account the dissociative states of CO2++ for a simplified single constituent atmosphere of a case-study planet. We compute the escape of fast ions using a Beer-Lambert approach. We study three test-cases. On a Mars-analog planet in today's conditions, we retrieve the measured electron escape flux. When comparing the two mechanisms (i.e. excluding solar wind effects, sputtering, etc.), the escape due to the fast ions issuing from the dissociation of dications may account for up to 6% of the total and the escape of thermal ions for the remaining. We show that these two mechanisms cannot explain the escape of the atmosphere since the magnetic field vanished and even contribute only marginally to this loss. We show that with these two mechanisms, the atmosphere of a Mars analog planet would empty in another giga years and a half. At Venus orbit, the contribution of the dications in the escape rate is negligible. When simulating the hot Jupiter HD 209458 b, the two processes cannot explain the measured escape flux of C+. This study shows that the dications may constitute a source of the escape of planetary atmospheres which had not been taken into account until now. This source, although marginal, is not negligible. The influence of the photoionization is of course large, but cannot explain alone the loss of Mars

  17. Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor PV1019 [7-Nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide

    Energy Technology Data Exchange (ETDEWEB)

    Jobson, Andrew G.; Lountos, George T.; Lorenzi, Philip L.; Llamas, Jenny; Connelly, John; Cerna, David; Tropea, Joseph E.; Onda, Akikazu; Zoppoli, Gabriele; Kondapaka, Sudhir; Zhang, Guangtao; Caplen, Natasha J.; Cardellina, II, John H.; Yoo, Stephen S.; Monks, Anne; Self, Christopher; Waugh, David S.; Shoemaker, Robert H.; Pommier, Yves; (NIH)

    2010-04-05

    Chk2 is a checkpoint kinase involved in the ataxia telangiectasia mutated pathway, which is activated by genomic instability and DNA damage, leading to either cell death (apoptosis) or cell cycle arrest. Chk2 provides an unexplored therapeutic target against cancer cells. We recently reported 4,4'-diacetyldiphenylurea-bis(guanylhydrazone) (NSC 109555) as a novel chemotype Chk2 inhibitor. We have now synthesized a derivative of NSC 109555, PV1019 (NSC 744039) [7-nitro-1H-indole-2-carboxylic acid {l_brace}4-[1-(guanidinohydrazone)-ethyl]-phenyl{r_brace}-amide], which is a selective submicromolar inhibitor of Chk2 in vitro. The cocrystal structure of PV1019 bound in the ATP binding pocket of Chk2 confirmed enzymatic/biochemical observations that PV1019 acts as a competitive inhibitor of Chk2 with respect to ATP. PV1019 was found to inhibit Chk2 in cells. It inhibits Chk2 autophosphorylation (which represents the cellular kinase activation of Chk2), Cdc25C phosphorylation, and HDMX degradation in response to DNA damage. PV1019 also protects normal mouse thymocytes against ionizing radiation-induced apoptosis, and it shows synergistic antiproliferative activity with topotecan, camptothecin, and radiation in human tumor cell lines. We also show that PV1019 and Chk2 small interfering RNAs can exert antiproliferative activity themselves in the cancer cells with high Chk2 expression in the NCI-60 screen. These data indicate that PV1019 is a potent and selective inhibitor of Chk2 with chemotherapeutic and radiosensitization potential.

  18. Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

    Directory of Open Access Journals (Sweden)

    Hale Ünal

    2015-02-01

    Full Text Available Background: The aim of this study was to design and evaluate hybrid cyclodextrin (CD nanocapsules intended for the oral delivery of the anticancer agent camptothecin (CPT in order to maintain drug stability in the body and to improve its eventual bioavailability. For this reason, an amphiphilic cyclodextrin (CD derivative per-modified on the primary face 6OCAPRO was used as core molecule to form nanocapsules with the nanoprecipitation technique. Nanocapsules were further coated with the cationic polymer chitosan to improve the cellular uptake and interaction with biological membranes through positive surface charge. Nanocapsules were evaluated for their in vitro characteristics such as particle size, zeta potential, drug loading and release profiles followed by cell culture studies with the MCF-7 and Caco-2 cell line evaluating their anticancer efficacy and permeability. The CD nanocapsules were imaged by scanning electron microscopy (SEM. The concentration of CPT entrapped in nanocapsules was determined by reversed phase HPLC. The in vitro release study of CPT was performed with a dialysis bag method under sink conditions mimicking the gastric and intestinal pH. The hydrolytic stability of CPT in nanocapsules was investigated in simulated gastric and intestinal fluids (SGF, SIF.Results: The mean particle sizes of both anionic and cationic CPT-loaded nanocapsules were in the range of 180–200 nm with polydispersity indices lower than 0.400 indicating monodisperse size distribution of nanocapsules with favourable potential for intracellular drug delivery to tumour cells. Surface charges of anionic and cationic nanocapsules were demonstrated as −21 mV and +18 mV, respectively. The stability of CPT in simulated release media, SGF and SIF were maintained suggesting the improved protection of the drug molecule from rapid hydrolysis degradation or gastrointestinal pH in nanocapsule oily core. Furthermore CD nanocapsules showed higher anticancer

  19. Xenon Fractionation, Hydrogen Escape, and the Oxidation of the Earth

    Science.gov (United States)

    Zahnle, K. J.; Catling, D. C.

    2014-12-01

    Xenon in Earth's atmosphere is severely mass fractionated and depleted compared to any plausible solar system source material, yet Kr is unfractionated. These observations seem to imply that Xe has escaped from Earth. Vigorous hydrodynamic hydrogen escape can produce mass fractionation in heavy gases. The required hydrogen flux is very high but within the range permitted by solar EUV heating when Earth was 100 Myrs old or younger. However this model cannot explain why Xe escapes but Kr does not. Recently, what appears to be ancient atmospheric xenon has been recovered from several very ancient (3-3.5 Ga) terrestrial hydrothermal barites and cherts (Pujol 2011, 2013). What is eye-catching about this ancient Xe is that it is less fractionated that Xe in modern air. In other words, it appears that a process was active on Earth some 3 to 3.5 billion years ago that caused xenon to fractionate. By this time the Sun was no longer the EUV source that it used to be. If xenon was being fractionated by escape — currently the only viable hypothesis — it had to be in Earth's Archean atmosphere and under rather modest levels of EUV forcing. It should be possible for Xe, but not Kr, to escape from Earth as an ion. In a hydrodynamically escaping hydrogen wind the hydrogen is partially ionized. The key concepts are that ions are much more strongly coupled to the escaping flow than are neutrals (so that a relatively modest flow of H and H+ to space could carry Xe+ along with it, the flux can be small enough to be consistent with diffusion-limited flux), and that Xe alone among the noble gases is more easily ionized than hydrogen. This sort of escape is possible along the polar field lines, although a weak or absent magnetic field would likely work as well. The extended history of hydrogen escape implicit in Xe escape in the Archean is consistent with other suggestions that hydrogen escape in the Archean was considerable. Hydrogen escape plausibly played the key role in creating

  20. Atomic hydrogen escape rate due to charge exchange with hot plasmaspheric ions

    Science.gov (United States)

    Maher, L. J.; Tinsley, B. A.

    1977-01-01

    Data on ion and electron temperatures and concentrations to several thousand kilometers of altitude were obtained from the Atmosphere Explorer C satellite for 1974 and to 850 km from Arecibo incoherent scatter radar measurements. These data were used to normalize diffusive equilibrium profiles. From these profiles and by using the neutral atmospheric model of Jacchia (1971) and a new hydrogen model, the charge-exchange-induced neutral hydrogen escape fluxes for equatorial and middle latitudes were calculated. The data confirm earlier estimates that the charge exchange loss is more important than Jeans escape for the earth. It is also found that inside the plasmapause this charge exchange process with hot plasmapheric ions is the major production and loss process for the satellite population in the hydrogen geocorona.

  1. Resonant phase escape in Bi2Sr2CaCu2O8+δ surface intrinsic Josephson junctions

    Science.gov (United States)

    Yu, H. F.; Zhu, X. B.; Ren, J. K.; Peng, Z. H.; Cui, D. J.; Deng, H.; Cao, W. H.; Tian, Ye; Chen, G. H.; Zheng, D. N.; Jing, X. N.; Lu, Li; Zhao, S. P.

    2013-09-01

    We present a study of phase escape in surface Bi2Sr2CaCu2O8+δ intrinsic Josephson junctions in the presence of microwave radiation. The measured switching current distributions display clear double-peak structures in the microwave field, which result from the single- and two-photon resonant escape processes accompanied by microwave-induced potential barrier suppression. We show that these results can be well explained by a quantum-mechanical model proposed by Fistul et al (2003 Phys. Rev. B 68 060504), from which the power and frequency dependences of the switching current distributions can be reproduced.

  2. Theoretical Study on Ion Escape in Martian Atmosphere

    Institute of Scientific and Technical Information of China (English)

    SHI Jian-Kui; LIU Zhen-Xing; Klaus TORKAR; Tielong ZHANG

    2007-01-01

    @@ Based on the observation that Martian magnetic moment is gradually reducing from the ancient to the present,we investigate the O+ ion flux distribution along magnetic field lines and the ion escaping flux in Martian tail with different assumed Martian magnetic moments. The results show that the O+ ion flux along magnetic field lines decreases with distance from Mars; the ion flux along the field line decreases more quickly if the magnetic moment is larger; the larger the magnetic moment, the smaller the ion escaping flux in the Martian tail. The ion escaping flux depends on Z-coordinate in the Martian tail. With decrease of the magnetic moment, the ion escaping flux in the Martian tail increases. The results are significant for studying the water loss from Mars surface.

  3. Pioneer Venus Orbiter (PVO) Ionosphere Evidence for Atmospheric Escape

    Science.gov (United States)

    Grebowsky, J. M.; Hoegy, W. R.

    2009-12-01

    An early estimate of escape of H2O from Venus [McElroy et al., 1982] using observed hot oxygen densities inferred by Nagy et al. [1981] from PVO OUVS 1304 Å dayglow and using ionization rates from photoionization and electron impact. This resulted in an estimated oxygen ionization rate planet-wide above the plasmapause of 3x1025 atoms/s. Based on the energetic O+ being swept up and removed by solar wind, McElroy et al. [1982] gave an estimate of a loss rate for O of 6x106 atoms/cm2/s. Using a different method of estimating escape based data in the ionotail of Venus, Brace et al. [1987] estimated a total planetary O+ escape rate of 5x1025 ions/s. Their estimate was based on PVO measurements of superthermal O+ (energy range 9-16 eV) in the tail ray plasma between 2000 and 3000 km. Their estimated global mean flux was 107 atoms/cm2/s. The two escape rates are remarkably close considering all the errors involved in such estimates of escape. A study of escape by Luhmann et al. [2008] using VEX observations at low solar activity finds modest escape rates, prompting the authors to reconsider the evidence from both PVO and VEX of the possibility of enhanced escape during extreme interplanetary conditions. We reexamine the variation of escape under different solar wind conditions using ion densities and plasma content in the dayside and nightside of Venus using PVO ionosphere density during times of high solar activity. Citations: Brace, L.H., W. T. Kasprzak, H.A. Taylor, R. F. Theis, C. T. Russess, A. Barnes, J. D. Mihalov, and D. M. Hunten, "The Ionotail of Venus: Its Configuration and Evidence for Ion Escape", J. Geophys. Res. 92, 15-26, 1987. Luhmann, J.G., A. Fedorov, S. Barabash, E. Carlsson, Y. Futaana, T.L. Zhang, C.T. Russell, J.G. Lyon, S.A. Ledvina, and D.A. Brain, “Venus Express observations of atmospheric oxygen escape during the passage of several coronal mass ejections”, J. Geophys. Res., 113, 2008. McElroy, M. B., M. J. Prather, J. M. Rodiquez, " Loss

  4. Speed kills: ineffective avian escape responses to oncoming vehicles

    OpenAIRE

    Travis L DeVault; Blackwell, Bradley F.; Seamans, Thomas W.; Lima, Steven L.; Fernández-Juricic, Esteban

    2015-01-01

    Animal–vehicle collisions cause high levels of vertebrate mortality worldwide, and what goes wrong when animals fail to escape and ultimately collide with vehicles is not well understood. We investigated alert and escape behaviours of captive brown-headed cowbirds (Molothrus ater) in response to virtual vehicle approaches of different sizes and at speeds ranging from 60 to 360 km h−1. Alert and flight initiation distances remained similar across vehicle speeds, and accordingly, alert and flig...

  5. Escape angles in bulk chi((2)) soliton interactions

    OpenAIRE

    Johansen, Steffen Kjær; Bang, Ole; Sørensen, Mads Peter

    2002-01-01

    We develop a theory for nonplanar interaction between two identical type I spatial solitons propagating at opposite, but arbitrary transverse angles in quadratic nonlinear (or so-called chi((2))) bulk, media. We predict quantitatively the outwards escape angle, below which the solitons turn around and collide, and above which they continue to move-away from each other. For in-plane interaction, the theory allows prediction of the Outcome of a collision through the inwards escape angle, i.e., ...

  6. Recording Field Potentials From Zebrafish Larvae During Escape Responses

    OpenAIRE

    Monesson-Olson, Bryan D.; Troconis, Eileen L.; Trapani, Josef G.

    2014-01-01

    Among vertebrates, startle responses are a ubiquitous method for alerting, and avoiding or escaping from alarming or dangerous stimuli. In zebrafish larvae, fast escape behavior is easily evoked through either acoustic or tactile stimuli. For example, a light touch to the head will excite trigeminal neurons that in turn excite a large reticulospinal neuron in the hindbrain called the Mauthner cell (M-cell). The M-cell action potential then travels down the contralateral trunk of the larva exc...

  7. On the escape of particles from cosmic ray modified shocks

    OpenAIRE

    Caprioli, D.; P. Blasi(INAF Arcetri); Amato, E.

    2008-01-01

    Stationary solutions to the problem of particle acceleration at shock waves in the non-linear regime, when the dynamical reaction of the accelerated particles on the shock cannot be neglected, are known to show a prominent energy flux escaping from the shock towards upstream infinity. On physical grounds, the escape of particles from the upstream region of a shock has to be expected in all those situations in which the maximum momentum of accelerated particles, $p_{max}$, decreases with time,...

  8. Non-linear diffusive shock acceleration with free escape boundary

    OpenAIRE

    Caprioli, D.; Amato, E.; P. Blasi(INAF Arcetri)

    2009-01-01

    We present here a semi-analytical solution of the problem of particle acceleration at non-linear shock waves with a free escape boundary at some location upstream. This solution, besides allowing us to determine the spectrum of particles accelerated at the shock front, including the shape of the cutoff at some maximum momentum, also allows us to determine the spectrum of particles escaping the system from upstream. This latter aspect of the problem is crucial for establishing a connection bet...

  9. Escaping From Predation At Low Reynolds Number: A Compensatory Mechanism

    Science.gov (United States)

    Gemmell, Brad; Sheng, Jian; Buskey, Ed

    2010-11-01

    Small planktonic organisms such as copepods are often the first foods for many species of fish and thus, subject to high predation rates. They have developed strong escape responses to attacks from visual predators and this behavior is found even in the youngest development stage. Because of their small size (approx. 100 μm), these juvenile copepods must contend with greater viscous forces than their predators during encounters. In this study, we investigate the role of viscosity on escape swimming performance of young copepods within the context of the environmental temperatures (10C-30C) these animals experience along the Texas coast. 3-Dimensional high speed (3000 frames per second) digital holographic techniques were used to elucidate kinematics and kinetics of swimming. Here we show that although escape velocity and acceleration are reduced as a function of both increasing viscosity and decreasing temperature, total escape distance is conserved. Interestingly, we observed no difference in the number swimming strokes per escape. Instead, the animals exhibit a compensatory mechanism based on increasing power stroke duration to recovery stroke duration to counter act the increasing viscosity at lower temperature. Flow analysis shows this results in the conservation of energy expenditure, and consequently escape distance.

  10. Optimal escapement in stage-structured fisheries with environmental stochasticity.

    Science.gov (United States)

    Holden, Matthew H; Conrad, Jon M

    2015-11-01

    Stage-structured population models are commonly used to understand fish population dynamics and additionally for stock assessment. Unfortunately, there is little theory on the optimal harvest of stage-structured populations, especially in the presence of stochastic fluctuations. In this paper, we find closed form optimal equilibrium escapement policies for a three-dimensional, discrete-time, stage-structured population model with linear growth, post-harvest nonlinear recruitment, and stage-specific pricing and extend the analytic results to structured populations with environmental stochasticity. When only fishing reproductive adults, stochasticity does not affect optimal escapement policies. However, when harvesting immature fish, the addition of stochasticity can increase or decrease optimal escapement depending on the second and third derivative of the recruitment function. For logistic recruitment, stochasticity reduces optimal immature escapement by a multiplicative factor of one over one plus the variance of the environmental noise. Using hard clam, Mercenaria mercenaria, as an example and assuming Beverton-Holt recruitment, we show that optimal fishing of hard clam targets the immature stage class exclusively and that environmental stochasticity increases optimal escapement for low discount rates and decreases optimal escapement for high discount rates. PMID:26362229

  11. Escape dynamics and fractal basin boundaries in Seyfert galaxies

    CERN Document Server

    Zotos, Euaggelos E

    2015-01-01

    The escape dynamics in a simple analytical gravitational model which describes the motion of stars in a Seyfert galaxy is investigated in detail. We conduct a thorough numerical analysis distinguishing between regular and chaotic orbits as well as between trapped and escaping orbits, considering only unbounded motion for several energy levels. In order to distinguish safely and with certainty between ordered and chaotic motion, we apply the Smaller ALingment Index (SALI) method. It is of particular interest to locate the escape basins through the openings around the collinear Lagrangian points $L_1$ and $L_2$ and relate them with the corresponding spatial distribution of the escape times of the orbits. Our exploration takes place both in the physical $(x,y)$ and in the phase $(x,\\dot{x})$ space in order to elucidate the escape process as well as the overall orbital properties of the galactic system. Our numerical analysis reveals the strong dependence of the properties of the considered escape basins with the...

  12. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape.

    Science.gov (United States)

    Hegde, Meenakshi; Mukherjee, Malini; Grada, Zakaria; Pignata, Antonella; Landi, Daniel; Navai, Shoba A; Wakefield, Amanda; Fousek, Kristen; Bielamowicz, Kevin; Chow, Kevin K H; Brawley, Vita S; Byrd, Tiara T; Krebs, Simone; Gottschalk, Stephen; Wels, Winfried S; Baker, Matthew L; Dotti, Gianpietro; Mamonkin, Maksim; Brenner, Malcolm K; Orange, Jordan S; Ahmed, Nabil

    2016-08-01

    In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected to single tumor antigens. Given the heterogeneous expression of antigens on glioblastomas, we hypothesized that a bispecific CAR molecule would mitigate antigen escape and improve the antitumor activity of T cells. Here, we created a CAR that joins a HER2-binding scFv and an IL13Rα2-binding IL-13 mutein to make a tandem CAR exodomain (TanCAR) and a CD28.ζ endodomain. We determined that patient TanCAR T cells showed distinct binding to HER2 or IL13Rα2 and had the capability to lyse autologous glioblastoma. TanCAR T cells exhibited activation dynamics that were comparable to those of single CAR T cells upon encounter of HER2 or IL13Rα2. We observed that TanCARs engaged HER2 and IL13Rα2 simultaneously by inducing HER2-IL13Rα2 heterodimers, which promoted superadditive T cell activation when both antigens were encountered concurrently. TanCAR T cell activity was more sustained but not more exhaustible than that of T cells that coexpressed a HER2 CAR and an IL13Rα2 CAR, T cells with a unispecific CAR, or a pooled product. In a murine glioblastoma model, TanCAR T cells mitigated antigen escape, displayed enhanced antitumor efficacy, and improved animal survival. Thus, TanCAR T cells show therapeutic potential to improve glioblastoma control by coengaging HER2 and IL13Rα2 in an augmented, bivalent immune synapse that enhances T cell functionality and reduces antigen escape. PMID:27427982

  13. Rømt regnbueørret blir i fjorden : Behaviour of escaped rainbow trout

    OpenAIRE

    Skilbrei, Ove

    2009-01-01

    Rainbow trout are mainly farmed in fjords. They are thought to be more sedentary after escaping than escaped salmon, however this has not previously been well documented. The behaviour of escaped rainbow trout is now being studied in the fjords around the island of Osterøy in Hordaland in order to increase our understanding of escaped fish and to develop recapture strategies.

  14. Mars atmospheric escape constrained using MAVEN IUVS coronal observations

    Science.gov (United States)

    Chaffin, Michael S.; Deighan, Justin; Chaufray, Jean-Yves; Jain, Sonal; Stewart, Ian; McClintock, Bill; Crismani, Matteo; Stiepen, Arnaud; Holsclaw, Greg; Clarke, John; Montmessin, Franck; Eparvier, Frank; Thiemann, Ed; Chamberlain, Phil; Schneider, Nick; Jakosky, Bruce

    2015-11-01

    Every planetary atmosphere is capped by a corona: an extended, extremely tenuous region where collisions are negligible and particles follow ballistic trajectories. At Mars, the corona is especially extended due to the low gravity of the planet, and a large number of coronal particles are on escaping trajectories. Such escape has played a critical role in the history of the Mars system, likely removing a substantial fraction of the water initially present on the planet, but the mechanism and magnitude of this escape remains poorly constrained. Currently in orbit at Mars, MAVEN's Imaging Ultraviolet Spectrograph (IUVS) is mapping the distribution of oxygen and hydrogen above 200 km at a high spatial and temporal cadence, revealing a dynamic corona in unprecedented detail. Results will be presented demonstrating that the H in the corona is not spherically symmetric in its distribution, and can potentially be used as a tracer of thermospheric general circulation; and that non-thermal "hot" O (in contrast with more spatially confined "cold" thermal O) is ionospherically sourced with a characteristic energy of 1.1 eV and responds to solar EUV forcing. These results will be interpreted in terms of their impact on our current understanding of how atmospheric escape operates today. We will also discuss how these processes may have acted in the past to deplete Mars' initial water inventory, potentially altering the redox balance of the planet and atmosphere through differential escape of H and O.

  15. History of oxygen and carbon escape from the Martian atmosphere

    Science.gov (United States)

    Luhmann, J. G.; Zhang, M. H. G.; Johnson, R. E.; Bougher, S. W.; Nagy, A. F.

    1992-01-01

    A fraction of the oxygen in the Martian atmosphere continually escapes to space because dissociative recombination of the O2(+) ions in the ionosphere can impart sufficient energy to the product O atoms. In addition, ionization of the extended atomic oxygen corona resulting from the above process adds to escape since the solar wind can carry away O(+) ions born above a few hundred km altitude. A further by-product of this ion-pickup by the solar wind is an additional population of escaping oxygen atoms that are sputtered from the atmosphere near the exobase by pickup ions that are on reentry rather than escaping trajectories. This sputtering process can also remove carbon in the form of intact or dissociated CO2 since all atoms and molecules in the 'target' gas are subject to the collisional energy transfer that characterizes sputtering. We have estimated the present rates of escape of oxygen and carbon due to these mechanisms, as well as the rates at several epochs in the history of the solar system.

  16. Single-File Escape of Colloidal Particles from Microfluidic Channels.

    Science.gov (United States)

    Locatelli, Emanuele; Pierno, Matteo; Baldovin, Fulvio; Orlandini, Enzo; Tan, Yizhou; Pagliara, Stefano

    2016-07-15

    Single-file diffusion is a ubiquitous physical process exploited by living and synthetic systems to exchange molecules with their environment. It is paramount to quantify the escape time needed for single files of particles to exit from constraining synthetic channels and biological pores. This quantity depends on complex cooperative effects, whose predominance can only be established through a strict comparison between theory and experiments. By using colloidal particles, optical manipulation, microfluidics, digital microscopy, and theoretical analysis we uncover the self-similar character of the escape process and provide closed-formula evaluations of the escape time. We find that the escape time scales inversely with the diffusion coefficient of the last particle to leave the channel. Importantly, we find that at the investigated microscale, bias forces as tiny as 10^{-15}  N determine the magnitude of the escape time by drastically reducing interparticle collisions. Our findings provide crucial guidelines to optimize the design of micro- and nanodevices for a variety of applications including drug delivery, particle filtering, and transport in geometrical constrictions. PMID:27472142

  17. Folding and escape of nascent proteins at ribosomal exit tunnel

    Science.gov (United States)

    Bui, Phuong Thuy; Hoang, Trinh Xuan

    2016-03-01

    We investigate the interplay between post-translational folding and escape of two small single-domain proteins at the ribosomal exit tunnel by using Langevin dynamics with coarse-grained models. It is shown that at temperatures lower or near the temperature of the fastest folding, folding proceeds concomitantly with the escape process, resulting in vectorial folding and enhancement of foldability of nascent proteins. The concomitance between the two processes, however, deteriorates as temperature increases. Our folding simulations as well as free energy calculation by using umbrella sampling show that, at low temperatures, folding at the tunnel follows one or two specific pathways without kinetic traps. It is shown that the escape time can be mapped to a one-dimensional diffusion model with two different regimes for temperatures above and below the folding transition temperature. Attractive interactions between amino acids and attractive sites on the tunnel wall lead to a free energy barrier along the escape route of the protein. It is suggested that this barrier slows down the escape process and consequently promotes correct folding of the released nascent protein.

  18. Escape dynamics in a binary system of interacting galaxies

    CERN Document Server

    Zotos, Euaggelos E

    2016-01-01

    The escape dynamics in an analytical gravitational model which describes the motion of stars in a binary system of interacting dwarf spheroidal galaxies is investigated in detail. We conduct a numerical analysis distinguishing between regular and chaotic orbits as well as between trapped and escaping orbits, considering only unbounded motion for several energy levels. In order to distinguish safely and with certainty between ordered and chaotic motion, we apply the Smaller ALingment Index (SALI) method. It is of particular interest to locate the escape basins through the openings around the collinear Lagrangian points $L_1$ and $L_2$ and relate them with the corresponding spatial distribution of the escape times of the orbits. Our exploration takes place both in the configuration $(x,y)$ and in the phase $(x,\\dot{x})$ space in order to elucidate the escape process as well as the overall orbital properties of the galactic system. Our numerical analysis reveals the strong dependence of the properties of the con...

  19. Single-File Escape of Colloidal Particles from Microfluidic Channels

    Science.gov (United States)

    Locatelli, Emanuele; Pierno, Matteo; Baldovin, Fulvio; Orlandini, Enzo; Tan, Yizhou; Pagliara, Stefano

    2016-07-01

    Single-file diffusion is a ubiquitous physical process exploited by living and synthetic systems to exchange molecules with their environment. It is paramount to quantify the escape time needed for single files of particles to exit from constraining synthetic channels and biological pores. This quantity depends on complex cooperative effects, whose predominance can only be established through a strict comparison between theory and experiments. By using colloidal particles, optical manipulation, microfluidics, digital microscopy, and theoretical analysis we uncover the self-similar character of the escape process and provide closed-formula evaluations of the escape time. We find that the escape time scales inversely with the diffusion coefficient of the last particle to leave the channel. Importantly, we find that at the investigated microscale, bias forces as tiny as 10-15 N determine the magnitude of the escape time by drastically reducing interparticle collisions. Our findings provide crucial guidelines to optimize the design of micro- and nanodevices for a variety of applications including drug delivery, particle filtering, and transport in geometrical constrictions.

  20. Extreme hydrodynamic atmospheric loss near the critical thermal escape regime

    CERN Document Server

    Erkaev, N V; Odert, P; Kulikov, Yu N; Kislyakova, K G

    2015-01-01

    By considering martian-like planetary embryos inside the habitable zone of solar-like stars we study the behavior of the hydrodynamic atmospheric escape of hydrogen for small values of the Jeans escape parameter $\\beta < 3$, near the base of the thermosphere, that is defined as a ratio of the gravitational and thermal energy. Our study is based on a 1-D hydrodynamic upper atmosphere model that calculates the volume heating rate in a hydrogen dominated thermosphere due to the absorption of the stellar soft X-ray and extreme ultraviolet (XUV) flux. We find that when the $\\beta$ value near the mesopause/homopause level exceeds a critical value of $\\sim$2.5, there exists a steady hydrodynamic solution with a smooth transition from subsonic to supersonic flow. For a fixed XUV flux, the escape rate of the upper atmosphere is an increasing function of the temperature at the lower boundary. Our model results indicate a crucial enhancement of the atmospheric escape rate, when the Jeans escape parameter $\\beta$ decr...

  1. MAVEN measurements of photochemical escape of oxygen from the Martian atmosphere

    Science.gov (United States)

    Lillis, R. J.; Deighan, J.; Fox, J. L.; Bougher, S. W.; Cravens, T. E.; Lee, Y.; Mahaffy, P. R.; Benna, M.; Elrod, M. K.; Andersson, L.; McFadden, J.

    2015-10-01

    One of the primary goals of the Mars Atmosphere and Volatile Evolution Mission (MAVEN) mission is to characterize rates of atmospheric escape at the present epoch and relate those escape rates to solar drivers [1]. One of the major escape processes is known as photochemical escape, which is broadly defined as a process by which a) an exothermic reaction in the atmosphere/ionosphere results in an upward-traveling neutral particle whose velocity exceeds planetary escape velocity and b) the particle is not prevented from escaping through any subsequent collisions[2].At Mars, photochemical escape of oxygen is expected to be a significant channel for atmospheric escape, particularly in the early solar system when extreme ultraviolet (EUV) fluxes were much higher[3]. Thus characterizing this escape process is central to understanding the role escape to space has played in Mars' climate evolution.

  2. Escape for System with Non-Fluctuating Potential Barrier Only Driven by Three-State Noise

    Institute of Scientific and Technical Information of China (English)

    LI Jing-Hui

    2007-01-01

    We study the escape for the mean first passage time (MFPT) over a potential barrier for a system with non-fluctuating potential barrier and only driven by a three-state noise. It is shown that in some circumstances, the three-state noise can induce the resonant activation for the MFPT over the potential barrier; but in other circumstances, it can not. There are three resonant activations for the MFPT over the potential barrier, which are respectively as the functions of the transition rates of the three-state noise.

  3. Can transgenic rice cause ecological risks through transgene escape?

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Alien transgene escape from genetically engineered rice to non-transgenic varieties or close wild relatives (including weedy rice) may lead to unpredictable ecological risks. However, for transgene escape to occur three conditions need to be met: (i) spatially, transgenic rice and its non-transgenic counterparts or wild relatives should have sympatric distributions; (ii) temporally, the flowering time of transgenic rice and the non-transgenic varieties or wild relatives should overlap; and (iii) biologically, transgenic rice and its wild relative species should have such a sufficiently close relationship that their interspecific hybrids can have normal generative reproduction. This paper presents research data on the geographic distribution, flowering habits, interspecific hybridization, and gene flow of cultivated rice (Oryza sativa) and its closely related wild relatives containing the AA genome. The objective is to estimate the possibility of transgene escape to non-transgenic rice varieties and wild relatives of rice, which may result in unpredictable ecological risks.

  4. Escape probability of the super-Penrose process

    CERN Document Server

    Ogasawara, Kota; Miyamoto, Umpei; Igata, Takahisa; Patil, Mandar

    2016-01-01

    We consider a head-on collision of two massive particles that move in the equatorial plane of an extremal Kerr black hole, which results in the production of two massless particles. Focusing a typical case, where both of the colliding particles have zero angular momenta, we show that a massless particle produced in such a collision can escape to infinity with arbitrarily large energy in the near-horizon limit of the collision point. Furthermore, if we assume that the emission of the produced massless particles is isotropic in the center-of-mass frame but confined to the equatorial plane, the escape probability of the produced massless particle approaches $5/12$ and almost all escaping massless particles have arbitrarily large energy at infinity and an impact parameter approaching $2M$.

  5. Group nightmares about escape from ex-homeland.

    Science.gov (United States)

    Cernovsky, Z

    1990-09-01

    Escape nightmares (recurrent nightmares about re-escaping ex-homeland) were studied via a 79-item questionnaire administered to 83 Czechoslovak refugees who were living in Switzerland. The key features of the nightmare were not related significantly to the refugees' age, gender, occupation, or educational level. Further analyses dealt with mutual relationships of the various reported aspects of the escape nightmares. The reports of dreaming about arrival in the ex-homeland by a "mistake," such as boarding a wrong airplane (i.e., a Freudian parapraxis), were associated with higher levels of (subsequent) dream anxiety, with waking up due to mounting dream tension, and with the dreamer not knowing at first upon awakening whether he was now in the free world or elsewhere. PMID:2246363

  6. Characterization of escape times of Josephson Junctions for signal detection

    CERN Document Server

    Addesso, Paolo; Pierro, Vincenzo

    2011-01-01

    The measurement of the escape time of a Josephson junction might be used to detect the presence of a sinusoidal signal embedded in noise when standard signal processing tools can be prohibitive. We show that the prescriptions for the experimental set-up and some physical behaviors depend on the detection strategy. More specifically, by exploiting the sample mean of escape times to perform detection, two resonant regions are identified. At low frequencies there is a stochastic resonance/activation phenomenon, while near the plasma frequency a geometric resonance appears. The naive sample mean detector is outperformed, in terms of error probability, by the optimal likelihood ratio test. The latter exhibits only geometric resonance, showing monotonically increasing performance as the bias current approaches the junction critical current. In this regime the escape times are vanishingly small and therefore performance are essentially limited by measurement electronics. The behavior of the likelihood ratio and samp...

  7. Water-escape velocities in jumping blacktip sharks.

    Science.gov (United States)

    Brunnschweiler, Juerg M

    2005-09-22

    This paper describes the first determination of water-escape velocities in free-ranging sharks. Two approximations are used to estimate the final swimming speed at the moment of penetrating the water surface. Blacktip sharks were videotaped from below the surface and parameters were estimated by analysing the sequences frame by frame. Water-escape velocities averaged 6.3 ms(-1). These velocities for blacktip sharks seem accurate and are similar to estimates obtained for other shark species of similar size. PMID:16849197

  8. Water-escape velocities in jumping blacktip sharks

    OpenAIRE

    Juerg M. Brunnschweiler

    2005-01-01

    This paper describes the first determination of water-escape velocities in free-ranging sharks. Two approximations are used to estimate the final swimming speed at the moment of penetrating the water surface. Blacktip sharks were videotaped from below the surface and parameters were estimated by analysing the sequences frame by frame. Water-escape velocities averaged 6.3 m s−1. These velocities for blacktip sharks seem accurate and are similar to estimates obtained for other shark species of ...

  9. Effects of alpha fetoprotein on escape of Bel 7402 cells from attack of lymphocytes

    Directory of Open Access Journals (Sweden)

    Li Pingfeng

    2005-08-01

    Full Text Available Abstract Background Involvement of AFP against apoptosis of tumor cell has been implicated in its evasion of immune surveillance. However, the molecular events of immune escape mechanisms are still unknown. The major observations reported here relate to a possible mechanism by which heptoloma Bel 7402 cells escape immune surveillance in vitro. Methods Western blotting and a well-characterized cofocal scanning image were performed to analyze the expression of Fas/FasL and caspase-3 in co-cultured Bel 7402 and Jurkat cells. Results After co-culture with Jurkat cells, up-regulated Fas and reduced FasL expression could be observed. Treatment with AFP could remarkably inhibit the elevated Fas and, whereas, induce the FasL expression in co-cultured Bel 7402 cells. Cells co-culture could induce the expression of caspase-3 in both cells line. The elevated caspase-3 in Bel 7402 cells was abolished following the treatment of AFP. The expression of caspase-3 was elevated in co-cultured Jurkat cells treated with AFP. No detectable change on the expression of survivin was examined in both cells line. Monoclonal antibody against AFP treatment alone did not obviously influence the growth of cells, as well as the expression of Fas/FasL and caspase-3. However, the effect of AFP could be blocked by antibody. Conclusions our results provide evidence that AFP could promote the escape of liver cancer cells from immune surveillance through blocking the caspase signal pathway of tumor cells and triggering the Fas/FasL interaction between tumor cells and lymphocytes.

  10. Effects of alpha fetoprotein on escape of Bel 7402 cells from attack of lymphocytes

    International Nuclear Information System (INIS)

    Involvement of AFP against apoptosis of tumor cell has been implicated in its evasion of immune surveillance. However, the molecular events of immune escape mechanisms are still unknown. The major observations reported here relate to a possible mechanism by which heptoloma Bel 7402 cells escape immune surveillance in vitro. Western blotting and a well-characterized cofocal scanning image were performed to analyze the expression of Fas/FasL and caspase-3 in co-cultured Bel 7402 and Jurkat cells. After co-culture with Jurkat cells, up-regulated Fas and reduced FasL expression could be observed. Treatment with AFP could remarkably inhibit the elevated Fas and, whereas, induce the FasL expression in co-cultured Bel 7402 cells. Cells co-culture could induce the expression of caspase-3 in both cells line. The elevated caspase-3 in Bel 7402 cells was abolished following the treatment of AFP. The expression of caspase-3 was elevated in co-cultured Jurkat cells treated with AFP. No detectable change on the expression of survivin was examined in both cells line. Monoclonal antibody against AFP treatment alone did not obviously influence the growth of cells, as well as the expression of Fas/FasL and caspase-3. However, the effect of AFP could be blocked by antibody. our results provide evidence that AFP could promote the escape of liver cancer cells from immune surveillance through blocking the caspase signal pathway of tumor cells and triggering the Fas/FasL interaction between tumor cells and lymphocytes

  11. Discrete dynamics and metastability: mean first passage times and escape rates

    International Nuclear Information System (INIS)

    The problem of escape from a domain of attraction is applied to the case of discrete dynamical systems possessing stable and unstable fixed points. In the presence of noise, the otherwise stable fixed point of a nonlinear map becomes metastable, due to the noise-induced hopping events, which eventually pass the unstable fixed point. Exact integral equations for the moments of the first passage time variable are derived, as well as an upper bound for the first moment. In the limit of weak noise, the integral equation for the first moment, i.e., the mean first passage time (MFPT), is treated, both numerically and analytically. The exponential leading part of the MFPT is given by the ratio of the noise-induced invariant probability at the stable fixed point and unstable fixed point, respectively. The evaluation of the prefactor is more subtle: It is characterized by a jump at the exit boundaries, which is the result of a discontinuous boundary layer function obeying an inhomogeneous integral equation. The jump at the boundary is shown to be always less than one-half of the maximum value of the MFPT. On the basis of a clear-cut separation of time scales, the MFPT is related to the escape rate to leave the domain of attraction and other transport coefficients, such as the diffusion coefficient. Alternatively, the rate can also be obtained if one evaluates the current-carrying flux that results if particles are continuously injected into the domain of attraction and captured beyond the exit boundaries. The two methods are shown to yield identical results for the escape rate of the weak noise result for the MFPT, respectively. As a byproduct of this study, they obtain general analytic expressions for the invariant probability of noisy maps with a small amount of nonlinearity

  12. Entropy, Lyapunov Exponents and Escape Rates in Open Systems

    CERN Document Server

    Demers, Mark; Young, Lai-Sang

    2011-01-01

    We study the relation between escape rates and pressure in general dynamical systems with holes, where pressure is defined to be the difference between entropy and the sum of positive Lyapunov exponents. Central to the discussion is the formulation of a class of invariant measures supported on the survivor set over which we take the supremum to measure the pressure. Upper bounds for escape rates are proved for general diffeomorphisms of manifolds, possibly with singularities, for arbitrary holes and natural initial distributions including Lebesgue and SRB measures. Lower bounds do not hold in such generality, but for systems admitting Markov tower extensions with spectral gaps, we prove the equality of the escape rate with the absolute value of the pressure and the existence of an invariant measure realizing the escape rate, i.e. we prove a full variational principle. As an application of our results, we prove a variational principle for the billiard map associated with a planar Lorentz gas of finite horizon ...

  13. 46 CFR 169.313 - Means of escape.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Means of escape. 169.313 Section 169.313 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Construction... apart, uniform for the length of the ladder; (3) At least 3 inches from the nearest permanent object...

  14. Escape angles in bulk chi((2)) soliton interactions

    DEFF Research Database (Denmark)

    Johansen, Steffen Kjær; Bang, Ole; Sørensen, Mads Peter

    2002-01-01

    We develop a theory for nonplanar interaction between two identical type I spatial solitons propagating at opposite, but arbitrary transverse angles in quadratic nonlinear (or so-called chi((2))) bulk, media. We predict quantitatively the outwards escape angle, below which the solitons turn aroun...

  15. Enuresis Control through Fading, Escape, and Avoidance Training.

    Science.gov (United States)

    Hansen, Gordon D.

    1979-01-01

    A twin signal device that provides both escape and avoidance conditioning in enuresis control was documented with case studies of two enuretic children (eight and nine years old). In addition, a technique of fading as an adjunct to the process was utilized with one subject. (Author/SBH)

  16. A Structural Soundness Proof for Shivers's Escape Technique

    DEFF Research Database (Denmark)

    Midtgaard, Jan; Adams, Michael D.; Matthew, Might

    2012-01-01

    Shivers’s escape technique enables one to analyse the control flow of higher-order program fragments. It is widely used, but its soundness has never been proven. In this paper, we present the first soundness proof for the technique. Our proof is structured as a composition of Galois connections and...

  17. Comparing the escape dynamics in tidally limited star cluster models

    CERN Document Server

    Zotos, Euaggelos E

    2015-01-01

    The aim of this work is to compare the orbital dynamics in three different models describing the properties of a star cluster rotating around its parent galaxy in a circular orbit. In particular, we use the isochrone and the Hernquist potentials to model the spherically symmetric star cluster and we compare our results with the corresponding ones of a previous work in which the Plummer model was applied for the same purpose. Our analysis takes place both in the configuration $(x,y)$ and in the phase $(x,\\dot{x})$ space in order to elucidate the escape process as well as the overall orbital properties of the tidally limited star cluster. We restrict our investigation into two dimensions and we conduct a thorough numerical analysis distinguishing between ordered and chaotic orbits as well as between trapped and escaping orbits, considering only unbounded motion for several energy levels above the critical escape energy. It is of particular interest to determine the escape basins towards the two exit channels (n...

  18. Recording field potentials from zebrafish larvae during escape responses.

    Science.gov (United States)

    Monesson-Olson, Bryan D; Troconis, Eileen L; Trapani, Josef G

    2014-01-01

    Among vertebrates, startle responses are a ubiquitous method for alerting, and avoiding or escaping from alarming or dangerous stimuli. In zebrafish larvae, fast escape behavior is easily evoked through either acoustic or tactile stimuli. For example, a light touch to the head will excite trigeminal neurons that in turn excite a large reticulospinal neuron in the hindbrain called the Mauthner cell (M-cell). The M-cell action potential then travels down the contralateral trunk of the larva exciting motoneurons, which subsequently excite the entire axial musculature, producing a large amplitude body bend away from the source of the stimulus. This body conformation is known as the "C-bend" due to the shape of the larva during the behavior. As a result of the semi-synchronized activation of the M-cell, the population of motor neurons, and the axial trunk muscles, a large field potential is generated and can be recorded from free-swimming or fixed-position larvae. Undergraduate laboratories that record field potentials during escape responses in larval zebrafish are relatively simple to setup and allow students to observe and study the escape reflex circuit. Furthermore, by testing hypotheses, analyzing data and writing journal-style laboratory reports, students have multiple opportunities to learn about many neuroscience topics including vertebrate reflexes; sensory transduction; synaptic-, neuro-, and muscle-physiology; the M-cell mediated escape response; and the zebrafish as a model organism. Here, we detail the equipment, software, and recording setup necessary to observe field potentials in an undergraduate teaching lab. Additionally, we discuss potential advanced laboratory exercises and pedagogical outcomes. Finally, we note possible low-cost alternatives for recording field potentials. PMID:25565920

  19. Towards an understanding of escape rate and state dependent diffusion for a quantum dissipative system

    International Nuclear Information System (INIS)

    Graphical abstract: The present work demonstrates that the temperature dependence of the escape rate is not only embedded in the so-called Arrhenius type factor, the second exponential factor also includes the temperature dependence which has a purely quantum origin that is entangled with dissipation. Display Omitted Highlights: → We explore the noise-induced barrier crossing dynamics of an open quantum system. → The bath coupled with the system is driven out of equilibrium by an external noise. → Nonlinear system-bath coupling and modulation of the bath affect the escape rate. → An additional exponential factor, other than Arrhenius is also temperature dependent. → This temperature dependence is purely quantum in origin. - Abstract: We address the stochastic dynamics of an open quantum system coupled to a heat reservoir that is driven out of thermal equilibrium by an external noise. By constructing Langevin and Fokker-Planck equations, we obtain the rate of decay from a metastable state of the system when the dissipation is state dependent. We discuss the effects and consequences of the non-linear interaction(s) stemming out of the system-bath coupling alongside the modulation of the bath by an external noise on the rate expression. We demonstrate that the temperature dependence of the escape rate is not only embedded in the so-called Arrhenius type factor, the second exponential factor also includes the temperature dependence. The last effect has a purely quantum origin. Interestingly, we also envisage that this quantum effect is entangled with dissipation. The results offer a basis for clarifying the relationship between the dissipation and exponential factor of the obtained rate expression.

  20. Towards an understanding of escape rate and state dependent diffusion for a quantum dissipative system

    Energy Technology Data Exchange (ETDEWEB)

    Shit, Anindita [Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711 103 (India); Chattopadhyay, Sudip, E-mail: sudip_chattopadhyay@rediffmail.com [Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711 103 (India); Ray Chaudhuri, Jyotipratim, E-mail: jprc_8@yahoo.com [Department of Physics, Katwa College, Katwa, Burdwan 713 130 (India)

    2011-07-28

    Graphical abstract: The present work demonstrates that the temperature dependence of the escape rate is not only embedded in the so-called Arrhenius type factor, the second exponential factor also includes the temperature dependence which has a purely quantum origin that is entangled with dissipation. Display Omitted Highlights: {yields} We explore the noise-induced barrier crossing dynamics of an open quantum system. {yields} The bath coupled with the system is driven out of equilibrium by an external noise. {yields} Nonlinear system-bath coupling and modulation of the bath affect the escape rate. {yields} An additional exponential factor, other than Arrhenius is also temperature dependent. {yields} This temperature dependence is purely quantum in origin. - Abstract: We address the stochastic dynamics of an open quantum system coupled to a heat reservoir that is driven out of thermal equilibrium by an external noise. By constructing Langevin and Fokker-Planck equations, we obtain the rate of decay from a metastable state of the system when the dissipation is state dependent. We discuss the effects and consequences of the non-linear interaction(s) stemming out of the system-bath coupling alongside the modulation of the bath by an external noise on the rate expression. We demonstrate that the temperature dependence of the escape rate is not only embedded in the so-called Arrhenius type factor, the second exponential factor also includes the temperature dependence. The last effect has a purely quantum origin. Interestingly, we also envisage that this quantum effect is entangled with dissipation. The results offer a basis for clarifying the relationship between the dissipation and exponential factor of the obtained rate expression.

  1. Nano scale self-emulsifying oil based carrier system for improved oral bioavailability of camptothecin derivative by P-Glycoprotein modulation.

    Science.gov (United States)

    Negi, Lalit Mohan; Tariq, Mohammad; Talegaonkar, Sushama

    2013-11-01

    Irinotecan is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein receptors. Hence, no oral formulation is marketed for Irinotecan till date. However, an optimized Self micro emulsifying drug delivery system (SMEDDS), formulated to produce nano range oil droplets by using P-gp modulator excipients can tackle the issue and elevate the systemic availability of Irinotecan. The present work focuses on the development of SMEDDS for Irinotecan and evaluation of its in vitro, ex vivo and in vivo potentials. The SMEDDS were developed using Capmul MCM-C8, Cremophor EL and Pluronic L-121 as oil, surfactant and co-surfactant respectively and has good oil carrying capacity (30%) with competence to produce nano-scale oil droplets (130 ± 2.13 nm) on spontaneous emulsification. A much deeper penetration to the intestine was observed with SMEDDS by using confocal laser scanning microscopy (CLSM). Flow-cytometric studies also revealed the greater uptake of fluorescent probe in Caco-2 cell-lines with the use of SMEDDS. Biochemical estimation of LDH from the intestinal tissues treated with SMEDDS and free drug suspension confirmed that the developed formulation is safe for use. Furthermore, the AUC0 → t of Irinotecan from the optimized SMEDDS formulation was found to be 4 folds higher than that from Irinotecan suspension on oral administration. The optimized SMEDDS formulation was found to be capable of maintaining the sustained plasma drug level of Irinotecan with better bioavailability. PMID:23850745

  2. Genotoxic profile of inhibitors of topoisomerases I (camptothecin) and II (etoposide) in a mitotic recombination and sex-chromosome loss somatic eye assay of Drosophila melanogaster.

    Science.gov (United States)

    Sortibrán, América Nitxin Castañeda; Téllez, María Guadalupe Ordaz; Rodríguez-Arnaiz, Rosario

    2006-04-30

    Genotoxic carcinogens which interact with DNA may produce double-strand breaks as normal intermediates of homologous mitotic recombination, and may give rise to structural chromosome aberrations and inter-chromosomal deletion-recombination. The genotoxic profile of two inhibitors of DNA topoisomerases were evaluated using an in vivo somatic w/w+ eye assay of Drosophila melanogaster for the detection of loss of heterozygosity (LOH) by homologous mitotic recombination, intra-chromosomal recombination and structural chromosomal aberrations. We studied camptothecin (CPT) as a topoisomerase-I-interactive agent and etoposide (ETOP) as a topoisomerase II inhibitor. These drugs act by stabilizing a ternary complex consisting of topoisomerases covalently linked to DNA at single-strand or at double-strand breaks, thereby preventing the relegation step of the breakage/rejoining reaction mediated by the enzyme. The genotoxic profiles were determined from the appearance of eye tissue in adult flies, in which LOH and expression of the reporter gene white produced light clones. The results demonstrated that both compounds were significantly genotoxic, with CPT being more effective than ETOP. Inter-chromosomal mitotic recombination was the major mechanism responsible for the induction of light spots by both compounds in XX females. Loss of the ring X chromosome (rX), was significantly enhanced by CPT, and this topoisomerase blocker also produced intra-chromosomal recombination (XY males). PMID:16529987

  3. Transcriptome analysis of stem wood of Nothapodytes nimmoniana (Graham) Mabb. identifies genes associated with biosynthesis of camptothecin, an anti-carcinogenic molecule

    Indian Academy of Sciences (India)

    BL Manjunatha; HR Singh; G Ravikanth; Karaba N Nataraja; Ravi Shankar; Sanjay Kumar; R Uma Shaanker

    2016-03-01

    Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of DNA topoisomerase I and has applications in treating ovarian, small lung and refractory ovarian cancers. Stem wood tissue of Nothapodytes nimmoniana (Graham) Mabb. (family Icacinaceae) is one of the richest sources of CPT. Since there is no genomic or transcriptome data available for the species, the present work sequenced and analysed transcriptome of stem wood tissue on an Illumina platform. From a total of 77,55,978 reads, 9,187 transcripts were assembled with an average length of 255 bp. Functional annotation and categorization of these assembled transcripts unraveled the transcriptome architecture and also a total of 13 genes associated with CPT biosynthetic pathway were identified in the stem wood tissue. Four genes of the pathway were cloned to full length by RACE to validate the transcriptome data. Expression analysis of 13 genes associated with CPT biosynthetic pathway in 11 different tissues vis-a-vis CPT content analysis suggested an important role of NnPG10H, NnPSLS and NnPSTR genes in the biosynthesis of CPT. These results indicated that CPT might be synthesized in the leaves and then perhaps exported to stem wood tissue for storage.

  4. Parameter Optimization on Experimental Study to Reduce Ammonia Escape in CO2 Absorption by Ammonia Scrubbing

    Institute of Scientific and Technical Information of China (English)

    Hao Leng; Jianmin Gao; Mingyue He; Min Xie; Qian Du; Rui Sun; Shaohua Wu

    2016-01-01

    In order to research ammonia escape in CO2 absorption by ammonia scrubbing, ammonia escape was studied in CO2 absorption process using the bubbling reactor in different conditions as gas flow rate, CO2 ratio, absorbent temperature and ammonia concentration and quantity of escaped ammonia was measured by chemical titration. The results indicated that, the amount of ammonia escape can be around 20% of original amount in 90 min and the escaped amount will increase with the rise of gas flow rate, absorbent temperature, concentration of ammonia while decrease as CO2 ratio goes up. Through the analysis of the law of ammonia escape, at the same time, combined with ammonia escape and the influence of the relationship between the CO2 absorption efficiency, reducing ammonia escape working condition parameter optimization is given.

  5. Fixation and escape times in stochastic game learning

    Science.gov (United States)

    Realpe-Gomez, John; Szczesny, Bartosz; Dall'Asta, Luca; Galla, Tobias

    2012-10-01

    Evolutionary dynamics in finite populations is known to fixate eventually in the absence of mutation. We here show that a similar phenomenon can be found in stochastic game dynamical batch learning, and investigate fixation in learning processes in a simple 2×2 game, for two-player games with cyclic interaction, and in the context of the best-shot network game. The analogues of finite populations in evolution are here finite batches of observations between strategy updates. We study when and how such fixation can occur, and present results on the average time-to-fixation from numerical simulations. Simple cases are also amenable to analytical approaches and we provide estimates of the behaviour of so-called escape times as a function of the batch size. The differences and similarities with escape and fixation in evolutionary dynamics are discussed.

  6. Kuiper Prize Lecture - Escape of atmospheres, ancient and modern

    Energy Technology Data Exchange (ETDEWEB)

    Hunten, D.M. (Arizona Univ., Tucson (USA))

    1990-05-01

    A development history is presented for theories concerning planetary atmosphere gas-escape phenomena, which although firmly grounded in the kinetics of gases achieved truly productive results only after spacecraft remote sensing data for both the earth atmosphere and the planets became widely available. The most significant initial advances, encompassing diffusion-limited flow, nonthermal escape mechanisms, bound nonthermal coronas, and mass fractionation during early blowoff, followed from sounding rocket studies of the earth upper atmosphere, Mariner 5 results on hydrogen near Venus, and the nitrogen isotopic composition discovered by Viking in Mars. Attention has more recently been given to the xenon isotopic patterns in various atmospheres, as well as to the puzzling behavior of the Io atmosphere and plasma torus. 126 refs.

  7. Quantum and thermal phase escape in extended Josephson systems

    International Nuclear Information System (INIS)

    In this work I examine phase escape in long annular Josephson tunnel junctions. The sine-Gordon equation governs the dynamics of the phase variable along the junction. This equation supports topological soliton solutions, which correspond to quanta of magnetic flux trapped in the junction barrier. For such Josephson vortices an effective potential is formed by an external magnetic field, while a bias current acts as a driving force. Both together form a metastable potential well, which the vortex is trapped in. When the driving force exceeds the pinning force of the potential, the vortex escapes and the junction switches to the voltage state. At a finite temperature the driving force fluctuates. If the junction's energy scale is small, the phase variable can undergo a macroscopic quantum tunneling (MQT) process at temperatures below the crossover temperature. Without a vortex trapped, the metastable state is not a potential minimum in space, but a potential minimum at zero phase difference. (orig.)

  8. Quantum and thermal phase escape in extended Josephson systems

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, A.

    2006-07-12

    In this work I examine phase escape in long annular Josephson tunnel junctions. The sine-Gordon equation governs the dynamics of the phase variable along the junction. This equation supports topological soliton solutions, which correspond to quanta of magnetic flux trapped in the junction barrier. For such Josephson vortices an effective potential is formed by an external magnetic field, while a bias current acts as a driving force. Both together form a metastable potential well, which the vortex is trapped in. When the driving force exceeds the pinning force of the potential, the vortex escapes and the junction switches to the voltage state. At a finite temperature the driving force fluctuates. If the junction's energy scale is small, the phase variable can undergo a macroscopic quantum tunneling (MQT) process at temperatures below the crossover temperature. Without a vortex trapped, the metastable state is not a potential minimum in space, but a potential minimum at zero phase difference. (orig.)

  9. Fractal escapes in Newtonian and relativistic multipole gravitational fields

    CERN Document Server

    Servio de Moura, A P; Moura, Alessandro P. S. de; Letelier, Patricio S.

    1999-01-01

    We study the planar motion of test particles in gravitational fields produced by an external material halo, of the type found in many astrophysical systems, such as elliptical galaxies and globular clusters. Both the Newtonian and the general-relativistic dynamics are examined, and in the relativistic case the dynamics of both massive and massless particles are investigated. The halo field is given in general by a multipole expansion; we restrict ourselves to multipole fields of pure order, whose Newtonian potentials are homogeneous polynomials in cartesian coordinates. A pure (n)-pole field has (n) different escapes, one of which is chosen by the particle according to its initial conditions. We find that the escape has a fractal dependency on the initial conditions for (n>2) both in the Newtonian and the relativistic cases for massive test particles, but with important differences between them. The relativistic motion of massless particles, however, was found to be regular for all the fields we could study. ...

  10. Kuiper Prize Lecture - Escape of atmospheres, ancient and modern

    International Nuclear Information System (INIS)

    A development history is presented for theories concerning planetary atmosphere gas-escape phenomena, which although firmly grounded in the kinetics of gases achieved truly productive results only after spacecraft remote sensing data for both the earth atmosphere and the planets became widely available. The most significant initial advances, encompassing diffusion-limited flow, nonthermal escape mechanisms, bound nonthermal coronas, and mass fractionation during early blowoff, followed from sounding rocket studies of the earth upper atmosphere, Mariner 5 results on hydrogen near Venus, and the nitrogen isotopic composition discovered by Viking in Mars. Attention has more recently been given to the xenon isotopic patterns in various atmospheres, as well as to the puzzling behavior of the Io atmosphere and plasma torus. 126 refs

  11. Fixation and escape times in stochastic game learning

    International Nuclear Information System (INIS)

    Evolutionary dynamics in finite populations is known to fixate eventually in the absence of mutation. We here show that a similar phenomenon can be found in stochastic game dynamical batch learning, and investigate fixation in learning processes in a simple 2×2 game, for two-player games with cyclic interaction, and in the context of the best-shot network game. The analogues of finite populations in evolution are here finite batches of observations between strategy updates. We study when and how such fixation can occur, and present results on the average time-to-fixation from numerical simulations. Simple cases are also amenable to analytical approaches and we provide estimates of the behaviour of so-called escape times as a function of the batch size. The differences and similarities with escape and fixation in evolutionary dynamics are discussed. (paper)

  12. Self-organized escape of oscillator chains in nonlinear potentials.

    Science.gov (United States)

    Hennig, D; Fugmann, S; Schimansky-Geier, L; Hänggi, P

    2007-10-01

    We present the noise-free escape of a chain of linearly interacting units from a metastable state over a cubic on-site potential barrier. The underlying dynamics is conservative and purely deterministic. The mutual interplay between nonlinearity and harmonic interactions causes an initially uniform lattice state to become unstable, leading to an energy redistribution with strong localization. As a result, a spontaneously emerging localized mode grows into a critical nucleus. By surpassing this transition state, the nonlinear chain manages a self-organized, deterministic barrier crossing. Most strikingly, these noise-free, collective nonlinear escape events proceed generally by far faster than transitions assisted by thermal noise when the ratio between the average energy supplied per unit in the chain and the potential barrier energy assumes small values. PMID:17994939

  13. Dynamics of the verge and foliot clock escapement

    CERN Document Server

    Hoyng, P

    2016-01-01

    The verge and foliot escapement has received relatively little attention in horology, despite the fact that it has been used in clocks for ages. We analyse the operation of a verge and foliot escapement in stationary swing. It is driven by a torque $m=\\pm\\mu$, switching sign at fixed swing angles $\\pm\\phi_0$, and $\\mu$ is taken to be constant. Friction is assumed to exert a torque proportional to the angular speed. We determine the shape of the swing angle $\\varphi(t)$, and compute the period and the swing amplitude of the foliot as a function of the model parameters. We find that the period of the foliot scales as $P\\propto\\mu^{-1}$ for weak driving, gradually changing into $P\\propto\\mu^{-1/3}$ for strong driving (large $\\mu$), which underlines that the motion of the foliot is not isochonous.

  14. Escape of Mars atmospheric carbon through time by photochemical means

    Science.gov (United States)

    Luhmann, J. G.; Kim, J.; Nagy, A. F.

    Luhmann et al. recently suggested that sputtering of the Martian atmosphere by re-entering O(+) pickup ions could have provided a significant route of escape for CO2 and its products throughout Mars' history. They estimated that the equivalent of C in an approximately 140-mbar CO2 atmosphere should have been lost this way if the Sun and solar wind evolved according to available models. Another source of escaping C (and O) that is potentially important is the dissociative recombination of ionospheric CO(+) near the exobase. We have evaluated the loss rates due to this process for 'ancient' solar EUV radiation fluxes of 1, 3, and 6 times the present flux in order to calculate the possible cumulative loss over the last 3.5 Gyr.

  15. Bacillus anthracis Factors for Phagosomal Escape

    Directory of Open Access Journals (Sweden)

    Irene Zornetta

    2012-07-01

    Full Text Available The mechanism of phagosome escape by intracellular pathogens is an important step in the infectious cycle. During the establishment of anthrax, Bacillus anthracis undergoes a transient intracellular phase in which spores are engulfed by local phagocytes. Spores germinate inside phagosomes and grow to vegetative bacilli, which emerge from their resident intracellular compartments, replicate and eventually exit from the plasma membrane. During germination, B. anthracis secretes multiple factors that can help its resistance to the phagocytes. Here the possible role of B. anthracis toxins, phospholipases, antioxidant enzymes and capsules in the phagosomal escape and survival, is analyzed and compared with that of factors of other microbial pathogens involved in the same type of process.

  16. Escape of Mars atmospheric carbon through time by photochemical means

    Science.gov (United States)

    Luhmann, J. G.; Kim, J.; Nagy, A. F.

    1993-01-01

    Luhmann et al. recently suggested that sputtering of the Martian atmosphere by re-entering O(+) pickup ions could have provided a significant route of escape for CO2 and its products throughout Mars' history. They estimated that the equivalent of C in an approximately 140-mbar CO2 atmosphere should have been lost this way if the Sun and solar wind evolved according to available models. Another source of escaping C (and O) that is potentially important is the dissociative recombination of ionospheric CO(+) near the exobase. We have evaluated the loss rates due to this process for 'ancient' solar EUV radiation fluxes of 1, 3, and 6 times the present flux in order to calculate the possible cumulative loss over the last 3.5 Gyr.

  17. The escape of natural satellites from Mercury and Venus

    International Nuclear Information System (INIS)

    It is suggested that the slow rotations of Mercury and Venus may be connected with the absence of natural satellites around them. If Mercury or Venus possessed a satellite at the time of formation, the tidal evolution would have caused the satellite to recede. At a sufficiently large distance from the planet, the Sun's gravitational influence makes the satellite orbit unstable. The natural satellites of Mercury and Venus might have escaped as a consequence of this instability. (Auth.)

  18. Brain size as a driver of avian escape strategy

    OpenAIRE

    Samia, Diogo S. M.; Pape Møller, Anders; Blumstein, Daniel T.

    2015-01-01

    After detecting an approaching predator, animals make a decision when to flee. Prey will initiate flight soon after detecting a predator so as to minimize attentional costs related to on-going monitoring of the whereabouts of the predator. Such costs may compete with foraging and other maintenance activities and hence be larger than the costs of immediate flight. The drivers of interspecific variation in escape strategy are poorly known. Here we investigated the morphological, life history an...

  19. Transcriptional control of behavior: Engrailed knockout changes cockroach escape trajectories

    OpenAIRE

    Booth, David; Marie, Bruno; Domenici, Paolo; Blagburn, Jonathan M.; Bacon, Jonathan P.

    2009-01-01

    The cerci of the cockroach are covered with identified sensory hairs, which detect air movements. The sensory neurons which innervate these hairs synapse with giant interneurons (GIs) in the terminal ganglion which in turn synapse with interneurons and leg motorneurons in thoracic ganglia. This neural circuit mediates the animal's escape behavior. The transcription factor Engrailed (En) is expressed only in the medially born sensory neurons, which suggested it could work as a positional deter...

  20. Viral Resistance Evolution Fully Escapes a Rationally Designed Lethal Inhibitor

    OpenAIRE

    Keller, Thomas E.; Molineux, Ian J.; Bull, James J

    2009-01-01

    Viruses are notoriously capable of evolving resistance to drugs. However, if the endpoint of resistance evolution is only partial escape, a feasible strategy should be to stack drugs, so the combined effect of partial inhibition by several drugs results in net inhibition. Assessing the feasibility of this approach requires quantitative data on viral fitness before and after evolution of resistance to a drug, as done here with bacteriophage T7. An inhibitory gene expressed from a phage promote...

  1. Self-organized escape of oscillator chains in nonlinear potentials

    OpenAIRE

    Hennig, D.; Fugmann, S.; Schimansky-Geier, L.; Hänggi, P

    2007-01-01

    We present the noise free escape of a chain of linearly interacting units from a metastable state over a cubic on-site potential barrier. The underlying dynamics is conservative and purely deterministic. The mutual interplay between nonlinearity and harmonic interactions causes an initially uniform lattice state to become unstable, leading to an energy redistribution with strong localization. As a result a spontaneously emerging localized mode grows into a critical nucleus. By surpassing this...

  2. Transitions between three swimming gaits in Paramecium escape

    OpenAIRE

    Hamel, Amandine; Fisch, C; Combettes, L; Dupuis-Williams, P.; Baroud, Charles,

    2011-01-01

    Paramecium and other protists are able to swim at velocities reaching several times their body size per second by beating their cilia in an organized fashion. The cilia beat in an asymmetric stroke, which breaks the time reversal symmetry of small scale flows. Here we show that Paramecium uses three different swimming gaits to escape from an aggression, applied in the form of a focused laser heating. For a weak aggression, normal swimming is sufficient and produces a steady swimming velocity....

  3. Amygdala involvement in human avoidance, escape and approach behavior

    OpenAIRE

    Schlund, Michael W.; Cataldo, Michael F

    2010-01-01

    Many forms of psychopathology and substance abuse problems are characterized by chronic ritualized forms of avoidance and escape behavior that are designed to control or modify external or internal (i.e, thoughts, emotions, bodily sensations) threats. In this functional magnetic resonance imaging investigation, we examined amygdala reactivity to threatening cues when avoidance responding consistently prevented contact with an upcoming aversive event (money loss). In addition, we examined esca...

  4. Escape rates for rotor walk in Z^d

    OpenAIRE

    Florescu, Laura; Ganguly, Shirshendu; Levine, Lionel; Peres, Yuval

    2013-01-01

    Rotor walk is a deterministic analogue of random walk. We study its recurrence and transience properties on Z^d for the initial configuration of all rotors aligned. If n particles in turn perform rotor walks starting from the origin, we show that the number that escape (i.e., never return to the origin) is of order n in dimensions d>=3, and of order n/log(n) in dimension 2.

  5. ESCAPE: an integrated climate model for the EC

    International Nuclear Information System (INIS)

    A framework has been developed for the evaluation of policy options for climate change, called ESCAPE (Evaluation of Strategies to address Climate change by Adapting to and Preventing Emissions). ESCAPE consists of a suite of linked models which enables scenarios of greenhouse gas emissions to be constructed and their impact on global and regional climate and sea level and sectors of the European economy to be assessed. Conclusions resulting from simulations with the ESCAPE 1.1 model include: the major problem of a climate change for the EC is a sea level rise; Greece, Italy, Portugal and Spain will be faced with higher costs in the agricultural sector; worldwide implementation of an EC carbon tax leads to about 12% lower worldwide CO2 emissions; to stabilize CO2 emissions an Ecotax of 18 dollars per barrel would be required; and in all cases the rate of global temperature increase will be above the rate of 0.1 degree C per decade for the coming 40 years. 2 figs

  6. The RAVE Survey: Constraining the Local Galactic Escape Speed

    CERN Document Server

    Smith, M C; Helmi, A; Wyse, R F G; Fulbright, J P; Freeman, K C; Navarro, J F; Seabroke, G M; Steinmetz, M; Williams, M; Bienaymé, O; Binney, J; Bland-Hawthorn, J; Dehnen, W; Gibson, B K; Gilmore, G; Grebel, E K; Munari, U; Parker, Q A; Scholz, R D; Siebert, A; Watson, F G; Zwitter, T

    2006-01-01

    We report new constraints on the local escape speed of our Galaxy. Our analysis is based on a sample of high velocity stars from the RAVE survey and two previously published datasets. We use cosmological simulations of disk galaxy formation to motivate our assumptions on the shape of the velocity distribution, allowing for a significantly more precise measurement of the escape velocity compared to previous studies. We find that the escape velocity lies within the range $498\\kms < \\ve < 608 \\kms$ (90 per cent confidence), with a median likelihood of $544\\kms$. The fact that $\\ve^2$ is significantly greater than $2\\vc^2$ (where $\\vc=220\\kms$ is the local circular velocity) implies that there must be a significant amount of mass exterior to the Solar circle, i.e. this convincingly demonstrates the presence of a dark halo in the Galaxy. For a simple isothermal halo, one can calculate that the minimum radial extent is $\\sim58$ kpc. We use our constraints on $\\ve$ to determine the mass of the Milky Way halo f...

  7. Transitions between three swimming gaits in Paramecium escape.

    Science.gov (United States)

    Hamel, Amandine; Fisch, Cathy; Combettes, Laurent; Dupuis-Williams, Pascale; Baroud, Charles N

    2011-05-01

    Paramecium and other protists are able to swim at velocities reaching several times their body size per second by beating their cilia in an organized fashion. The cilia beat in an asymmetric stroke, which breaks the time reversal symmetry of small scale flows. Here we show that Paramecium uses three different swimming gaits to escape from an aggression, applied in the form of a focused laser heating. For a weak aggression, normal swimming is sufficient and produces a steady swimming velocity. As the heating amplitude is increased, a higher acceleration and faster swimming are achieved through synchronized beating of the cilia, which begin by producing oscillating swimming velocities and later give way to the usual gait. Finally, escape from a life-threatening aggression is achieved by a "jumping" gait, which does not rely on the cilia but is achieved through the explosive release of a group of trichocysts in the direction of the hot spot. Measurements through high-speed video explain the role of trichocysts in defending against aggressions while showing unexpected transitions in the swimming of microorganisms. These measurements also demonstrate that Paramecium optimizes its escape pattern by taking advantage of its inertia. PMID:21464291

  8. Effective climate-energy solutions, escape routes and peak oil

    International Nuclear Information System (INIS)

    Many well-intended climate-energy strategies are ineffective in the absence of serious environmental regulation. This holds, among others, for direct support of clean energy, voluntary energy conservation, technical standards on a limited set of products, unilateral stringent carbon pricing, and awaiting peak oil as a climate strategy. All of these suffer from “escape routes” that indirectly increase CO2 emissions and thus make the original strategy ineffective. On the other hand, environmental regulation alone may lead to a myopia-bias, stimulating early dominance of cost-effective technologies and a focus on incremental innovations associated with such technologies rather than on radical innovations. Although adopting a partial viewpoint keeps the analysis simple, we urgently need a more inclusive systems perspective on climate solutions. This will allow the formulation of an effective climate policy package that addresses the various escape routes. - Highlights: ► Many well-intended climate-energy strategies are ineffective because of escape routes. ► In this context the relationship between peak oil and climate policy receives attention. ► Environmental regulation alone creates myopia-bias, the resolution of which requires technology-specific policies. ► To formulate an effective climate policy package an inclusive systems perspective is needed.

  9. Fleeing to refuge: Escape decisions in the race for life.

    Science.gov (United States)

    Cooper, William E

    2016-10-01

    Economic escape theory that predicts that flight initiation distance (FID=predator-prey distance when a prey begins to flee from an approaching predator) increases as predation risk increases has been overwhelmingly supported. However, the vast majority of empirical tests have focused on effects of single predation risk factors. Even studies that have included multiple risk factors have not predicted how they jointly affect FID. I present a model that predicts joint effects of several predation risk factors that affect the outcome of a race between predator and prey to the prey's refuge. As a prey's distance to refuge and predator attack speed increase, and as the prey's location forces it to flee more toward a predator to reach refuge, FID increases. A published model proposed and experiment showed that FID is longer when prey flee directly toward than directly away from a predator to a refuge. We present a new geometric model that predicts FID for all angles between the prey's and predator's paths to refuge, distance of the prey from refuge when escape begins, predator and prey speeds, and a margin of safety allowing the prey to reach refuge before the predator. The model provides many new, testable predictions about relationships among its variables and FID. Most notably, it predicts that FID increases sigmoidally as the angle between predator and prey paths to refuge increases. Although the model is not economic (cost-benefit), we discuss its relationship to economic escape theory. PMID:27343624

  10. 46 CFR 108.155 - Restrictions on means of escape utilized.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Restrictions on means of escape utilized. 108.155 Section 108.155 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE... means of escape utilized. A required means of escape may not be a vertical ladder or deck...

  11. Background intercomparison with escape-suppressed germanium detectors in underground mines

    International Nuclear Information System (INIS)

    A key requirement for underground nuclear astrophysics experiments is the very low background level in germanium detectors underground. The reference for these purposes is the world's so far only underground accelerator laboratory for nuclear astrophysics, LUNA. LUNA is located deep underground in the Gran Sasso laboratory in Italy, shielded from cosmic rays by 1400 m of rock. The background at LUNA was studied in detail using an escape-suppressed Clover-type HPGe detector. Exactly the same detector was subsequently transported to the Felsenkeller underground laboratory in Dresden, shielded by 45 m of rock, and the background was shown to be only a factor of three higher than at LUNA when comparing the escape-suppressed spectra, with interesting consequences for underground nuclear astrophysics. As the next step of a systematic study of the effects of a combination of active and passive shielding on the cosmic ray induced background, this detector is now being brought to the ''Reiche Zeche'' mine in Freiberg/Sachsen, shielded by 150 m of rock. The data from the Freiberg measurement are shown and discussed.

  12. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers.

    Science.gov (United States)

    Fuchs, Hendrik; Weng, Alexander; Gilabert-Oriol, Roger

    2016-01-01

    The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments. PMID:27376327

  13. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers

    Directory of Open Access Journals (Sweden)

    Hendrik Fuchs

    2016-07-01

    Full Text Available The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments.

  14. [Contribution to tumor escape and chemotherapy response: A choice between senescence and apoptosis in heterogeneous tumors].

    Science.gov (United States)

    Jonchère, Barbara; Vétillard, Alexandra; Toutain, Bertrand; Guette, Catherine; Coqueret, Olivier

    2016-01-01

    Understanding adaptive signaling pathways in response to chemotherapy is one of the main challenges of cancer treatment. Activated in response to DNA damage, cell cycle and mitotic checkpoints activate the p53-p21 and p16-Rb pathways and induce apoptosis or senescence. Since senescent cells survive and produce a secretome that influences neighbouring cells, it is not particularly clear whether these responses are equivalent and if tumor cells escape these two suppressive pathways to the same extent. Predicting escape is also complicated by the fact that cancer cells adapt to treatments by activating the epithelial-mesenchymal transition and by producing clones with cancer-initiating cells features. Dedifferentiation pathways used in stressful conditions reconstitute dividing and sometimes more aggressive populations in response to chemotherapy. These observations illustrate the importance of tumor heterogeneity and the adaptation capacities of different intra-tumoral subclones. Depending on their oncogenic profile, on their localisation within the tumor and on their interaction with stromal cells, these subclones are expected to have different responses and adaptation capacities to chemotherapy. A complete eradication will certainly rely on combination therapies that can kill at the same time the bulk of the sensitive tumor but can also prevent plasticity and the generation of persistent clones. PMID:26762946

  15. Making sense of the local Galactic escape speed estimates in direct dark matter searches

    CERN Document Server

    Lavalle, Julien

    2014-01-01

    Direct detection (DD) of dark matter (DM) candidates in the $\\lesssim$10 GeV mass range is very sensitive to the tail of their velocity distribution. The important quantity is the maximum WIMP speed in the observer's rest frame, i.e. in average the sum of the local Galactic escape speed $v_{\\rm esc}$ and of the circular velocity of the Sun $v_c$. While the latter has been receiving continuous attention, the former is more difficult to constrain. The RAVE Collaboration has just released a new estimate of $v_{\\rm esc}$ (Piffl {\\em et al.}, 2014 --- P14) that supersedes the previous one (Smith {\\em et al.}, 2007), which is of interest in the perspective of reducing the astrophysical uncertainties in DD. Nevertheless, these new estimates cannot be used blindly as they rely on assumptions in the dark halo modeling which induce tight correlations between the escape speed and other local astrophysical parameters. We make a self-consistent study of the implications of the RAVE results on DD assuming isotropic DM velo...

  16. Escape conditioning and low-frequency whole-body vibration - The effects of frequency, amplitude, and controls for noise and activation.

    Science.gov (United States)

    Wike, E. L.; Wike, S. S.

    1972-01-01

    Seven experiments are reported on low-frequency whole-body vibration and rats' escape conditioning in a modified Skinner box. In the first three studies, conditioning was observed but was independent of frequency. In experiment four, the number of escape responses was directly related to vibration amplitude. Experiment five was a control for vibration noise and noise termination; experiments six and seven studied vibration-induced activation. Noise termination did not produce conditioning. In experiment six, subjects made more responses when responding led to termination than when it did not. In experiment seven, subjects preferred a bar which terminated vibration to one which did not.

  17. MAVEN in situ measurements of photochemical escape of oxygen from Mars

    Science.gov (United States)

    Lillis, Robert; Deighan, Justin; Fox, Jane; Bougher, Stephen; Lee, Yuni; Cravens, Thomas; Rahmati, Ali; Mahaffy, Paul; Benna, Mehdi; Groller, Hannes; Jakosky, Bruce

    2016-04-01

    One of the primary goals of the MAVEN mission is to characterize rates of atmospheric escape from Mars at the present epoch and relate those escape rates to solar drivers. One of the known escape processes is photochemical escape, where a) an exothermic chemical reaction in the atmosphere results in an upward-traveling neutral particle whose velocity exceeds planetary escape velocity and b) the particle is not prevented from escaping through subsequent collisions. At Mars, photochemical escape of oxygen is expected to be a significant channel for atmospheric escape, particularly in the early solar system when extreme ultraviolet (EUV) fluxes were much higher. Thus characterizing this escape process and its variability with solar drivers is central to understanding the role escape to space has played in Mars' climate evolution. We use near-periapsis (CO2+ to calculate the probability distribution for the initial energies of the resulting hot oxygen atoms. The second is a Monte Carlo hot atom transport model that takes that distribution of initial O energies and the measured neutral density profiles and calculates the probability that a hot atom born at that altitude will escape. The third takes the measured electron and ion densities and electron temperatures and calculates the production rate of hot O atoms. We then multiply together the profiles of hot atom production and escape probability to get profiles of the production rate of escaping atoms. We integrate with respect to altitude to give us the escape flux of hot oxygen atoms for that periapsis pass. We have sufficient coverage in solar zenith angle (SZA) to estimate total escape rates for two intervals with the obvious assumption that escape rates are the same at all points with the same SZA. We estimate total escape rates of 3.5-5.8 x 1025 s-1 for Ls = 289° to 319° and 1.6-2.6 x 1025 s-1 for Ls = 326° to 348°. The latter is the most directly comparable to previous model-based estimates and is roughly in

  18. Alveolar Type II Cells Escape Stress Failure Caused by Tonic Stretch through Transient Focal Adhesion Disassembly

    Directory of Open Access Journals (Sweden)

    Xiao-Yang Liu, Xiao-Fei Chen, Yan-Hong Ren, Qing-Yuan Zhan, Chen Wang, Chun Yang

    2011-01-01

    Full Text Available Mechanical ventilation-induced excessive stretch of alveoli is reported to induce cellular stress failure and subsequent lung injury, and is therefore an injurious factor to the lung. Avoiding cellular stress failure is crucial to ventilator-induced lung injury (VILI treatment. In the present study, primary rat alveolar type II (ATII cells were isolated to evaluate their viability and the mechanism of their survival under tonic stretch. By the annexin V/ PI staining and flow cytometry assay, we demonstrated that tonic stretch-induced cell death is an immediate injury of mechanical stress. In addition, immunofluorescence and immunoblots assay showed that the cells experienced an expansion-contraction-reexpansion process, accompanied by partial focal adhesion (FA disassembly during contraction. Manipulation of integrin adherent affinity by altering bivalent cation levels in the culture medium and applying an integrin neutralizing antibody showed that facilitated adhesion affinity promoted cell death under tonic stretch, while lower level of adhesion protected the cells from stretch-induced stress failure. Finally, a simplified numerical model was established to reveal that adequate disassembly of FAs reduced the forces transmitting throughout the cell. Taken together, these results indicate that ATII cells escape stress failure caused by tonic stretch via active cell morphological remodeling, during which cells transiently disassemble FAs to unload mechanical forces.

  19. Kramers escape rate in overdamped systems with the power-law distribution

    OpenAIRE

    Zhou, Yanjun; Du, Jiulin

    2014-01-01

    Kramers escape rate in the overdamped systems with the power-law distribution is studied. By using the mean first passage time, we derive the escape rate for the power-law distribution and obtain the Kramers' infinite barrier escape rate in this case. It is shown that the escape rate for the power-law distribution extends the Kramers' overdamped result to the relatively low barrier. Furthermore, we apply the escape rate for the power-law distribution to the unfolding of titin and show a bette...

  20. Plasmid linking number change induced by topoisomerase I-mediated DNA damage.

    OpenAIRE

    Duann, P; M. Sun; Lin, C T; Zhang, H.; Liu, L F

    1999-01-01

    The state of cellular chromatin in response to DNA damage has been examined by monitoring the change in the linking number of circular episomes. COS cells transfected with an SV40-based vector were treated with camptothecin (CPT), a eukaryotic DNA topoisomerase I (TOP1) poison which induces TOP1-mediated DNA damage. Within minutes, a large increase in the linking number (over 10 linking number) of a small fraction (5-15%) of the episomal DNA was observed. A similar CPT-induced increase in pla...

  1. Cell-specific expression of tryptophan decarboxylase and 10-hydroxygeraniol oxidoreductase, key genes involved in camptothecin biosynthesis in Camptotheca acuminata Decne (Nyssaceae

    Directory of Open Access Journals (Sweden)

    Santamaria Anna

    2010-04-01

    Full Text Available Abstract Background Camptotheca acuminata is a major natural source of the terpenoid indole alkaloid camptothecin (CPT. At present, little is known about the cellular distribution of the biosynthesis of CPT, which would be useful knowledge for developing new strategies and technologies for improving alkaloid production. Results The pattern of CPT accumulation was compared with the expression pattern of some genes involved in CPT biosynthesis in C. acuminata [i.e., Ca-TDC1 and Ca-TDC2 (encoding for tryptophan decarboxylase and Ca-HGO (encoding for 10-hydroxygeraniol oxidoreductase]. Both CPT accumulation and gene expression were investigated in plants at different degrees of development and in plantlets subjected to drought-stress. In all organs, CPT accumulation was detected in epidermal idioblasts, in some glandular trichomes, and in groups of idioblast cells localized in parenchyma tissues. Drought-stress caused an increase in CPT accumulation and in the number of glandular trichomes containing CPT, whereas no increase in epidermal or parenchymatous idioblasts was observed. In the leaf, Ca-TDC1 expression was detected in some epidermal cells and in groups of mesophyll cells but not in glandular trichomes; in the stem, it was observed in parenchyma cells of the vascular tissue; in the root, no expression was detected. Ca-TDC2 expression was observed exclusively in leaves of plantlets subjected to drought-stress, in the same sites described for Ca-TDC1. In the leaf, Ca-HGO was detected in all chlorenchyma cells; in the stem, it was observed in the same sites described for Ca-TDC1; in the root, no expression was detected. Conclusions The finding that the sites of CPT accumulation are not consistently the same as those in which the studied genes are expressed demonstrates an organ-to-organ and cell-to-cell translocation of CPT or its precursors.

  2. Escaping stars from young low-N clusters

    OpenAIRE

    Weidner, Carsten; Bonnell, Ian A.; Moeckel, Nickolas

    2010-01-01

    With the use of N-body calculations the amount and properties of escaping stars from low-N (N = 100 and 1000) young embedded star clusters prior to gas expulsion are studied over the first 5 Myr of their existence. Besides the number of stars also different initial radii and binary populations are examined as well as virialised and collapsing clusters. It is found that these clusters can loose substantial amounts (up to 20%) of stars within 5 Myr with considerable velocities up to more than 1...

  3. First-passage and escape problems in the Feller process

    CERN Document Server

    Masoliver, Jaume

    2012-01-01

    The Feller process is an one-dimensional diffusion process with linear drift and state-dependent diffusion coefficient vanishing at the origin. The process is positive definite and it is this property along with its linear character that have made Feller process a convenient candidate for the modeling of a number of phenomena ranging from single neuron firing to volatility of financial assets. While general properties of the process are well known since long, less known are properties related to level crossing such as the first-passage and the escape problems. In this work we thoroughly address these questions.

  4. The mirror of the escaped God – Alejandra Pizarnik

    OpenAIRE

    Mariano Carou

    2015-01-01

    Alejandra Pizarnik (1936-1972) shows many different stands regarding to “God’s escape” in her poetry and his diaries: from the psalmist’s request to the more combative atheism. There is, however, a constant development of a symbolic constellation to speak about God’s mistery, and the certitude –inherited from German romanticism– that the poet has always something to say about God’s escape, searching for a new hope in which is maybe a new form of mysticism.

  5. Chases and escapes the mathematics of pursuit and evasion

    CERN Document Server

    Nahin, Paul J

    2012-01-01

    We all played tag when we were kids. What most of us don't realize is that this simple chase game is in fact an application of pursuit theory, and that the same principles of games like tag, dodgeball, and hide-and-seek are also at play in military strategy, high-seas chases by the Coast Guard, and even romantic pursuits. In Chases and Escapes, Paul Nahin gives us the first complete history of this fascinating area of mathematics, from its classical analytical beginnings to the present day. Drawing on game theory, geometry, linear algebra, target-tracking algorithms, and much

  6. Nuclear reaction diagnostics of fast confined and escaping alpha particles

    International Nuclear Information System (INIS)

    The resonant radiative capture nuclear reactions D(α,γ)6Li, 6Li(α,γ) 19B and 7Li(α,γ)11B are examined as diagnostics of the energy distribution of confined fast alpha particles in tokamak plasmas. Count rates for realistic Q=1 DT plasma conditions are presented and compared to expected backgrounds. The design of and preliminary results from the prototype fusion gamma ray detector on TFTR are presented. The activation reactions are similarly examined as diagnostics of escaping fast alpha particles. Where possible, count rate estimates for Q=1 DT plasmas and proposed ignition devices are presented

  7. Escape from a potential well with a randomly switching boundary

    International Nuclear Information System (INIS)

    We consider diffusion in a potential well with a boundary that randomly switches between absorbing and reflecting and show how the switching boundary affects the classical escape theory. Using the theory of stochastic hybrid systems, we derive boundary value problems for the mean first passage time and splitting probability and find explicit solutions in terms of the spectral decomposition of the associated differential operator. Further, using a more probabilistic approach, we prove asymptotic formulae for these statistics in the small diffusion limit. In particular, we show that the statistical behavior depends critically on the gradient of the potential near the switching boundary and we derive corrections to Kramers’ reaction rate theory. (paper)

  8. Escaping the poverty trap in a developing rural economy

    OpenAIRE

    Nguyen Manh Hung; Paul Makdissi

    2004-01-01

    In this paper, we examine the economic policies that might allow a developing rural economy to escape from the poverty trap characterized by a subsistence level of per capita consumption in the long run. In our model where labour is combined to land available in fixed quantity to produce a homogeneous good, saving could be made through only having children, the number of which is an endogenous decision. We provide conditions under which the economy runs into a poverty trap, and proceed to ana...

  9. Readout of a superconducting qubit. A problem of quantum escape processes for driven systems

    International Nuclear Information System (INIS)

    density in the rotating frame. We found that a position-position interaction between system and bath in the laboratory frame translates into additional momentum-momentum couplings in the rotating frame. We introduced the concept of an effective temperature to analyze the energy exchange between system and bath. For a structured environment we found a negative effective temperature physically corresponding to the fact that absorption becomes more probable than emission and a population inversion is induced. This effect can explain recent experimental observations of enhanced relaxation in a quantronium circuit coupled to a cavity bifurcation amplifier. Finally we applied the approach on the new master equation in the rotating frame to calculate the quantum escape rate for the Duffing oscillator. We discovered that there is an additional quantum effect compared to the case of a static barrier. In the rotating frame the quantum fluctuations that accompany relaxation of the system coupled to a bath lead to diffusion away from one stationary state and to a transition over the dynamic barrier to the second stationary state. This mechanism is due to the particular form of the interaction between system and bath. We found also that by tuning the bifurcation parameter we can change the effective friction. So, we easily can move from the underdamped regime, studied in this work, to the classical overdamped regime and finally to the quantum overdamped regime. (orig.)

  10. FEM analysis of escape capsule suffered to gas explosion

    Science.gov (United States)

    Li, Chang-lu; Mei, Rui-bin; Li, Chang-sheng; Cai, Ban; Liu, Xiang-hua

    2013-05-01

    Escape capsules are new devices for underground coal mines that provide air, water, food and supplies in the event of an emergency in where miners are unable to escape. It is difficult to carry out the experiments of explosion and safety because the danger and nonrepeatability of explosion. The structure deformation and distribution of equivalent stress has been investigated under different impact pressure conditions including unimodal and bimodal loads based on the FEM and software LS-DYNA. The results show that the distribution of deformation and equivalent stress has the same trend on the same surface with the increment of explosion pressure. The deformation and stress are larger with side impact pressure compared with that of the same front impact pressure. Furthermore, the maximum equivalent stress is 246MPa and 260MPa on the front and sides of capsule with five times for national standard impact pressure 1.5MPa. Under these conditions, the deformation is less than about 9.97mm and 10.47mm, respectively. When the front impact pressure is 2.0MPa, the deformation of capsule still belongs to elasticity but the less plastic deformation occurs on the Ushape stiffening channels with the same side impact pressure. However, it is safe for capsule structure because the equivalent stress 283MPa is much less than the tensile strength. It is noted that bimodal load accelerates the capsule deformation so that it is more dangerous compared with unimodal load.

  11. Viral resistance evolution fully escapes a rationally designed lethal inhibitor.

    Science.gov (United States)

    Keller, Thomas E; Molineux, Ian J; Bull, James J

    2009-09-01

    Viruses are notoriously capable of evolving resistance to drugs. However, if the endpoint of resistance evolution is only partial escape, a feasible strategy should be to stack drugs, so the combined effect of partial inhibition by several drugs results in net inhibition. Assessing the feasibility of this approach requires quantitative data on viral fitness before and after evolution of resistance to a drug, as done here with bacteriophage T7. An inhibitory gene expressed from a phage promoter aborts wild-type T7 infections. The effect is so severe that the phage population declines when exposed to the inhibitor but expands a billion-fold per hour in its absence. In prior work, T7 evolved modest resistance to this inhibitor, an expected result. Given the nature of the inhibitor, that it used the phage's own promoter to target the phage's destruction, we anticipated that resistance evolution would be limited as the phage may need to evolve a new regulatory system, with simultaneous changes in its RNA polymerase (RNAP) and many of its promoters to fully escape inhibition. We show here that further adaptation of the partially resistant phage led to complete resistance. Resistance evolution was due to three mutations in the RNAP gene and two other genes; unexpectedly, no changes were observed in promoters. Consideration of other mechanisms of T7 inhibition leaves hope that permanent inhibition of viral growth with drugs can in principle be achieved. PMID:19494036

  12. Ultra-fast Escape of a Octopus-inspired Rocket

    Science.gov (United States)

    Weymouth, Gabriel; Triantafyllou, Michael

    2013-11-01

    The octopus, squid, and other cephalopods inflate with water and then release a jet to accelerate in the opposite direction. This escape mechanism is particularly interesting in the octopus because they become initially quite bluff, yet this does not hinder them in achieving impressive bursts of speed. We examine this somewhat paradoxical maneuver using a simple deflating spheroid model in both potential and viscous flow. We demonstrate that the dynamic reduction of the width of the body completely changes the flow and forces acting on the escaping rocket in three ways. First, a body which reduces in size can generate an added mass thrust which counteracts the added mass inertia. Second, the motion of the shrinking wall acts similar to suction on a static wall, reducing separation and drag forces in a viscous fluid, but that this effects depends on the rate of size change. Third, using a combination of these two features it is possible to initially load the fluid with kinetic energy when heavy and bluff and then recover that energy when streamlined and light, enabling ultra-fast accelerations. As a notable example, these mechanisms allow a shrinking spheroid rocket in a heavy inviscid fluid to achieve speeds greater than an identical rocket in the vacuum of space. Southampton Marine and Maritime Institute.

  13. The C. elegans touch response facilitates escape from predacious fungi.

    Science.gov (United States)

    Maguire, Sean M; Clark, Christopher M; Nunnari, John; Pirri, Jennifer K; Alkema, Mark J

    2011-08-01

    Predator-prey interactions are vital determinants in the natural selection of behavioral traits. Gentle touch to the anterior half of the body of Caenorhabditis elegans elicits an escape response in which the animal quickly reverses and suppresses exploratory head movements [1, 2]. Here, we investigate the ecological significance of the touch response in predator-prey interactions between C. elegans and predacious fungi that catch nematodes using constricting hyphal rings. We show that the constricting rings of Drechslerella doedycoides catch early larval stages with a diameter similar to the trap opening. There is a delay between the ring entry and ring closure, which allows the animal to withdraw from the trap before being caught. Mutants that fail to suppress head movements in response to touch are caught more efficiently than the wild-type. This demonstrates that the coordination of motor programs allows C. elegans to smoothly retract from a fungal noose and evade capture. Our results suggest that selective pressures imposed by predacious fungi have shaped the evolution of C. elegans escape behavior. PMID:21802299

  14. Group chase and escape model with chasers' interaction

    Science.gov (United States)

    Saito, Takuya; Nakamura, Tomomichi; Ohira, Toru

    2016-04-01

    Group chase and escape is a new direction of studying collective behaviors merged with the traditional mathematical problems of chases and escapes proposed by Kamimura and Ohira in 2010. In their model, the chasers recognize only the escapees and pursue the nearest neighbor escapee, and the escapees recognize only the chasers and flee from the nearest neighbor chaser. We call the basic moving rule the nearest opponent interaction (NOI) strategy. In this paper we introduce a new strategy in the model. It is a local interaction that the chasers do not get too close each other, where we call the chasers' local interaction (CLI) strategy. The result of comparisons of the two strategies shows that when the number of the chasers is relatively small compared to the number of the escapees, the trapping time by the CLI strategy is much shorter than that by the NOI strategy. On the other hand, when the number of the chasers is larger than that of the escapees, this advantage of the CLI strategy does not appear. Also, we find that although chasers form clusters (spatial aggregates of chasers) when we apply the NOI strategy, the clusters appear less when we apply the CLI strategy.

  15. Pair interaction of catalytically active colloids: from assembly to escape

    Science.gov (United States)

    Sharifi-Mood, Nima; Mozaffari, Ali; Córdova-Figueroa, Ubaldo M.

    2016-07-01

    The dynamics and pair trajectory of two self-propelled colloids are reported. The autonomous motions of the colloids are due to a catalytic chemical reaction taking place asymmetrically on their surfaces that generates a concentration gradient of interactive solutes around the particles and actuate particle propulsion. We consider two spherical particles with symmetric catalytic caps extending over the local polar angles $\\theta^1_{cap}$ and $\\theta^2_{cap}$ from the centers of active sectors in an otherwise quiescent fluid. A combined analytical-numerical technique was developed to solve the coupled mass transfer equation and the hydrodynamics in the Stokes flow regime. The ensuing pair trajectory of the colloids is controlled by the reacting coverages $\\theta^j_{cap}$ and their initial relative orientation with respect to each other. Our analysis indicates two possible scenarios for pair trajectories of catalytic self-propelled particles: either the particles approach, come into contact and assemble or they interact and move away from each other (escape). For arbitrary motions of the colloids, it is found that the direction of particle rotations is the key factor in determining the escape or assembly scenario. Based on the analysis, a phase diagram is sketched for the pair trajectory of the catalytically active particles as a function of active coverages and their initial relative orientations. We believe this study has important implications in elucidation of collective behaviors of auotophoretically self-propelled colloids.

  16. Formation and Internal Structure of Terrestrial Planets, and Atmospheric Escape

    Science.gov (United States)

    Jin, S.

    2014-11-01

    As of 2014 April 21, over 1490 confirmed exoplanets and 3705 Kepler candidates have been detected. This implies that exoplanets may be ubiquitous in the universe. In this paper, we focus on the formation, evolution, and internal structure of terrestrial planets, and the atmospheric escape of close-in planets. In chapter 2, we investigate the dynamical evolution of planetary system after the protoplanetary disk has dissipated. We find that in the final assembly stage, the occurrence of terrestrial planets is quite common and in 40% of our simulations finally at least one planet is formed in the habitable zone. We also find that if there is a highly-inclined giant planet in the system, a great many bodies will be either driven out of the system, or collide with the giant planet or the central star. This will lead to the difficulty in planetary accretion. Moreover, our results show that planetary migration can lead to the formation of close-in planets. Besides migration, close-in terrestrial planets can also be formed by a collision-merger mechanism, which means that planetary embryos can kick terrestrial planets directly into orbits that are extremely close to their parent stars. In chapter 3, we construct numerically an internal structure model for terrestrial planets, and provide three kinds of possible internal structures of Europa (Jupiter's moon) based on this model. Then, we calculate the radii of low-mass exoplanets for various mass combinations of core and mantle, and find that some of them are inconsistent with the observed radius of rocky planets. This phenomenon can be explained only if there exists a large amount of water in the core, or they own gaseous envelopes. In chapter 4, we improve our planetary evolution codes using the semi-gray model of Guillot (2010), which includes the incident flux from the host star as a heating source in planetary atmosphere. The updated codes can solve the structure of the top radiative zone of intensely irradiated

  17. Integrating geographical information and augmented reality techniques for mobile escape guidelines on nuclear accident sites

    International Nuclear Information System (INIS)

    During nuclear accidents, when radioactive materials spread into the environment, the people in the affected areas should evacuate immediately. However, few information systems are available regarding escape guidelines for nuclear accidents. Therefore, this study constructs escape guidelines on mobile phones. This application is called Mobile Escape Guidelines (MEG) and adopts two techniques. One technique is the geographical information that offers multiple representations; the other is the augmented reality that provides semi-realistic information services. When this study tested the mobile escape guidelines, the results showed that this application was capable of identifying the correct locations of users, showing the escape routes, filtering geographical layers, and rapidly generating the relief reports. Users could evacuate from nuclear accident sites easily, even without relief personnel, since using slim devices to access the mobile escape guidelines is convenient. Overall, this study is a useful reference for a nuclear accident emergency response.

  18. Experimental measurements of Doppler broadening of escape peaks in HPGe detectors

    International Nuclear Information System (INIS)

    Single-escape, double-escape, and annihilation peak widths from eleven spectra taken with differing HPGe coaxial detectors and differing primary gamma sources were measured. For each of these, the Doppler broadening component of the peak width was derived. Significant Doppler broadening was observed only in the single escape peak and in the annihilation peak width. Averaged values and their uncertainties useful for modeling each type of peak width in nuclear radiation spectra are presented. (author)

  19. Light Primes the Escape Response of the Calanoid Copepod, Calanus finmarchicus

    OpenAIRE

    2012-01-01

    The timing and magnitude of an escape reaction is often the determining factor governing a copepod’s success at avoiding predation. Copepods initiate rapid and directed escapes in response to fluid signals created by predators; however little is known about how copepods modulate their behavior in response to additional sensory input. This study investigates the effect of light level on the escape behavior of Calanus finmarchicus. A siphon flow was used to generate a consistent fluid signal an...

  20. Light Primes the Escape Response of the Calanoid Copepod, Calanus finmarchicus

    OpenAIRE

    Fields, David M.; Shema, Steven D.; Browman, Howard I.; Browne, Thomas Q.; Skiftesvik, Anne Berit

    2012-01-01

    The timing and magnitude of an escape reaction is often the determining factor governing a copepod’s success at avoiding predation. Copepods initiate rapid and directed escapes in response to fluid signals created by predators; however little is known about how copepods modulate their behavior in response to additional sensory input. This study investigates the effect of light level on the escape behavior of Calanus finmarchicus. A siphon flow was used to generate a consistent fluid ...

  1. When a Fish is a Fish: The Economic Impacts of Escaped Farmed Fish

    OpenAIRE

    Yajie Liu; Jon Olaf Olaussen; Anders Skonhoft

    2011-01-01

    The escape of cultured fish from a marine aquaculture facility is a type of biological invasion that may lead to a variety of potential ecological and economic effects on native fish. This paper develops a general invasive species impact model to capture explicitly both the ecological and economic effects of invasive species, especially escaped farmed fish, on native stocks and harvests. First, the possible effects of escaped farmed fish on the growth and stock size of a native fish are exami...

  2. Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases

    International Nuclear Information System (INIS)

    The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-β and TNF-α were increased during tumor growth whereas IFN-γ showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver metastases mouse model simulating the

  3. On the hydrodynamic model of thermal escape from planetary atmospheres and its comparison with kinetic simulations

    Science.gov (United States)

    Volkov, A. N.

    2016-06-01

    Parkers' model of thermal escape implies the search of solutions of one-dimensional hydrodynamic equations for an inviscid but thermally conducting gas with a critical point and vanishing temperature far from the source. The properties of solutions of this model are studied for neutral mon- and diatomic gases with the viscosity index varying from 1/2 to 1. The domains of existence and uniqueness of solutions in terms of the source Jeans escape parameter and Knudsen number are established. The solutions are found to exist only in a narrow range of the critical point Jeans parameter. The lower and upper limits of this range correspond to solutions that are dominated by either heat conduction or adiabatic expansion. Thermal escape described by Parker's model occurs in two asymptotic regimes: the low-density (LD) regime, when escape is dominated by heat conduction, and the high-density (HD) regime, when escape is dominated by adiabatic expansion. Expressions for the mass and energy escape rates in these regimes are found theoretically. The comparison of results of hydrodynamic and kinetic simulations performed in identical conditions shows that Parker's model is capable of describing thermal escape only in the HD regime, providing decent agreement with the kinetic model in terms of the atmospheric structure below the exobase and the mass and energy escape rates. In the LD regime, Parker's model predicts a much faster drop in atmospheric temperature and less extended atmospheres, and can both over- and underestimate the escape rates in orders of magnitude.

  4. Test of time: what if little Albert had escaped?

    Science.gov (United States)

    Field, Andy P; Nightingale, Zoë C

    2009-04-01

    Watson and Rayner's (1920) ;Little Albert' experiment has become one of the most famous studies in psychology. It is a staple of many general psychology textbooks and is part of the very fabric of the discipline's folklore. Despite this fame, the study has been widely criticized in the nearly 90 years since it was published for its lack of methodological rigour. This article attempts to evaluate the contribution of the ;little Albert' study to modern clinical psychology by speculating on what theories and treatments of child anxiety would look like in a parallel universe in which the study never took place because ;little Albert' escaped from the hospital in which Watson tested him. PMID:19293325

  5. Escape and avoidance learning in the earthworm Eisenia hortensis

    Directory of Open Access Journals (Sweden)

    W. Jeffrey Wilson

    2014-01-01

    Full Text Available Interest in instrumental learning in earthworms dates back to 1912 when Yerkes concluded that they can learn a spatial discrimination in a T-maze. Rosenkoetter and Boice determined in the 1970s that the “learning” that Yerkes observed was probably chemotaxis and not learning at all. We examined a different form of instrumental learning: the ability to learn both to escape and to avoid an aversive stimulus. Freely moving “master” worms could turn off an aversive white light by increasing their movement; the behavior of yoked controls had no effect on the light. We demonstrate that in as few as 12 trials the behavior of the master worms comes under the control of this contingency.

  6. Energetic particle recurrence and escape during solar cycle 20

    Science.gov (United States)

    Gold, R. E.; Roelof, E. C.

    1980-10-01

    Low-energy solar particle data have been combined from a multi-spacecraft near-earth data set covering most of solar cycle 20 (1966-1976). Particle intensity profiles have been ordered in the natural heliographic coordinate system of the estimated high coronal connection longitude of the foot point of the interplanetary field line. The recurrence trends of approximately 1-MeV solar particles become more apparent in this coordinate system than when plotted versus time, and thereby extend the evidence for regions of continual injection and escape from the corona. Intercomparison of solar particles and solar wind streams in heliographic longitude suggests that the origin of stream-associated spatial particle events seen at 1 AU is solar rather than interplanetary.

  7. The resonance escape probability during the neutron slowing down

    International Nuclear Information System (INIS)

    Three different methods were used to calculate the neutron resonance escape probability during neutron slowing down in homogeneous media : two Monte Carlo simulations and a determinist method. The first simulation is based on a natural process intervening in neutron transport, the second is a nonanalog simulation while the determinist method is based on an iterative solution of the neutron slowing down equation. The results are in a good agreement for the three methods . The second simulation was found to be more efficient than the first one for high dilutions . In fact we have attained a better figure of merite ( FOM = 1/ (sigma sup 2 ) T) by the second simulation than by the first one . 2 figs. ; 2 refs ( author )

  8. Escaping from the labyrinth. Reason and freedom in Comenius’ thought

    Directory of Open Access Journals (Sweden)

    Antonella Cagnolati

    2009-12-01

    Full Text Available The aim of this essay consists in investigating in depth the fundamental work of Jan Amos Komenský, The Labirinth of the World and the Paradise of Hearth. In this work, some relevant elements such as irony, allegory, the search for his calling, are mixed up to show a sort of journey that can give the chance to understand the real world, made of irrationality and con- fusion. Komenský sets himself as a pilgrim who would like to unveil traps and false ideas so widespread amongst men. At the end of the Labirinth, Komenský recovers the evangelical mes- sage and looks at the world through different eyes. So the word of Christ can transform chaos into harmony. The pilgrim finds his way to escape and gains again his freedom at last.

  9. Will 3552 Don Quixote escape from the Solar System?

    Directory of Open Access Journals (Sweden)

    Suryadi Siregar

    2011-05-01

    Full Text Available Asteroid 1983 SA, well known as 3552 Don Quixote, is one of Near Earth Asteroids (NEAs which is the most probable candidate for the cometary origin, or otherwise as Jupiter-Family-Comets (JFCs. The aim of this study is to investigate the possibility of 3552 Don Quixote to be ejected from the Solar System. This paper presents an orbital evolution of 100 hypothetical asteroids generated by cloning 3552 Don Quixote. Investigation of its orbital evolution is conducted by using the SWIFT subroutine package, where the gravitational perturbations of eight major planets in the Solar System are considered. Over very short time scales (220 kyr relative to the Solar System life time (10 Gyr, the asteroid 3552 Don Quixote gave an example of chaotic motion that can cause asteroid to move outward and may be followed by escaping from the Solar System. Probability of ejection within the 220 kyr time scale is 50%.

  10. Bacillus cereus immune escape: a journey within macrophages.

    Science.gov (United States)

    Tran, Seav-Ly; Ramarao, Nalini

    2013-10-01

    During bacterial infection, professional phagocytes are attracted to the site of infection, where they constitute a first line of host cell defense. Their function is to engulf and destroy the pathogens. Thus, bacteria must withstand the bactericidal activity of professional phagocytes, including macrophages to counteract the host immune system. Bacillus cereus infections are characterized by bacteremia despite the accumulation of inflammatory cells at the site of infection. This implies that the bacteria have developed means of resisting the host immune system. Bacillus cereus spores survive, germinate, and multiply in contact with macrophages, eventually producing toxins that kill these cells. However, the exact mechanism by which B. cereus evades immune attack remains unclear. This review addresses the interaction between B. cereus and macrophages, highlighting, in particular, the ways in which the bacteria escape the microbicidal activities of professional phagocytes. PMID:23827020

  11. ESCAP holds expert group meeting on population issues facing adolescents.

    Science.gov (United States)

    1997-01-01

    This article summarizes the activities at the ESCAP Population Division Expert Group Meeting on Adolescents that was held during September-October 1997 in Bangkok, Thailand. The meeting was a follow-up to the 1994 International Conference on Population and Development (ICPD). The meeting considered 1) the ICPD recommendations; 2) the recommendations contained in the Jakarta Plan of Action on Human Resource Development; and 3) the Proposals for Action on Human Resources Development for Youth in Asia and the Pacific. Participants included about 25 people from Australia, Bangladesh, China, India, Indonesia, Philippines, Sri Lanka, and Thailand. The conference relied on 8 invited experts, two resource persons, advisors from the UNFPA Country Support Team for East and Southeast Asia, and representatives of UNFPA, the Population Council, and the East-West Center. A concern was the declining age of menarche of girls in the ESCAP region and the increasing age of marriage. During the time of menarche and marriage, girls are migrating and moving away from their family and community in rural areas. Family structure and relationships are changing. Increases are observed in adolescent premarital sexual activity, the incidence of sexually transmitted diseases, substance abuse, teenage pregnancy, and abortion. The mass media and information technologies have both a positive and a negative influence on adolescents. Parent-child communication exchanges and teacher-student exchanges are "less than ideal." Old traditions and practices change slower than people change. Boys and girls are affected differently by the sociocultural and economic environment. The societal norms set expectations for behavior that may conflict with individual beliefs and practices. Changes brought by globalization and rapid economic growth provide greater opportunity for young girls and women to obtain employment and autonomy. PMID:12293003

  12. Phenotypic mismatches reveal escape from arms-race coevolution.

    Directory of Open Access Journals (Sweden)

    Charles T Hanifin

    2008-03-01

    Full Text Available Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight into these features of coevolution by sampling across a diverse set of conditions and histories. We used measures of prey traits (tetrodotoxin toxicity in newts and predator traits (tetrodotoxin resistance of snakes to assess the degree of phenotypic mismatch across the range of their coevolutionary interaction. Geographic patterns of phenotypic exaggeration were similar in prey and predators, with most phenotypically elevated localities occurring along the central Oregon coast and central California. Contrary to expectations, however, these areas of elevated traits did not coincide with the most intense coevolutionary selection. Measures of functional trait mismatch revealed that over one-third of sampled localities were so mismatched that reciprocal selection could not occur given current trait distributions. Estimates of current locality-specific interaction selection gradients confirmed this interpretation. In every case of mismatch, predators were "ahead" of prey in the arms race; the converse escape of prey was never observed. The emergent pattern suggests a dynamic in which interacting species experience reciprocal selection that drives arms-race escalation of both prey and predator phenotypes at a subset of localities across the interaction. This coadaptation proceeds until the evolution of extreme phenotypes by predators, through genes of large effect, allows snakes to, at least temporarily, escape the arms race.

  13. The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Akerblom, L; Heegaard, P M; Nielsen, Jens Ole; Hansen, J E

    1995-01-01

    The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates to...... induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding to...... autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding...

  14. Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test.

    Science.gov (United States)

    Biagioni, Audrey Francisco; dos Anjos-Garcia, Tayllon; Ullah, Farhad; Fisher, Isaac René; Falconi-Sobrinho, Luiz Luciano; de Freitas, Renato Leonardo; Felippotti, Tatiana Tocchini; Coimbra, Norberto Cysne

    2016-02-01

    Inhibition of GABAergic neural inputs to dorsal columns of the periaqueductal grey matter (dPAG), posterior (PH) and dorsomedial (DMH) hypothalamic nuclei elicits distinct types of escape behavioural reactions. To differentiate between the variety and intensity of panic-related behaviours, the pattern of defensive behaviours evoked by blockade of GABAA receptors in the DMH, PH and dPAG were compared in a circular open-field test and in a recently designed polygonal arena. In the circular open-field, the defensive behaviours induced by microinjection of bicuculline into DMH and PH were characterised by defensive alertness behaviour and vertical jumps preceded by rearing exploratory behaviour. On the other hand, explosive escape responses interspersed with horizontal jumps and freezing were observed after the blockade of GABAA receptors on dPAG neurons. In the polygonal arena apparatus, the escape response produced by GABAergic inhibition of DMH and PH neurons was directed towards the burrow. In contrast, the blockade of GABAA receptors in dPAG evoked non-oriented escape behaviour characterised by vigorous running and horizontal jumps in the arena. Our findings support the hypothesis that the hypothalamic nuclei organise oriented escape behavioural responses whereas non-oriented escape is elaborated by dPAG neurons. Additionally, the polygonal arena with a burrow made it easy to discriminate and characterise these two different patterns of escape behavioural responses. In this sense, the polygonal arena with a burrow can be considered a good methodological tool to discriminate between these two different patterns of escape behavioural responses and is very useful as a new experimental animal model of panic attacks. PMID:26545831

  15. Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis

    International Nuclear Information System (INIS)

    Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC). RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis

  16. Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis

    Directory of Open Access Journals (Sweden)

    Nakamura Shinichiro

    2011-01-01

    Full Text Available Abstract Background Runt-related transcription factor 3 (RUNX3 is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC. Methods RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results RUNX3 protein expression was frequently inactivated in the HCC cell lines (91% and tissues (90%. RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

  17. Microenvironmental interactions in classical Hodgkin lymphoma and their role in promoting tumor growth, immune escape and drug resistance.

    Science.gov (United States)

    Aldinucci, Donatella; Celegato, Marta; Casagrande, Naike

    2016-09-28

    Classical Hodgkin lymphoma (cHL) is characterized by few tumor cells surrounded by immune cells, fibroblasts, specialized mesenchymal stromal cells and endothelial cells, representing together with their products an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells can secrete cytokines/chemokines and angiogenic factors capable of recruiting and/or inducing the proliferation of the surrounding cells and can also interact with distant sites of the microenvironment by secreting exosomes. To escape from a useful anti-tumor response due to the recognition by T and NK cells, HRS cells down-regulate HLA molecules, produce immune suppressive cytokines that inhibit cytotoxic responses, and induce an immunosuppressive phenotype on T lymphocytes and Monocytes. HRS cells survive, proliferate and are protected from the cytotoxic effects of chemotherapy agents by soluble factors or by the direct contact with inflammatory and stromal cells of the tumor microenvironment (TME). A summary of the current knowledge about classical Hodgkin Lymphoma focusing on the cross-talk between tumor cells and the microenvironment leading to immune-escape, angiogenesis tumor growth/survival and drug resistance will be reviewed here. PMID:26474544

  18. 77 FR 28601 - Announcement of an Opportunity for Manufacturers and Designers of Closed Circuit Escape...

    Science.gov (United States)

    2012-05-15

    ...://www.gpo.gov/fdsys/pkg/FR-2012-03-08/pdf/2012-4691.pdf ), Approval Tests and Standards for Closed-Circuit Escape Respirators (CCERs) on March 8th 2012. This final rule revised and updated the requirements... Manufacturers and Designers of Closed Circuit Escape Respirators To Participate in Performance Testing Within...

  19. Unsteady motion: escape jumps in planktonic copepods, their kinematics and energetics

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Andersen, Anders Peter; Langlois, Vincent J.; Jakobsen, Hans Henrik

    2010-01-01

    We describe the kinematics of escape jumps in three species of 0.3–3.0 mm-sized planktonic copepods. We find similar kinematics between species with periodically alternating power strokes and passive coasting and a resulting highly fluctuating escape velocity. By direct numerical simulations, we...

  20. The Efficacy of Noncontingent Escape for Decreasing Children's Disruptive Behavior during Restorative Dental Treatment

    Science.gov (United States)

    O'Callaghan, Patrick M.; Allen, Keith D.; Powell, Shawn; Salama, Fouad

    2006-01-01

    We evaluated the effectiveness of a dentist-implemented behavioral intervention in which brief escape from dental treatment was provided on a regular basis, independent of the child's behavior. Within a multiple baseline design across subjects, 5 children, ages 4 to 7 years, were provided with temporary escape from dental treatment on a fixed-time…

  1. 46 CFR 56.50-25 - Safety and relief valve escape piping.

    Science.gov (United States)

    2010-10-01

    ... 56.50-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING... or flexible pipe connections shall be fitted in escape piping. The piping shall be adequately... discharge to a common escape pipe relieving simultaneously at full capacity....

  2. Computer Self-Efficacy, Competitive Anxiety and Flow State: Escaping from Firing Online Game

    Science.gov (United States)

    Hong, Jon-Chao; Pei-Yu, Chiu; Shih, Hsiao-Feng; Lin, Pei-Shin; Hong, Jon-Chao

    2012-01-01

    Flow state in game playing affected by computer self-efficacy and game competitive anxiety was studied. In order to examine the effect of those constructs with high competition, this study select "Escaping from firing online game" which require college students to escape from fire and rescue people and eliminate the fire damage along the way of…

  3. The Effects of Fixed-Time Escape on Inappropriate and Appropriate Classroom Behavior

    Science.gov (United States)

    Waller, Rachael D.; Higbee, Thomas S.

    2010-01-01

    Few studies have explored the effects of fixed-time (FT) reinforcement on escape-maintained behavior of students in a classroom setting. We measured the effects of an FT schedule on the disruptive and appropriate academic behaviors of 2 junior high students in a public school setting. Results demonstrated that FT escape from tasks resulted in a…

  4. The use of an escape contingency and a token economy to increase food acceptance.

    OpenAIRE

    Kahng, SungWoo; Boscoe, James H; Byrne, Shannon

    2003-01-01

    Escape (termination of a meal) and token-based differential reinforcement of alternative behavior were used as reinforcement to increase acceptance of food. Using a changing criterion design, the number of bites accepted and consumed was gradually increased to 15 bites per meal. These data suggest that, in some cases, escape may be a potent reinforcer for food acceptance.

  5. Assessing Scientific and Technological Enquiry Skills at Age 11 Using the E-Scape System

    Science.gov (United States)

    Davies, Dan; Collier, Chris; Howe, Alan

    2012-01-01

    This article reports on the outcomes from the "e-scape Primary Scientific and Technological Understanding Assessment Project" (2009-2010), which aimed to support primary teachers in developing valid portfolio-based tasks to assess pupils' scientific and technological enquiry skills at age 11. This was part of the wider "e-scape" project…

  6. Plasma clouds and snowplows: Bulk plasma escape from Mars observed by MAVEN

    Science.gov (United States)

    Halekas, J. S.; Brain, D. A.; Ruhunusiri, S.; McFadden, J. P.; Mitchell, D. L.; Mazelle, C.; Connerney, J. E. P.; Harada, Y.; Hara, T.; Espley, J. R.; DiBraccio, G. A.; Jakosky, B. M.

    2016-02-01

    We present initial Mars Atmosphere and Volatile EvolutioN (MAVEN) observations and preliminary interpretation of bulk plasma loss from Mars. MAVEN particle and field measurements show that planetary heavy ions derived from the Martian atmosphere can escape in the form of discrete coherent structures or "clouds." The ions in these clouds are unmagnetized or weakly magnetized, have velocities well above the escape speed, and lie directly downstream from magnetic field amplifications, suggesting a "snowplow" effect. This postulated escape process, similar to that successfully used to explain the dynamics of active gas releases in the solar wind and terrestrial magnetosheath, relies on momentum transfer from the shocked solar wind protons to the planetary heavy ions, with the electrons and magnetic field acting as intermediaries. Fluxes of planetary ions on the order of 107 cm-2 s-1 can escape by this process, and if it operates regularly, it could contribute 10-20% of the current ion escape from Mars.

  7. Photochemical escape of oxygen from the Martian atmosphere: new insights from MAVEN

    Science.gov (United States)

    Lillis, R. J.; Deighan, J.; Bougher, S. W.; Cravens, T.; Fox, J. L.; Lee, Y.; Rahmati, A.; McFadden, J. P.; Benna, M.; Mahaffy, P. R.; Elrod, M. K.; Andersson, L.; Fowler, C. M.; Curry, S.; Gröller, H.; Jakosky, B. M.

    2015-12-01

    One of the primary goals of the MAVEN mission is to characterize rates of atmospheric escape from Mars at the present epoch and relate those escape rates to solar drivers. One of the known escape processes is photochemical escape, where a) an exothermic chemical reaction in the atmosphere results in an upward-traveling neutral particle whose velocity exceeds planetary escape velocity and b) the particle is not prevented from escaping through any subsequent collisions. Because escaping hot atoms are not directly measured, models of production and transport (through the atmosphere) of such atoms must be used to constrain photochemical escape rates. These models require altitude profiles of neutral densities and electron and ion densities and temperatures, as well as compositional information, all of which are measured by MAVEN instruments at the relevant altitudes (150-300 km). For every altitude profile: Profiles of O2+ dissociative recombination (DR) rates will be calculated from electron temperature, electron density and O2+ density. Profiles of energy distributions of hot O atoms will be calculated from profiles of electron and ion temperatures. Profiles of all neutral densities will be input into models of hot O transport in order to calculate photochemical escape fluxes from DR of O2+. We will present photochemical escape fluxes as a function of several factors, in particular solar zenith angle and EUV flux. This, combined with further simulations with progressively higher EUV fluxes, will eventually enable a total integrated loss estimate over the course of Martian history and hence a determination of the impact of this loss process on the evolution of the Martian climate.

  8. Escape of the martian protoatmosphere and initial water inventory

    CERN Document Server

    Erkaev, N V; Elkins-Tanton, L; Stökl, A; Odert, P; Marcq, E; Dorfi, E A; Kislyakova, K G; Kulikov, Yu N; Leitzinger, M; Güdel, M

    2013-01-01

    Latest research in planet formation indicate that Mars formed within a few million years (Myr) and remained a planetary embryo that never grew to a more massive planet. It can also be expected from dynamical models, that most of Mars' building blocks consisted of material that formed in orbital locations just beyond the ice line which could have contained ~0.1-0.2 wt. % of H2O. By using these constraints, we estimate the nebula-captured and catastrophically outgassed volatile contents during the solidification of Mars' magma ocean and apply a hydrodynamic upper atmosphere model for the study of the soft X-ray and extreme ultraviolet (XUV) driven thermal escape of the martian protoatmosphere during the early active epoch of the young Sun. The amount of gas that has been captured from the protoplanetary disk into the planetary atmosphere is calculated by solving the hydrostatic structure equations in the protoplanetary nebula. Depending on nebular properties such as the dust grain depletion factor, planetesimal...

  9. ESCAPE. Energy Security and ClimAte Policy Evaluation

    International Nuclear Information System (INIS)

    Climate change and energy supply security policy are currently not integrated in most countries, despite possible synergies. The ESCAPE approach suggests that linking climate change policy with security of energy supply could improve climate change policy at both a national and international level. The report explores the interaction between policies of energy security and climate change and the options of inclusion of energy security issues into national and international post-2012 climate negotiations. It emphasises the importance of the US in this regard and takes a close look at US energy policy documents. It appears that current US energy policy is not directed towards reducing its reliance on imported fossil fuel, even though the government has a strong preference for this. This study shows that measures to reduce import dependency are mostly synergetic with climate policy and gives some options that can be implemented. On an international level, linkages of energy security into post-2012 climate policy may be possible in sectoral bottom-up approaches or technology frameworks. As well, inclusion of a security of supply criterion in international emission trading instruments may provide potential benefits

  10. Nosema Tolerant Honeybees (Apis mellifera) Escape Parasitic Manipulation of Apoptosis

    Science.gov (United States)

    Kurze, Christoph; Le Conte, Yves; Dussaubat, Claudia; Erler, Silvio; Kryger, Per; Lewkowski, Oleg; Müller, Thomas; Widder, Miriam; Moritz, Robin F. A.

    2015-01-01

    Apoptosis is not only pivotal for development, but also for pathogen defence in multicellular organisms. Although numerous intracellular pathogens are known to interfere with the host’s apoptotic machinery to overcome this defence, its importance for host-parasite coevolution has been neglected. We conducted three inoculation experiments to investigate in the apoptotic respond during infection with the intracellular gut pathogen Nosema ceranae, which is considered as potential global threat to the honeybee (Apis mellifera) and other bee pollinators, in sensitive and tolerant honeybees. To explore apoptotic processes in the gut epithelium, we visualised apoptotic cells using TUNEL assays and measured the relative expression levels of subset of candidate genes involved in the apoptotic machinery using qPCR. Our results suggest that N. ceranae reduces apoptosis in sensitive honeybees by enhancing inhibitor of apoptosis protein-(iap)-2 gene transcription. Interestingly, this seems not be the case in Nosema tolerant honeybees. We propose that these tolerant honeybees are able to escape the manipulation of apoptosis by N. ceranae, which may have evolved a mechanism to regulate an anti-apoptotic gene as key adaptation for improved host invasion. PMID:26445372

  11. Dynamical correlations in the escape strategy of Influenza A virus

    Science.gov (United States)

    Taggi, L.; Colaiori, F.; Loreto, V.; Tria, F.

    2013-03-01

    The evolutionary dynamics of human Influenza A virus presents a challenging theoretical problem. An extremely high mutation rate allows the virus to escape, at each epidemic season, the host immune protection elicited by previous infections. At the same time, at each given epidemic season a single quasi-species, that is a set of closely related strains, is observed. A non-trivial relation between the genetic (i.e., at the sequence level) and the antigenic (i.e., related to the host immune response) distances can shed light into this puzzle. In this paper we introduce a model in which, in accordance with experimental observations, a simple interaction rule based on spatial correlations among point mutations dynamically defines an immunity space in the space of sequences. We investigate the static and dynamic structure of this space and we discuss how it affects the dynamics of the virus-host interaction. Interestingly we observe a staggered time structure in the virus evolution as in the real Influenza evolutionary dynamics.

  12. Nosema Tolerant Honeybees (Apis mellifera Escape Parasitic Manipulation of Apoptosis.

    Directory of Open Access Journals (Sweden)

    Christoph Kurze

    Full Text Available Apoptosis is not only pivotal for development, but also for pathogen defence in multicellular organisms. Although numerous intracellular pathogens are known to interfere with the host's apoptotic machinery to overcome this defence, its importance for host-parasite coevolution has been neglected. We conducted three inoculation experiments to investigate in the apoptotic respond during infection with the intracellular gut pathogen Nosema ceranae, which is considered as potential global threat to the honeybee (Apis mellifera and other bee pollinators, in sensitive and tolerant honeybees. To explore apoptotic processes in the gut epithelium, we visualised apoptotic cells using TUNEL assays and measured the relative expression levels of subset of candidate genes involved in the apoptotic machinery using qPCR. Our results suggest that N. ceranae reduces apoptosis in sensitive honeybees by enhancing inhibitor of apoptosis protein-(iap-2 gene transcription. Interestingly, this seems not be the case in Nosema tolerant honeybees. We propose that these tolerant honeybees are able to escape the manipulation of apoptosis by N. ceranae, which may have evolved a mechanism to regulate an anti-apoptotic gene as key adaptation for improved host invasion.

  13. Narrow escape for a stochastically gated Brownian ligand.

    Science.gov (United States)

    Reingruber, Jürgen; Holcman, David

    2010-02-17

    Molecular activation in cellular microdomains is usually characterized by a forward binding rate, which is the reciprocal of the arrival time of a ligand to a key target. Upon chemical interactions or conformational changes, a Brownian ligand may randomly switch between different states, and when target activation is possible in a specific state only, switching can significantly alter the activation process. The main goal of this paper is to study the mean time for a switching ligand to activate a small substrate, modelled as the time to exit a microdomain through a small absorbing window on the surface. We present the equations for the mean sojourn times the ligand spends in each state, and study the escape process with switching between two states in dimension one and three. When the ligand can exit in only one of the two states, we find that switching always decreases its sojourn time in the state where it can exit. Moreover, the fastest exit is obtained when the ligand diffuses most of the time in the state with the maximal diffusion coefficient, although this may imply that it spends most of the time 'hidden' in the state where it cannot exit. We discuss the physical mechanisms responsible for this apparent paradox. In dimension three we confirm our results with Brownian simulations. Finally, we suggest possible applications in cellular biology. PMID:21389363

  14. Escape probability of Martian atmospheric particles: controlling effects of the electromagnetic fields

    Science.gov (United States)

    Fang, X.; Liemohn, M. W.; Nagy, A. F.; Luhmann, J. G.; Ma, Y.

    2009-12-01

    This study quantifies several factors controlling the probability of a pickup oxygen ion to escape from the Mars upper atmosphere. Our Monte Carlo model releases billions of test particles through the electromagnetic fields of a magnetohydrodynamic model solution, monitoring their motion due to gravity and the Lorentz force throughout the simulation domain, which extends from the 200 km exobase altitude to 5 Martian radii from the center. We focus on the escape chances of the ions created at low altitudes on the dayside, where most ion production is located. The simulation results show that the electromagnetic fields are the dominant factor, surpassing the deceleration of gravity, in controlling ion transport and thus determine whether particles ultimately escape Mars or return to the planet. In a simulation case in which the strongest crustal fields face the Sun at nominal solar minimum conditions, on average only 45% of isotropically distributed new-born particles at ~400 km altitude are able to escape, even with a relatively high initial energy of ~10 eV. The percentage value slightly increases to 47%, if the velocity distribution is assumed to be half-isotropic without downward moving particles. The particle kinetic energy and the local time of the crustal fields are also important factors greatly influencing the escape probability. Furthermore, there is a distinct hemispheric asymmetry in the escape probability distribution, as defined by the upstream convection electric field direction. These findings imply that electromagnetic field effects are crucial in estimating Martian atmospheric loss for comparison with photochemical escape rates

  15. Light primes the escape response of the calanoid copepod, Calanus finmarchicus.

    Science.gov (United States)

    Fields, David M; Shema, Steven D; Browman, Howard I; Browne, Thomas Q; Skiftesvik, Anne Berit

    2012-01-01

    The timing and magnitude of an escape reaction is often the determining factor governing a copepod's success at avoiding predation. Copepods initiate rapid and directed escapes in response to fluid signals created by predators; however little is known about how copepods modulate their behavior in response to additional sensory input. This study investigates the effect of light level on the escape behavior of Calanus finmarchicus. A siphon flow was used to generate a consistent fluid signal and the behavioral threshold and magnitude of the escape response was quantified in the dark and in the light. The results show that C. finmarchicus initiated their escape reaction further from the siphon and traveled with greater speed in the light than in the dark. However, no difference was found in the escape distance. These results suggest that copepods use information derived from multiple sensory inputs to modulate the sensitivity and strength of the escape in response to an increase risk of predation. Population and IBM models that predict optimal vertical distributions of copepods in response to visual predators need to consider changes in the copepod's behavioral thresholds when predicting predation risk within the water column. PMID:22761834

  16. Reporter Assay for Endo/Lysosomal Escape of Toxin-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Roger Gilabert-Oriol

    2014-05-01

    Full Text Available Protein-based therapeutics with cytosolic targets are capable of exhibiting their therapeutic effect once they have escaped from the endosomes or lysosomes. In this study, the reporters—horseradish peroxidase (HRP, Alexa Fluor 488 (Alexa and ricin A-chain (RTA—were investigated for their capacity to monitor the endo/lysosomal escape of the ribosome-inactivating protein, saporin. The conjugates—saporin-HRP, Alexasaporin and saporin-KQ-RTA—were constructed, and the endo/lysosomal escape of these conjugates alone (lack of endo/lysosomal release or in combination with certain structurally-specific triterpenoidal saponins (efficient endo/lysosomal escape was characterized. HRP failed in reporting the endo/lysosomal escape of saporin. Contrastingly, Alexa Fluor 488 successfully allowed the report of the process at a toxin concentration of 1000 nM. In addition, single endo/lysosome analysis facilitated the determination of the amount of Alexasaporin released from each vesicle. RTA was also successful in reporting the endo/lysosomal escape of the enzymatically inactive mutant, saporin-KQ, but in this case, the sensitivity of the method reached a toxin concentration of 10 nM. In conclusion, the simultaneous usage of Alexa Fluor 488 and RTA as reporters may provide the possibility of monitoring the endo/lysosomal escape of protein-based therapeutics in the concentration range of 10–1000 nM.

  17. The impact of escaped farmed Atlantic salmon (Salmo salar L. on catch statistics in Scotland.

    Directory of Open Access Journals (Sweden)

    Darren M Green

    Full Text Available In Scotland and elsewhere, there are concerns that escaped farmed Atlantic salmon (Salmo salar L. may impact on wild salmon stocks. Potential detrimental effects could arise through disease spread, competition, or inter-breeding. We investigated whether there is evidence of a direct effect of recorded salmon escape events on wild stocks in Scotland using anglers' counts of caught salmon (classified as wild or farmed and sea trout (Salmo trutta L.. This tests specifically whether documented escape events can be associated with reduced or elevated escapes detected in the catch over a five-year time window, after accounting for overall variation between areas and years. Alternate model frameworks were somewhat inconsistent, however no robust association was found between documented escape events and higher proportion of farm-origin salmon in anglers' catch, nor with overall catch size. A weak positive correlation was found between local escapes and subsequent sea trout catch. This is in the opposite direction to what would be expected if salmon escapes negatively affected wild fish numbers. Our approach specifically investigated documented escape events, contrasting with earlier studies examining potentially wider effects of salmon farming on wild catch size. This approach is more conservative, but alleviates some potential sources of confounding, which are always of concern in observational studies. Successful analysis of anglers' reports of escaped farmed salmon requires high data quality, particularly since reports of farmed salmon are a relatively rare event in the Scottish data. Therefore, as part of our analysis, we reviewed studies of potential sensitivity and specificity of determination of farmed origin. Specificity estimates are generally high in the literature, making an analysis of the form we have performed feasible.

  18. An improved installation for control moment gyros and its applications on reconfiguration and singular escape

    Science.gov (United States)

    Jingrui, Zhang; Jin, Jin; Zaozhen, Liu

    2013-04-01

    A cluster of control moment gyros (CMGs) is widely used as the actuator of attitude control for modern satellite. However, to use CMGs will induce some accessional problems, like the singularity and the failure of them. In this paper, a rotator for the support bracket of each control moment gyro (CMG) is adopted and its application on reconfiguration and singular escape is discussed. The first step puts forward a novel reconfiguration scheme for the CMGs and applied on a satellite, which can adjust the installation angles of the remaining CMGs and make the CMGs remain axial symmetry. Then the characteristic of the output torque is studied in the process of reconfiguration of the CMGs. Based on this characteristic, a special steering law of the CMGs is designed to counteract the disturbance from the reconfiguration. The feasibility of singularity avoidance via the reconfiguration is also discussed by calculating the derivative of the singularity measurement to the installation angle. A singularity avoidance steering law is proposed based on the above calculation.

  19. Ultra-fast escape maneuver of an octopus-inspired robot

    CERN Document Server

    Weymouth, G D; Triantafyllou, M S

    2014-01-01

    We design and test an octopus-inspired flexible hull robot that demonstrates outstanding fast-starting performance. The robot is hyper-inflated with water, and then rapidly deflates to expel the fluid so as to power the escape maneuver. Using this robot we verify for the first time in laboratory testing that rapid size-change can be used to induce separation elimination in bluff bodies travelling several body lengths, and recover fluid energy which can be employed to improve the propulsive performance. The robot is found to experience extraordinary speeds, over ten body lengths per second, exceeding that of a similarly propelled optimally streamlined rigid rocket. The net thrust force on the robot is over 30\\% \\textit{larger} than the theoretical value for a rocket in vacuo, resulting in the rapid acceleration. Finally, over 53\\% of the initial energy is converted into payload kinetic energy, a performance that exceeds the estimated energy conversion efficiency of fast-starting fish. The Reynolds number based...

  20. Differentiation of Human Malignant Melanoma Cells that Escape Apoptosis After Treatment with 9-Nitrocamptothecin In Vitro

    Directory of Open Access Journals (Sweden)

    Panayotis Pantazis

    1999-08-01

    Full Text Available After in-vitro exposure to 0.05 μmol/L 9-nitrocamptothecin (9NC for periods of time longer than 5 days, 65% to 80% of the human malignant melanoma SB1 B cells die by apoptosis, whereas the remaining cells are arrested at the G2-phase of the cell cycle. Upon discontinuation of exposure to 9NC the G2-arrested cells resume cell cycling or remain arrested depending on the duration of 9NC exposure. In contrast to cycling malignant cells, the cells irreversibly arrested at G2 exhibit features of normal-like cells, the melanocytes, as assessed by the appearance of dendrite-like structures; loss of proliferative activity; synthesis of the characteristic pigment, melanin; and, particularly, loss of tumorigenic ability after xenografting in immunodeficient mice. Further, the expression of the cyclin-dependent kinase inhibitor p16 is upregulated in the 9NC-treated, G1-arrested, but downregulated in density G1-arrested cells, whereas the reverse is observed in the expression of another cyclin-dependent kinase inhibitor, p21. These results suggest that malignant melanoma SB1B cells that escape 9NC-induced death by apoptosis undergo differentiation toward nonmalignant, normal-like cells.

  1. Water Vapor Permeability of the Advanced Crew Escape Suit

    Science.gov (United States)

    Bue, Grant; Kuzneth, Larry; Gillis, David; Jones, Jeffery; Daniel, Brian; Gernhardt, Michael; Hamilton, Douglas

    2009-01-01

    Crew Exploration Vehicle (CEV) crewmembers are expected to return to earth wearing a suit similar to the current Advanced Crew Escape Suit (ACES). To ensure optimum cognitive performance, suited crewmembers must maintain their core body temperature within acceptable limits. There are currently several options for thermal maintenance in the post-landing phase. These include the current baseline, which uses an ammonia boiler, purge flow using oxygen in the suit, accessing sea water for liquid cooling garment (LCG) cooling and/or relying on the evaporative cooling capacity of the suit. These options vary significantly in mass, power, engineering and safety factors, with relying on the evaporative cooling capacity of the suit being the least difficult to implement. Data from previous studies indicates that the evaporative cooling capacity of the ACES was much higher than previously expected, but subsequent tests were performed for longer duration and higher metabolic rates to better define the water vapor permeability of the ACES. In these tests five subjects completed a series of tests performing low to moderate level exercise in order to control for a target metabolic rate while wearing the ACES in an environmentally controlled thermal chamber. Four different metabolic profiles at a constant temperature of 95 F and relative humidity of 50% were evaluated. These tests showed subjects were able to reject about twice as much heat in the permeable ACES as they were in an impermeable suit that had less thermal insulation. All of the heat rejection differential is attributed to the increased evaporation capability through the Gortex bladder of the suit.

  2. The calculation of the resonance escape factor of helium for Lorentzian and Voigt profiles

    Energy Technology Data Exchange (ETDEWEB)

    He Jian [School of Science, Henan University of Science and Technology, Luoyang 471003 (China)]. E-mail: hejian405@163.com; Zhang Qingguo [School of Science, Henan University of Science and Technology, Luoyang 471003 (China)

    2006-11-27

    The resonance escape factors of helium 10830.34 A, 10830.25 A and 10829.08 A that making up the 10830 A emission lines are calculated, for both Lorentzian profile and Voigt profile. The total number of absorbing atoms in the ground state is calculated. The dependence of the escape factors on the optical depth in the line center is considered. The resonance escape factors of helium 3889 and 3118 emission lines are discussed also. This calculation is useful in the research on the helium in the sun and remote stars from the helium emission lines.

  3. Fractional extension of Kramers rate and barrier escaping from metastable potential well

    CERN Document Server

    Wang, Chun-Yang

    2015-01-01

    The reactive process of barrier escaping from the metastable potential well is studied together with the extension of Kramers' rate formula to the fractional case. Characteristic quantities are computed for an thimbleful of insight into the near barrier escaping and recrossing dynamics. Where the stationary transmission coefficient is revealed to be larger than the usual cases which implies less barrier recrossing. And the non-monotonic varying of it reveals a close dependence to the fractional exponent $\\alpha$. In most cases, the near barrier behavior of the escaping dynamics is equivalent to the diffusion in the two-dimensional non-Ohmic damping system.

  4. CTL escape mediated by proteasomal destruction of an HIV-1 cryptic epitope.

    Directory of Open Access Journals (Sweden)

    Sylvain Cardinaud

    2011-05-01

    Full Text Available Cytotoxic CD8+ T cells (CTLs play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF. We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07. Using PBMCs of HIV-infected patients, we first cloned and sequenced proviral DNA encoding for Q9VF. We identified several polymorphisms with a minority of proviruses encoding at position 5 an aspartic acid (Q9VF/5D and a majority encoding an asparagine (Q9VF/5N. We compared the prevalence of each variant in PBMCs of HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were significantly less represented in HLA-B*07+ than in HLA-B*07- patients, suggesting that Q9FV/5D encoding viruses might be under selective pressure in HLA-B*07+ individuals. We thus analyzed ex vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around 16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of the same CTLs on the two peptides. We then dissected the cellular mechanisms involved in the presentation of Q9VF variants. As expected, cells infected with HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions and MS/MS analysis, we demonstrate that the 5N variation introduces a strong proteasomal cleavage site within the epitope, leading to a dramatic reduction of Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL surveillance by introducing mutations leading to HIV ARF-epitope destruction by proteasomes.

  5. Action and mechanism of Fas and Fas ligand in immune escape of gallbladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li-Ning Xu; Sheng-Quan Zou; Jian-Ming Wang

    2005-01-01

    in Nevin Ⅳ-Ⅴ carcinoma (t = 1.42, P>0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.

  6. Escape rate for a quantum particle moving in a time-periodic rapidly oscillating potential: a time-independent approach.

    Science.gov (United States)

    Shit, Anindita; Chattopadhyay, Sudip; Chaudhuri, Jyotipratim Ray

    2012-05-01

    We explore, in the quantum regime, the stochastic dynamics of a time-periodic, rapidly oscillating potential (having a characteristic frequency of ω) within the framework of a time-dependent system-reservoir Hamiltonian. We invoke the idea of a quantum gauge transformation in light of the standard Floquet theorem in an attempt to construct a Langevin equation (bearing a time-independent effective potential) by employing a systematic perturbative expansion in powers of ω^{-1} using the natural time-scale separation. The time-independent effective potential (corrected to ω^{-2} in leading order) that acts on the slow motion of the driven particle can be employed for trapping. We proceed further to evaluate the rate of escape of the driven particle from the metastable state in the high-temperature limit. We also envisage a resonance phenomena, a true hallmark of the system-reservoir quantization. This development would thus serve as a model template to investigate the trapping mechanism, as well as an appropriate analog to understand the dynamics of a fluctuation-induced escape process from the trap. PMID:23004698

  7. Reduced transcapillary escape of albumin during acute blood pressure-lowering in type 1 (insulin-dependent) diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Kastrup, J; Smidt, U M

    1985-01-01

    The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance...... injection induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p less than 0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p less than 0.01), albuminuria diminished from 1434 to 815 micrograms/min (p less...... than 0.01), and plasma volume raised slightly from 2916 to 2995 ml (p less than 0.05). Our findings demonstrate that the enhanced albumin passage through the wall of the microvasculature characteristically found in long-term Type 1 diabetic patients with clinical microangiopathy is pressure...

  8. Carrier escape from ground state and non-zero resonance frequency at low bias powers for semiconductor quantum-dot lasers

    Science.gov (United States)

    Wang, C.; Grillot, F.; Even, J.

    2012-06-01

    The three-dimensional confinement of electrons and holes in the semiconductor quantum dot (QD) structure profoundly changes its density of states compared to the bulk semiconductor or the thin-film quantum well (QW) structure. The aim of this paper is to theoretically investigate the microwave properties of InAs/InP(311B) QD lasers. A new expression of the modulation transfer function is derived for the analysis of QD laser modulation properties based on a set of four rate equations. Analytical calculations point out that carrier escape from ground state (GS) to excited state (ES) induces a non-zero resonance frequency at low bias powers. Calculations also show that the carrier escape leads to a larger damping factor offset as compared to conventional QW lasers. These results are of prime importance for a better understanding of the carrier dynamics in QD lasers as well as for further optimization of low cost sources for optical telecommunications.

  9. Escaping the poverty trap: modeling the interplay between economic growth and the ecology of infectious disease

    CERN Document Server

    Goerg, Georg M; Hébert-Dufresne, Laurent; Althouse, Benjamin M

    2013-01-01

    The dynamics of economies and infectious disease are inexorably linked: economic well-being influences health (sanitation, nutrition, treatment capacity, etc.) and health influences economic well-being (labor productivity lost to sickness and disease). Often societies are locked into ``poverty traps'' of poor health and poor economy. Here, using a simplified coupled disease-economic model with endogenous capital growth we demonstrate the formation of poverty traps, as well as ways to escape them. We suggest two possible mechanisms of escape both motivated by empirical data: one, through an influx of capital (development aid), and another through changing the percentage of GDP spent on healthcare. We find that a large influx of capital is successful in escaping the poverty trap, but increasing health spending alone is not. Our results demonstrate that escape from a poverty trap may be possible, and carry important policy implications in the world-wide distribution of aid and within-country healthcare spending.

  10. Ceramide formation mediated by acid sphingomyelinase facilitates endosomal escape of caliciviruses.

    Science.gov (United States)

    Shivanna, Vinay; Kim, Yunjeong; Chang, Kyeong-Ok

    2015-09-01

    Our recent results demonstrated that bile acids facilitate virus escape from the endosomes into the cytoplasm for successful replication of porcine enteric calicivirus (PEC). We report a novel finding that bile acids can be substituted by cold treatment for endosomal escape and virus replication. This endosomal escape by cold treatment or bile acids is associated with ceramide formation by acid sphingomyelinase (ASM). ASM catalyzes hydrolysis of sphingomyelin into ceramide, which is known to destabilize lipid bilayer. Treatment of LLC-PK cells with bile acids or cold led to ceramide formation, and small molecule antagonists or siRNA of ASM blocked ceramide formation in the endosomes and significantly reduced PEC replication. Inhibition of ASM resulted in the retention of PEC, feline calicivirus or murine norovirus in the endosomes in correlation with reduced viral replication. These results suggest the importance of viral escape from the endosomes for the replication of various caliciviruses. PMID:25985440

  11. Microcrustaceans escape behavior as an early bioindicator of copper, chromium and endosulfan toxicity.

    Science.gov (United States)

    Gutierrez, María Florencia; Paggi, Juan César; Gagneten, Ana María

    2012-03-01

    The purpose of this work was to experimentally analyze the impact of copper, chromium and a commercial pesticide with endosulfan on the escape behavior of two copepods (Notodiaptomus conifer, Argyrodiaptomus falcifer) and three cladocerans (Daphnia magna, Pseudosida variabilis and Ceriodaphnia dubia). The experimental assays were carried out using a novel hydraulic devise designed to mimic three-speed predator capture behavior. Two concentrations, one "high" and one "low", were employed and the exposure time was 15 (±5) minutes. With two exceptions, the species exposed to heavy metals manifested higher ability to escape than controls. Both concentrations of the pesticide reduced the escape ability of cladocerans but copepods responded, in general, in a similar manner as for heavy metals. The immediate apparent advantage of low and early toxic effects is discussed and the high sensitivity of the escape behavior suggests that it could be a complementary endpoint to be used in future ecotoxicological tests. PMID:22038688

  12. Escape of photons from two fixed extreme Reissner-Nordstr\\"om black holes

    CERN Document Server

    Alonso, Daniel; Sánchez-Hernández, Manuel; 10.1103/PhysRevD.78.104024

    2008-01-01

    We study the scattering of light (null geodesics) by two fixed extreme Reissner-Nordstr\\"om black holes, in which the gravitational attraction of their masses is exactly balanced with the electrostatic repulsion of their charges, allowing a static spacetime. We identify the set of unstable periodic orbits that constitute the fractal repeller that completely describes the chaotic escape dynamics of photons. In the framework of periodic orbit theory, the analysis of the linear stability of the unstable periodic orbits is used to obtain the main quantities of chaos that characterize the escape dynamics of the photons scattered by the black holes. In particular, the escape rate which is compared with the result obtained from numerical simulations that consider statistical ensembles of photons. We also analyze the dynamics of photons in the proximity of a perturbed black hole and give an analytical estimation for the escape rate in this system.

  13. Analytical Approximations for Calculating the Escape and Absorption of Radiation in Clumpy Dusty Environments

    CERN Document Server

    Varosi, F; Varosi, Frank; Dwek, Eli

    1999-01-01

    We present analytical approximations for the scattering, absorption and escape of non-ionizing photons from spherically symmetric two-phase clumpy media, with either a central point source of isotropic radiation, a uniform distribution of isotropic emitters, or uniformly illuminated by external sources. The analytical approximations are based on the mega-grains model of two-phase clumpy media, as proposed by Hobson & Padman, combined with escape and absorption probability formulae for homogeneous media. The accuracy of the approximations is examined by comparison with 3D Monte Carlo simulations of radiative transfer, including multiple scattering. Our studies show that the combined mega-grains and escape/absorption probability formulae provide a good approximation of the escaping and absorbed radiation fractions for a wide range of parameters characterizing the medium. A realistic test is performed by modeling the absorption of a stellar-like source of radiation by interstellar dust in a clumpy medium, an...

  14. Pizza or Pancake? Formation Models of Gas Escape Biosignatures in Terrestrial and Martian Sediments

    Science.gov (United States)

    Bonaccorsi, R.; Fairen, A. G.; Baker, L.; McKay, C. P.; Willson, D.

    2016-05-01

    Fine-grained sedimentary hollowed structures were imaged in Gale Crater, but no biomarkers identified to support biology. Our observation-based (gas escape) terrestrial model could inform on possible martian paleoenvironments at time of formation.

  15. The relationship between migration and development in the ESCAP region.

    Science.gov (United States)

    Skeldon, R

    1991-01-01

    The relationship between migration and development in the ESCAP region including southeast and south Asian countries and the Pacific island of Fiji, Papua New Guinea, Vanuatu, Kiribati, Samoa, and the Solomon Islands is discussed in terms of mobility transition and origin and destination factors. The changing patterns of mobility in Asia are further delineated in the discussion of internal movements and international movement. Emigration in the smaller countries of the Pacific are treated separately. Future predictions are that the Asia Pacific region will experience continued fertility decline and stabilization of low rates over the next 20 years. The declines will result in slow labor force growth, and increased demand for labor in traditional core and neocore countries as defined and presented in table form by Friedman will be heightened. International movements are likely to increase in large urban areas within destination countries. Tokyo and Singapore are the principal cities in Asia. Tokyo by restrictive government policy has limited immigration, but future labor shortages of unskilled labor from southeast Asia and China are expected. Singapore is already dependent on foreign labor by 10%. Current labor shortages have led to the creation of a growth triangle between Singapore, Indonesia, and Malaysia. Other cities expected to emerge as primary cities in international regional complexes with spillover into the hinterlands include the Hong Kong, Guangzhou, and Macau triangle in the Pearl River delta, Taipei and Seoul, and possibly Kuala Lumpur. Internal migration is expected to increase in the capital cities of Bangkok, Manila,j and centers such as Shanghai, Beijing, and other large cities of southeast Asia. These cities will be linked through the flows of skilled international migrants, which began in the 1960s and is expected to become a future major flow. Recreational and resource niches will be left in much of the Pacific, the Himalayan Kingdoms, and

  16. CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape

    OpenAIRE

    Wang, Gang; Zhao, Na; Berkhout, Ben; Das, Atze T.

    2016-01-01

    Several recent studies demonstrated that the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 can be used for guide RNA (gRNA)-directed, sequence-specific cleavage of HIV proviral DNA in infected cells. We here demonstrate profound inhibition of HIV-1 replication by harnessing T cells with Cas9 and antiviral gRNAs. However, the virus rapidly and consistently escaped from this inhibition. Sequencing of the HIV-1 escape variants revealed nucleotide...

  17. Inhibition of chaotic escape from a potential well using small parametric modulations

    International Nuclear Information System (INIS)

    It is shown theoretically for the first time that, depending on its period, amplitude, and initial phase, a periodic parametric modulation can suppress a chaotic escape from a potential well. The instance of the Helmholtz oscillator is used to demonstrate, by means of Melnikov close-quote s method, that parametric modulations of the linear or quadratic potential terms inhibit chaotic escape when certain resonance conditions are met. copyright 1996 American Institute of Physics

  18. Swimming and escape behavior of copepod nauplii: implications for predator-prey interactions among copepods

    DEFF Research Database (Denmark)

    Titelman, Josefin

    2001-01-01

    This study focuses on how prey behavior may affect predation risk through encounter rates and the escape success of the prey given an encounter. Temora longicornis nauplii require stronger hydrodynamic signals to elicit escape than Acartia tonsa nauplii (critical fluid deformation rates, Delta* o...... behavior of A. tonsa acts predominantly at the post-encounter stage where its sensitivity to hydrodynamic signals (i,e., low Delta*) effectively compensates for the high predator encounter rate generated by its motility....

  19. Progesterone After Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

    OpenAIRE

    Mayeaux, Darryl J.; Tandle, Sarah M.; Cilano, Sean M.; Fitzharris, Matthew J.

    2016-01-01

    In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized fem...

  20. Choices between positive and negative reinforcement during treatment for escape-maintained behavior.

    OpenAIRE

    DeLeon, I G; Neidert, P L; Anders, B M; Rodriguez-Catter, V

    2001-01-01

    Positive reinforcement was more effective than negative reinforcement in promoting compliance and reducing escape-maintained problem behavior for a child with autism. Escape extinction was then added while the child was given a choice between positive or negative reinforcement for compliance and the reinforcement schedule was thinned. When the reinforcement requirement reached 10 consecutive tasks, the treatment effects became inconsistent and reinforcer selection shifted from a strong prefer...

  1. Characterizing Atmospheric Escape from Mars Today and Through Time, with MAVEN

    Science.gov (United States)

    Lillis, R. J.; Brain, D. A.; Bougher, S. W.; Leblanc, F.; Luhmann, J. G.; Jakosky, B. M.; Modolo, R.; Fox, J.; Deighan, J.; Fang, X.; Wang, Y. C.; Lee, Y.; Dong, C.; Ma, Y.; Cravens, T.; Andersson, L.; Curry, S. M.; Schneider, N.; Combi, M.; Stewart, I.; Clarke, J.; Grebowsky, J.; Mitchell, D. L.; Yelle, R.; Nagy, A. F.; Baker, D.; Lin, R. P.

    2015-12-01

    Two of the primary goals of the MAVEN mission are to determine how the rate of escape of Martian atmospheric gas to space at the current epoch depends upon solar influences and planetary parameters and to estimate the total mass of atmosphere lost to space over the history of the planet. Along with MAVEN's suite of nine science instruments, a collection of complementary models of the neutral and plasma environments of Mars' upper atmosphere and near-space environment are an indispensable part of the MAVEN toolkit, for three primary reasons. First, escaping neutrals will not be directly measured by MAVEN and so neutral escape rates must be derived, via models, from in situ measurements of plasma temperatures and neutral and plasma densities and by remote measurements of the extended exosphere. Second, although escaping ions will be directly measured, all MAVEN measurements are limited in spatial coverage, so global models are needed for intelligent interpolation over spherical surfaces to calculate global escape rates. Third, MAVEN measurements will lead to multidimensional parameterizations of global escape rates for a range of solar and planetary parameters, but further global models informed by MAVEN data will be required to extend these parameterizations to the more extreme conditions that likely prevailed in the early solar system, which is essential for determining total integrated atmospheric loss. We describe these modeling tools and the strategies for using them in concert with MAVEN measurements to greater constrain the history of atmospheric loss on Mars.

  2. Orbital and escape dynamics in barred galaxies - I. The 2D system

    CERN Document Server

    Jung, Christof

    2016-01-01

    In this paper we use the two-dimensional (2D) version of a new analytical gravitational model in order to explore the orbital as well as the escape dynamics of the stars in a barred galaxy composed of a spherically symmetric central nucleus, a bar, a flat disk and a dark matter halo component. A thorough numerical investigation is conducted for distinguishing between bounded and escaping motion. Furthermore bounded orbits are further classified into non-escaping regular and trapped chaotic using the Smaller ALingment Index (SALI) method. Our aim is to determine the basins of escape through the two symmetrical escape channels around the Lagrange points $L_2$ and $L_3$ and also to relate them with the corresponding distribution of the escape rates of the orbits. We integrate initial conditions of orbits in several types of planes so as to obtain a more complete view of the overall orbital properties of the dynamical system. We also present evidence that the unstable manifolds which guide the orbits in and out t...

  3. Enhancing usability of augmented-reality-based mobile escape guidelines for radioactive accidents

    International Nuclear Information System (INIS)

    When radioactive accidents occur, modern tools in information technology for emergency response are good solutions to reduce the impact. Since few information-technology-based applications were developed for people during radioactive accidents, a previous study (Tsai et al., 2012) proposed augmented-reality-based mobile escape guidelines. However, because of the lack of transparent escape routes and indoor escape guidelines, the usability of the guidelines is limited. Therefore, this study introduces route planning and mobile three-dimensional (3D) graphics techniques to address the identified problems. The proposed approach could correctly present the geographical relationship from user locations to the anticipated shelters, and quickly show the floor-plan drawings as users are in the buildings. Based on the testing results, in contrast to the previous study, this study offered better escape routes, when the participants performed self-evacuation in outdoor and indoor environments. Overall, this study is not only a useful reference for similar studies, but also a beneficial tool for emergency response during radioactive accidents. -- Highlights: ► Enhancing the efficiency when people escape from radioactive accidents. ► The spatial relationship is transparently displayed in real time. ► In contrast to a previous study, this study offers better escape guidelines

  4. Usefulness and Limitations of Energy Limited Escape: Titan and Other Planetary Atmospheres

    Science.gov (United States)

    Johnson, Robert E.; Volkov, Alexey N.; Tucker, Orenthal J.

    2015-11-01

    Because thermal conduction and IR cooling are inefficient heat transfer processes, adiabatic expansion leading to molecular escape is often the dominant cooling process for energy deposited in the upper atmosphere of planetary bodies. This led to the use of the energy-limited escape (EL) approximation in which the loss rate is roughly proportional to the heating rate, Q. In applying the EL approximation, it was also frequently assumed that the adiabatic expansion resulted in the gas outflow going sonic. Johnson et al. (2013) used molecular kinetic simulations of an atmosphere with a heated layer to show this was not necessarily the case and estimated a critical heating rate, Qc. For Q greater than ~Qc a sonic point formed below the exobase where the gas properties were collision dominated. As Q increased above ~Qc sonic escape was eventually limited by the energy and number fluxes from the below the heated layer. In that case, adiabatic cooling did dominate upper atmosphere cooling, but the escape rate did not increase with increasing Q as predicted by the EL model. Instead, the escape rate remained nearly constant and the energy per molecule carried off increased nearly monotonically with Q. For heating rates from about twice Qc to more than an order of magnitude lower, the molecular escape rate was well approximated by the energy limited rate, but the upper atmospheric structure could not be described by a fluid model with a sonic point and escape was Jeans-like although the Jeans expressions was often a poor approximation. That is, molecules escape from well below the nominal exobase and collisions remained important well above it (Tucker et al. 2009; 2013) resulting in enhanced-Jeans-like escape (Volkov et al. 2011a,b; Erwin et al. 2013). Here we give a new expression for the escape rate produced by adiabatic cooling and expansion of the upper atmosphere and apply it to atmospheric loss from an early Titan atmosphere and related atmospheres.Ref.: Erwin,J.T., et

  5. Immunoproteasomes edit tumors, which then escapes immune recognition.

    Science.gov (United States)

    Joyce, Sebastian

    2015-12-01

    In 1985, John Monaco--the discoverer of LMP-2 and -7, the inducible components of the immunoproteasome--asked his advanced immunology class as to why the MHC region contained not only structural genes, but several others as well, whose functions were then unknown. As we drew a blank, he quipped: perchance because many of the MHC genes are induced by IFN-γ! The ensuing three decades have witnessed the unveiling of the profound fundamental and clinical implications of that classroom tête-à-tête. Amongst its multitudinous effects, IFN-γ induces genes enhancing antigen processing and presentation to T cells; such as those encoding cellular proteases and activators of proteases. In this issue, Keller et al. [Eur. J. Immunol. 2015. 45: 3257-3268] demonstrate that the limited success of MART-1/Melan-A-targeted immunotherapy in melanoma patients could be due to inefficient MART-1(26-35) presentation, owing to the proteolytic activities of IFN-γ-inducible β2i/MECL-1, proteasome activator 28 (PA28), and endoplasmic reticulum-associated aminopeptidase-associated with antigen processing (ERAP). Specifically, whilst β2i and PA28 impede MART-1(26-35) liberation from its precursor protein, ERAP-1 degrades this epitope. Hence, critical to effective cancer immunotherapy is deep knowledge of T-cell-targeted tumor antigens and how cellular proteases generate protective epitope(s) from them, or destroy them. PMID:26527367

  6. MAVEN Imaging UV Spectrograph Results on the Mars Atmosphere and Atmospheric Escape

    Science.gov (United States)

    Chaffin, Michael; Schneider, Nick; McClintock, Bill; Stewart, Ian; Deighan, Justin; Jain, Sonal; Clarke, John; Holsclaw, Greg; Montmessin, Franck; Lefevre, Franck; Chaufray, Jean-Yves; Stiepen, Arnaud; Crismani, Matteo; Mayyasi, Majd; Evans, Scott; Stevens, Mike; Yelle, Roger; Jakosky, Bruce

    2016-04-01

    The Imaging Ultraviolet Spectrograph (IUVS) is one of nine science instruments aboard the Mars Atmosphere and Volatile and EvolutioN (MAVEN) spacecraft, whose payload is dedicated to exploring the upper atmosphere of Mars and understanding the magnitude and drivers of Mars' atmospheric escape rate. IUVS uses ultraviolet light to investigate the lower and upper atmosphere and ionosphere of Mars. The instrument is among the most powerful spectrographs sent to another planet, with several key capabilities: (1) separate Far-UV & Mid-UV channels for stray light control, (2) a high resolution echelle mode to resolve deuterium and hydrogen emission, (3) internal instrument pointing and scanning capabilities to allow complete mapping and nearly continuous operation, and (4) optimization for airglow studies. IUVS, along with other MAVEN instruments, obtains a comprehensive picture of the current state of the Mars upper atmosphere and ionosphere and the processes that control atmospheric escape. We present an overview of selected IUVS results, including (1) the discovery of diffuse aurora at Mars, and its contrast with previously detected discrete aurora localized near crustal magnetic fields; (2) widespread detection of mesospheric clouds; (3) Significant seasonal and short-timescale variability in thermospheric composition; (4) Global ozone maps spanning six months of seasonal evolution; and (5) mapping of the Mars H and O coronas, deriving the escape rates of H and O and their variability. This last is of particular importance for understanding the long term evolution of Mars and its atmosphere, with the observed preset escape of H potentially capable of removing a large fraction of Mars' initial water inventory, and the differential escape of O relative to H potentially providing a net source of oxidizing power to the atmosphere and planet at present, in contrast with a photochemical theory that predicts stoichiometrically balanced escape. The atmospheric and escape

  7. Temporal and ontogenetic variation in the escape response of Ameiva festiva (Squamata, Teiidae

    Directory of Open Access Journals (Sweden)

    Lattanzio

    2014-08-01

    Full Text Available Several factors have been shown to affect lizard escape behavior (flight initiation distance or FID, the distance between predator and prey when the prey initiates escape. Patterns of daily activity, such as foraging or movement behavior, vary with respect to time of day, supporting that escape responses may vary temporally as well. However, there remains scant information regarding the effects of time of day on FID. During peak activity, FID may decrease due to increased cost of giving up resources (e.g., prey or potential mates. An alternative hypothesis is that FID may increase because lizard activity in general may serve to alert a predator in advance of its approach. A lizard in this scenario may be favored to flee sooner rather than later. Moreover, juvenile and adult lizards of multiple species may differ in behavioral, ecological, and morphological traits that could influence escape decisions. I tested the effects of time of day (in 30-min intervals and age (juvenile or adult on the FID of a tropical whiptail lizard, Ameiva festiva in Costa Rica. I found that A. festiva escape responses varied with time of day such that in general, their FID decreased throughout the day. In addition, I observed a peak in FID from mid to late-morning that matches published estimates of peak activity times for A. festiva. Overall, juvenile A. festiva initiated an escape response sooner than adults, which may be related to differences in perceived risk associated with differences in size and predator experience between the two age groups. I conclude that escape responses may be contingent on both the activity level of the animal at the time of approach and its age.

  8. Comparative pick-up ion distributions at Mars and Venus: Consequences for atmospheric deposition and escape

    Science.gov (United States)

    Curry, Shannon M.; Luhmann, Janet; Ma, Yingjuan; Liemohn, Michael; Dong, Chuanfei; Hara, Takuya

    2015-09-01

    Without the shielding of a substantial intrinsic dipole magnetic field, the atmospheres of Mars and Venus are particularly susceptible to similar atmospheric ion energization and scavenging processes. However, each planet has different attributes and external conditions controlling its high altitude planetary ion spatial and energy distributions. This paper describes analogous test particle simulations in background MHD fields that allow us to compare the properties and fates, precipitation or escape, of the mainly O+ atmospheric pick-up ions at Mars and Venus. The goal is to illustrate how atmospheric and planetary scales affect the upper atmospheres and space environments of our terrestrial planet neighbors. The results show the expected convection electric field-related hemispheric asymmetries in both precipitation and escape, where the degree of asymmetry at each planet is determined by the planetary scale and local interplanetary field strength. At Venus, the kinetic treatment of O+ reveals a strong nightside source of precipitation while Mars' crustal fields complicate the simple asymmetry in ion precipitation and drive a dayside source of precipitation. The pickup O+ escape pattern at both Venus and Mars exhibits low energy tailward escape, but Mars exhibits a prominent, high energy 'polar plume' feature in the hemisphere of the upward convection electric field while the Venus ion wake shows only a modest poleward concentration. The overall escape is larger at Venus than Mars (2.1 ×1025 and 4.3 ×1024 at solar maximum, respectively), but the efficiency (likelihood) of O+ escaping is 2-3 times higher at Mars. The consequences of these comparisons for pickup ion related atmospheric energy deposition, loss rates, and detection on spacecraft including PVO, VEX, MEX and MAVEN are considered. In particular, both O+ precipitation and escape show electric field controlled asymmetries that grow with energy, while the O+ fluxes and energy spectra at selected spatial

  9. Natural killer cells and neuroblastoma: tumor recognition, escape mechanisms, and possible novel immunotherapeutic approaches.

    Science.gov (United States)

    Bottino, Cristina; Dondero, Alessandra; Bellora, Francesca; Moretta, Lorenzo; Locatelli, Franco; Pistoia, Vito; Moretta, Alessandro; Castriconi, Roberta

    2014-01-01

    Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland, or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients' age over 18 months, and the presence at diagnosis of a metastatic disease (stage IV, M) identify NB at high risk of treatment failure. Conventional therapies did not significantly improve the overall survival of these patients. Moreover, the limited landscape of somatic mutations detected in NB is hampering the development of novel pharmacological approaches. Major efforts aim to identify novel NB-associated surface molecules that activate immune responses and/or direct drugs to tumor cells and tumor-associated vessels. PVR (Poliovirus Receptor) and B7-H3 are promising targets, since they are expressed by most high-risk NB, are upregulated in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a ligand of DNAM-1 activating receptor that triggers the cytolytic activity of natural killer (NK) cells against NB. In animal models, targeting of PVR with an attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7-H3 was successfully targeted in preclinical studies and is now being tested in phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB with a mechanism of escape from immune response. The immunosuppressive potential of NB can be enhanced by the release of soluble factors that impair NK cell function and/or recruitment. Among these, TGF-β1 modulates the cytotoxicity receptors and the chemokine receptor repertoire of NK cells. Here, we summarize the current knowledge on the main cell surface molecules and soluble mediators that modulate the function of NK cells in NB, considering the pros and cons that must be taken into account in the design of novel NK cell-based immunotherapeutic approaches

  10. Hypoxia promotes tumor growth in linking angiogenesis to immune escape

    Directory of Open Access Journals (Sweden)

    Salem eCHOUAIB

    2012-02-01

    Full Text Available Despite the impressive progress over the past decade, in the field of tumor immunology, such as the identification of tumor antigens and antigenic peptides as potential targets, there are still many obstacles in eliciting an effective immune response to eradicate cancer. It has become increasingly clear that tumor microenvironment plays a crucial role in the control of immune protection and contains many overlapping mechanisms to evade antigen specific immunotherapy. Obviously, tumors have evolved to utilize hypoxic stress to their own advantage by activating key biochemical and cellular pathways that are important in progression, survival and metastasis. Among the hypoxia-induced genes, hypoxia-inducible factor (HIF-1 and vascular endothelial growth factor (VEGF play a determinant role in promoting tumor cell growth and survival. In this regard, hypoxia is emerging as an attractive target for cancer therapy. How the microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions will be discussed.

  11. Evolutionary dynamics of viral escape under antibodies stress: A biophysical model.

    Science.gov (United States)

    Chéron, Nicolas; Serohijos, Adrian W R; Choi, Jeong-Mo; Shakhnovich, Eugene I

    2016-07-01

    Viruses constantly face the selection pressure of antibodies, either from innate immune response of the host or from administered antibodies for treatment. We explore the interplay between the biophysical properties of viral proteins and the population and demographic variables in the viral escape. The demographic and population genetics aspect of the viral escape have been explored before; however one important assumption was the a priori distribution of fitness effects (DFE). Here, we relax this assumption by instead considering a realistic biophysics-based genotype-phenotype relationship for RNA viruses escaping antibodies stress. In this model the DFE is itself an evolvable property that depends on the genetic background (epistasis) and the distribution of biophysical effects of mutations, which is informed by biochemical experiments and theoretical calculations in protein engineering. We quantitatively explore in silico the viability of viral populations under antibodies pressure and derive the phase diagram that defines the fate of the virus population (extinction or escape from stress) in a range of viral mutation rates and antibodies concentrations. We find that viruses are most resistant to stress at an optimal mutation rate (OMR) determined by the competition between supply of beneficial mutation to facilitate escape from stressors and lethal mutagenesis caused by excess of destabilizing mutations. We then show the quantitative dependence of the OMR on genome length and viral burst size. We also recapitulate the experimental observation that viruses with longer genomes have smaller mutation rate per nucleotide. PMID:26939576

  12. The escape of ionising radiation from high-redshift dwarf galaxies

    CERN Document Server

    Paardekooper, Jan-Pieter; Altay, Gabriel; Kruip, Chael

    2011-01-01

    The UV escape fraction from high-redshift galaxies plays a key role in models of cosmic reionisation. Because it is currently not possible to deduce the escape fractions during the epoch of reionisation from observations, we have to rely on numerical simulations. Our aim is to better constrain the escape fraction from high-redshift dwarf galaxies, as these are the most likely sources responsible for reionising the Universe. We employ a N-body/SPH method that includes realistic prescriptions for the physical processes that are important for the evolution of dwarf galaxies. These models are post-processed with radiative transfer to determine the escape fraction of ionising radiation. We perform a parameter study to assess the influence of the spin parameter, gas fraction and formation redshift of the galaxy and study the importance of numerical parameters as resolution, source distribution and local gas clearing. We find that the UV escape fraction from high-redshift dwarf galaxies that have formed a rotational...

  13. The Lyman Continuum Escape Fraction of Low-Mass Star-Forming Galaxies at z~1

    CERN Document Server

    Rutkowski, Michael J; Haardt, Francesco; Siana, Brian; Henry, Alaina; Rafelski, Marc; Hayes, Matthew; Salvato, Mara; Pahl, Anthony J; Mehta, Vihang; Beck, Melanie; Malkan, Matthew; Teplitz, Harry I

    2015-01-01

    To date no direct detection of Lyman continuum emission has been measured for intermediate--redshift z~1 star-forming galaxies . We combine HST grism spectroscopy with GALEX UV and ground--based optical imaging to extend the search for escaping Lyman continuum to a large (~600) sample of z~1 low-mass, moderately star-forming galaxies selected initially on H$\\alpha$ emission. The characteristic escape fraction of LyC from SFGs that populate this parameter space remains weakly constrained by previous surveys, but these faint SFGs are assumed to play a significant role in the reionization of neutral hydrogen in the intergalactic medium (IGM) at high redshift (z>6). We do not make an unambiguous detection of escaping LyC radiation from this $z\\sim1$ sample, individual non--detections to constrain the absolute Lyman continuum escape fraction, $f_{esc}$200\\AA), which are thought to be close analogs of high redshift sources of reionization. For reference, we also present an emissivity--weighted escape fraction which...

  14. Escape Distance in Ground-Nesting Birds Differs with Individual Level of Camouflage.

    Science.gov (United States)

    Wilson-Aggarwal, Jared K; Troscianko, Jolyon T; Stevens, Martin; Spottiswoode, Claire N

    2016-08-01

    Camouflage is one of the most widespread antipredator strategies in the animal kingdom, yet no animal can match its background perfectly in a complex environment. Therefore, selection should favor individuals that use information on how effective their camouflage is in their immediate habitat when responding to an approaching threat. In a field study of African ground-nesting birds (plovers, coursers, and nightjars), we tested the hypothesis that individuals adaptively modulate their escape behavior in relation to their degree of background matching. We used digital imaging and models of predator vision to quantify differences in color, luminance, and pattern between eggs and their background, as well as the plumage of incubating adult nightjars. We found that plovers and coursers showed greater escape distances when their eggs were a poorer pattern match to the background. Nightjars sit on their eggs until a potential threat is nearby, and, correspondingly, they showed greater escape distances when the pattern and color match of the incubating adult's plumage-rather than its eggs-was a poorer match to the background. Finally, escape distances were shorter in the middle of the day, suggesting that escape behavior is mediated by both camouflage and thermoregulation. PMID:27420787

  15. Fluctuating bottleneck model studies on kinetics of DNA escape from α-hemolysin nanopores.

    Science.gov (United States)

    Bian, Yukun; Wang, Zilin; Chen, Anpu; Zhao, Nanrong

    2015-11-14

    We have proposed a fluctuation bottleneck (FB) model to investigate the non-exponential kinetics of DNA escape from nanometer-scale pores. The basic idea is that the escape rate is proportional to the fluctuating cross-sectional area of DNA escape channel, the radius r of which undergoes a subdiffusion dynamics subjected to fractional Gaussian noise with power-law memory kernel. Such a FB model facilitates us to obtain the analytical result of the averaged survival probability as a function of time, which can be directly compared to experimental results. Particularly, we have applied our theory to address the escape kinetics of DNA through α-hemolysin nanopores. We find that our theoretical framework can reproduce the experimental results very well in the whole time range with quite reasonable estimation for the intrinsic parameters of the kinetics processes. We believe that FB model has caught some key features regarding the long time kinetics of DNA escape through a nanopore and it might provide a sound starting point to study much wider problems involving anomalous dynamics in confined fluctuating channels. PMID:26567685

  16. The First Billion Years Project: The escape fraction of ionising photons in the epoch of reionisation

    CERN Document Server

    Paardekooper, Jan-Pieter; Vecchia, Claudio Dalla

    2015-01-01

    Proto-galaxies forming in low-mass dark matter haloes are thought to provide the majority of ionising photons needed to reionise the Universe, due to their high escape fractions of ionising photons. We study how the escape fraction in high-redshift galaxies relates to the physical properties of the halo in which the galaxies form by computing escape fractions for 75801 haloes between redshifts 27 and 6 that were extracted from the FiBY project, high-resolution cosmological hydrodynamics simulations of galaxy formation. We find that the main constraint on the escape fraction is the presence of dense gas within 10 pc of the young sources that emit the majority of the ionising photons produced over the lifetime of the stellar population. This results in a strong mass dependence of the escape fraction. The lower potential well in haloes with virial mass below 10^8 solar mass results in lower column densities close to the sources that can be penetrated by the radiation from young, massive stars. In general only a ...

  17. The Escape of Ionizing Photons from OB Associations in Disk Galaxies Radiation Transfer Through Superbubbles

    CERN Document Server

    Dove, J B; Ferrara, A; Dove, James B.; Ferrara, Andrea

    1999-01-01

    By solving the time-dependent radiation transfer problem of stellar radiation through evolving superbubbles within a smoothly varying H I distribution, we have estimated the fraction of ionizing photons emitted by OB associations that escapes the H I disk of our Galaxy. We considered a coeval star-formation history and a Gaussian star-formation history with a time spread sigma_t = 2 Myr. We find that the shells of the expanding superbubbles quickly trap or attenuate the ionizing flux, such that most of the escaping radiation escapes shortly after the formation of the superbubble. Superbubbles of large associations can blowout of the H I disk and form dynamic chimneys, which allow the ionizing radiation directly to escape the H I disk. However, blowout occurs when the ionizing photon luminosity has dropped well below the association's maximum luminosity. For the coeval star-formation history, the fraction of photons that escape each side of the disk in the solar vicinity is f_esc approx 6% (the total fraction ...

  18. Fluctuating bottleneck model studies on kinetics of DNA escape from α-hemolysin nanopores

    Science.gov (United States)

    Bian, Yukun; Wang, Zilin; Chen, Anpu; Zhao, Nanrong

    2015-11-01

    We have proposed a fluctuation bottleneck (FB) model to investigate the non-exponential kinetics of DNA escape from nanometer-scale pores. The basic idea is that the escape rate is proportional to the fluctuating cross-sectional area of DNA escape channel, the radius r of which undergoes a subdiffusion dynamics subjected to fractional Gaussian noise with power-law memory kernel. Such a FB model facilitates us to obtain the analytical result of the averaged survival probability as a function of time, which can be directly compared to experimental results. Particularly, we have applied our theory to address the escape kinetics of DNA through α-hemolysin nanopores. We find that our theoretical framework can reproduce the experimental results very well in the whole time range with quite reasonable estimation for the intrinsic parameters of the kinetics processes. We believe that FB model has caught some key features regarding the long time kinetics of DNA escape through a nanopore and it might provide a sound starting point to study much wider problems involving anomalous dynamics in confined fluctuating channels.

  19. Ion-induced gamma-ray detection of fast ions escaping from fusion plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Nishiura, M., E-mail: nishiura@ppl.k.u-tokyo.ac.jp; Mushiake, T. [Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561 (Japan); Doi, K.; Wada, M. [Graduate School of Science and Engineering, Doshisha University, Kyotanabe 610-0321 (Japan); Taniike, A.; Matsuki, T. [Graduate School of Maritime Sciences, Kobe University, Kobe 658-0022 (Japan); Shimazoe, K. [Graduate School of Engineering, The University of Tokyo, Tokyo 113-8654 (Japan); Yoshino, M. [Furukawa Co. Ltd., Tsukuba, Ibaraki 305-0856 (Japan); Nagasaka, T.; Tanaka, T.; Kisaki, M. [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan); Fujimoto, Y.; Fujioka, K. [Institute of Laser Engineering, Osaka University, Osaka 565-0871 (Japan); Yamaoka, H. [RIKEN SPring-8 center, RIKEN, Sayo, Hyogo 679-5148 (Japan); Matsumoto, Y. [Tokushima Bunri University, Tokushima 770-8514 (Japan)

    2014-11-15

    A 12 × 12 pixel detector has been developed and used in a laboratory experiment for lost fast-ion diagnostics. With gamma rays in the MeV range originating from nuclear reactions {sup 9}Be(α, nγ){sup 12}C, {sup 9}Be(d, nγ){sup 12}C, and {sup 12}C(d, pγ){sup 13}C, a high purity germanium (HPGe) detector measured a fine-energy-resolved spectrum of gamma rays. The HPGe detector enables the survey of background-gamma rays and Doppler-shifted photo peak shapes. In the experiments, the pixel detector produces a gamma-ray image reconstructed from the energy spectrum obtained from total photon counts of irradiation passing through the detector's lead collimator. From gamma-ray image, diagnostics are able to produce an analysis of the fast ion loss onto the first wall in principle.

  20. A phase I study of concurrent 9-nitro-20(s)-camptothecin (9NC/Orathecin) and radiation therapy in the treatment of locally advanced adenocarcinoma of the pancreas

    International Nuclear Information System (INIS)

    Background and purpose: In vitro studies have suggested that 9-nitro-20(s)-Camptothecin (9NC/Orathecin/Rubitecan) can enhance the effects of radiation. We conducted a phase I study to assess the toxicity and determine the maximum tolerated dose of 9NC when combined with radiation in patients with locally advanced adenocarcinoma of the pancreas. Patients and methods: Eleven patients with locally advanced adenocarcinoma of the pancreas received 9NC, orally during radiation. Radiation therapy consisted of 45 Gy in 25 fractions given over 5 weeks. The starting dose of 9NC was 1 mg/m2/day. Results: Eight patients received 9NC at a dose of 1 mg/m2/day and three patients received a dose of 1.25 mg/m2/day. Dose-limiting toxicity (DLT) was defined as ≥grade 3 non-hematologic toxicity and ≥grade 4 hematologic toxicity. Dose-limiting toxicity of grade 3 nausea/vomiting developed in one patient at the first dose level. At dose level 2, two of three patients developed DLT. Both developed grade 3 nausea, fatigue, and anorexia. Additionally, one of these patients had grade 3 dehydration and the other had grade 4 leukopenia, grade 3 vomiting, and grade 3 weakness. Conclusions: 9NC, 1 mg/m2/day, can be given concurrently with radiation with acceptable toxicity

  1. CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape

    Science.gov (United States)

    Wang, Gang; Zhao, Na; Berkhout, Ben; Das, Atze T

    2016-01-01

    Several recent studies demonstrated that the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 can be used for guide RNA (gRNA)-directed, sequence-specific cleavage of HIV proviral DNA in infected cells. We here demonstrate profound inhibition of HIV-1 replication by harnessing T cells with Cas9 and antiviral gRNAs. However, the virus rapidly and consistently escaped from this inhibition. Sequencing of the HIV-1 escape variants revealed nucleotide insertions, deletions, and substitutions around the Cas9/gRNA cleavage site that are typical for DNA repair by the nonhomologous end-joining pathway. We thus demonstrate the potency of CRISPR-Cas9 as an antiviral approach, but any therapeutic strategy should consider the viral escape implications. PMID:26796669

  2. Role of Energy Exchange in the Deterministic Escape of a Coupled Nonlinear Oscillator Chain

    International Nuclear Information System (INIS)

    We consider the deterministic escape of a chain of harmonically coupled units from a metastable state over a cubic potential barrier. The underlying dynamics is conservative and noise-free. The supply of a sufficient total energy transforms the chain into the nonlinear regime from which an initially, nearly uniform lattice configuration becomes unstable, yielding a redistribution of energy. In an early stage of the dynamics, we estimate the degree of energy exchange enabling the coupled system to form strongly localized modes which eventually grow into a critical nucleus. Upon passing this transition state, the nonlinear chain performs a collective, deterministic escape. We analyze the associated nonlinear dynamics in phase space and relate the escape to diffusion in a separatrix layer. (author)

  3. Mitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement

    Science.gov (United States)

    Sorce, Barbara; Escobedo, Carlos; Toyoda, Yusuke; Stewart, Martin P.; Cattin, Cedric J.; Newton, Richard; Banerjee, Indranil; Stettler, Alexander; Roska, Botond; Eaton, Suzanne; Hyman, Anthony A.; Hierlemann, Andreas; Müller, Daniel J.

    2015-11-01

    Little is known about how mitotic cells round against epithelial confinement. Here, we engineer micropillar arrays that subject cells to lateral mechanical confinement similar to that experienced in epithelia. If generating sufficient force to deform the pillars, rounding epithelial (MDCK) cells can create space to divide. However, if mitotic cells cannot create sufficient space, their rounding force, which is generated by actomyosin contraction and hydrostatic pressure, pushes the cell out of confinement. After conducting mitosis in an unperturbed manner, both daughter cells return to the confinement of the pillars. Cells that cannot round against nor escape confinement cannot orient their mitotic spindles and more likely undergo apoptosis. The results highlight how spatially constrained epithelial cells prepare for mitosis: either they are strong enough to round up or they must escape. The ability to escape from confinement and reintegrate after mitosis appears to be a basic property of epithelial cells.

  4. European policymaking on the tobacco advertising ban: the importance of escape routes.

    Science.gov (United States)

    Adamini, Sandra; Versluis, Esther; Maarse, Hans

    2011-01-01

    This article analyses the European Union policymaking process regarding tobacco advertising. While others already highlighted the importance of intergovernmental bargaining between member states to explain the outcome of the tobacco advertising case, the main aim of this article is to identify the use of escape routes by the Commission, the European Parliament, the Council and interest groups that played an important role in overcoming the deadlock. When looking at the different institutions that structure policymaking, we argue that indeed focusing on escape routes provides a clear insight in the process and in what strategies were necessary to 'make Europe work'. In the end, it appears to be a combination of escape routes that resulted in the final decision. PMID:20199714

  5. Escape and collision dynamics in the planar equilateral restricted four-body problem

    CERN Document Server

    Zotos, Euaggelos E

    2016-01-01

    We consider the planar circular equilateral restricted four body-problem where a test particle of infinitesimal mass is moving under the gravitational attraction of three primary bodies which move on circular orbits around their common center of gravity, such that their configuration is always an equilateral triangle. The case where all three primaries have equal masses is numerically investigated. A thorough numerical analysis takes place in the configuration $(x,y)$ as well as in the $(x,C)$ space in which we classify initial conditions of orbits into four main categories: (i) bounded regular orbits, (ii) trapped chaotic orbits, (iii) escaping orbits and (iv) collision orbits. Interpreting the collision motion as leaking in the phase space we related our results to both chaotic scattering and the theory of leaking Hamiltonian systems. We successfully located the escape and the collision basins and we managed to correlate them with the corresponding escape and collision times of orbits. We hope our contribut...

  6. The great escape: the role of self-esteem and self-related cognition in terror management

    OpenAIRE

    Wisman, Arnaud; Heflick, Nathan A; Goldenberg, Jamie L.

    2015-01-01

    Integrating terror management theory and objective self-awareness theory, we propose the existential escape hypothesis, which states that people with low self-esteem should be especially prone to escaping self-awareness as a distal response to thoughts of death. This is because they lack the means to bolster the self as a defense, and the propensity to bolster the self reduces the motivation to escape from self-awareness. Five studies supported this hypothesis. Individuals low,...

  7. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

  8. Synchronous activity lowers the energetic cost of nest escape for sea turtle hatchlings.

    Science.gov (United States)

    Rusli, Mohd Uzair; Booth, David T; Joseph, Juanita

    2016-05-15

    A potential advantage of group movement in animals is increased locomotion efficiency. This implies a reduced energetic cost for individuals that occur in larger groups such as herds, flocks and schools. When chelonian hatchlings hatch in the underground nest with finite energy for their post-hatching dispersal phase, they face the challenge of minimizing energetic expenditure while escaping the nest. The term 'social facilitation' has been used to describe the combined digging effort of sea turtle hatchlings during nest escape. Given that in a normal clutch, a substantial part of the energy reserve within the residual yolk is used by hatchlings in the digging out process, a decreased cohort size may reduce the energy reserve available to cross the beach and sustain the initial swimming frenzy. This hypothesis was experimentally tested by varying cohort size in hatchling green turtles (Chelonia mydas) and measuring energy expenditure during the nest escape process using open-flow respirometry. The energetic cost of escaping through 40 cm of sand was calculated to vary between 4.4 and 28.3 kJ per individual, the cost decreasing as the number of individuals in the cohort increased. This represents 11-68% of the energy contained in a hatchling's residual yolk at hatching. The reduced energetic cost associated with large cohorts resulted from both a lower metabolic rate per individual and a shortened nest escape time. We conclude that synchronous digging activity of many hatchlings during nest escape evolved not only to facilitate rapid nest emergence but also to reduce the energetic cost to individuals. PMID:27207954

  9. Generalized Jeans' Escape of Pick-Up Ions in Quasi-Linear Relaxation

    Science.gov (United States)

    Moore, T. E.; Khazanov, G. V.

    2011-01-01

    Jeans escape is a well-validated formulation of upper atmospheric escape that we have generalized to estimate plasma escape from ionospheres. It involves the computation of the parts of particle velocity space that are unbound by the gravitational potential at the exobase, followed by a calculation of the flux carried by such unbound particles as they escape from the potential well. To generalize this approach for ions, we superposed an electrostatic ambipolar potential and a centrifugal potential, for motions across and along a divergent magnetic field. We then considered how the presence of superthermal electrons, produced by precipitating auroral primary electrons, controls the ambipolar potential. We also showed that the centrifugal potential plays a small role in controlling the mass escape flux from the terrestrial ionosphere. We then applied the transverse ion velocity distribution produced when ions, picked up by supersonic (i.e., auroral) ionospheric convection, relax via quasi-linear diffusion, as estimated for cometary comas [1]. The results provide a theoretical basis for observed ion escape response to electromagnetic and kinetic energy sources. They also suggest that super-sonic but sub-Alfvenic flow, with ion pick-up, is a unique and important regime of ion-neutral coupling, in which plasma wave-particle interactions are driven by ion-neutral collisions at densities for which the collision frequency falls near or below the gyro-frequency. As another possible illustration of this process, the heliopause ribbon discovered by the IBEX mission involves interactions between the solar wind ions and the interstellar neutral gas, in a regime that may be analogous [2].

  10. Oxygen Pickup Ions at Mars: Model Comparisons with MAVEN Data and Implications for Oxygen Escape

    Science.gov (United States)

    Cravens, Tom; Rahmati, Ali; Larsen, Davin; Lillis, Rob; Connerney, Jack; Halekas, Jasper; Bougher, Stephen W.

    2015-04-01

    A major source of atmospheric escape on Mars is the dissociative recombination of O2+ in the ionosphere, which creates oxygen atoms with energies exceeding the escape energy. These atoms are the source of the hot oxygen exosphere of Mars, which extends to tens of Martian radii. Direct measurement of the distant oxygen exosphere, which is mainly populated with escaping neutral oxygen atoms, is difficult due to the very low densities at these distances. However, ionization of these atoms creates pickup ions that are accelerated by the solar wind convective electric field to high energies, allowing them to be measured by the SEP (Solar Energetic Particle) instrument onboard the MAVEN (Mars Atmosphere and Volatile EvolutioN) spacecraft.We modeled the hot oxygen at Mars and its interaction with the solar wind using Monte Carlo and test particle methods and using densities and temperatures from the MTGCM (Mars Thermospheric General Circulation Model). The distribution function of hot oxygen atoms at 300 km is calculated using a two-stream method, and the Liouville theorem extends this distribution for the gravitationally bound and escaping parts to high altitudes. We determined the O+ flux upstream of Mars as a function of energy, and separate it into parts due both the gravitationally bound and the escaping oxygen. Significant fluxes of O+ ions are predicted for energies greater than 60 keV and have been observed by the SEP instrument, even when MAVEN was several Martian radii away from the planet. These data-model comparisons will be presented and then interpreted in terms of the escape of oxygen from Mars.

  11. GSK-3β inhibition by lithium confers resistance to chemotherapy-induced apoptosis through the repression of CD95 (Fas/APO-1) expression

    International Nuclear Information System (INIS)

    Lithium exerts neuroprotective actions that involve the inhibition of glycogen synthase kinase-3β (GSK-3β). Otherwise, recent studies suggest that sustained GSK-3β inhibition is a hallmark of tumorigenesis. In this context, the present study was undertaken to examine whether lithium modulated cancer cell sensitivity to apoptosis induced by chemotherapy agents. We observed that, in different human cancer cell lines, lithium significantly reduced etoposide- and camptothecin-induced apoptosis. In HepG2 cells, lithium repressed drug induction of CD95 expression and clustering at the cell surface as well as caspase-8 activation. Lithium acted through deregulation of GSK-3β signaling since (1) it provoked a rapid and sustained phosphorylation of GSK-3β on the inhibitory serine 9 residue; (2) the GSK-3β inhibitor SB-415286 mimicked lithium effects by repressing drug-induced apoptosis and CD95 membrane expression; and (3) lithium promoted the disruption of nuclear GSK-3β/p53 complexes. Moreover, the overexpression of an inactivated GSK-3β mutant counteracted the stimulatory effects of etoposide and camptothecin on a luciferase reporter plasmid driven by a p53-responsive sequence from the CD95 gene. In conclusion, we provide the first evidence that lithium confers resistance to apoptosis in cancer cells through GSK-3β inhibition and subsequent repression of CD95 gene expression. Our study also highlights the concerted action of GSK-3β and p53 on CD95 gene expression

  12. Lorentz alpha orbit calculation in search of position suitable for escaping alpha particle diagnostics in ITER

    International Nuclear Information System (INIS)

    The Lorentz orbit code is developed to understand escaping alpha particle orbits and to contribute to the design of an escaping alpha particle probe in ITER. The code follows the full gyromotion of an alpha particle in ITER equilibrium, considering the toroidal field magnetic field ripple produced by the finite number of toroidal field coils as well as full three-dimensional first wall panels placed at the outboard side of the torus. It is shown that alpha particles that exist in the peripheral region and have banana orbits intersect the first wall placed at the outboard side on the lower plane. (author)

  13. Rate of escape of random walks on wreath products and related groups

    OpenAIRE

    Revelle, David

    2003-01-01

    This article examines the rate of escape for a random walk on $G\\wr \\Z$ and proves laws of the iterated logarithm for both the inner and outer radius of escape. The class of G for which these results hold includes finite, G as well as groups of the form $H\\wr \\Z$, so the construction can be iterated. Laws of the iterated logarithm are also found for random walk on Baumslag--Solitar groups and a discrete version of the Sol geometry.

  14. Ultra-fast escape of a deformable jet-propelled body

    OpenAIRE

    Weymouth, G. D.; Triantafyllou, M. S.

    2013-01-01

    In this work a cephalopod-like deformable body that fills an internal cavity with fluid and expels it to propel an escape manoeuvre, while undergoing a drastic external shape change through shrinking, is shown to employ viscous as well as mainly inviscid hydrodynamic mechanisms to power an impressively fast start. First, we show that recovery of added-mass energy enables a shrinking rocket in a dense inviscid flow to achieve greater escape speed than an identical rocket in a vacuum. Next, we ...

  15. Escape of a driven particle from a metastable state: A semiclassical approach.

    Science.gov (United States)

    Ghosh, Pradipta; Shit, Anindita; Chattopadhyay, Sudip; Chaudhuri, Jyotipratim Ray

    2010-06-28

    In this article we explore the dynamics of escape of a particle in the semiclassical regime by driving the particle externally. We demonstrate that under suitable approximations the semiclassical escape rate essentially assumes the structure of classical Kramers rate. Both internal (due to thermal bath) as well as external noises (due to driving) are being considered. The noises are stationary, Gaussian, and are characterized by arbitrary decaying memory kernel. Finally, we subject our formulation to rigorous numerical test under variedly changing conditions of the parameters. PMID:20590205

  16. Cubic Polynomial Maps with Periodic Critical Orbit, Part II: Escape Regions

    CERN Document Server

    Bonifant, Araceli; Milnor, John

    2009-01-01

    The parameter space $\\mathcal{S}_p$ for monic centered cubic polynomial maps with a marked critical point of period $p$ is a smooth affine algebraic curve whose genus increases rapidly with $p$. Each $\\mathcal{S}_p$ consists of a compact connectedness locus together with finitely many escape regions, each of which is biholomorphic to a punctured disk and is characterized by an essentially unique Puiseux series. This note will describe the topology of $\\mathcal{S}_p$, and of its smooth compactification, in terms of these escape regions. It concludes with a discussion of the real sub-locus of $\\mathcal{S}_p$.

  17. Assessment of mortality of Antarctic krill (Euphausia superba) escaping from a trawl

    DEFF Research Database (Denmark)

    Krafft, Bjørn A.; Krag, Ludvig Ahm

    2015-01-01

    The overall purpose of this study was to estimate the mortality of Antarctic krill (Euphausia superba) that escape from the most common mesh size used for codends (16mm) in the current commercial fishery. The experiment was carried out off the South Orkney Islands (60°35′S, 45°30′W) using a covered...... codend sampling technique for retaining escaped krill, which thereafter were observed in holding tanks to monitor their mortality rate. Our results suggest that krill with smaller body lengths suffered higher mortality. However, sampling depth, haul duration and catch accumulation as well as handling...

  18. The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

    OpenAIRE

    Ponich E.S.; Kruglova L.S.; Babushkin A.M.

    2015-01-01

    Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control...

  19. Spiders do not escape reproductive manipulations by Wolbachia

    Directory of Open Access Journals (Sweden)

    Hendrickx Frederik

    2011-01-01

    Full Text Available Abstract Background Maternally inherited bacteria that reside obligatorily or facultatively in arthropods can increase their prevalence in the population by altering their hosts' reproduction. Such reproductive manipulations have been reported from the major arthropod groups such as insects (in particular hymenopterans, butterflies, dipterans and beetles, crustaceans (isopods and mites. Despite the observation that endosymbiont bacteria are frequently encountered in spiders and that the sex ratio of particular spider species is strongly female biased, a direct relationship between bacterial infection and sex ratio variation has not yet been demonstrated for this arthropod order. Results Females of the dwarf spider Oedothorax gibbosus exhibit considerable variation in the sex ratio of their clutches and were infected with at least three different endosymbiont bacteria capable of altering host reproduction i.e. Wolbachia, Rickettsia and Cardinium. Breeding experiments show that sex ratio variation in this species is primarily maternally inherited and that removal of the bacteria by antibiotics restores an unbiased sex ratio. Moreover, clutches of females infected with Wolbachia were significantly female biased while uninfected females showed an even sex ratio. As female biased clutches were of significantly smaller size compared to non-distorted clutches, killing of male embryos appears to be the most likely manipulative effect. Conclusions This represents to our knowledge the first direct evidence that endosymbiont bacteria, and in particular Wolbachia, might induce sex ratio variation in spiders. These findings are pivotal to further understand the diversity of reproductive phenotypes observed in this arthropod order.

  20. Exosomes as a tumor immune escape mechanism: possible therapeutic implications

    Directory of Open Access Journals (Sweden)

    Hanley Harold H

    2008-07-01

    Full Text Available Abstract Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology

  1. Enhancing endosomal escape of transduced proteins by photochemical internalisation.

    Directory of Open Access Journals (Sweden)

    Kevin Mellert

    Full Text Available Induced internalisation of functional proteins into cultured cells has become an important aspect in a rising number of in vitro and in vivo assays. The endo-lysosomal entrapment of the transduced proteins remains the major problem in all transduction protocols. In this study we compared the efficiency, cytotoxicity and protein targeting of different commercially available transduction reagents by transducing a well-studied fluorescently labelled protein (Atto488-bovine serum albumin into cultured human sarcoma cells. The amount of internalised protein and toxicity differed between the different reagents, but the percentage of transduced cells was consistently high. Furthermore, in all protocols the signals of the transduced Atto488-BSA were predominantly punctual consistent with an endosomal localisation. To overcome the endosomal entrapment, the transduction protocols were combined with a photochemical internalisation (PCI treatment. Using this combination revealed that an endosomal disruption is highly effective in cell penetrating peptide (CPP mediated transduction, whereas lipid-mediated transductions lead to a lower signal spreading throughout the cytosol. No change in the signal distribution could be achieved in treatments using non-lipid polymers as a transduction reagent. Therefore, the combination of protein transduction protocols based on CPPs with the endosomolytic treatment PCI can facilitate protein transduction experiments in vitro.

  2. Avian Bornaviruses Escape Recognition by the Innate Immune System

    Directory of Open Access Journals (Sweden)

    Antje Reuter

    2010-04-01

    Full Text Available Like other pathogens that readily persist in animal hosts, members of the Bornaviridae family have evolved effective mechanisms to evade the innate immune response. The prototype of this virus family, Borna disease virus employs an unusual replication strategy that removes the triphosphates from the 5’ termini of the viral RNA genome. This strategy allows the virus to avoid activation of RIG-I and other innate immune response receptors in infected cells. Here we determined whether the newly discovered avian bornaviruses (ABV might use a similar strategy to evade the interferon response. We found that de novo infection of QM7 and CEC32 quail cells with two different ABV strains was efficiently inhibited by exogenous chicken IFN-α. IFN-α also reduced the viral load in QM7 and CEC32 cells persistently infected with both ABV strains, suggesting that ABV is highly sensitive to type I IFN. Although quail cells persistently infected with ABV contained high levels of viral RNA, the supernatants of infected cultures did not contain detectable levels of biologically active type I IFN. RNA from cells infected with ABV failed to induce IFN-β synthesis if transfected into human cells. Furthermore, genomic RNA of ABV was susceptible to 5’-monophosphate-specific RNase, suggesting that it lacks 5’-triphospates like BDV. These results indicate that bornaviruses of mammals and birds use similar strategies to evade the host immune response.

  3. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory; Korber, Bette M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  4. Diving through Membranes: Molecular Cunning to Enforce the Endosomal Escape of Antibody-Targeted Anti-Tumor Toxins

    Directory of Open Access Journals (Sweden)

    David J. Flavell

    2013-04-01

    Full Text Available Membranes are vital barriers by which cells control the flux of molecules and energy between their exterior and interior and also between their various intracellular compartments. While numerous transport systems exist for ions and small molecules, the cytosolic uptake of larger biological molecules and in particular antibody-targeted drugs, is a big challenge. Inducing leakage of the plasma membrane is unfavorable since the target cell specificity mediated by the antibody would likely be lost in this case. After binding and internalization, the antibody drug conjugates reach the endosomes. Thus, enforcing the endosomal escape of anti-tumor toxins without affecting the integrity of other cellular membranes is of paramount importance. Different strategies have been developed in the last decades to overcome endosomal accumulation and subsequent lysosomal degradation of targeted protein-based drugs. In this review we summarize the various efforts made to establish efficient techniques to disrupt the endosomal membrane barrier including the use of molecular ferries such as cell penetrating peptides or viral membrane fusion proteins, endosomal leakage inducing molecules such as saponins or monensin and physicochemical methods as represented by photochemical internalization.

  5. Self-awareness review Part 2: Changing or escaping the self

    OpenAIRE

    Morin, Alain

    2003-01-01

    When we become self-aware we see who we are and what we would like to be. What do we do? Do we change who we are? Or do we escape self-awareness by watching TV—or worst, by drinking alcohol, doing drugs, or committing suicide?

  6. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

    International Nuclear Information System (INIS)

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects

  7. Panic escape polyethism in worker and soldier Coptotermes formosanus (Isoptera: Rhinotermitidae).

    Science.gov (United States)

    Wang, Cai; Henderson, Gregg; Gautam, Bal K; Chen, Jie; Bhatta, Dependra

    2016-04-01

    Termites were the first animal to form societies. Two hundred million years of evolution provide for a multitude of innate social behaviors that can be experimentally dissected. These fine-tuned patterns of behavior are especially interesting when observing group decision making in the panic mode. In this study, we examined behavioral patterns of termites under panic conditions to gain insight into how an escape flow self-organizes. One hundred worker and 10 soldier Coptotermes formosanus were released into agar plates. After a disturbance was created most workers followed each other and ran along the wall of dishes, thus forming a unidirectional escape flow, whereas soldiers showed a significantly higher frequency of moving to the center of the arena or on periphery of the escape flow as compared to workers. Agonistic behavior was usually observed as soldiers moved to center or periphery. This is the first report on the behavioral repertoire of termites when panicked, with details on the behavioral polymorphism of workers and soldiers during an escape. PMID:25630524

  8. Using Stochastic Effciency Analysis To Factor Distribution Of Weed Escapes Into Weed Management Decisions

    Science.gov (United States)

    Weeds in patches may be more easily managed than the same number of weeds spread throughout the field. We explored choosing weed management strategies based on both net return and the distribution of weed escapes within a field. Expected net returns with several different postemergence herbicides of...

  9. Monoclonal antibody-escape variant of dengue virus serotype 1: Genetic composition and envelope protein expression.

    Science.gov (United States)

    Chem, Y K; Chua, K B; Malik, Y; Voon, K

    2015-06-01

    Monoclonal antibody-escape variant of dengue virus type 1 (MabEV DEN-1) was discovered and isolated in an outbreak of dengue in Klang Valley, Malaysia from December 2004 to March 2005. This study was done to investigate whether DEN152 (an isolate of MabEV DEN-1) is a product of recombination event or not. In addition, the non-synonymous mutations that correlate with the monoclonal antibody-escape variant were determined in this study. The genomes of DEN152 and two new DEN-1 isolates, DENB04 and DENK154 were completely sequenced, aligned, and compared. Phylogenetic tree was plotted and the recombination event on DEN152 was investigated. DEN152 is sub-grouped under genotype I and is closely related genetically to a DEN-1 isolated in Japan in 2004. DEN152 is not a recombinant product of any parental strains. Four amino acid substitutions were unique only to DEN 152. These amino acid substitutions were (Ser)[326](Leu), (Ser)[340](Leu) at the deduced E protein, (Ile)[250](Thr) at NS1 protein, and (Thr)[41](Ser) at NS5 protein. Thus, DEN152 is an isolate of the emerging monoclonal antibody-escape variant DEN-1 that escaped diagnostic laboratory detection. PMID:26691263

  10. Tumor cell survival and immune escape mechanisms in classical Hodgkin lymphoma

    NARCIS (Netherlands)

    Liang, Zheng

    2015-01-01

    Tumor cell survival and immune escape mechanisms in classical Hodgkin lymphoma The nature of classical Hodgkin lymphoma (HL), a minority of tumor cells in a reactive background and loss of B cell phenotype, decides its dependence on the microenvironment for signals to contribute to survival and prol

  11. Feedback-regulated escape of LyC photons from mini-haloes during reionisation

    CERN Document Server

    Kimm, Taysun; Haehnelt, Martin; Rosdahl, Joakim; Devriendt, Julien; Slyz, Adrianne

    2016-01-01

    Reionisation in the early Universe is likely driven by dwarf galaxies. Using cosmological, zoom-in, radiation-hydrodynamic simulations, we study the escape of Lyman continuum (LyC) photons from mini-haloes with $M_{\\rm halo} \\le 10^8\\,M_\\odot$. Our simulations include a new thermo-turbulent star formation model, non-equilibrium chemistry, and relevant stellar feedback processes (photoionisation by young massive stars, radiation pressure, and mechanical supernova explosions). We find that the photon number-weighted mean escape fraction in mini-haloes is higher ($\\sim20$-$40\\%$) than that in atomic-cooling haloes, although the instantaneous fraction in individual haloes varies significantly. The escape fraction from Pop III stars is found to be significant ($\\ge10\\%$) only when the mass is greater than $\\sim$100\\,\\msun. Because star formation is stochastic and dominated by a few gas clumps, the escape fraction is generally determined by radiation feedback (heating due to photo-ionisation), rather than supernova...

  12. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

    Energy Technology Data Exchange (ETDEWEB)

    Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.; Krylov, Petr S. [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation); Ilyushina, Natalia A., E-mail: Natalia.Ilyushina@fda.hhs.gov [FDA CDER, 29 Lincoln Drive, Bethesda, MD 20892 (United States); Kaverin, Nikolai V., E-mail: nik.kaverin@gmail.com [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation)

    2013-12-15

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects.

  13. Function-Based Modification of Check-In/Check-Out to Influence Escape-Maintained Behavior

    Science.gov (United States)

    Kilgus, Stephen P.; Fallon, Lindsay M.; Feinberg, Adam B.

    2016-01-01

    Prior research has suggested Check-In/Check-Out (CICO) effectiveness is linked to the function of problem behavior. Though effective for students whose misbehavior occurs to gain attention, findings are equivocal for behavior that occurs to escape academic tasks. The purpose of this study was to therefore evaluate a modification to CICO, wherein…

  14. The dynamics of a rapidly escaping atmosphere - Applications to the evolution of earth and Venus

    Science.gov (United States)

    Watson, A. J.; Donahue, T. M.; Walker, J. C. G.

    1981-01-01

    A simple model for the rapid escape of a hydrogen thermosphere is presented in order to establish the energy-limited flux of escaping particles. The model assumes that the atmosphere is tightly bound by gravity at the lower boundary, that all the EUV is absorbed in a narrow region where the optical depth is unity, and that the main source of heating is solar EUV. The flux is limited by the amount of EUV energy absorbed, which is in turn controlled by the radial extent of the thermosphere. It is found that, regardless of the amount of hydrogen in the thermosphere, the low temperatures which accompany rapid escape limit its extent and thus constrain the flux. The results are applied to the earth and Venus, showing that the escape of hydrogen from these planets would have been energy-limiting if their primordial atmospheres contained total hydrogen mixing ratios exceeding only a few percent. This conclusion places a constraint on the theory of the origin and evolution of the planets.

  15. Low-energy gamma-ray spectroscopy using an X-ray-escape gated proportional counter

    DEFF Research Database (Denmark)

    Gregers Hansen, P.; Nielsen, H.L.; Williams, E.T.; Wilsky, K.

    1965-01-01

    The utility of a gas-filled proportional counter in low-energy γ spectroscopy is greatly increased if it is operated in coincidence with an escaping fluorescent X-ray. An apparatus, having an efficiency greater than 10% of singles, is described and several examples are given. An efficiency curve is...

  16. Revealing the escape mechanism of three-dimensional orbits in a tidally limited star cluster

    CERN Document Server

    Zotos, Euaggelos E

    2014-01-01

    The aim of this work is to explore the escape process of three-dimensional orbits in a star cluster rotating around its parent galaxy in a circular orbit. The gravitational field of the cluster is represented by a smooth, spherically symmetric Plummer potential, while the tidal approximation was used to model the steady tidal field of the galaxy. We conduct a thorough numerical analysis distinguishing between regular and chaotic orbits as well as between trapped and escaping orbits, considering only unbounded motion for several energy levels. It is of particular interest to locate the escape basins towards the two exit channels and relate them with the corresponding escape times of the orbits. For this purpose, we split our investigation into three cases depending on the initial value of the $z$ coordinate which was used for launching the stars. The most noticeable finding is that the majority of stars initiated very close to the primary $(x,y)$ plane move in chaotic orbits and they remain trapped for vast ti...

  17. The decline of the European eel Anguilla anguilla: quantifying and managing escapement to support conservation.

    Science.gov (United States)

    Bilotta, G S; Sibley, P; Hateley, J; Don, A

    2011-01-01

    A method was developed to quantify the number and biomass of European eels Anguilla anguilla escaping to the ocean for breeding. The non-intrusive method, involving a fixed-position, high-frequency multi-beam sonar, permitted constant surveillance of A. anguilla movements throughout their 5 month escapement season (July to December). During this period, >1000 individuals were monitored escaping to the Atlantic Ocean from their freshwater habitat in the River Huntspill study site (Somerset, U.K.). The total length of each fish was measured using the sonar software. These measurements were then converted to an estimate of mass using a length:mass regression relationship derived from historical fyke-net data from this site, comprising c. 500 A. anguilla length:mass measurements collected over a 10 year period. The net biomass of escapement from the study site was equivalent to c. 6 kg ha⁻¹ year⁻¹, lower than the present European target which would require at least 7 kg ha⁻¹ year⁻¹ from this habitat. These findings demonstrate the capabilities of this monitoring technique and its usefulness both as a tool to assess the compliance with conservation targets and as a tool to evaluate the success of conservation measures for elusive aquatic species such as A. anguilla. PMID:21235544

  18. Escaping the Poverty Trap in Latin America: The Role of Family Factors

    OpenAIRE

    2001-01-01

    Much like an inherited trait, poverty trends to pass from parent to child. How prevalent is this "curse of the poor," why do some escape it, and how can we help improve the odds? This study sets out to gauge the extent of this "Intergenerational transmiss

  19. SUSCEPTIBILITY TO GLYPHOSATE OF WEED ESCAPES IN GLYPHOSATE-TOLERANT SOYBEAN

    Science.gov (United States)

    Plots of glyphosate-tolerant soybeans at twelve locations in five states were monitored for weed escapes. Seeds were collected from each of these sites in the glyphosate and non-treated weedy check plots. These seeds were planted and grown in a greenhouse and then sprayed one time with 10% of a stan...

  20. Hydrodynamics of C-Start Escape Responses of Fish as Studied with Simple Physical Models.

    Science.gov (United States)

    Witt, William C; Wen, Li; Lauder, George V

    2015-10-01

    One of the most-studied unsteady locomotor behaviors exhibited by fishes is the c-start escape response. Although the kinematics of these responses have been studied extensively and two well-defined kinematic stages have been documented, only a few studies have focused on hydrodynamic patterns generated by fishes executing escape behaviors. Previous work has shown that escape responses by bluegill sunfish generate three distinct vortex rings, each with central orthogonal jet flows, and here we extend this conclusion to two other species: stickleback and mosquitofish. Jet #1 is formed by the tail during Stage 1, and moves in the same direction as Stage-2 movement of the fish, thereby reducing final escape-velocity but also rotating the fish. Jet #2, in contrast, moves approximately opposite to the final direction of the fish's motion and contains the bulk of the total fluid-momentum powering the escape response. Jet #3 forms during Stage 2 in the mid-body region and moves in a direction approximately perpendicular to jets 1 and 2, across the direction of movement of the body. In this study, we used a mechanical controller to impulsively move passively flexible plastic panels of three different stiffnesses in heave, pitch, and heave + pitch motions to study the effects of stiffness on unsteady hydrodynamics of escape. We were able to produce kinematics very similar to those of fish c-starts and also to reproduce the 3-jet hydrodynamic pattern of the c-start using a panel of medium flexural stiffness and the combined heave + pitch motion. This medium-stiffness panel matched the measured stiffness of the near-tail region of fish bodies. This motion also produced positive power when the panel straightened during stage 2 of the escape response. More flexible and stiffer panels resulted in non-biological kinematics and patterns of flow for all motions. The use of simple flexible models with a mechanical controller and program of fish-like motion is a promising approach

  1. From Rio to Rio: a global carbon price signal to escape the great climate inconsistency

    International Nuclear Information System (INIS)

    Two decades after the 1992 Rio Conference, we must admit to collective failure in combating human-induced climate change. The problem is not that no efforts have been undertaken, but that these efforts have just not been enough. We cannot escape serious climate disruption - which, to some extent, has already begun - if we keep going down that road. We must change direction, and we must move quickly. To this end, we call in this paper for a fine-tuning of the international negotiations on climate. We propose refocusing these international efforts on negotiating a global carbon price signal, harmonized in principle but flexible in practice, instead of doggedly spending the next few years attempting to convince countries to accept stricter national targets for quantitative reduction of their greenhouse gas (GHG) emissions. We cannot afford to spend the next few years missing the wrong targets. Simply put, we must move away, collectively, from an ineffective logic of constraint to a pragmatic logic of price incentives. The December 2011 Durban Conference proved, once again, that the 'to each their own target' approach does not work. We must instead adopt a 'one price signal for all' strategy. If there were a single reason to improve the current mitigation logic, it would be this evident fact: developing countries, which now account for 60% of emissions worldwide, cannot accept what they perceive as an obstacle to their economic development, when developed countries have been able to get rich on unlimited use of fossil fuel energy. Indeed, in the foreseeable future, emerging economies, particularly China and India with Gross Domestic Product (GDP) annual growth rates of between 8% and 10%, will not accept absolute reduction targets for GHG emissions. On the other hand, these countries might be more open to the idea of a flexible levy of a price per tonne of carbon dioxide, a price from which they would derive revenues, and which their economic

  2. Escapism among players of MMORPGs--conceptual clarification, its relation to mental health factors, and development of a new measure.

    Science.gov (United States)

    Hagström, David; Kaldo, Viktor

    2014-01-01

    Previous studies show that the concept of escapism needs to be clarified and that its relation to problematic online gaming and other factors needs further examination. This study uses well-established, basic learning theory to clarify the concept of escapism, and examines its relation to problematic gaming, psychological distress, and satisfaction with life among players of massively multiplayer online role-playing games (MMORPGs). MMORPG players (n=201) answered an online questionnaire where these factors were measured and correlated with a previously developed scale on motivation to play (MTPI), including extra items to cover positive and negative aspects of escapism. Factor analysis and construct validation show that positive aspects of escapism are theoretically and empirically unstable and that escapism is best clarified as purely "negative escapism," corresponding to playing being negatively reinforced as a way of avoiding everyday hassles and distress. Negative escapism had a stronger relationship to symptoms of Internet addiction, psychological distress, and life satisfaction than other variables and other more positive motivations to play. Future studies should use the revised subscale for escapism (in the MTPI-R) presented in the present study, for example when screening for Internet addiction. PMID:24003967

  3. Escape fraction of ionizing photons during reionization: Effects due to supernova feedback and runaway ob stars

    International Nuclear Information System (INIS)

    The fraction of hydrogen ionizing photons escaping from galaxies into the intergalactic medium is a critical ingredient in the theory of reionization. We use two zoomed-in, high-resolution (4 pc), cosmological radiation hydrodynamic simulations with adaptive mesh refinement to investigate the impact of two physical mechanisms (supernova, SN, feedback, and runaway OB stars) on the escape fraction (f esc) at the epoch of reionization (z ≥ 7). We implement a new, physically motivated SN feedback model that can approximate the Sedov solutions at all (from the free expansion to snowplow) stages. We find that there is a significant time delay of about ten million years between the peak of star formation and that of escape fraction, due to the time required for the build-up and subsequent destruction of the star-forming cloud by SN feedback. Consequently, the photon number-weighted mean escape fraction for dwarf galaxies in halos of mass 108-1010.5 M ☉ is found to be 〈fesc〉∼11%, although instantaneous values of f esc > 20% are common when star formation is strongly modulated by the SN explosions. We find that the inclusion of runaway OB stars increases the mean escape fraction by 22% to 〈fesc〉∼14%. As SNe resulting from runaway OB stars tend to occur in less dense environments, the feedback effect is enhanced and star formation is further suppressed in halos with Mvir≳109 M⊙ in the simulation with runaway OB stars compared with the model without them. While both our models produce enough ionizing photons to maintain a fully ionized universe at z ≤ 7 as observed, a still higher amount of ionizing photons at z ≥ 9 appears necessary to accommodate the high observed electron optical depth inferred from cosmic microwave background observations.

  4. Oxygen escape from the Earth during geomagnetic reversals: Implications to mass extinction

    Science.gov (United States)

    Wei, Yong; Pu, Zuyin; Zong, Qiugang; Wan, Weixing; Ren, Zhipeng; Fraenz, Markus; Dubinin, Eduard; Tian, Feng; Shi, Quanqi; Fu, Suiyan; Hong, Minghua

    2014-05-01

    The evolution of life is affected by variations of atmospheric oxygen level and geomagnetic field intensity. Oxygen can escape into interplanetary space as ions after gaining momentum from solar wind, but Earth's strong dipole field reduces the momentum transfer efficiency and the ion outflow rate, except for the time of geomagnetic polarity reversals when the field is significantly weakened in strength and becomes Mars-like in morphology. The newest databases available for the Phanerozoic era illustrate that the reversal rate increased and the atmospheric oxygen level decreased when the marine diversity showed a gradual pattern of mass extinctions lasting millions of years. We propose that accumulated oxygen escape during an interval of increased reversal rate could have led to the catastrophic drop of oxygen level, which is known to be a cause of mass extinction. We simulated the oxygen ion escape rate for the Triassic-Jurassic event, using a modified Martian ion escape model with an input of quiet solar wind inferred from Sun-like stars. The results show that geomagnetic reversal could enhance the oxygen escape rate by 3-4 orders only if the magnetic field was extremely weak, even without consideration of space weather effects. This suggests that our hypothesis could be a possible explanation of a correlation between geomagnetic reversals and mass extinction. Therefore, if this causal relation indeed exists, it should be a "many-to-one" scenario rather the previously considered "one-to-one", and planetary magnetic field should be much more important than previously thought for planetary habitability.

  5. Changing the habitat: the evolution of intercorrelated traits to escape from predators.

    Science.gov (United States)

    Mikolajewski, D J; Scharnweber, K; Jiang, B; Leicht, S; Mauersberger, R; Johansson, F

    2016-07-01

    Burst escape speed is an effective and widely used behaviour for evading predators, with burst escape speed relying on several different morphological features. However, we know little about how behavioural and underlying morphological attributes change in concert as a response to changes in selective predation regime. We studied intercorrelated trait differentiation of body shape and burst-swim-mediating morphology in response to a habitat shift-related reduction in burst escape speed using larvae of the dragonfly genus Leucorrhinia. Species in this genus underwent a well-known habitat shift from predatory fish lakes (fish lakes) to predatory fish-free lakes dominated by large predatory dragonflies (dragonfly lakes) accompanied by relaxed selection on escape burst speed. Results revealed that species from fish lakes that possess faster burst speed have evolved a suite of functionally intercorrelated traits, expressing a wider abdomen, a higher abdominal muscles mass and a larger branchial chamber compared with species from dragonfly lakes. In contrast, populations within species did not show significant differences in muscle mass and branchial chamber size between lake types in three of the species. High multicollinearity among variables suggests that traits have evolved in concert rather than independently when Leucorrhinia shifted from fish lakes to dragonfly lakes. Thus, relaxed selection on burst escape speed in dragonfly-lake species resulted in a correlated reduction of abdominal muscles and a smaller branchial chamber, likely to save production and/or maintenance costs. Our results highlight the importance of studying integrated behavioural and morphological traits to fully understand the evolution of complex phenotypes. PMID:27062155

  6. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States.

    Directory of Open Access Journals (Sweden)

    Angela B Brueggemann

    2007-11-01

    Full Text Available The heptavalent pneumococcal conjugate vaccine (PCV7 was introduced in the United States (US in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990, but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny, recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.

  7. Inspired by nonenveloped viruses escaping from endo-lysosomes: a pH-sensitive polyurethane micelle for effective intracellular trafficking

    Science.gov (United States)

    Song, Nijia; Zhou, Lijuan; Li, Jiehua; Pan, Zhicheng; He, Xueling; Tan, Hong; Wan, Xinyuan; Li, Jianshu; Ran, Rong; Fu, Qiang

    2016-03-01

    A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo-lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH-sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core exposure, resulting from the detachment of the hydrophilic polyethylene glycol (PEG) shell, are similar to the behavior of a nonenveloped virus when trapped in acidic endo-lysosomes. Moreover, the degradation mechanism was verified by gel permeation chromatography (GPC). The endo-lysosomal membrane rupture induced by these transformed micelles is clearly observed by transmission electron microscopy. Consequently, excellent antitumor activity is confirmed both in vitro and in vivo. The results verify that the pHPM could be a promising new drug delivery tool for the treatment of cancer and other diseases.A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo-lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH-sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core

  8. Modelling rip current flow and bather escape strategies across a transverse bar and rip channel morphology

    Science.gov (United States)

    McCarroll, R. Jak; Castelle, Bruno; Brander, Robert W.; Scott, Timothy

    2015-10-01

    Rip currents are a hazard to bathers on surf beaches worldwide, yet due to logistical and ethical concerns there has been minimal examination of how bathers caught in them should attempt to escape. This study presents the first numerical model of simulated bathers escaping from a rip current. An understanding of the underlying coastal geomorphology and hydrodynamics form a critical basis for the model, with the intention that outcomes of the model should be evaluated from a physical science perspective. Field observations of a transverse bar rip channel were used as model inputs. Escape simulations were performed with moderate energy (Hs ≈ 1 m), oblique offshore wave forcing, used to generate two non-stationary, asymmetric flow fields (dominant surfzone exits and dominant recirculation). The model treats bathers as particles that move with the underlying flow, with an additional swimming velocity added, iterating until a safety condition, based on depth and current speed, is satisfied or until a maximum time limit is reached. Simulations compared the strategies of "stay afloat" and various fixed swim directions, using two bather heights and four swim speeds (up to 0.4 m/s). The overall optimal escape strategy was to swim parallel in the direction of alongshore flow. Time to safety was less for: (i) recirculating flow; (ii) taller bathers; and (iii) greater swim speeds. Across all simulations, 44% of "floaters" reached safety within 10 min, while 80% of slow swimmers (0.2 m/s) succeeded in the same time interval. This suggests that slow sustainable swimming may be a preferable escape action to floating. Optimal swim direction varied with start location, from onshore (near the shoreline), parallel to shore (mid-rip channel) and diagonally onshore (outer rip channel). At lower swim speeds, the optimal swim direction had greater dependence on the underlying flow field, as opposed to distance to safety, therefore choice of direction is more complex for slower swimmers

  9. HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins.

    Directory of Open Access Journals (Sweden)

    Zabrina L Brumme

    Full Text Available BACKGROUND: Despite the extensive genetic diversity of HIV-1, viral evolution in response to immune selective pressures follows broadly predictable mutational patterns. Sites and pathways of Human Leukocyte-Antigen (HLA-associated polymorphisms in HIV-1 have been identified through the analysis of population-level data, but the full extent of immune escape pathways remains incompletely characterized. Here, in the largest analysis of HIV-1 subtype B sequences undertaken to date, we identify HLA-associated polymorphisms in the three HIV-1 proteins most commonly considered in cellular-based vaccine strategies. Results are organized into protein-wide escape maps illustrating the sites and pathways of HLA-driven viral evolution. METHODOLOGY/PRINCIPAL FINDINGS: HLA-associated polymorphisms were identified in HIV-1 Gag, Pol and Nef in a multicenter cohort of >1500 chronically subtype-B infected, treatment-naïve individuals from established cohorts in Canada, the USA and Western Australia. At q< or =0.05, 282 codons commonly mutating under HLA-associated immune pressures were identified in these three proteins. The greatest density of associations was observed in Nef (where close to 40% of codons exhibited a significant HLA association, followed by Gag then Pol (where approximately 15-20% of codons exhibited HLA associations, confirming the extensive impact of immune selection on HIV evolution and diversity. Analysis of HIV codon covariation patterns identified over 2000 codon-codon interactions at q< or =0.05, illustrating the dense and complex networks of linked escape and secondary/compensatory mutations. CONCLUSIONS/SIGNIFICANCE: The immune escape maps and associated data are intended to serve as a user-friendly guide to the locations of common escape mutations and covarying codons in HIV-1 subtype B, and as a resource facilitating the systematic identification and classification of immune escape mutations. These resources should facilitate

  10. Lyman Continuum Escape Fraction of Star-forming Dwarf Galaxies at z ˜ 1

    Science.gov (United States)

    Rutkowski, Michael J.; Scarlata, Claudia; Haardt, Francesco; Siana, Brian; Henry, Alaina; Rafelski, Marc; Hayes, Matthew; Salvato, Mara; Pahl, Anthony J.; Mehta, Vihang; Beck, Melanie; Malkan, Matthew; Teplitz, Harry I.

    2016-03-01

    To date, no direct detection of Lyman continuum emission has been measured for intermediate-redshift (z˜ 1) star-forming galaxies. We combine Hubble Space Telescope grism spectroscopy with GALEX UV and ground-based optical imaging to extend the search for escaping Lyman continuum to a large (˜600) sample of z˜ 1 low-mass ({log}(\\bar{M}) ≃ 9.3{M}⊙ ), moderately star-forming (\\bar{{{\\Psi }}} ≲ 10{M}⊙ yr-1) galaxies selected initially on Hα emission. The characteristic escape fraction of LyC from star-forming galaxies (SFGs) that populate this parameter space remains weakly constrained by previous surveys, but these faint (sub-L⋆) SFGs are assumed to play a significant role in the reionization of neutral hydrogen in the intergalactic medium (IGM) at high redshift z\\gt 6. We do not make an unambiguous detection of escaping LyC radiation from this z˜ 1 sample, individual non-detections to constrain the absolute Lyman continuum escape fraction, {f}{esc} \\lt 2.1% (3σ). We measure an upper limit of {f}{esc} \\lt 9.6% from a sample of SFGs selected on high Hα equivalent width (EW \\gt 200 {{\\mathringA }}), which are thought to be close analogs of high redshift sources of reionization. For reference, we also present an emissivity-weighted escape fraction that is useful for measuring the general contribution SFGs to the ionizing UV background. In the discussion, we consider the implications of these intermediate redshift constraints for the reionization of hydrogen in the IGM at high (z\\gt 6) redshift. If we assume our z˜ 1 SFGs, for which we measure this emissivity-weighted {f}{esc}, are analogs to the high redshift sources of reionization, we find it is difficult to reconcile reionization by faint ({M}{UV}≲ -13) SFGs with a low escape fraction ({f}{esc} \\lt 3%), with constraints from independent high redshift observations. If {f}{esc} evolves with redshift, reionization by SFGs may be consistent with observations from Planck.

  11. Elliptic Anisotropy $v_2$ May Be Dominated by Particle Escape instead of Hydrodynamic Flow

    CERN Document Server

    Lin, Zi-Wei; Edmonds, Terrence; Liu, Feng; Molnar, Denes; Wang, Fuqiang

    2015-01-01

    It is commonly believed that azimuthal anisotropies in relativistic heavy ion collisions are generated by hydrodynamic evolution of the strongly interacting quark-gluon plasma. Here we use transport models to study how azimuthal anisotropies depend on the number of collisions that each parton suffers. We find that the majority of $v_2$ comes from the anisotropic escape of partons, not from the parton collective flow, for semi-central Au+Au collisions at 200A GeV. As expected, the fraction of $v_2$ from the anisotropic particle escape is even higher for smaller systems such as d+Au. Our transport model results also confirm that azimuthal anisotropies would be dominated by hydrodynamic flow at unrealistically-high parton cross sections. Our finding thus naturally explains the similarity of azimuthal anisotropies in small and large systems; however, it presents a challenge to the paradigm of anisotropic flow.

  12. Simulating the escaping atmospheres of hot gas planets in the solar neighborhood

    CERN Document Server

    Salz, M; Schneider, P C; Schmitt, J H M M

    2016-01-01

    Absorption of high-energy radiation in planetary thermospheres is believed to lead to the formation of planetary winds. The resulting mass-loss rates can affect the evolution, particularly of small gas planets. We present 1D, spherically symmetric hydrodynamic simulations of the escaping atmospheres of 18 hot gas planets in the solar neighborhood. Our sample only includes strongly irradiated planets, whose expanded atmospheres may be detectable via transit spectroscopy. The simulations were performed with the PLUTO-CLOUDY interface, which couples a detailed photoionization and plasma simulation code with a general MHD code. We study the thermospheric escape and derive improved estimates for the planetary mass-loss rates. Our simulations reproduce the temperature-pressure profile measured via sodium D absorption in HD 189733 b, but show unexplained differences in the case of HD 209458 b. In contrast to general assumptions, we find that the gravitationally more tightly bound thermospheres of massive and compact...

  13. Escape time from potential wells of strongly nonlinear oscillators with slowly varying parameters

    Directory of Open Access Journals (Sweden)

    Cai Jianping

    2005-01-01

    Full Text Available The effect of negative damping to an oscillatory system is to force the amplitude to increase gradually and the motion will be out of the potential well of the oscillatory system eventually. In order to deduce the escape time from the potential well of quadratic or cubic nonlinear oscillator, the multiple scales method is firstly used to obtain the asymptotic solutions of strongly nonlinear oscillators with slowly varying parameters, and secondly the character of modulus of Jacobian elliptic function is applied to derive the equations governing the escape time. The approximate potential method, instead of Taylor series expansion, is used to approximate the potential of an oscillation system such that the asymptotic solution can be expressed in terms of Jacobian elliptic function. Numerical examples verify the efficiency of the present method.

  14. Expanding the locomotion repertoire of the eigenfish: Study of wildtype zebrafish larva escape response

    Science.gov (United States)

    Benitez-Jones, Maria; Girdhar, Kiran; Chemla, Yann; Gruebele, Martin

    2014-03-01

    The zebrafish larva is a thoroughly studied and an extensively used model for behavioral and biomedical research. The Zebrafish Laboratory at the University of Illinois at Urbana-Champaign has applied a mathematical method to describe quantitatively the larva's swimming behavior. With this method, the 98% of the larva's free-swimming behavior is described by its simplifiedeigen-fish model, which is a linear combination of its three characteristic components, or three eigen-modes. This presentation focuses on the quantification of a different swimming behavior called escape response in wildtype (WT) zebrafish larvae. Although more data is required before assuming certainty in our results, the escape response of the WT was also described up to 98% by three eigen-modes. This REU program is supported by NSF Grant PHY-1062690.

  15. Deterministic escape dynamics of two-dimensional coupled nonlinear oscillator chains.

    Science.gov (United States)

    Fugmann, S; Hennig, D; Schimansky-Geier, L; Hänggi, P

    2008-06-01

    We consider the deterministic escape dynamics of a chain of coupled oscillators under microcanonical conditions from a metastable state over a cubic potential barrier. The underlying dynamics is conservative and noise free. We introduce a two-dimensional chain model and assume that neighboring units are coupled by Morse springs. It is found that, starting from a homogeneous lattice state, due to the nonlinearity of the external potential the system self-promotes an instability of its initial preparation and initiates complex lattice dynamics leading to the formation of localized large amplitude breathers, evolving in the direction of barrier crossing, accompanied by global oscillations of the chain transverse to the barrier. A few chain units accumulate locally sufficient energy to cross the barrier. Eventually the metastable state is left and either these particles dissociate or pull the remaining chain over the barrier. We show this escape for both linear rodlike and coil-like configurations of the chain in two dimensions. PMID:18643245

  16. Hepatitis B surface antigen escape mutations: Indications for initiation of antiviral therapy revisited.

    Science.gov (United States)

    Leong, Jennifer; Lin, Derek; Nguyen, Mindie H

    2016-03-16

    Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. Herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection. PMID:26989671

  17. Escape process in systems characterized by stable noises and position-dependent resting times.

    Science.gov (United States)

    Srokowski, Tomasz

    2016-06-01

    Stochastic systems characterized by a random driving in a form of the general stable noise are considered. The particle experiences long rests due to the traps the density of which is position dependent and obeys a power-law form attributed to the underlying self-similar structure. Both the one- and two-dimensional cases are analyzed. The random walk description involves a position-dependent waiting time distribution. On the other hand, the stochastic dynamics is formulated in terms of the subordination technique where the random time generator is position dependent. The first passage time problem is addressed by evaluating a first passage time density distribution and an escape rate. The influence of the medium nonhomogeneity on those quantities is demonstrated; moreover, the dependence of the escape rate on the stability index and the memory parameter is evaluated. Results indicate essential differences between the Gaussian case and the case involving Lévy flights. PMID:27415243

  18. Escape Kinetics of Self-Propelled Janus Particles from a Cavity: Numerical Simulations

    CERN Document Server

    Ghosh, Pulak Kumar

    2014-01-01

    We numerically investigate the escape kinetics of elliptic Janus particles from narrow two-dimensional cavities with reflecting walls. The self-propulsion velocity of the Janus particle is directed along either their major (prolate) or minor axis (oblate). We show that the mean exit time is very sensitive to the cavity geometry, particle shape and self-propulsion strength. The mean exit time is found to be a minimum when the self-propulsion length is equal to the cavity size. We also find the optimum mean escape time as a function of the self-propulsion velocity, translational diffusion, and particle shape. Thus, effective transport control mechanisms for Janus particles in a channel can be implemented.

  19. Anisotropic parton escape is the dominant source of azimuthal anisotropy from A Multi-Phase Transport

    CERN Document Server

    He, Liang; Lin, Zi-Wei; Liu, Feng; Molnar, Denes; Wang, Fuqiang

    2015-01-01

    We trace the development of azimuthal anisotropy ($v_n$) in A Multi-Phase Transport (AMPT) model using parton-parton collision history. The parton $v_n$ is studied as a function of the number of collisions of each parton in Au+Au and d+Au collisions at $\\sqrt{S_{NN}}$=200~GeV. It is found that the majority of $v_n$ comes from the anisotropic escape probability of partons, with no fundamental difference at low and high transverse momenta. The contribution to $v_n$ from the parton collective flow appears small; however, it is this small anisotropy from the collective flow, not that from the anisotropic escape probability, that is most relevant for medium properties in heavy ion collisions.

  20. Calculation of the escape probabilities of Fe ⅹⅦ resonance lines for the Voigt profile

    Institute of Scientific and Technical Information of China (English)

    Jian HE; Qing-guo ZHANG

    2008-01-01

    Using the Voigt profile we obtained, we cal-culate the escape probabilities of Fe ⅹⅦ resonance lines at 15.02, 13.28, 12.12, 11.13, 11.02 and 10.12 A for op-tically thick plasma, both for slab and cylindrical ge-ometry. The oscillator strength, the number density of the absorbing atoms in the ground state, and the optical depth in the line center are discussed in this calculation. Results show that the escape probabilities for the slab geometry are larger than that for the cylindrical geom-etry. This calculation is useful for the study of the Fe ⅹⅦ resonance lines.

  1. Transcapillary escape rate of albumin in hypertensive patients with type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Nørgaard, K; Jensen, T; Feldt-Rasmussen, B

    1993-01-01

    Diabetic patients with elevated urinary albumin excretion rate (incipient or clinical nephropathy) also have an increased transcapillary escape rate of albumin. This study was designed to clarify whether this is caused by a general vascular dysfunction or by elevated systemic blood pressure. The...... systemic blood pressure and the transcapillary escape rate of albumin were measured in the following groups after 4 weeks without antihypertensive treatment: Group 1--eleven healthy control subjects. Group 2--ten Type 1 (insulin-dependent) diabetic patients with incipient nephropathy (urinary albumin...... excretion rate: 30-300 mg/24 h) and normal blood pressure. Group 3--eleven non-diabetic patients with essential hypertension. Group 4--nine Type 1 diabetic patients with hypertension but normal urinary albumin excretion (< 30 mg/24 h). Group 5--eleven Type 1 diabetic patients with nephropathy (urinary...

  2. Simulación mediante APPLETS de Java de Sistemas Dinámicos con Escape

    OpenAIRE

    Andrés Sánchez, Pablo

    2010-01-01

    Proyecto Fin de Carrera leído en la Universidad Rey Juan Carlos en el curso académico 2009/2010. Tutores del Proyecto: Jesús M. Seoane Sepúlveda e Inés Pérez Mariño En este documento se va describir el comportamiento de tres sistemas físicos que pueden presentar comportamiento caótico y que están enmarcados dentro de los sistemas dinámicos con escape, que son modelos prototipo en Dinámica Galáctica. Los sistemas dinámicos con escape que se van a describir serán los Sistemas de Hén...

  3. Inter-basin dynamics on multidimensional potential surfaces. I. Escape rates on complex basin surfaces

    Science.gov (United States)

    Despa, Florin; Berry, R. Stephen

    2001-11-01

    In this report, we present a general prescription for computing the escape rate of the system from a basin with full consideration of the topographical fingerprint of that basin. The method is based on a solution of the reduced Fokker-Planck equation and built up to allow the separation of the inter-basin dynamics from that of the intra-basin motion. The main result is that when local well populations thermalize within a basin, local minima, especially those of higher energy, enhance the escape rate from the basin. Also, numerical analyses lead to the inference that kinetic traps of "wrong" structures are distinctive topographical patterns which may produce kinetic properties similar to those of the primary basin, i.e., that containing the global minimum, but lie in other basins.

  4. Stochastic narrow escape in molecular and cellular biology analysis and applications

    CERN Document Server

    Holcman, David

    2015-01-01

    This book covers recent developments in the non-standard asymptotics of the mathematical narrow escape problem in stochastic theory, as well as applications of the narrow escape problem in cell biology. The first part of the book concentrates on mathematical methods, including advanced asymptotic methods in partial equations, and is aimed primarily at applied mathematicians and theoretical physicists who are interested in biological applications. The second part of the book is intended for computational biologists, theoretical chemists, biochemists, biophysicists, and physiologists. It includes a summary of output formulas from the mathematical portion of the book and concentrates on their applications in modeling specific problems in theoretical molecular and cellular biology. Critical biological processes, such as synaptic plasticity and transmission, activation of genes by transcription factors, or double-strained DNA break repair, are controlled by diffusion in structures that have both large and small sp...

  5. Damage Escape and Repair in Dried Chroococcidiopsis spp. from Hot and Cold Deserts Exposed to Simulated Space and Martian Conditions

    Science.gov (United States)

    Billi, Daniela; Viaggiu, Emanuela; Cockell, Charles S.; Rabbow, Elke; Horneck, Gerda; Onofri, Silvano

    2011-01-01

    The cyanobacterium Chroococcidiopsis, overlain by 3mm of Antarctic sandstone, was exposed as dried multilayers to simulated space and martian conditions. Ground-based experiments were conducted in the context of Lichens and Fungi Experiments (EXPOSE-E mission, European Space Agency), which were performed to evaluate, after 1.5 years on the International Space Station, the survival of cyanobacteria (Chroococcidiopsis), lichens, and fungi colonized on Antarctic rock. The survival potential and the role played by protection and repair mechanisms in the response of dried Chroococcidiopsis cells to ground-based experiments were both investigated. Different methods were employed, including evaluation of the colony-forming ability, single-cell analysis of subcellular integrities based on membrane integrity molecular and redox probes, evaluation of the photosynthetic pigment autofluorescence, and assessment of the genomic DNA integrity with a PCR-based assay. Desiccation survivors of strain CCMEE 123 (coastal desert, Chile) were better suited than CCMEE 134 (Beacon Valley, Antarctica) to withstand cellular damage imposed by simulated space and martian conditions. Exposed dried cells of strain CCMEE 123 formed colonies, maintained subcellular integrities, and, depending on the exposure conditions, also escaped DNA damage or repaired the induced damage upon rewetting.

  6. Hepatitis C Virus Immune Escape via Exploitation of a Hole in the T cell Repertoire

    OpenAIRE

    Wolfl, Matthias; Rutebemberwa, Alleluiah; Mosbruger, Timothy; Mao, Qing; Li, Hongmei; Netski, Dale; Ray, Stuart C.; Pardoll, Drew; Sidney, John; Sette, Alessandro; Allen, Todd; Kuntzen, Thomas; Kavanagh, Daniel G.; Kuball, Jurgen; Greenberg, Philip D.

    2008-01-01

    Hepatitis C virus (HCV) infection frequently persists despite eliciting substantial virus-specific immune responses. Thus, HCV infection provides a setting in which to investigate mechanisms of immune escape that allow for viral persistence. Viral amino acid substitutions resulting in decreased MHC binding or impaired antigen processing of T cell epitopes reduce antigen density on the cell surface, permitting evasion of T cell responses in chronic viral infection. Substitutions in viral epito...

  7. Fires in hospital buildings: knowledge held by nursing professionals regarding prevention, combat and escape

    OpenAIRE

    Renato Santiago Costa Rodrigues; Ana Elisa Bauer de Camargo Silva; Lizete Malagoni de Almeida Cavalcante Oliveira; Virginia Visconde Brasil; Katarinne Lima Moraes; Jacqueline Andréia Bernardes Leão Cordeiro

    2014-01-01

    This study analyzes the knowledge and conduct of nursing professionals regarding hospital fire prevention, combat and escape. A descriptive study conducted in a public teaching hospital in Goiânia/GO, Brazil, with 109 nursing professionals. Data was collected in 2011 using structured interviews with questionnaires, and descriptive statistics for analysis. Most subjects were female, nursing technicians/assistants (67.9%), knew the Fire Department’s number (85.3%) and the extinguisher’s locatio...

  8. Molecular pathology of mismatch repair deficient tumours with emphasis on immune escape mechanisms

    OpenAIRE

    Dierssen, Jan Willem Frederik

    2010-01-01

    This thesis describes molecular methods to distinguish separate colon tumour entities. Furthermore, it shows that distinct immune escape mechanisms, in particular distinct mechanisms of corrupting the HLA system, are operational in subsets of colon tumours. The apparent necessity of some colon tumours to circumvent the immune system might underscore the potential of immune based therapy approaches. Alternatively, it may suggest that such therapies will only lead to selection of tumour cells w...

  9. On the Roles of Escape Erosion and the Relaxation of Craters on Pluto

    OpenAIRE

    Stern, S. Alan; Porter, Simon; Zangari, Amanda

    2014-01-01

    Pluto and its satellites will be the most distant objects ever reconnoitered when NASA's New Horizons spacecraft conducts its intensive flyby of this system in 2015. The size-frequency distribution (SFD) of craters on the surfaces in the Pluto system have long been expected to provide a useful measure of the size distribution of Kuiper Belt Objects (KBOs) down to much smaller size scales than presently observed. However, currently predicted escape rates of Pluto's atmosphere suggest that of o...

  10. Accounting for escape mortality in fisheries: implications for stock productivity and optimal management.

    Science.gov (United States)

    Baker, Matthew R; Schindler, Daniel E; Essington, Timothy E; Hilborn, Ray

    2014-01-01

    Few studies have considered the management implications of mortality to target fish stocks caused by non-retention in commercial harvest gear (escape mortality). We demonstrate the magnitude of this previously unquantified source of mortality and its implications for the population dynamics of exploited stocks, biological metrics, stock productivity, and optimal management. Non-retention in commercial gillnet fisheries for Pacific salmon (Oncorhynchus spp.) is common and often leads to delayed mortality in spawning populations. This represents losses, not only to fishery harvest, but also in future recruitment to exploited stocks. We estimated incidence of non-retention in Alaskan gillnet fisheries for sockeye salmon (O. nerka) and found disentanglement injuries to be extensive and highly variable between years. Injuries related to non-retention were noted in all spawning populations, and incidence of injury ranged from 6% to 44% of escaped salmon across nine river systems over five years. We also demonstrate that non-retention rates strongly correlate with fishing effort. We applied maximum likelihood and Bayesian approaches to stock-recruitment analyses, discounting estimates of spawning salmon to account for fishery-related mortality in escaped fish. Discounting spawning stock estimates as a function of annual fishing effort improved model fits to historical stock-recruitment data in most modeled systems. This suggests the productivity of exploited stocks has been systematically underestimated. It also suggests that indices of fishing effort may be used to predict escape mortality and correct for losses. Our results illustrate how explicitly accounting for collateral effects of fishery extraction may improve estimates of productivity and better inform management metrics derived from estimates of stock-recruitment analyses. PMID:24640534

  11. A tale of two tumours: Comparison of the immune escape strategies of contagious cancers ☆

    OpenAIRE

    Siddle, Hannah V; Kaufman, Jim

    2013-01-01

    The adaptive immune system should prevent cancer cells passing from one individual to another, in much the same way that it protects against pathogens. However, in rare cases cancer cells do not die within a single individual, but successfully pass between individuals, escaping the adaptive immune response and becoming a contagious cancer. There are two naturally occurring contagious cancers, Devil Facial Tumour Disease (DFTD), found in Tasmanian devils, and Canine Transmissible Venereal Tumo...

  12. The Relationship between Endorsing Gambling as an Escape and the Display of Gambling Problems

    OpenAIRE

    Weatherly, Jeffrey N.

    2012-01-01

    Previous research has reported a strong relationship between endorsing gambling as an escape and problem/pathological gambling as measured by the South Oaks Gambling Screen (SOGS). The present study recruited 249 university students to complete the Gambling Functional Assessment-Revised (GFA-R), which measures the function of the respondent’s gambling, as well as the SOGS and the Problem Gambling Severity Index (PGSI), which was designed to identify gambling problems in the general population...

  13. First escaping fast ion mesurements in ITER-like geometry using an activation probe

    OpenAIRE

    BONHEURE Georges; Hult, Mikael; Fenyvesi, A.; ÄKÄSLOMPOLO S.; Carralero, D.; DEGERING Detlef; DE-VISMES OTT A.; Garcia-Munoz, M; Gmeiner, B.; Herrmann, A.; Laubenstein, Matthias; LUTTER GUILLAUME; Mlynar, J.; Mueller, H. W.; ROHDE V.

    2015-01-01

    More research is needed to develop suitable diagnostics for measuring alpha particle confinement in ITER and techniques relevant for fusion reactor conditions need further development. Based on nuclear reactions, the activation probe is a novel concept first tested in JET. It may offer a more robust solution for performing alpha particle measurements in ITER. This paper describes the first escaping fast ion measurements performed at ASDEX Upgrade (AUG) tokamak using an activation probe. A det...

  14. Faster-is-slower effect in escaping ants revisited: Ants do not behave like humans

    OpenAIRE

    Parisi, Daniel R.; Soria, Sabrina A; Josens, Roxana

    2014-01-01

    In this work we studied the trajectories, velocities and densities of ants when egressing under controlled levels of stress produced by a chemical repellent at different concentrations. We found that, unlike other animals escaping under life-and-death conditions and pedestrian simulations, ants do not produce a higher density zone near the exit door. Instead, ants are uniformly distributed over the available space allowing for efficient evacuations. Consequently, the faster-is-slower effect o...

  15. Comparison of cap lamp and laser illumination for detecting visual escape cues in smoke

    OpenAIRE

    Lutz, T.J.; Sammarco, J.J.; Srednicki, J.R.; Gallagher, S.

    2013-01-01

    The Illuminating Engineering Society of North America reports that an underground mine is the most difficult environment to illuminate (Rea, 2000). Researchers at the U.S. National Institute for Occupational Safety and Health (NIOSH) Office of Mine Safety and Health Research (OMSHR) are conducting ongoing studies designed to explore different lighting technologies for improving mine safety. Underground miners use different visual cues to escape from a smoke-filled environment. Primary and sec...

  16. Light activated escape circuits : a behavior and neurophysiology lab module using Drosophila optogenetics

    OpenAIRE

    Titlow, Joshua S.; Johnson, Bruce R.; Pulver, Stefan R.

    2015-01-01

    The neural networks that control escape from predators often show very clear relationships between defined sensory inputs and stereotyped motor outputs. This feature provides unique opportunities for researchers, but it also provides novel opportunities for neuroscience educators. Here we introduce new teaching modules using adult Drosophila that have been engineered to express csChrimson, a red-light sensitive channelrhodopsin, in specific sets of neurons and muscles mediating visually guide...

  17. Ultra-fast escape maneuver of an octopus-inspired robot

    OpenAIRE

    Weymouth, G D; Subramaniam, V.; Triantafyllou, M. S.

    2014-01-01

    We design and test an octopus-inspired flexible hull robot that demonstrates outstanding fast-starting performance. The robot is hyper-inflated with water, and then rapidly deflates to expel the fluid so as to power the escape maneuver. Using this robot we verify for the first time in laboratory testing that rapid size-change can substantially reduce separation in bluff bodies traveling several body lengths, and recover fluid energy which can be employed to improve the propulsive performance....

  18. Thermal Escape from a Metastable State in Periodically Driven Josephson Junctions

    OpenAIRE

    Sun, Guozhu; Jian CHEN; Xu, Weiwei; Ji, Zhengming; Kang, Lin; Wu, Peiheng; Mao, Guangfeng; Dong, Ning; Yu, Yang; Xing, Dingyu

    2006-01-01

    Resonant activation and noise-enhanced stability were observed in an underdamped real physical system, i.e., Josephson tunnel junctions. With a weak sinusoidal driving force applied, the thermal activated escape from a potential well underwent resonance-like behavior as a function of the driving frequency. The resonance also crucially depended on the initial condition of the system. Numerical simulations showed good agreement with the experimental results.

  19. Low LET radiolysis escape yields for reducing radicals and H2 in pressurized high temperature water

    Science.gov (United States)

    Sterniczuk, Marcin; Yakabuskie, Pamela A.; Wren, J. Clara; Jacob, Jasmine A.; Bartels, David M.

    2016-04-01

    Low Linear Energy Transfer (LET) radiolysis escape yields (G values) are reported for the sum (G(radH)+G(e-)aq) and for G(H2) in subcritical water up to 350 °C. The scavenger system 1-10 mM acetate/0.001 M hydroxide/0.00048 M N2O was used with simultaneous mass spectroscopic detection of H2 and N2 product. Temperature-dependent measurements were carried out with 2.5 MeV electrons from a van de Graaff accelerator, while room temperature calibration measurements were done with a 60Co gamma source. The concentrations and dose range were carefully chosen so that initial spur chemistry is not perturbed and the N2 product yield corresponds to those reducing radicals that escape recombination in pure water. In comparison with a recent review recommendation of Elliot and Bartels (AECL report 153-127160-450-001, 2009), the measured reducing radical yield is seven percent smaller at room temperature but in fairly good agreement above 150 °C. The H2 escape yield is in good agreement throughout the temperature range with several previous studies that used much larger radical scavenging rates. Previous analysis of earlier high temperature measurements of Gesc(radOH) is shown to be flawed, although the actual G values may be nearly correct. The methodology used in the present report greatly reduces the range of possible error and puts the high temperature escape yields for low-LET radiation on a much firmer quantitative foundation than was previously available.

  20. Escaping Dante’s hell with an informed virtual environment for interactive bodies in movement

    Directory of Open Access Journals (Sweden)

    Rousseaux Francis

    2011-12-01

    Full Text Available The paper addresses the question of Informed Virtual Environments from the point of view of some philosophical and ethical key-issues. By browsing some eclectic experiences like dancing, serving Asturian cider, trying to escape Dante’s Hell or manufacturing a tyre, important questions are raised, and some answers are sketched about some possible ways of designing our future environments: but gestures have then to be considered as cultural objects too, being not reducible to their physical traces.

  1. Longitudinal asymmetry of the Jovian magnetosphere and the periodic escape of energetic particles

    International Nuclear Information System (INIS)

    We utilize an earlier model of the Jovian magnetosphere in which the centrifugal stress of corotating plasma distends the outer magnetosphere and opens the tail field. Because of a longitudinal asymmetry in the ionospheric plasma source strength, caused principally by the nonaxisymmetric surface field, the closed field region in the tail expands and contracts with the rotation period, resulting in a 10-hour modulation of the flux of energetic particles escaping from the magnetosphere into interplanetary space

  2. The Effects of Stress on Cognitive Aging, Physiology and Emotion (ESCAPE) Project

    OpenAIRE

    SCOTT, STACEY B.; Graham-Engeland, Jennifer E.; Engeland, Christopher G.; Smyth, Joshua M.; Almeida, David M.; Katz, Mindy J.; Lipton, Richard B.; Mogle, Jacqueline A.; Munoz, Elizabeth; Ram, Nilam; Sliwinski, Martin J.

    2015-01-01

    Background Despite evidence that psychological stress is an important risk factor for age-related cognitive loss, little research has directly evaluated psychological and physiological mediators of the relationship between stressful experiences and cognitive function. A key objective of the ESCAPE (Effects of Stress on Cognitive Aging, Physiology, and Emotion) project is to evaluate whether engaging in stress-related unconstructive repetitive thought (URT) is a pathway through which stressful...

  3. STRUGGLES TO ESCAPE POVERTY IN SOUTH AFRICA: RESULTS FROM A PURPOSIVE RURAL SURVEY

    OpenAIRE

    John Sender

    2000-01-01

    Results of a purposive sample of the poorest are contrasted with the methods and conclusions of other research into ‘income poverty’. The deprivation suffered by an important class of rural women in South Africa is documented. Escape routes from poverty are described that have a more realistic prospect of success than those promoted in the international and South African policy literature, including the literature on land reform. The distinguishing demographic characteristics of women who...

  4. Quantum and classical resonant escapes of a strongly driven Josephson junction

    Science.gov (United States)

    Yu, H. F.; Zhu, X. B.; Peng, Z. H.; Cao, W. H.; Cui, D. J.; Tian, Ye; Chen, G. H.; Zheng, D. N.; Jing, X. N.; Lu, Li; Zhao, S. P.; Han, Siyuan

    2010-04-01

    The properties of phase escape in a dc superconducting quantum interference device (SQUID) at 25 mK, which is well below quantum-to-classical crossover temperature Tcr , in the presence of strong resonant ac driving have been investigated. The SQUID contains two Nb/Al-AlOx/Nb tunnel junctions with Josephson inductance much larger than the loop inductance so it can be viewed as a single junction having adjustable critical current. We find that with increasing microwave power W and at certain frequencies ν and ν/2 , the single primary peak in the switching current distribution, which is the result of macroscopic quantum tunneling of the phase across the junction, first shifts toward lower bias current I and then a resonant peak develops. These results are explained by quantum resonant phase escape involving single and two photons with microwave-suppressed potential barrier. As W further increases, the primary peak gradually disappears and the resonant peak grows into a single one while shifting further to lower I . At certain W , a second resonant peak appears, which can locate at very low I depending on the value of ν . Analysis based on the classical equation of motion shows that such resonant peak can arise from the resonant escape of the phase particle with extremely large oscillation amplitude resulting from bifurcation of the nonlinear system. Our experimental result and theoretical analysis demonstrate that at T≪Tcr , escape of the phase particle could be dominated by classical process, such as dynamical bifurcation of nonlinear systems under strong ac driving.

  5. Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1

    OpenAIRE

    Béguelin, Charles Antoine; Vázquez, Miriam; Bertschi, Manuel; Yerly, S; de Jong, Denise; Gutbrod, Klemens; Rauch, Andri; Cusini, Alexia

    2016-01-01

    In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.

  6. Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1.

    Science.gov (United States)

    Béguelin, C; Vázquez, M; Bertschi, M; Yerly, S; de Jong, D; Gutbrod, K; Rauch, A; Cusini, A

    2016-01-01

    In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms. PMID:26885540

  7. New constraints on the escape of ionizing photons from starburst galaxies using ionization-parameter mapping

    International Nuclear Information System (INIS)

    The fate of ionizing radiation in starburst galaxies is key to understanding cosmic reionization. However, the galactic parameters on which the escape fraction of ionizing radiation depend are not well understood. Ionization-parameter mapping provides a simple, yet effective, way to study the radiative transfer in starburst galaxies. We obtain emission-line ratio maps of [S III]/[S II] for six, nearby, dwarf starbursts: NGC 178, NGC 1482, NGC 1705, NGC 3125, NGC 7126, and He 2-10. The narrowband images are obtained with the Maryland-Magellan Tunable Filter at Las Campanas Observatory. Using these data, we previously reported the discovery of an optically thin ionization cone in NGC 5253, and here we also discover a similar ionization cone in NGC 3125. This latter cone has an opening angle of 40° ± 5° (0.4 sr), indicating that the passageways through which ionizing radiation may travel correspond to a small solid angle. Additionally, there are three sample galaxies that have winds and/or superbubble activity, which should be conducive to escaping radiation, yet they are optically thick. These results support the scenario that an orientation bias limits our ability to directly detect escaping Lyman continuum in many starburst galaxies. A comparison of the star formation properties and histories of the optically thin and thick galaxies is consistent with the model that high escape fractions are limited to galaxies that are old enough (≳3 Myr) for mechanical feedback to have cleared optically thin passageways in the interstellar medium, but young enough (≲5 Myr) that the ionizing stars are still present.

  8. The Aeronomy of Mars: Characterization by MAVEN of the Upper Atmosphere Reservoir That Regulates Volatile Escape

    Science.gov (United States)

    Bougher, S. W.; Cravens, T. E.; Grebowsky, J.; Luhmann, J.

    2015-12-01

    The Mars thermosphere-ionosphere-exosphere (TIE) system constitutes the atmospheric reservoir (i.e. available cold and hot planetary neutral and thermal ion species) that regulates present day escape processes from the planet. The characterization of this TIE system, including its spatial and temporal (e.g., solar cycle, seasonal, diurnal, episodic) variability is needed to determine present day escape rates. Without knowledge of the physics and chemistry creating this TIE region and driving its variations, it is not possible to constrain either the short term or long term histories of atmosphere escape from Mars. MAVEN (Mars Atmosphere and Volatile Evolution Mission) will make both in-situ and remote measurements of the state variables of the Martian TIE system. A full characterization of the thermosphere (˜100-250 km) and ionosphere (˜100-400 km) structure (and its variability) will be conducted with the collection of spacecraft in-situ measurements that systematically span most local times and latitudes, over a regular sampling of Mars seasons, and throughout the bottom half of the solar cycle. Such sampling will far surpass that available from existing spacecraft and ground-based datasets. In addition, remote measurements will provide a systematic mapping of the composition and structure of Mars neutral upper atmosphere and coronae (e.g. H, C, N, O), as well as probe lower altitudes. Such a detailed characterization is a necessary first step toward answering MAVEN's three main science questions (see Jakosky et al. 2014, this issue). This information will be used to determine present day escape rates from Mars, and provide an estimate of integrated loss to space throughout Mars history.

  9. Escaping Poverty

    Institute of Scientific and Technical Information of China (English)

    LI LI

    2010-01-01

    @@ While the global economic crisis still threatens to trap tens of millions of people in extreme poverty, alleviation initiatives in China are gaining new momentum and increasing recognition from the international community. From lifting innumerable people out of poverty by satisfying basic needs of food, clothes and shelter during the past three decades, the Chinese Government's antipoverty drive is now to focus more on helping rural poor to start small businesses and guaranteeing access to public services and social welfare.

  10. Symmetry breaking on density in escaping ants: experiment and alarm pheromone model.

    Directory of Open Access Journals (Sweden)

    Geng Li

    Full Text Available The symmetry breaking observed in nature is fascinating. This symmetry breaking is observed in both human crowds and ant colonies. In such cases, when escaping from a closed space with two symmetrically located exits, one exit is used more often than the other. Group size and density have been reported as having no significant impact on symmetry breaking, and the alignment rule has been used to model symmetry breaking. Density usually plays important roles in collective behavior. However, density is not well-studied in symmetry breaking, which forms the major basis of this paper. The experiment described in this paper on an ant colony displays an increase then decrease of symmetry breaking versus ant density. This result suggests that a Vicsek-like model with an alignment rule may not be the correct model for escaping ants. Based on biological facts that ants use pheromones to communicate, rather than seeing how other individuals move, we propose a simple yet effective alarm pheromone model. The model results agree well with the experimental outcomes. As a measure, this paper redefines symmetry breaking as the collective asymmetry by deducing the random fluctuations. This research indicates that ants deposit and respond to the alarm pheromone, and the accumulation of this biased information sharing leads to symmetry breaking, which suggests true fundamental rules of collective escape behavior in ants.

  11. Energy-limited escape revised. The transition from strong planetary winds to stable thermospheres

    Science.gov (United States)

    Salz, M.; Schneider, P. C.; Czesla, S.; Schmitt, J. H. M. M.

    2016-01-01

    Gas planets in close proximity to their host stars experience photoevaporative mass loss. The energy-limited escape concept is generally used to derive estimates for the planetary mass-loss rates. Our photoionization hydrodynamics simulations of the thermospheres of hot gas planets show that the energy-limited escape concept is valid only for planets with a gravitational potential lower than log 10(-ΦG)< 13.11 erg g-1 because in these planets the radiative energy input is efficiently used to drive the planetary wind. Massive and compact planets with log 10(-ΦG) ≳ 13.6 erg g-1 exhibit more tightly bound atmospheres in which the complete radiative energy input is re-emitted through hydrogen Lyα and free-free emission. These planets therefore host hydrodynamically stable thermospheres. Between these two extremes the strength of the planetary winds rapidly declines as a result of a decreasing heating efficiency. Small planets undergo enhanced evaporation because they host expanded atmospheres that expose a larger surface to the stellar irradiation. We present scaling laws for the heating efficiency and the expansion radius that depend on the gravitational potential and irradiation level of the planet. The resulting revised energy-limited escape concept can be used to derive estimates for the mass-loss rates of super-Earth-sized planets as well as massive hot Jupiters with hydrogen-dominated atmospheres.

  12. Two Escape Mechanisms of Influenza A Virus to a Broadly Neutralizing Stalk-Binding Antibody

    Science.gov (United States)

    Chai, Ning; Swem, Lee R.; Reichelt, Mike; Chen-Harris, Haiyin; Luis, Elizabeth; Park, Summer; Fouts, Ashley; Lupardus, Patrick; Wu, Thomas D.; Li, Olga; McBride, Jacqueline; Lawrence, Michael; Xu, Min; Tan, Man-Wah

    2016-01-01

    Broadly neutralizing antibodies targeting the stalk region of influenza A virus (IAV) hemagglutinin (HA) are effective in blocking virus infection both in vitro and in vivo. The highly conserved epitopes recognized by these antibodies are critical for the membrane fusion function of HA and therefore less likely to be permissive for virus mutational escape. Here we report three resistant viruses of the A/Perth/16/2009 strain that were selected in the presence of a broadly neutralizing stalk-binding antibody. The three resistant viruses harbor three different mutations in the HA stalk: (1) Gln387Lys; (2) Asp391Tyr; (3) Asp391Gly. The Gln387Lys mutation completely abolishes binding of the antibody to the HA stalk epitope. The other two mutations, Asp391Tyr and Asp391Gly, do not affect antibody binding at neutral pH and only slightly reduce binding at low pH. Interestingly, they enhance the fusion ability of the HA, representing a novel mechanism that allows productive membrane fusion even in the presence of antibody and hence virus escape from antibody neutralization. Therefore, these mutations illustrate two different resistance mechanisms used by IAV to escape broadly neutralizing stalk-binding antibodies. Compared to the wild type virus, the resistant viruses release fewer progeny viral particles during replication and are more sensitive to Tamiflu, suggesting reduced viral fitness. PMID:27351973

  13. Outgassing History and Escape of the Martian Atmosphere and Water Inventory

    CERN Document Server

    Lammer, H; Karatekin, Ö; Morschhauser, A; Niles, P B; Mousis, O; Odert, P; Möstl, U V; Breuer, D; Dehant, V; Grott, M; Gröller, H; Hauber, E; Pham, L B S

    2015-01-01

    The evolution and escape of the martian atmosphere and the planet's water inventory can be separated into an early and late evolutionary epoch. The first epoch started from the planet's origin and lasted $\\sim$500 Myr. Because of the high EUV flux of the young Sun and Mars' low gravity it was accompanied by hydrodynamic blow-off of hydrogen and strong thermal escape rates of dragged heavier species such as O and C atoms. After the main part of the protoatmosphere was lost, impact-related volatiles and mantle outgassing may have resulted in accumulation of a secondary CO$_2$ atmosphere of a few tens to a few hundred mbar around $\\sim$4--4.3 Gyr ago. The evolution of the atmospheric surface pressure and water inventory of such a secondary atmosphere during the second epoch which lasted from the end of the Noachian until today was most likely determined by a complex interplay of various nonthermal atmospheric escape processes, impacts, carbonate precipitation, and serpentinization during the Hesperian and Amazon...

  14. The Lyman Continuum Escape Fraction of The Cosmic Horseshoe: A Test of Indirect Estimates

    CERN Document Server

    Vasei, Kaveh; Shapley, Alice E; Quider, Anna M; Alavi, Anahita; Rafelski, Marc; Steidel, Charles C; Pettini, Max; Lewis, Geraint F

    2016-01-01

    High redshift star-forming galaxies are likely responsible for the reionization of the Universe, yet direct detection of their escaping ionizing (Lyman continuum) photons has proven to be extremely challenging. In this study, we search for escaping Lyman continuum of the Cosmic Horseshoe, a gravitationally lensed, star-forming galaxy at z=2.38 with a large magnification of $\\sim24$. Transmission at wavelengths of low ionization interstellar absorption lines in the rest-frame ultraviolet suggest a patchy, partially transparent interstellar medium. This makes it an ideal candidate for direct detection of the Lyman continuum. We obtained a 10-orbit Hubble near-UV image using the WFC3/UVIS F275W filter that probes wavelengths just below the Lyman limit at the redshift of the Horseshoe in an attempt to detect escaping Lyman continuum radiation. After fully accounting for the uncertainties in the opacity of the intergalactic medium as well as accounting for the charge transfer inefficiency in the WFC3 CCDs, we find...

  15. The Hyades Cluster: Identification of a Planetary System and Escaping White Dwarfs

    Science.gov (United States)

    Zuckerman, B.; Xu, S.; Klein, B.; Jura, M.

    2013-06-01

    Recently, some hot DA-type white dwarfs have been proposed to plausibly be escaping members of the Hyades. We used hydrogen Balmer lines to measure the radial velocities of seven such stars and confirm that three, and perhaps two others, are/were indeed cluster members and one is not. The other candidate Hyad is strongly magnetic and its membership status remains uncertain. The photospheres of at least one quarter of field white dwarf stars are "polluted" by elements heavier than helium that have been accreted. These stars are orbited by extended planetary systems that contain both debris belts and major planets. We surveyed the seven classical single Hyades white dwarfs and the newly identified (escaping) Hyades white dwarfs and found calcium in the photosphere of LP 475-242 of type DBA (now DBAZ), thus implying the presence of an orbiting planetary system. The spectrum of white dwarf GD 31, which may be, but probably is not, an escaping member of the Hyades, displays calcium absorption lines; these originate either from the interstellar medium or, less likely, from a gaseous circumstellar disk. If GD 31 was once a Hyades member, then it would be the first identified white dwarf Hyad with a cooling age >340 Myr.

  16. Escape dynamics and fractal basins boundaries in the three-dimensional Earth-Moon system

    CERN Document Server

    Zotos, Euaggelos E

    2016-01-01

    The orbital dynamics of a spacecraft, or a comet, or an asteroid in the Earth-Moon system in a scattering region around the Moon using the three dimensional version of the circular restricted three-body problem is numerically investigated. The test particle can move in bounded orbits around the Moon or escape through the openings around the Lagrange points $L_1$ and $L_2$ or even collide with the surface of the Moon. We explore in detail the first four of the five possible Hill's regions configurations depending on the value of the Jacobi constant which is of course related with the total orbital energy. We conduct a thorough numerical analysis on the phase space mixing by classifying initial conditions of orbits in several two-dimensional types of planes and distinguishing between four types of motion: (i) ordered bounded, (ii) trapped chaotic, (iii) escaping and (iv) collisional. In particular, we locate the different basins and we relate them with the corresponding spatial distributions of the escape and c...

  17. Finite escape fraction for ultrahigh energy collisions around Kerr naked singularity

    Indian Academy of Sciences (India)

    Mandar Patil; Pankaj S Joshi

    2015-04-01

    We investigate the issue of observability of high-energy collisions around Kerr naked singularity and show that results are in contrast with the Kerr black hole case. We had shown that it would be possible to have ultrahigh energy collisions between the particles close to the location = M around the Kerr naked singularity if the Kerr spin parameter transcends unity by an infinitesimally small amount → 1+. The collision is between initially ingoing particle that turns back as an outgoing particle due to angular momentum barrier, with another ingoing particle. We assume that two massless particles are produced in such a collision and their angular distribution is isotropic in the centre-of-mass frame. We calculated the escape fraction for the massless particles to reach infinity. We showed that the escape fraction is finite and approximately equal to half for the ultrahigh energy collisions. Therefore, the particles produced in high-energy collisions would escape to infinity providing the signature of the nature of basic interactions at those energies. This result is in contrast with the case of extremal Kerr black hole where almost all particles produced in high-energy collisions are absorbed by the black hole rendering collisions unobservable.

  18. Investigating Possible Effects of Ethnicity and Age on Gambling as an Escape.

    Science.gov (United States)

    Cookman, Matthew L; Weatherly, Jeffrey N

    2016-06-01

    Previous research has shown that there are a number of risk factors for disordered and problem gambling, including an individual's ethnicity and age. Endorsing gambling as an escape has also been shown to contribute to and maintain disordered gambling. The present study examined potential interactions between ethnicity and age as they relate to disordered gambling, as well as if ethnicity and age would be predictors of endorsing gambling as an escape. Three hundred fifteen adults from the United States completed measures relating to gambling. Participants were grouped into ethnic categories of Caucasian and non-Caucasian, and age groups of 18-25, 26-35, 36-55, and 56 years old and above. Non-Caucasians reported more gambling problems than Caucasians. A significant interaction was found between ethnicity and age for 36-55 year olds. Overall, participants were more likely to gamble for positive than negative reinforcement. However, only gambling as an escape was a significant predictor of disordered gambling. Implications and limitations are discussed with the thought that these results are informative to practitioners treating disordered gambling. PMID:26032667

  19. Escape from R-peptide deletion in a γ-retrovirus

    International Nuclear Information System (INIS)

    The R peptide in the cytoplasmic tail (C-tail) of γ-retroviral envelope proteins (Env) prevents membrane fusion before budding. To analyse its role in the formation of replication competent, infectious particles, we developed chimeric murine leukaemia viruses (MLV) with unmodified or R-peptide deleted Env proteins of the gibbon ape leukaemia virus (GaLV). While titres of these viruses were unaffected, R-peptide deficiency led to strongly impaired spreading. Most remarkably, we isolated an escape mutant which had restored an open reading frame for a C-terminal extension of the truncated C-tail. A reconstituted virus encoding this escape C-tail replicated in cell culture. In contrast to R-peptide deficient Env, particle incorporation of the escape Env was effective due to an enhanced protein expression and restored intracellular co-localisation with Gag proteins. Our data demonstrate that the R peptide not only regulates membrane fusion but also mediates efficient Env protein particle incorporation in γ-retrovirus infected cells.

  20. Indirect Evidence for Escaping Ionizing Photons in Local Lyman Break Galaxy Analogs

    CERN Document Server

    Alexandroff, Rachael; Borthakur, Sanchayeeta; Overzier, Roderik; Leitherer, Claus

    2015-01-01

    A population of early star-forming galaxies is the leading candidate for the re-ionization of the universe. It is still unclear what conditions and physical processes would enable a significant fraction of the ionizing photons to escape from these gas-rich galaxies. In this paper we present the results of the analysis of HST COS far-UV spectroscopy plus ancillary multi-waveband data of a sample of 22 low-redshift galaxies that are good analogs to typical star-forming galaxies at high-redshift. We measure three parameters that provide indirect evidence of the escape of ionizing radiation: (1) the residual intensity in the cores of saturated interstellar low-ionization absorption-lines. (2) The relative amount of blue-shifted Lyman alpha line emission, and (3) the relative weakness of the [SII] optical emission lines. We use these diagnostics to rank-order our sample in terms of likely leakiness, noting that a direct measure of escaping Lyman continuum has recently been made for one of the leakiest members of o...

  1. Limits on Lyman Continuum Escape from z = 2.2 Hα-emitting Galaxies

    Science.gov (United States)

    Sandberg, A.; Östlin, G.; Melinder, J.; Bik, A.; Guaita, L.

    2015-11-01

    The leakage of Lyman continuum (LyC) photons from star-forming galaxies is an elusive parameter. When observed, it provides a wealth of information on star formation in galaxies and on the geometry of the interstellar medium, and puts constraints on the role of star-forming galaxies in the reionization of the universe. Hα-selected galaxies at z∼ 2 trace the highest star formation population at the peak of cosmic star formation history, providing a base for directly measuring LyC escape. Here we present this method and highlight its benefits as well as caveats. We also use the method on 10 Hα emitters in the Chandra Deep Field South at z=2.2, also imaged with the Hubble Space Telescope in the ultraviolet. We find no individual LyC detections, and our stack puts a 5σ upper limit on the average absolute escape fraction of <24%, consistent with similar studies. With future planned observations, the sample sizes should rapidly increase and the method presented here should provide very robust constraints on the escape fraction.

  2. Residual Rate and Escape Route Preference of Juvenile Carassius auratus grandoculis Reared in Paddy Fields

    Science.gov (United States)

    Maehata, Masayoshi; Ohtsuka, Taisuke; Mizuno, Toshiaki; Kanao, Shigefumi

    Gathering paddy-reared juvenile fish (0-year fish) at the paddy's drain outlet at the time of the mid-summer drainage often results in many unharvested fish being left behind. To devise ways of reducing this wastage as much as possible, we performed two experiments during the irrigation season in modernized, consolidated paddy fields as follows. Experiment I: an investigation into the numbers of juvenile Carassius auratus grandoculis that succeeded in leaving a paddy field through the drain outlet. Experiment II: an investigation into their preferred route of escape from the paddy, either via the drain outlet or the water inlet, when both were available. In Experiment I, more than 39.1% of the number of fish that escaped from the paddy were still left behind in the paddy more than three days after the mid-summer drainage had begun. In Experiment II, most of the juveniles, i.e., 99.8% of the fish that escaped from the paddy, left from the water inlet. These results suggest that greater efficiency in reducing the numbers of unharvested juvenile fish in paddy culture may be achieved by first capturing fish at the drain outlet with the irrigation water shut off, and then partially refilling the paddy while using traps or other gear to catch the remaining fish that are attracted towards the water inlet.

  3. Escape of high-energy oxygen ions through magnetopause reconnection under northward IMF

    Directory of Open Access Journals (Sweden)

    S. Kasahara

    2008-12-01

    Full Text Available During a storm recovery phase on 15 May 2005, the Geotail spacecraft repeatedly observed high-energy (>180 keV oxygen ions in the dayside magnetosheath near the equatorial plane. We focused on the time period from 11:20 UT to 13:00 UT, when Geotail observed the oxygen ions and the interplanetary magnetic field (IMF was constantly northward. The magnetic reconnection occurrence northward and duskward of Geotail is indicated by the Walén analysis and convective flows in the magnetopause boundary layer. Anisotropic pitch angle distributions of ions suggest that high-energy oxygen ions escaped from the northward of Geotail along the reconnected magnetic field lines. From the low-energy particle precipitation in the polar cap observed by DMSP, which is consistent with magnetic reconnection occurring between the magnetosheath field lines and the magnetospheric closed field lines, we conclude that these oxygen ions are of ring current origin. Our results thus suggest a new escape route of oxygen ions during northward IMF. In the present event, this escape mechanism is more dominant than the leakage via the finite Larmor radius effect across the dayside equatorial magnetopause.

  4. Hubble space telescope emission line galaxies at z ∼ 2: the Lyα escape fraction

    International Nuclear Information System (INIS)

    We compare the Hβ line strengths of 1.90 < z < 2.35 star-forming galaxies observed with the near-IR grism of the Hubble Space Telescope with ground-based measurements of Lyα from the HETDEX Pilot Survey and narrow-band imaging. By examining the line ratios of 73 galaxies, we show that most star-forming systems at this epoch have a Lyα escape fraction below ∼6%. We confirm this result by using stellar reddening to estimate the effective logarithmic extinction of the Hβ emission line (c Hβ = 0.5) and measuring both the Hβ and Lyα luminosity functions in a ∼100, 000 Mpc3 volume of space. We show that in our redshift window, the volumetric Lyα escape fraction is at most 4.4−1.2+2.1%, with an additional systematic ∼25% uncertainty associated with our estimate of extinction. Finally, we demonstrate that the bulk of the epoch's star-forming galaxies have Lyα emission line optical depths that are significantly greater than that for the underlying UV continuum. In our predominantly [O III] λ5007-selected sample of galaxies, resonant scattering must be important for the escape of Lyα photons.

  5. Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape

    Science.gov (United States)

    Peacock, Thomas; Reddy, Kolli; James, Joe; Adamiak, Beata; Barclay, Wendy; Shelton, Holly; Iqbal, Munir

    2016-01-01

    H9N2 avian influenza virus is a major cause of poultry production loss across Asia leading to the wide use of vaccines. Efficacy of vaccines is often compromised due to the rapid emergence of antigenic variants. To improve the effectiveness of vaccines in the field, a better understanding of the antigenic epitopes of the major antigen, hemagglutinin, is required. To address this, a panel of nine monoclonal antibodies were generated against a contemporary Pakistani H9N2 isolate, which represents a major Asian H9N2 viral lineage. Antibodies were characterized in detail and used to select a total of 26 unique ‘escape’ mutants with substitutions across nine different amino acid residues in hemagglutinin including seven that have not been described as antigenic determinants for H9N2 viruses before. Competition assays and structural mapping revealed two novel, discrete antigenic sites “H9-A” and “H9-B”. Additionally, a second subset of escape mutants contained amino acid deletions within the hemagglutinin receptor binding site. This constitutes a novel method of escape for group 1 hemagglutinins and could represent an alternative means for H9N2 viruses to overcome vaccine induced immunity. These results will guide surveillance efforts for arising antigenic variants as well as evidence based vaccine seed selection and vaccine design. PMID:26738561

  6. Indirect Evidence for Escaping Ionizing Photons in Local Lyman Break Galaxy Analogs

    Science.gov (United States)

    Alexandroff, Rachael M.; Heckman, Timothy M.; Borthakur, Sanchayeeta; Overzier, Roderik; Leitherer, Claus

    2015-09-01

    A population of early star-forming galaxies is the leading candidate for the re-ionization of the universe. It is still unclear, however, what conditions and physical processes would enable a significant fraction of the ionizing (Lyman continuum) photons to escape from these gas-rich galaxies. In this paper we present the results of the analysis of Hubble Space Telescope Cosmic Origins Spectrograph far-UV (FUV) spectroscopy plus ancillary multi-waveband data of a sample of 22 low-redshift galaxies that are good analogs to typical star-forming galaxies at high redshift. We measure three parameters that provide indirect evidence of the escape of ionizing radiation (leakiness): (1) the residual intensity in the cores of saturated interstellar low-ionization absorption lines, which indicates incomplete covering by that gas in the galaxy; (2) the relative amount of blueshifted Lyα line emission, which can indicate the existence of holes in the neutral hydrogen on the front-side of the galaxy outflow, and (3) the relative weakness of the [S ii] optical emission lines that trace matter-bounded H ii regions. We show that our residual intensity measures are only negligibly affected by infilling from resonance emission lines. We find all three diagnostics agree well with one another. We use these diagnostics to rank-order our sample in terms of likely leakiness, noting that a direct measure of escaping Lyman continuum has recently been made for one of the leakiest members of our sample. We then examine the correlations between our ranking and other proposed diagnostics of leakiness. We find a good correlation with the equivalent width of the Lyα emission line, but no significant correlations with either the flux ratio of the [O iii]/[O ii] emission lines or the ratio of star-formation rates derived from the (dust-corrected) FUV and Hα luminosities. Turning to galaxy properties, we find the strongest correlations with leakiness are with the compactness of the star

  7. Burkholderia cenocepacia type VI secretion system mediates escape of type II secreted proteins into the cytoplasm of infected macrophages.

    Directory of Open Access Journals (Sweden)

    Roberto Rosales-Reyes

    Full Text Available Burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. We have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (BcCVs resembling arrested autophagosomes. Intracellular bacteria stimulate IL-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion system (T6SS is required for these phenotypes but surprisingly it is not required for the maturation arrest of the BcCV. Here, we show that macrophages infected with B. cenocepacia employ the NLRP3 inflammasome to induce IL-1β secretion and pyroptosis. Moreover, IL-1β secretion by B. cenocepacia-infected macrophages is suppressed in deletion mutants unable to produce functional Type VI, Type IV, and Type 2 secretion systems (SS. We provide evidence that the T6SS mediates the disruption of the BcCV membrane, which allows the escape of proteins secreted by the T2SS into the macrophage cytoplasm. This was demonstrated by the activity of fusion derivatives of the T2SS-secreted metalloproteases ZmpA and ZmpB with adenylcyclase. Supporting this notion, ZmpA and ZmpB are required for efficient IL-1β secretion in a T6SS dependent manner. ZmpA and ZmpB are also required for the maturation arrest of the BcCVs and bacterial intra-macrophage survival in a T6SS-independent fashion. Our results uncover a novel mechanism for inflammasome activation that involves cooperation between two bacterial secretory pathways, and an unanticipated role for T2SS-secreted proteins in intracellular bacterial survival.

  8. [Socialist escapes. Breaking away from ideology and everday routine in Eastern Europe 1945-1989] / Karsten Brüggemann

    Index Scriptorium Estoniae

    Brüggemann, Karsten, 1965-

    2014-01-01

    Arvustus: Socialist escapes: Breaking away from ideology and everday routine in Eastern Europe 1945-1989, co-edited with Cathleen M. Giustino and Catherine J. Plum (New York and Oxford: Berghahn Books, 2013).

  9. IN VIVO NEUROTOXIC EFFECTS OF DIELDRIN ON GIANT NERVE FIBERS AND ESCAPE REFLEX FUNCTION IN THE EARTHWORM, 'EISENIA FOETIDA'

    Science.gov (United States)

    Neurotoxicological effects of dieldrin were assessed in adult earthworms, Eisenia foetida, using noninvasive electrophysiological recordings of escape reflex activity. After 48 hr body surface exposure to aqueous suspensions of dieldrin, dose-dependent reductions in medial and la...

  10. The relationship of pink salmon escapement to returning runs in Prince William Sound and the expected return in 1957

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The long and consistent records of escapement that have been obtained in Prince William Sound show clearly that there is a direct relation between the number of...

  11. Selectivity and escape percentages during three phases of the towing process for codends fitted with different selection systems

    DEFF Research Database (Denmark)

    Grimaldo, E.; Larsen, R.B.; Sistiaga, M.;

    2009-01-01

    We investigated the selectivity of cod (Gadus morhua) and haddock (Melanogrammus aeglefinus) escaping from three different selection systems (a conventional diamond-mesh codend, a codend fitted with escape windows, and a codend fitted with a sorting grid) using the covered codend technique. By...... using a MultiSampler attached to the codend cover to partition the collection of escaping fish, we were able to determine the partitioned selectivity of each of these devices at different phases during the towing process: at depth, during the haul back, and at the surface. The percentages of escaping...... other two systems at depth. The partitioned selectivity parameters, 150 and SR, were estimated and modelled for each of the three phases of the towing process and used to compare the selective properties of the three selection systems. A comparison was also made with a traditional whole haul selectivity...

  12. Escaping the accelerator; how, when and in what numbers do cosmic rays get out of supernova remnants?

    CERN Document Server

    Drury, Luke O'C

    2010-01-01

    The escape of charged particles accelerated by diffusive shock acceleration from supernova remnants is shown to be a more complex process than normally appreciated. Using a box model it is shown that the high-energy end of the spectrum can exhibit spectral breaks even with no formal escape as a result of geometrical dilution and changing time-scales. It is pointed out that the bulk of the cosmic ray particles at lower energies must be produced and released in the late stages of the remnant's evolution whereas the high energy particles are produced early on; this may explain recent observations of slight compositional variations with energy. Escape resulting from ion-neutral friction in dense and partially ionized media is discussed briefly and some comments made on the use of so-called "free escape boundary conditions". Finally estimates are made of the total production spectrum integrated over the life of the remnant.

  13. Effect of sub-lethal exposure to ultraviolet radiation on the escape performance of Atlantic cod larvae (Gadus morhua.

    Directory of Open Access Journals (Sweden)

    Yuichi Fukunishi

    Full Text Available The amount of ultraviolet (UV radiation reaching the earth's surface has increased due to depletion of the ozone layer. Several studies have reported that UV radiation reduces survival of fish larvae. However, indirect and sub-lethal impacts of UV radiation on fish behavior have been given little consideration. We observed the escape performance of larval cod (24 dph, SL: 7.6±0.2 mm; 29 dph, SL: 8.2±0.3 mm that had been exposed to sub-lethal levels of UV radiation vs. unexposed controls. Two predators were used (in separate experiments: two-spotted goby (Gobiusculus flavescens; a suction predator and lion's mane jellyfish (Cyanea capillata; a "passive" ambush predator. Ten cod larvae were observed in the presence of a predator for 20 minutes using a digital video camera. Trials were replicated 4 times for goby and 5 times for jellyfish. Escape rate (total number of escapes/total number of attacks ×100, escape distance and the number of larvae remaining at the end of the experiment were measured. In the experiment with gobies, in the UV-treated larvae, both escape rate and escape distance (36%, 38±7.5 mm respectively were significantly lower than those of control larvae (75%, 69±4.7 mm respectively. There was a significant difference in survival as well (UV: 35%,63%. No apparent escape response was observed, and survival rate was not significantly different, between treatments (UV: 66%,74% in the experiment with jellyfish. We conclude that the effect and impact of exposure to sub-lethal levels of UV radiation on the escape performance of cod larvae depends on the type of predator. Our results also suggest that prediction of UV impacts on fish larvae based only on direct effects are underestimations.

  14. Molecular Complexity Orchestrates Modulation of Phagosome Biogenesis and Escape to the Cytosol of macrophages by Francisella tularensis

    OpenAIRE

    Asare, Rexford; Kwaik, Yousef Abu

    2010-01-01

    Upon entry of Francisella tularensis to macrophages, the Francisella-containing phagosome (FCP) is trafficked into an acidified late endosome-like phagosome with limited fusion to the lysosomes followed by rapid escape into the cytosol where the organism replicates. Although the Francisella Pathogenicity Island (FPI), which encodes a type VI-like secretion apparatus, is required for modulation of phagosome biogenesis and escape into the cytosol, the mechanisms involved are not known. To decip...

  15. Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4.

    Directory of Open Access Journals (Sweden)

    K Ruckemann-Dziurdzińska

    2010-05-01

    Full Text Available Lithium (Li is still useful in the treatment of bipolar disorder. Cellular mechanisms of Li action are not fully understood and include some cytoprotective properties. Data concerning Li effect on the apoptotic mechanisms in cells other than neurons are fragmentary and contradictory. We have investigated anti-apoptotic activity of Li in a lymphoid derived MOLT-4 cell line. Spontaneous and camptothecin-induced apoptosis was analyzed in cells treated with 0-20 mM Li carbonate. Early apoptosis was identified as significant mitochondrial depolarization (JC-1 staining. Later stages of apoptosis were estimated with annexin V binding and by the proportion of cells containing sub-G1 amounts of DNA (PI staining. We have observed a biphasic effect of Li on the proportion of spontaneously apoptotic cells;namely, low (therapeutic concentrations of Li had a significant effect stabilizing the mitochondrial membrane polarization, while 10 and 20mM Li increased apoptosis. The latter could be seen both as mitochondrial depolarization as well as an increased proportion of sub-G1 cells, accompanied by reduced proportion of S phase cells. Li at concentrations above 2 mM had a significant, dose-dependent, anti-apoptotic effect on the cells undergoing camptothecin induced apoptosis. In conclusion, demonstrated cytoprotective effect of Li is at least partially related to stabilization of mitochondrial membrane potential and to the reduction of DNA damaging effects in proliferating cells; both may form part of the mechanism through which Li is useful in therapy of bipolar disorder, but may have more general consequences.

  16. The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

    Directory of Open Access Journals (Sweden)

    Ponich E.S.

    2015-09-01

    Full Text Available Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control meets the standard management of patients in biological therapy. Results. The study shows that in the case of the resistance progressing when applying preparations of biological therapy, methotrexate is useful at a dose of 15-20mg/week for up to 6 months. The combined use of biologic therapy and methotrexate in the treatment of patients with psoriasis vulgaris, "escape effect" contributes to the marked regression of clinical symptoms and allows to control the process long enough, which is confirmed by the dynamics of the index PASI, BRS and DLQI. The combined method is highly safe, as evidenced by the lack of inhibition of hematopoiesis, the normal level of hepatic transaminases and serum creatinine, which greatly improves patient compliance in this type of therapy. Conclusion. The article presents the data of the combined application of biological medication therapy (ustekinumab and methotrexate for the treatment of patients with the common form of psoriasis vulgaris. In the case of the development of resistance of biological therapy recommended the appointment of methotrexate. The combined use of methotrexate and biologic therapy in the treatment of patients with psoriasis vulgaris contributes to marked regression of clinical symptoms and allows to control the process for a long time.

  17. Forest edge burning in the Brazilian Amazon promoted by escaping fires from managed pastures

    Science.gov (United States)

    Cano-Crespo, Ana; Oliveira, Paulo J. C.; Boit, Alice; Cardoso, Manoel; Thonicke, Kirsten

    2015-10-01

    Understanding to what extent different land uses influence fire occurrence in the Amazonian forest is particularly relevant for its conservation. We evaluate the relationship between forest fires and different anthropogenic activities linked to a variety of land uses in the Brazilian states of Mato Grosso, Pará, and Rondônia. We combine the new high-resolution (30 m) TerraClass land use database with Moderate Resolution Imaging Spectroradiometer burned area data for 2008 and the extreme dry year of 2010. Excluding the non-forest class, most of the burned area was found in pastures, primary and secondary forests, and agricultural lands across all three states, while only around 1% of the total was located in deforested areas. The trend in burned area did not follow the declining deforestation rates from 2001 to 2010, and the spatial overlap between deforested and burned areas was only 8% on average. This supports the claim of deforestation being disconnected from burning since 2005. Forest degradation showed an even lower correlation with burned area. We found that fires used in managing pastoral and agricultural lands that escape into the neighboring forests largely contribute to forest fires. Such escaping fires are responsible for up to 52% of the burned forest edges adjacent to burned pastures and up to 22% of the burned forest edges adjacent to burned agricultural fields, respectively. Our findings call for the development of control and monitoring plans to prevent fires from escaping from managed lands into forests to support effective land use and ecosystem management.

  18. Risk of Hormone Escape in a Human Prostate Cancer Model Depends on Therapy Modalities and Can Be Reduced by Tyrosine Kinase Inhibitors

    Science.gov (United States)

    Guyader, Charlotte; Céraline, Jocelyn; Gravier, Eléonore; Morin, Aurélie; Michel, Sandrine; Erdmann, Eva; de Pinieux, Gonzague; Cabon, Florence; Bergerat, Jean-Pierre; Poupon, Marie-France; Oudard, Stéphane

    2012-01-01

    Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape -frequency and delay- are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH) antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR) antagonists (bicalutamide or flutamide). Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration), but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR) as compared to continuous castration (RRintermittent: 14.5, RRcomplete blockade: 6.5 and 1.35). All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17) and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent tumors displayed

  19. Escaping low-earnings in Germany - do employer characteristics make a difference?

    OpenAIRE

    Heinze, Anja; Gürtzgen, Nicole

    2010-01-01

    This paper studies the importance of employer-specific determinants in escaping low earnings in Germany. To address the initial conditions problem and the endogeneity of employer retention, we model (intra-firm) low-pay transitions using a multivariate Probit model that accounts for selection into low-wage employment and non-random employer drop-out. Using data from the LIAB Linked Employer-Employee panel, our results for the service sector indicate that for male workers the probability of es...

  20. Ion escape from Mars as a function of solar wind conditions: A statistical study

    OpenAIRE

    Nilsson, Hans; Carlsson, Ella; Brain, Dave; Yamauchi, Masatoshi; Holmström, Mats; Barabash, Stas; Lundin, Rickard; Futaana, Yoshifumi

    2010-01-01

    Abstract The influence of solar EUV and solar wind conditions on ion escape at Mars is investigated using ion data from the Aspera-3 instrument on Mars Express, combined with solar wind proxy data obtained from the Mars Global Surveyor (MGS) spacecraft. A solar EUV flux proxy based on data from the Earth position, scaled and shifted in time for Mars, is used to study relatively long time scale changes related to solar EUV variability. Data from May 2004 until November 2005 has been...