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Sample records for camptothecin induces escape

  1. Identification and replication of loci involved in camptothecin-induced cytotoxicity using CEPH pedigrees.

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    Venita Gresham Watson

    Full Text Available To date, the Centre d'Etude Polymorphism Humain (CEPH cell line model has only been used as a pharmacogenomic tool to evaluate which genes are responsible for the disparity in response to a single drug. The purpose of this study was demonstrate the model's ability to establish a specific pattern of quantitative trait loci (QTL related to a shared mechanism for multiple structurally related drugs, the camptothecins, which are Topoisomerase 1 inhibitors. A simultaneous screen of six camptothecin analogues for in vitro sensitivity in the CEPH cell lines resulted in cytotoxicity profiles and orders of potency which were in agreement with the literature. For all camptothecins studied, heritability estimates for cytotoxic response averaged 23.1 ± 2.6%. Nonparametric linkage analysis was used to identify a relationship between genetic markers and response to the camptothecins. Ten QTLs on chromosomes 1, 3, 5, 6, 11, 12, 16 and 20 were identified as shared by all six camptothecin analogues. In a separate validation experiment, nine of the ten QTLs were replicated at the significant and suggestive levels using three additional camptothecin analogues. To further refine this list of QTLs, another validation study was undertaken and seven of the nine QTLs were independently replicated for all nine camptothecin analogues. This is the first study using the CEPH cell lines that demonstrates that a specific pattern of QTLs could be established for a class of drugs which share a mechanism of action. Moreover, it is the first study to report replication of linkage results for drug-induced cytotoxicity using this model. The QTLs, which have been identified as shared by all camptothecins and replicated across multiple datasets, are of considerable interest; they harbor genes related to the shared mechanism of action for the camptothecins, which are responsible for variation in response.

  2. Camptothecin resistance

    DEFF Research Database (Denmark)

    Brangi, M; Litman, Thomas; Ciotti, M;

    1999-01-01

    The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells...... and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines...... demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment...

  3. Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis.

    Science.gov (United States)

    Mei, Yide; Xie, Chongwei; Xie, Wei; Tian, Xu; Li, Mei; Wu, Mian

    2007-10-01

    Although camptothecin (CPT) has been reported to induce apoptosis in various cancer cells, the molecular details of this regulation remain largely unknown. In this study, we demonstrate that BH3-only protein Noxa is upregulated during CPT-induced apoptosis, which is independent of p53. In addition, we show that phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is responsible for Noxa's induction. Luciferase assay and cAMP response element binding protein (CREB) knockdown experiments further demonstrate that CREB is involved in the transcriptional upregulation of Noxa. Moreover, blocking Noxa expression using specific small interfering ribonucleic acid (siRNA) significantly reduces the apoptosis in response to CPT, indicating that Noxa is an essential mediator for CPT-induced apoptosis. Interestingly, antiapoptotic Mcl-1 was also upregulated through PI3K/Akt signaling pathway upon CPT treatment. Using immunoprecipitation assay, Noxa was found to interact with Mcl-1 in the presence or absence of CPT. Knockdown of Mcl-1 expression by short hairpin ribonucleic acid (shRNA) was shown to potentiate CPT-induced apoptosis. Consistently, ectopic overexpression of Mcl-1 rescued cells from apoptosis induced by CPT. Cells coexpressing Noxa and Mcl-1 at different ratio correlates well with the extent of apoptosis, suggesting that the balance between Noxa and Mcl-1 may determine the susceptibility of HeLa cells to CPT-induced apoptosis.

  4. Noxa/Mcl-1 Balance Regulates Susceptibility of Cells to Camptothecin-Induced Apoptosis

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    Yide Mei

    2007-10-01

    Full Text Available Although camptothecin (CPT has been reported to induce apoptosis in various cancer cells, the molecular details of this regulation remain largely unknown. In this study, we demonstrate that 131-113-only protein Noxa is upregulated during CPT-induced apoptosis, which is independent of p53. In addition, we show that phosphatidylinositol 3-kinase (PI3K/Akt signaling pathway is responsible for Noxa's induction. Luciferase assay, cAMP response element binding protein (CREB knockdown experiments further demonstrate that CREB is involved in the transcriptional upregulation of Noxa. Moreover, blocking Noxa expression using specific small interfering ribonucleic acid (siRNA significantly reduces the apoptosis in response to CPT, indicating that Noxa is an essential mediator for CPT-induced apoptosis. Interestingly, antiapoptotic Mcl-1 was also upregulated through PI3K/Akt signaling pathway upon CPT treatment. Using immunoprecipitation assay, Noxa was found to interact with Mcl-1 in the presence or absence of CPT. Knockdown of Mcl-1 expression by short hairpin ribonucleic acid (shRNA was shown to potentiate CPT-induced apoptosis. Consistently, ectopic overexpression of Mcl-1 rescued cells from apoptosis induced by CPT. Cells coexpressing Noxa, Mcl-1 at different ratio correlates well with the extent of apoptosis, suggesting that the balance between Noxa, Mcl-1 may determine the susceptibility of HeLa cells to CPT-induced apoptosis.

  5. Topoisomerase I inhibitor, camptothecin, induces apoptogenic signaling in human embryonic stem cells

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    Carolina Paola García

    2014-03-01

    Full Text Available Embryonic stem cells (ESCs need to maintain their genomic integrity in response to DNA damage to safeguard the integrity of the organism. DNA double strand breaks (DSBs are one of the most lethal forms of DNA damage and, if not repaired correctly, they can lead to cell death, genomic instability and cancer. How human ESCs (hESCs maintain genomic integrity in response to agents that cause DSBs is relatively unclear. In the present study we aim to determine the hESC response to the DSB inducing agent camptothecin (CPT. We find that hESCs are hypersensitive to CPT, as evidenced by high levels of apoptosis. CPT treatment leads to DNA-damage sensor kinase (ATM and DNA-PKcs phosphorylation on serine 1981 and serine 2056, respectively. Activation of ATM and DNA-PKcs was followed by histone H2AX phosphorylation on Ser 139, a sensitive reporter of DNA damage. Nuclear accumulation and ATM-dependent phosphorylation of p53 on serine 15 were also observed. Remarkably, hESC viability was further decreased when ATM or DNA-PKcs kinase activity was impaired by the use of specific inhibitors. The hypersensitivity to CPT treatment was markedly reduced by blocking p53 translocation to mitochondria with pifithrin-μ. Importantly, programmed cell death was achieved in the absence of the cyclin dependent kinase inhibitor, p21Waf1, a bona fide p53 target gene. Conversely, differentiated hESCs were no longer highly sensitive to CPT. This attenuated apoptotic response was accompanied by changes in cell cycle profile and by the presence of p21Waf1. The results presented here suggest that p53 has a key involvement in preventing the propagation of damaged hESCs when genome is threatened. As a whole, our findings support the concept that the phenomenon of apoptosis is a prominent player in normal embryonic development.

  6. Phosphorylation of β-actin by protein kinase C-delta in camptothecin analog-induced leukemic cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Shuang WANG; Ying ZHENG; Yun YU; Li XIA; Guo-qiang CHEN; Yong-zong YANG; Li-shun WANG

    2008-01-01

    Aim: This study was conducted to reveal new proteins involved in acute myeloid leukemia (AML) cell apoptosis. Methods: Using camptothecin analog NSC606985-induced leukemic U937 cell apoptosis as a model, this study performed a differen-tial proteomic analysis during apoptosis induction. The significantly modulated protein was underwent further investigation in the apoptotic process. Results: We found that β-actin protein presented two different spots on the two-dimen-sional electrophoresis (2-DE) map, which shared similar molecular weight and different pI. Those two spots demonstrated contrary changes (disappeared on the basic-end and increased on the acid-end spot) during apoptosis induction, although the total level of β-actin kept constant. This observation was further confirmed by immunoblot analysis on 2-DE gel. When NSC606985-treated cell iysate was incubated with alkaline phosphotase, β-actin on the basic-end spot was restored, indicating increased phosphorylation of β-actin during NSC606985-induced apoptosis. Moreover, the polymerization of actin also decreased after NSC606985 treatment. The increased β-actin phosphorylation and decreased ac-tin polymerization was antagonized by pre-treatment of rottlerin, a specific protein kinase C-delta (PKCδ) inhibitor. Conclusion: All these results indicate that β-actin was phosphorylated during apoptosis induction, which was mediated by acti-vated PKCδ.

  7. 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.

  8. Protection of halogenated DNA from strand breakage and sister-chromatid exchange induced by the topoisomerase I inhibitor camptothecin

    Energy Technology Data Exchange (ETDEWEB)

    Orta, Manuel Luis; Mateos, Santiago; Cantero, Gloria [Department of Cell Biology, Faculty of Biology, University of Seville (Spain); Wolff, Lisa J. [Sweet Briar College, VA (United States); Cortes, Felipe [Department of Cell Biology, Faculty of Biology, University of Seville (Spain)], E-mail: cortes@us.es

    2008-01-01

    The fundamental nuclear enzyme DNA topoisomerase I (topo I), cleaves the double-stranded DNA molecule at preferred sequences within its recognition/binding sites. We have recently reported that when cells incorporate halogenated nucleosides analogues of thymidine into DNA, it interferes with normal chromosome segregation, as shown by an extraordinarily high yield of endoreduplication, and results in a protection against DNA breakage induced by the topo II poison m-AMSA [F. Cortes, N. Pastor, S. Mateos, I. Dominguez, The nature of DNA plays a role in chromosome segregation: endoreduplication in halogen-substituted chromosomes, DNA Repair 2 (2003) 719-726; G. Cantero, S. Mateos, N. Pastor; F. Cortes, Halogen substitution of DNA protects from poisoning of topoisomerase II that results in DNA double-strand breaks (DSBs), DNA Repair 5 (2006) 667-674]. In the present investigation, we have assessed whether the presence of halogenated nucleosides in DNA diminishes the frequency of interaction of topo I with DNA and thus the frequency with which the stabilisation of cleavage complexes by the topo I poison camptothecin (CPT) takes place, in such a way that it protects from chromosome breakage and sister-chromatid exchange. This protective effect is shown to parallel a loss in halogen-substituted cells of the otherwise CPT-increased catalytic activity bound to DNA.

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

    OpenAIRE

    Shibakura M; Niiya K; Kiguchi T; Nakata Y; Tanimoto M

    2002-01-01

    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, significan...

  10. 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

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    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.

  11. 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

  12. 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.

    2013-01-01

    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...

  13. 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.

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

    Science.gov (United States)

    Shibakura, Misako; Niiya, Kenji; Kiguchi, Toru; Nakata, Yasunari; Tanimoto, Mitsune

    2002-10-01

    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.

  15. 喜树碱诱导的草地贪夜蛾Sf9细胞凋亡%Induced apoptosis of camptothecin in Spodoptera frugiperda Sf9 cells

    Institute of Scientific and Technical Information of China (English)

    王文祥; 钟国华; 胡美英; 黄劲飞; 葛萃萃

    2011-01-01

    传统植物源杀虫剂喜树碱具有优异的抑制昆虫生长发育活性,其诱导昆虫细胞凋亡的作用方式和机制尚不明确,极大地限制了喜树碱在植物保护领域的应用开发.本研究以1 μmol/L喜树碱诱导草地贪夜蛾Spodoptera frugiperda Sf9细胞呈现细胞皱缩、微绒毛消失和染色质边集等典型细胞凋亡早期超微结构形态特征,中期凋亡小体逐渐出现并急剧增多,DNA电泳分析可见清晰DNA片段化凋亡特征.流式细胞术分析表明1μmol/L喜树碱诱导Sf9细胞12h凋亡率达到最大值39.67%,是对照的13.13倍,随后减小.喜树碱诱导Sf9细胞凋亡在12h和24h时Sf caspase-l分别出现两个活性高峰,表明其作为效应因子在细胞凋亡级联反应过程中具有影响作用.喜树碱显著抑制St9细胞拓扑异构酶Ⅰ活性,阻断解旋负超螺旋pBR322 DNA,导致DNA损伤进而启动细胞凋亡级联反应使Sf caspase-1活性增加,提示其信号转导过程是细胞凋亡诱导机制之一.本研究通过分析喜树碱的诱导昆虫Sf9细胞凋亡,对揭示喜树碱诱导昆虫细胞凋亡的作用机制具有重要启示和帮助.%Camptothecin possesses excellent inhibitive effects on insect growth and development. The apoptotic induction mode and mechanism of camptothecin are ambiguous, which restricts the application of camptothecin in plant protection. In order to investigate its inhibitive effect at the cellular level, the apoptotic induction effect of camptothecin on Spodoptera frugiperda Sf9 cells was studied. Induced with 1 p,mol/L camptothecin, Sf9 cells showed typical morphological changes such as cell shrinkage, loss of microvilli and chromatin condensation under the transmission electron microscope. DNA Ladder assay indicated that camptothecin induced apoptosis in Sf9 cells. Apoptotic rate of Sf9 cells treated with 1 μmol/ L camptothecin increased within 12 h, and reached the maximum of 39. 67% at 12 h, which was 13. 13 times as high

  16. Spectroscopic Study of The Interaction between Camptothecin and DNA%喜树碱与DNA相互作用的光谱学研究

    Institute of Scientific and Technical Information of China (English)

    于岚岚; 杨冉; 白希希; 陈晓英; 李建军; 屈凌波

    2011-01-01

    The interaction of an anti-cancer drug camptothecin with salmon sperm DNA was studied by spec-troscopic techniques. DNA induced slight hypochromic and bathochromic effects on the UV-Vis absorption spectra of camptothecin, but strong fluorescence quenching of camptothecin, which suggest the formation of ground-state camptothecin-DNA complex. The binding constant and number of binding site were calculated and the main interaction force was determined. The effect of salt, phosphate and negatively charged quencher KI on camptothecin-DNA interaction was investigated and the interaction of camptothecin with double-stranded DNA and single-stranded DNA was compared. The melting temperature of camptothecin-DNA complex was 60 ℃ , which is 18℃ lower than that of pure DNA. All the results indicate that groove binding mode is the main interaction mode between camptothecin and DNA.

  17. DR-induced escape of O and C from early Mars

    Science.gov (United States)

    Zhao, Jinjin; Tian, Feng; Ni, Yufang; Huang, Xiaomeng

    2017-03-01

    Energetic particles produced in Dissociative recombination (DR) reactions could escape planets with low gravity, such as Mars, if they could overcome collisions with the surrounding background gases. In this work, a 3-D Monte Carlo model is developed to study these photochemical escape processes on early Mars. Although the DR reaction rates of O2+, CO2+, and CO+ increase monotonically with solar soft X-ray and extreme ultraviolet (XUV) flux, the peak of the calculated DR-induced escape rates of O is near 3 × XUV, and the DR-induced escape rates of C increase with XUV until 10 × XUV. The non-monotonic behavior can be explained by the increased column densities of background species in high XUV conditions, which can deflect energetic particles through collisions more efficiently. At 20 × XUV, CO+ DR is the main source of escaping O and C, and the escape of secondary particles could contribute to 30∼40% and 10% of the total escape of O and C respectively. The time-integrated DR-induced escape of O and C is equivalent to 1 m of H2O and 20 mbar of CO2 escaping early Mars since 4.5 billion years ago. The accumulated CO2 loss is much lower than what's needed to explain the carbon isotopic ratios on Mars and much lower than the total CO2 needed to warm up early Mars. If more vigorous escape mechanisms were absent on early Mars, substantial inventories of volatiles have not been detected yet.

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

    Science.gov (United States)

    Martins, Susana M; Sarmento, Bruno; Nunes, Cláudia; Lúcio, Marlene; Reis, Salette; Ferreira, Domingos C

    2013-11-01

    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. Synchrotron small and wide angle X-ray scattering (SAXS/WAXS) analysis indicates that SLN maintain their physical stability in contact with DMPC membrane, whereas SLN change the lamellar structure of DMPC into a cubic phase, which is associated with efficient release of the incorporated drugs. Cytotoxicity 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 organs, when encapsulated into SLN, with consequent decrease in potential side toxicological effects. These results confirmed the potential of camptothecin-loaded SLN for antitumour brain treatments.

  19. 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.

  20. 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.

  1. 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.

  2. bcl-xs mediated sensitization of human nasopharyngeal carcinoma cells to camptothecin-induced apoptosis%bcl-xs增加鼻咽癌细胞对喜树碱诱导凋亡敏感性的实验研究

    Institute of Scientific and Technical Information of China (English)

    张月飞; 陈扬超; 周克元; 梁统

    2001-01-01

    Objective: In order to detect the effect of bcl-xs on camptothecin-induced apoptosis in human nasopharyngeal carcinoma CNE-2Z cells in vitro.Methods:bcl-xs gene-bearing mammalian expression vector(pcDNA3xs)was transfected into CNE-2Z cells using LipofectAmine.The expression of bcl-xs was determined with western blot.Cells which were transfected with native pcDNA3 vector were used as control.Apoptotic cells were detected with flow cytometry after exposure to camptothecin for 24h.Results:Cell clone(CNE-2Zxs)with stable expression of bcl-xs was obtained as confirmed with western blot.Results from flow cytometry analysis showed a significant increase of apoptotic cells in CNE-2Zxs as compared with CNE-2Zneo after treatment with the same dose of camptothecin.Conclusion:Exogenous bcl-xs expression sensitized nasopharyngeal carcinoma CNE-2Z cells to camptothecin-induced apoptosis.%目的:研究bcl-xs基因对喜树碱(CPT)诱导鼻咽癌CNE-2Z细胞凋亡的影响。方法:利用脂质体LipofectAmine将含有人bcl-xs基因的重组真核表达质粒pcDNA3xs导入人鼻咽癌低分化上皮细胞株CNE-2Z,G418筛选培养后,经Western blot检测bcl-xs的表达。以不含有bcl-xs基因的pcDNA3质粒转染CNE-2Z作为对照细胞。喜树碱处理两种细胞一定时间后,通过激光流式细胞仪检测凋亡细胞百分比。结果:Western blot检测证实获得稳定表达bcl-xs的细胞,经过0.5μmol/L,1.0μmol/L CPT处理24小时后,激光流式细胞仪检测的凋亡峰值均高于对照细胞。结论:bcl-xs能显著增加鼻咽癌CNE-2Z细胞对喜树碱诱导凋亡的敏感性。

  3. 喜树碱对炎症诱导的多巴胺能神经元损伤的保护作用%The protective effect of camptothecin on inflammation-induced dopaminergic neurons injury

    Institute of Scientific and Technical Information of China (English)

    沈荣; 李学忠; 周小平; 丁卫祥; 陈强; 沈卉君

    2011-01-01

    目的 探讨喜树碱对炎症诱导的多巴胺能神经元(DN)损伤的保护作用及其可能机制.方法 建立DN培养体系及混合培养体系,观察不同干预下DN的生存率、酪氨酸羟化酶(TH)mRNA表达及肿瘤坏死因子α(TNF-α)、一氧化氮(NO)、白细胞介素6(IL-6)、胶质源性神经生长因子(GDNF)含量的变化.结果 在DN培养体系中,喜树碱10 mg/L较对照组明显促进DN凋亡(P<0.05).在混合培养体系中,与对照组比较,不同浓度喜树碱均增加TH阳性细胞数和THmRNA的表达(P<0.05),降低NO、TNF-α及IL-6的含量(P<0.05),但只有喜树碱10 mg/L能促进DN的凋亡(P<0.05).结论 适量的喜树碱能抑制星形胶质细胞分泌炎性介质,保护神经元.%Objective To investigate the protective effect and possible mechanism of camptothecin in the lipopolysaccharide-induced dopaminergic neurons (DN) injury. Methods After establishing DN and neuron-astrocyte mixed culture systems, the survival rate of DN, expression of tyrosine hydroxylase(TH) mRNA, the levels of tumor necrosis factor-α(TNFα), nitrogen monoxidum (NO), interleukin 6 (IL-6) and glial cell line-derived neurotrophic factor(GDNF) were detected in response to different treatments. Results Camptothecin 10 mg/L significantly promoted DN apoptosis in DN culture system (P< 0. 05 ). Compared with control group, different concentrations of camptothecin increased positive cell population and mRNA expression of TH (P<0. 05), decreased the levels of NO, TNF-α and IL-6(P<0. 05), but only carnptothecin 10 mg/L enhanced DN apoptosis in neuroN-astrocyte mixed culture system (P< 0. 05 ). Conclusion Camptothecin in a proper concentration can inhibit proinflammatory factors secreted by astrocyte, which in turn protects neuron.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. Overestimating climate warming-induced methane gas escape from the seafloor by neglecting multiphase flow dynamics

    Science.gov (United States)

    Stranne, C.; O'Regan, M.; Jakobsson, M.

    2016-08-01

    Continental margins host large quantities of methane stored partly as hydrates in sediments. Release of methane through hydrate dissociation is implicated as a possible feedback mechanism to climate change. Large-scale estimates of future warming-induced methane release are commonly based on a hydrate stability approach that omits dynamic processes. Here we use the multiphase flow model TOUGH + hydrate (T + H) to quantitatively investigate how dynamic processes affect dissociation rates and methane release. The simulations involve shallow, 20-100 m thick hydrate deposits, forced by a bottom water temperature increase of 0.03°C yr-1 over 100 years. We show that on a centennial time scale, the hydrate stability approach can overestimate gas escape quantities by orders of magnitude. Our results indicate a time lag of > 40 years between the onset of warming and gas escape, meaning that recent climate warming may soon be manifested as widespread gas seepages along the world's continental margins.

  9. Solar cycle dynamic of the Martian induced magnetosphere. Planetary ions acceleration zones and escape.

    Science.gov (United States)

    Fedorov, Andrey; Modolo, Ronan; Jarvinen, Riku; Barabash, Stas

    2016-10-01

    This work presents a massive statistical analysis of the ion flows in the Martian induced magnetosphere. We performed this analysis using Mars Express ion mass spectrometer data taken during 2008 - 2013 time interval. This data allows to make an enhanced study of the induced magnetosphere variations as a response of the solar activity level. Since Mars Express has no onboard magnetometer, we used the hybrid models of the Martian plasma environment to get a proper frame to make an adequate statistics of the magnetospheric response. In this paper we present a spatial distribution of the planetary plasma properties in the planetary wake as well as the ionosospheric escape as a function of the solar activity.

  10. Genomic profiling in CEPH cell lines distinguishes between the camptothecins and indenoisoquinolines.

    Science.gov (United States)

    Watson, Venita Gresham; Hardison, Nicholas E; Harris, Tyndall; Motsinger-Reif, Alison; McLeod, Howard L

    2011-10-01

    We have attempted to use a familial genetics strategy to study mechanisms of topoisomerase 1 (Top1) inhibition. Investigations have steadily been chipping away at the pathways involved in cellular response following Top1 inhibition for more than 20 years. Our system-wide approach, which phenotypes a collection of genotyped human cell lines for sensitivity to compounds and interrogates all genes and molecular pathways simultaneously. Previously, we characterized the in vitro sensitivity of 15 families of Centre d'Etude Polymorphisme Humain (CEPH) cell lines (n = 142) to 9 camptothecin analogues. Linkage analysis revealed a pattern of 7 quantitative trait loci (QTL) shared by all of the camptothecins. To identify which, if any, QTLs are related to the general mechanism of Top1 inhibition or should be considered camptothecin specific, we characterized the in vitro sensitivity of the same panel of CEPH cell lines to the indenisoquinolones, a structurally distinct class of Top1 inhibitors. Four QTLs on chromosomes 1, 5, 11, and 16 were shared by both the camptothecins and the indenoisoquinolines and are considered associated with the general mechanism of Top1 inhibition. The remaining 3 QTLs (chromosomes 6 and 20) are considered specific to camptothecin-induced cytotoxicity. Finally, 8 QTLs were identified, which were unique to the indenoisoquinolines.

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

    Energy Technology Data Exchange (ETDEWEB)

    Krieger, N.S.; Tashjian, A.H. Jr.; Feldman, R.S.

    1982-01-01

    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, (/sup 3/H)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 /sup 125/I-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.

  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. Leishmania mexicana promastigotes down regulate JNK and p-38 MAPK activation: Role in the inhibition of camptothecin-induced apoptosis of monocyte-derived dendritic cells.

    Science.gov (United States)

    Rodríguez-González, Jorge; Wilkins-Rodríguez, Arturo; Argueta-Donohué, Jesús; Aguirre-García, Magdalena; Gutiérrez-Kobeh, Laila

    2016-04-01

    Dendritic cells (DC) are one of the principal host cells of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. We have previously shown that the infection of monocyte-derived dendritic cells (moDC) with Leishmania mexicana inhibits campthotecin-induced apoptosis. Nevertheless, the mechanisms involved in the inhibition of apoptosis of dendritic cells by Leishmania have not been established. Mitogen-activated protein kinases (MAPK) are key participants in the process of apoptosis and different species of Leishmania have been shown to regulate these kinases. In the present study, we analyzed the effect of L. mexicana promastigotes in the activation of JNK and p38 MAP kinase and their participation in the inhibition of apoptosis. The infection of moDC with L. mexicana promastigotes diminished significantly the phosphorylation of the MAP kinases JNK and p38. The inhibition of both kinases diminished DNA fragmentation, but in a major extent was the reduction of DNA fragmentation when JNK was inhibited. The capacity of L. mexicana promastigotes to diminish MAP kinases activation is probably one of the strategies employed to delay apoptosis induction in the infected moDC and may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.

  14. Production of camptothecin in cultures of Chonemorpha grandiflora

    Directory of Open Access Journals (Sweden)

    A V Kulkarni

    2010-01-01

    Full Text Available Background : Chonemorpha grandiflora (Syn. Chonemorpha fragrans (Apocynaceae is an endangered medicinal plant. It is used in different preparations, such as sudarsanasavam and kumaryasavam used in Kerala Ayurvedic system. C. grandiflora is used for the treatment of fever and stomach disorders. Phytochemical investigations have revealed the presence of steroidal alkaloids, such as chonemorphine and funtumafrine in C. grandiflora. Camptothecin, a well-known anticancer alkaloid has been detected in ethanolic extracts of stem with bark and callus cultures derived from C. grandiflora. Methods: Callus cultures of C. grandiflora were raised on Murashige and Skoog′s medium supplemented with 2, 4-D. Stem with bark and callus were used for phytochemical analysis mainly the alkaloids. Detection and identification of camptothecin was carried out using thin-layer chromatography (TLC, high-performance thin-layer chromatography, (HPTLC and high-performance liquid chromatography (HPLC. Results: An important anticancer alkaloid, camptothecin was detected in ethanolic extracts of stem with bark and callus cultures of C. grandiflora. camptothecin content was 0.013 mg/g in stem with bark and 0.003 mg/g in callus. Conclusion : This is the first report on in vivo and in vitro production of camptothecin in C. grandiflora. Camptothecin is known to occur only in six plant sources so, alternative sources for camptothecin are needed. Thus of C. grandiflora could be a new promising alternative source of camptothecin.

  15. 3-甲基腺嘌呤对喜树碱诱导的宫颈癌Hela细胞凋亡的影响%Effect of 3-MA on camptothecin-induced cervical cancer Hela cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    王晓娜; 任来峰; 赵安江; 杨万霞; 任云青

    2016-01-01

    Objective:To explore the effect of autophagy inhibitor 3-methyladenine(3-MA) on camptothecin(CPT)-induced Hela cell apoptosis.Methods:MTT assays were carried out to determine the optimal concentration and time of CPT on Hela cells and the effect of different drugs on Hela cell proliferation activity .After Hela cells were treated with different drugs ,the changes of autophagy marker protein( microtubule-associated protein 1 light chain 3,LC3),p62 and apoptosis-related protein were detected using Western blot and immunofluorescence ( IF) .DAPI ( nuclear ) staining was used to observe cell apoptosis rate .Results: In CPC-treated Hela cells,Hela cell proliferation activity declined dramatically ,and autophagy could be induced to occur .Compared with CPT group ,the cell proliferation activity was lower in CPT combined with 3-MA group,the level of autophagy decreased ,but the apoptosis rate significantly increased.Conclusion:CPT can induce autophagy while inducing Hela cell death .Hela cells chemosensitivity to CPT treatment can be enhanced by 3-MA inhibiting autophagy .%目的:本研究探讨自噬抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)对喜树碱(Camptothecin,CPT)诱导的Hela细胞凋亡的影响。方法:用四甲基偶氮唑盐比色法( MTT方法)检测CPT对Hela细胞作用的最佳药物浓度和时间,以及不同药物对Hela细胞增殖活性的影响;用免疫印迹及免疫荧光检测不同药物作用于Hela细胞后,Hela细胞自噬标志蛋白微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)、p62及凋亡相关蛋白的变化;DAPI核染色观察细胞凋亡。结果:CPT作用于Hela细胞后,Hela细胞增殖活性明显下降,并且可诱导自噬现象的发生。 CPT和3-MA联合作用较单独CPT作用Hela细胞的增殖活性降低,细胞自噬水平下降,凋亡率明显升高。结论:CPT在诱导Hela细胞凋亡的同时可诱导自噬,通过3-MA

  16. Automatic mode switching of a dual chamber implantable cardioverter-defibrillator induced by a ventricular escape rhythm.

    Science.gov (United States)

    Barold, S Serge; Van Heuverswyn, Frederic; Stroobandt, Roland X

    2013-01-01

    This report describes a form of group beating induced by a St Jude dual chamber ICD which interpreted a ventricular escape rhythm (with retrograde conduction) as premature ventricular complexes (PVC). These pacemaker-defined PVCs activated the atrial pace-PVC algorithm in 2 steps. 1. The postventricular atrial refractory period (PVARP) was terminated upon detecting a retrograde P wave within its unblanked portion, and 2. An atrial stimulus was released 330ms after the end of the PVARP. This response resulted in automatic mode switching because the 330ms interatrial interval was shorter than the atrial tachycardia detection interval. The arrhythmia may be considered to represent an unusual form of pacemaker escape-capture bigeminy.

  17. 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.

  18. Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting Listeria-induced phagosomal escape.

    Directory of Open Access Journals (Sweden)

    Suraj P Parihar

    Full Text Available Statins are well-known cholesterol lowering drugs targeting HMG-CoA-reductase, reducing the risk of coronary disorders and hypercholesterolemia. Statins are also involved in immunomodulation, which might influence the outcome of bacterial infection. Hence, a possible effect of statin treatment on Listeriosis was explored in mice. Statin treatment prior to subsequent L. monocytogenes infection strikingly reduced bacterial burden in liver and spleen (up to 100-fold and reduced histopathological lesions. Statin-treatment in infected macrophages resulted in increased IL-12p40 and TNF-α and up to 4-fold reduced bacterial burden within 6 hours post infection, demonstrating a direct effect of statins on limiting bacterial growth in macrophages. Bacterial uptake was normal investigated in microbeads and GFP-expressing Listeria experiments by confocal microscopy. However, intracellular membrane-bound cholesterol level was decreased, as analyzed by cholesterol-dependent filipin staining and cellular lipid extraction. Mevalonate supplementation restored statin-inhibited cholesterol biosynthesis and reverted bacterial growth in Listeria monocytogenes but not in listeriolysin O (LLO-deficient Listeria. Together, these results suggest that statin pretreatment increases protection against L. monocytogenes infection by reducing membrane cholesterol in macrophages and thereby preventing effectivity of the cholesterol-dependent LLO-mediated phagosomal escape of bacteria.

  19. A process for preparation of anticancer drug 9-nitro camptothecin

    Institute of Scientific and Technical Information of China (English)

    FU Qing-Quan; CHEN Zhi-Yong; WANG Yuan-Hua; LIU Wei-Jun; HUANG Hao-Xi; HU Wen-Hao

    2004-01-01

    Camptothecin and some of its semisythetic derivatives such as topotecan, irinotecan and 9-nitrocamptothecin, have exhibited strong antitumor activity against various experimental tumor model. The water insoluble 9-nitrocamptothecin demonstrated very potent antitumor activity against many different types of human cancers and HIV. Literature procedures for preparing 9-nitrocamptothecin are direct nitration of camptothecin using a concentrated nitric/concentrated sulfuric acid system or a combination of two or more different nitrate salts/concentrated sulfuric acid system. The two systems demand on the chromatographically separation, which is a hindrance to industrial production. We found that the main products of nitration of camptothecin,9-nitrocamptothecin and 12-nitrocamptothecin, have the great difference for the solubility in the organic solvent. So we studied various organic solvent for the crude product obtained from nitration of camptothecin using KNO3/concentrated sulfuric acid system. At last we found that the ethyl acetate is the best solvent for extraction of the reaction solution and tchloroform and the ether is the best solvent for recrystalization by screening various polarity of organic solvent.

  20. Different Sensitivities to Apoptotic Induction by Camptothecin between Normal and Senescent Lens Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Haike Guo; Haiying Jin; Liya Wang; Hongyang Zhang; Xin Yang

    2002-01-01

    Purpose: To investigate whether normal and senescent lens epithelial cells have different defense abilities to apoptotic induction factor in vitro.Methods: Rabbit lens epithelial cells were cultured, passed. When reaching confluence, cells from the first and seventh passage were stained by x-gal staining to detect cell senescence. Cell apoptosis was detected by TUNEL(Roche).10μmol/L camptothecin was used to induce cell apoptosis from the lens epithelial cells of the first and seventh passage to distinguish different sensitivities to apoptotic induction factor between normal and senescent cells.Results: The senescent cells (41.17% ± 5.24% ) were detected in the lens epithelial cell culture of the seventh passage, which are higher than those of the first passage (0.98% ±0. 39% ). There was no apoptotic cell detected in the cell cultures undisturbed. Exposure of the first passage cells to camptothecin resulted in death of approximately 23.87% ± 3.45% of the cells during a 36 hour exposure period. In contrast, significantly more lens epithelial cells died through the apoptosis (38.29% ±4. 01% ) from the seventh passage.Conclusion: Senescent cells increased with cell passage. Senescence lens epithelial cells do not undergo apoptosis if they were not disturbed. But the vulnerabilities to apoptotic induction between health and senescence cells were different.

  1. Bioreactor studies on the endophytic fungus Entrophospora infrequens for the production of an anticancer alkaloid camptothecin.

    Science.gov (United States)

    Amna, Touseef; Puri, Satish C; Verma, V; Sharma, Jai P; Khajuria, Rajinder K; Musarrat, Javed; Spiteller, Michael; Qazi, G N

    2006-03-01

    Twigs (young and old) from Nothapodytes foetida growing in the Jammu and Mahabaleshwar regions in India were used for the isolation of 52 strains of endophytic fungi and were tested for their ability to produce the anticancer alkaloid camptothecin. One of the isolates from the inner bark tissue of the N. foetida plant growing in the Jammu region of J&K state, India, was found to produce detectable quantities of camptothecin and its derivatives when grown in a semi-synthetic liquid medium. Camptothecin was identified by physicochemical analysis and further confirmed by spectroscopic studies. No camptothecin was detected in zero time cultures or in uninoculated culture broth. The maximum yield of camptothecin was 0.575 +/- 0.031 mg/100 g of dry cell mass in 96 h in shake flasks, whereas 4.96 +/- 0.73 mg/100 g of dry mass was recorded in 48 h in a bioreactor.

  2. Synthesis and anti-tumor activity of alkenyl camptothecin esters

    Institute of Scientific and Technical Information of China (English)

    Zhi-song CAO; John MENDOZA; Albert DEJESUS; Beppino GIOVANELLA

    2005-01-01

    Aim: To study the degrees of influence of changing side ester chains at position C20 of camptothecin on the anti-tumor activity of the molecules. Methods: The esterification reaction of camptothecin 1 and 9-nitrocamptothecin 2 with crotonic anhydride in pyridine gave the corresponding esters 3 and 4, respectively. The acylation of 1 and 2 with cinnamoyl chloride gave products 7 and 8. Epoxidation reaction of 3 and 4 with m-chloroperoxybenzoic acid in benzene solvent gave the products 5 and 6. Esters 3, 4, and 5 were tested for anti-tumor activity against 14 human cancer cell lines. Results: Both in vitro and in vivo anti-tumor activity studies for these esters were conducted and the data demonstrated positive results, that is, these esters were active against the tested tumor lines. Conclusion: Alkenyl esters 3 and 4 showed strong anti-tumor activity in vitro against 14 different cancer cell lines. Ester 3 was active against human breast carcinoma in mice and the toxicity of the agent was not observed in mice during the treatment, implying that this agent is effective for treatment with low toxicity.

  3. Genome-wide transcriptional effects of the anti-cancer agent camptothecin.

    Directory of Open Access Journals (Sweden)

    Artur Veloso

    Full Text Available The anti-cancer drug camptothecin inhibits replication and transcription by trapping DNA topoisomerase I (Top1 covalently to DNA in a "cleavable complex". To examine the effects of camptothecin on RNA synthesis genome-wide we used Bru-Seq and show that camptothecin treatment primarily affected transcription elongation. We also observed that camptothecin increased RNA reads past transcription termination sites as well as at enhancer elements. Following removal of camptothecin, transcription spread as a wave from the 5'-end of genes with no recovery of transcription apparent from RNA polymerases stalled in the body of genes. As a result, camptothecin preferentially inhibited the expression of large genes such as proto-oncogenes, and anti-apoptotic genes while smaller ribosomal protein genes, pro-apoptotic genes and p53 target genes showed relative higher expression. Cockayne syndrome group B fibroblasts (CS-B, which are defective in transcription-coupled repair (TCR, showed an RNA synthesis recovery profile similar to normal fibroblasts suggesting that TCR is not involved in the repair of or RNA synthesis recovery from transcription-blocking Top1 lesions. These findings of the effects of camptothecin on transcription have important implications for its anti-cancer activities and may aid in the design of improved combinatorial treatments involving Top1 poisons.

  4. Camptothecin-Based Regimens for Treatment of Ewing Sarcoma: sPast Studies and Future Directions

    Directory of Open Access Journals (Sweden)

    Lars Wagner

    2011-01-01

    Full Text Available New therapies are needed to improve survival for patients with Ewing sarcoma. Over the past decade, camptothecin agents such as topotecan and irinotecan have demonstrated activity against Ewing sarcoma, especially in combination with alkylating agents. Previous studies have shown camptothecin-based combinations to be tolerable outpatient strategies that are attractive for salvage therapy. This paper highlights important issues related to drug dosing, schedule of administration, pharmacokinetics, toxicity, and activity of commonly used camptothecin-based regimens. Also discussed are strategies for incorporating these regimens into therapy for newly diagnosed patients, including several potential possibilities for combination with targeted agents.

  5. Investigation on Voltammetric Behavior of Camptothecin and Its Analytical Application

    Institute of Scientific and Technical Information of China (English)

    ZHENG, Jian-Bin; MENG, Zu-Chao; LIU, Bo; ZHANG, Hong-Fang

    2006-01-01

    The voltammetric behavior of camptothecin (CPT) in Britton-Robinson (B-R) buffer solutions (pH 2.09-9.07)was studied by the means of linear sweep voltammetry (LSV), cyclic voltammetry (CV) and normal pulse voltammetry (NPV) at a hanging mercury drop electrode. In different pH range of B-R buffer solutions, CPT could cause three reduction waves. In B-R buffer solutions (pH 2.09-5.46), wave P1 yielded by CPT was a two-electron wave.Between pH 6.01 and 9.07, CPT could yield two reduction waves P2 and P3. In addition, the pure CPT obtained from camptotheca acumina grown only in China was determined by NPV, and a linear response was observed in the tion limit for CPT.

  6. 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.

  7. 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.

  8. Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin induces the escape of highly pathogenic avian influenza A H5N1 viruses from vaccine-induced immunity.

    Science.gov (United States)

    Hervé, Pierre-Louis; Lorin, Valérie; Jouvion, Grégory; Da Costa, Bruno; Escriou, Nicolas

    2015-12-01

    Highly pathogenic avian influenza A H5N1 viruses remain endemic in poultry in several countries and still constitute a pandemic threat. Since the early 20th century, we experienced four influenza A pandemics. H3N2 and H1N1pdm09 viruses that respectively emerged during 1968 and 2009 pandemics are still responsible for seasonal epidemics. These viruses evolve regularly by substitutions in antigenic sites of the hemagglutinin (HA), which prevent neutralization by antibodies directed against previous strains (antigenic drift). For seasonal H3N2 viruses, an addition of N-glycosylation sites (glycosites) on H3 contributed to this drift. Here, we questioned whether additional glycosites on H5 could induce an escape of H5N1 virus from neutralization, as it was observed for seasonal H3N2 viruses. Seven H5N1 mutants were produced by adding glycosites on H5. The most glycosylated virus escaped from neutralizing antibodies, in vitro and in vivo. Furthermore, a single additional glycosite was responsible for this escape.

  9. Multi-stress resistance in Lactococcus lactis is actually escape from purine-induced stress sensitivity

    DEFF Research Database (Denmark)

    Ryssel, Mia; Hviid, Anne-Mette Meisner; Dawish, Mohamed S.

    2014-01-01

    in the rich and complex M17 medium. When salvage of purines and subsequent conversion to GTP was permitted in various genetic backgrounds of L. lactis MG1363, the cells became sensitive to acid stress, indicating that an excess of guanine nucleotides induces stress sensitivity. The addition of phosphate......Multi-stress resistance is a widely documented and fascinating phenotype of lactococci where single mutations, preferentially in genes involved in nucleotide metabolism and phosphate uptake, result in elevated tolerance to multiple stresses simultaneously. In this report, we have analysed...... nucleotides is formed as a result of an improved conversion of guanosine in the salvage pathway. Based upon our findings, we suggest that L. lactis MG1363 is naturally multi-stress resistant in habitats devoid of any purine source. However, any exogenous purine that results in increased guanine nucleotide...

  10. Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer

    Science.gov (United States)

    Tsai, Hsiang-Ping; An, Herng-Wei; Lee, Chi-Ming; Wu, Jen-Chine; Chen, Chien-Shu; Huang, Shih-Hao; Hwang, Jaulang; Cheng, Kur-Ta; Leiw, Phui-Ly; Chen, Chi-Long; Lin, Chun-Mao

    2015-01-01

    DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers. PMID:26207989

  11. Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Yu-Chieh Lee

    Full Text Available DNA topoisomerase I (TOP1 levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT resistance in ovarian cancers and identified evodiamine (EVO, a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024. EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01 in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.

  12. Cold Ion Escape from Mars

    Science.gov (United States)

    Fränz, M.; Dubinin, E.; Wei, Y.; Morgan, D.; Andrews, D.; Barabash, S.; Lundin, R.; Fedorov, A.

    2013-09-01

    It has always been challenging to observe the flux of ions with energies of less than 10eV escaping from the planetary ionospheres. We here report on new measurements of the ionospheric ion flows at Mars by the ASPERA-3 experiment on board Mars Express in combination with the MARSIS radar experiment. We first compare calculations of the mean ion flux observed by ASPERA-3 alone with previously published results. We then combine observations of the cold ion velocity by ASPERA-3 with observations of the cold plasma density by MARSIS since ASPERA-3 misses the cold core of the ion distribution. We show that the mean density of the nightside plasma observed by MARSIS is about two orders higher than observed by ASPERA-3 (Fig.1). Combining both datasets we show that the main escape channel is along the shadow boundary on the tailside of Mars (Fig. 2). At a distance of about 0.5 R_M the flux settles at a constant value (Fig. 3) which indicates that about half of the transterminator ionospheric flow escapes from the planet. Possible mechanism to generate this flux can be the ionospheric pressure gradient between dayside and nightside or momentum transfer from the solar wind via the induced magnetic field since the flow velocity is in the Alfvénic regime.

  13. Escape from attracting sets in randomly perturbed systems.

    Science.gov (United States)

    Rodrigues, Christian S; Grebogi, Celso; de Moura, Alessandro P S

    2010-10-01

    The dynamics of escape from an attractive state due to random perturbations is of central interest to many areas in science. Previous studies of escape in chaotic systems have rather focused on the case of unbounded noise, usually assumed to have Gaussian distribution. In this paper, we address the problem of escape induced by bounded noise. We show that the dynamics of escape from an attractor's basin is equivalent to that of a closed system with an appropriately chosen "hole." Using this equivalence, we show that there is a minimum noise amplitude above which escape takes place, and we derive analytical expressions for the scaling of the escape rate with noise amplitude near the escape transition. We verify our analytical predictions through numerical simulations of two well-known two-dimensional maps with noise.

  14. Escape in Hill's Problem

    CERN Document Server

    Heggie, D C

    2000-01-01

    This didactic paper is motivated by the problem of understanding how stars escape from globular star clusters. One formulation of this problem is known, in dynamical astronomy, as Hill's problem. Originally intended as a model for the motion of the moon around the earth with perturbations by the sun, with simple modifications it also serves as a model for the motion of a star in a star cluster with perturbations by the galaxy. The paper includes introductory sections on the derivation of the equations of motion of Hill's problem, their elementary properties, and extensions to deal with non-point masses and non-circular orbits. We then show how the rate of escape may be calculated numerically and estimated theoretically, and discuss how this simple picture is modified if the stars in a cluster are also undergoing two-body relaxation. Finally we introduce some established ideas for obtaining the distribution of escape times.

  15. Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer.

    Science.gov (United States)

    Shamanna, Raghavendra A; Lu, Huiming; Croteau, Deborah L; Arora, Arvind; Agarwal, Devika; Ball, Graham; Aleskandarany, Mohammed A; Ellis, Ian O; Pommier, Yves; Madhusudan, Srinivasan; Bohr, Vilhelm A

    2016-03-22

    Werner syndrome protein (WRN) is a RecQ helicase that participates in DNA repair, genome stability and cellular senescence. The five human RecQ helicases, RECQL1, Bloom, WRN, RECQL4 and RECQL5 play critical roles in DNA repair and cell survival after treatment with the anticancer drug camptothecin (CPT). CPT derivatives are widely used in cancer chemotherapy to inhibit topoisomerase I and generate DNA double-strand breaks during replication. Here we studied the effects of CPT on the stability and expression dynamics of human RecQ helicases. In the cells treated with CPT, we observed distinct effects on WRN compared to other human RecQ helicases. CPT altered the cellular localization of WRN and induced its degradation by a ubiquitin-mediated proteasome pathway. WRN knockdown cells as well as CPT treated cells became senescent and stained positive for senescence-associated β-galactosidase at a higher frequency compared to control cells. However, the senescent phenotype was attenuated by ectopic expression of WRN suggesting functional implication of WRN degradation in CPT treated cells. Approximately 5-23% of breast cancer tumors are known to respond to CPT-based chemotherapy. Interestingly, we found that the extent of CPT-induced WRN degradation correlates with increasing sensitivity of breast cancer cells to CPT. The abundance of WRN decreased in CPT-treated sensitive cells; however, WRN remained relatively stable in CPT-resistant breast cancer cells. In a large clinical cohort of breast cancer patients, we find that WRN and topoisomerase I expression correlate with an aggressive tumor phenotype and poor prognosis. Our novel observations suggest that WRN abundance along with CPT-induced degradation could be a promising strategy for personalizing CPT-based cancer chemotherapeutic regimens.

  16. Deep sequencing reveals direct targets of gammaherpesvirus-induced mRNA decay and suggests that multiple mechanisms govern cellular transcript escape.

    Directory of Open Access Journals (Sweden)

    Karen Clyde

    Full Text Available One characteristic of lytic infection with gammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV, Epstein-Barr virus (EBV and murine herpesvirus 68 (MHV68, is the dramatic suppression of cellular gene expression in a process known as host shutoff. The alkaline exonuclease proteins (KSHV SOX, MHV-68 muSOX and EBV BGLF5 have been shown to induce shutoff by destabilizing cellular mRNAs. Here we extend previous analyses of cellular mRNA abundance during lytic infection to characterize the effects of SOX and muSOX, in the absence of other viral genes, utilizing deep sequencing technology (RNA-seq. Consistent with previous observations during lytic infection, the majority of transcripts are downregulated in cells expressing either SOX or muSOX, with muSOX acting as a more potent shutoff factor than SOX. Moreover, most cellular messages fall into the same expression class in both SOX- and muSOX-expressing cells, indicating that both factors target similar pools of mRNAs. More abundant mRNAs are more efficiently downregulated, suggesting a concentration effect in transcript targeting. However, even among highly expressed genes there are mRNAs that escape host shutoff. Further characterization of select escapees reveals multiple mechanisms by which cellular genes can evade downregulation. While some mRNAs are directly refractory to SOX, the steady state levels of others remain unchanged, presumably as a consequence of downstream effects on mRNA biogenesis. Collectively, these studies lay the framework for dissecting the mechanisms underlying the susceptibility of mRNA to destruction during lytic gammaherpesvirus infection.

  17. New Topoisomerase I mutations are associated with resistance to camptothecin

    Directory of Open Access Journals (Sweden)

    Pourquier Philippe

    2011-05-01

    Full Text Available Abstract Background Topoisomerase I (TOP1 is a nuclear enzyme that catalyzes the relaxation of supercoiled DNA during DNA replication and transcription. TOP1 is the molecular target of camptothecin and related drugs such as irinotecan and SN38 (irinotecan's active metabolite. Irinotecan is widely used as an anti-cancer agent in the treatment of metastatic colon cancer. However, its efficacy is often limited by the development of resistance. Methods We previously established several SN38 resistant HCT116-derived clones to study the mechanisms underlying resistance to SN38. Here, we investigated whether resistance to SN38 in these cell lines could be linked to the presence of TOP1 mutations and changes in its expression and activity. Functional analyses were performed on these cell lines challenged with SN38 and we specifically monitored the double strands breaks with γH2AX staining and replication activity with molecular combing. Results In SN38 resistant HCT116 clones we identified three new TOP1 mutations, which are located in the core subdomain III (p.R621H and p.L617I and in the linker domain (p.E710G and are packed together at the interface between these two domains. The presence of these TOP1 mutations in SN38 resistant HCT116 cells did not modify TOP1 expression or intrinsic activity. Conversely, following challenge with SN38, we observed a decrease of TOP1-DNA cleavage complexes and a reduction in double-stranded break formation. In addition, we showed that SN38 resistant HCT116 cells present a strong decrease in the SN38-dependent asymmetry of replication forks that is characteristic of SN38 sensitive HCT116 cells. Conclusions These results indicate that the TOP1 mutations are involved in the development of SN38 resistance. We hypothesize that p.L617, p.R621 and p.E710 TOP1 residues are important for the functionality of the linker and that mutation of one of these residues is sufficient to alter or modulate its flexibility

  18. A Lucky Escape

    Institute of Scientific and Technical Information of China (English)

    王道庚

    2009-01-01

    @@ This story concerns(有关)a spider(蜘蛛)and a certain general of ancient times who had lost a battle and,in the company of(在……陪同下)a faithful(忠诚的)servant,was trying to escape(逃脱)from the enemy.Both were extremely(极度,非常)tired,and both were hungry and thirsty,but they did not dare to go into any town for fear of (担心,害怕)being discovered and captured(捉)by the enemy.Toward evening they arrived at a mountain where there was a small cave.

  19. Escape from the Alternative

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2006-12-01

    Full Text Available This paper sets out to elaborate on Romania’s specific agenda regarding the approach to the integration process in the EU as a project of modernization. The focus is on the functional aspects, the type of strategic solutions destined to consolidate the specific transformations belonging to post-communist transition seen as an internal transition, on the one hand and on the other hand to push convergence as the essence of integration, marked by the vision of EU integration as a continuation of change, which is the stage of external transition. Identifying the prominent factors and the pragmatic priorities of the escape from the peripheries of development by engaging in evolution by way of the second modernization constitutes as well a target for analysis. One particularity of the method of analysis is the review if the value-set of the bobsled effect of path dependency – the path of the peripheries – as well as of the set of values of the escape from the peripheries.

  20. Effect of precursors feeding and media manipulation on production of novel anticancer pro-drug camptothecin from endophytic fungus.

    Science.gov (United States)

    Amna, Touseef; Amina, Musarat; Sharma, P R; Puri, S C; Al-Youssef, Hanan M; Al-Taweel, Areej M; Qazi, G N

    2012-10-01

    We have established methodology for the isolation and characterization of a novel endophytic fungus from the inner bark of medicinal plant Nothapodytes foetida, which produced camptothecin in Sabouraud broth (SB) under shake flask conditions. Camptothecin and its related compounds are at present obtained by extraction from intact plants, but fungal endopytes may be an alternative source of production. In present study we have observed the effect of different nutrient combinations and precursors (tryptophan, tryptamine, geraniol, citral, mevalonic acid and leucine) on the accumulation of camptothecin by endophytic fungus Entrophospora infrequens. The precursors were fed either alone or in combinations (tryptophan and geraniol, tryptophan and citral, tryptophan and mevalonic acid, tryptophan and leucine). The highest camptothecin content was observed in the range of 503 ± 25µg/100g dry cell mass in Sabouraud medium. Camptothecin content in the medium was increased by 2.5 folds by the presence of tryptophan and leucine whereas the production with trytophan was also significantly different from other treatments. Furthermore, the effect of fungal camptothecin on the morphology of human cancer cell lines was also studied. The treated cells showed reduction in size, condensation of nucleus and the protoplasmic extensions were reduced. All these characteristics are found in apoptotic cells.

  1. 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...... interstrand crosslinked adducts with dsDNA dramatically decreased the frequency of targeted repair/correction. The PNA conjugates were also studied in mammalian cell lines upon transfection of PNA bound EGFP reporter vector and scoring repair of the EGFP gene by FACS analysis of functional EGFP expression...... 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...

  2. Mars - an escaping planet?

    CERN Document Server

    Dvorak, R

    2005-01-01

    The chaotic behaviour of the motion of the planets in our Solar System is well established. Numerical experiments with a modified Solar System consisting of a more massive Earth have shown, that for special values of an enlargement factor K around 5 the dynamical state of a truncated planetary system (excluding Mercury and the outer planets Uranus and Neptune) is highly chaotic. On the contrary for values of the mass of the Earth up to the mass of Saturn no irregular dynamical behaviour was observed. We extended our investigations to the complete planetary system and showed, that this chaotic window found before still exists. Tests in different 'Solar Systems' showed that only including Jupiter and Saturn with their actual masses together with a 'massive' Earth (between 4 and 6 times more massive) destabilize the orbit of Mars so that even escapes from the system are possible.

  3. A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity

    OpenAIRE

    2012-01-01

    Type IB topoisomerases (Top1Bs) relax excessive DNA supercoiling associated with replication and transcription by catalyzing a transient nick in one strand to permit controlled rotation of the DNA about the intact strand. The natural compound camptothecin (CPT) and the cancer chemotherapeutics derived from it, irinotecan and topotecan, are highly specific inhibitors of human nuclear Top1B (nTop1). Previous work on vaccinia Top1B led to an elegant model that describes a straightforward depende...

  4. Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

    Science.gov (United States)

    Alibolandi, Mona; Taghdisi, Seyed Mohammad; Ramezani, Pouria; Hosseini Shamili, Fazileh; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

    2017-03-15

    In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line. Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer.

  5. HPLC analysis of camptothecin content in various parts of Nothapodytes foetida collected on different periods

    Institute of Scientific and Technical Information of China (English)

    AG Namdeo; A Sharma

    2012-01-01

    Objective: To investigate the content of topoisomerase I-DNA inhibitor alkaloid camptothecin (CPT) from various parts of Nothapodytes foetida (N. foetida) collected from the month of October to February. Methods: The content of CPT was quantified in the methanolic extract of various parts of N. foetida using high performance liquid chromatography (HPLC). Quantification was performed with the regression analysis and the method was validated as per ICH guidelines. Results: The results revealed that maximum concentrations of camptothecin were found in root (2.62%) collected in the month of February followed by fruits (January, 1.22%), stem (January, 0.81%) and leaves (February, 0.70%). Roots were found to have 3-fold higher concentration of CPT than the leaves and stem, while the fruits showed 2-fold higher concentration. Maximum concentration of camptothecin in fruits was observed in month of January, when they were not fully mature, which was 2-fold higher than that of young and fully mature fruits. Conclusions: These findings indicate that the synthesis of CPT differs in different parts of N. foetida and the content varies periodically.

  6. 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.

  7. 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

  8. Nociception and escape behavior in planarians

    Science.gov (United States)

    Schoetz Collins, Eva-Maria

    2015-03-01

    Planarians are famous and widely studied for their regenerative capabilities. When a moving planarian is cut through the middle, the resulting head and tail pieces instantaneously retract and exhibit a characteristic escape response that differs from normal locomotion. In asexual animals, a similar reaction is observed when the planarian undergoes fission, suggesting that reproduction through self-tearing is a rather traumatic event for the animal. Using a multiscale approach, we unravel the dynamics, mechanics, and functional aspects of the planarian escape response. This musculature-driven gait was found to be a dominating response that supersedes the urge to feed or reproduce and quantitatively differs from other modes of planarian locomotion (gliding, peristalsis). We show that this escape gait constitutes the animal's pain response mediated by TRP like receptors and the neurotransmitter histamine, and that it can be induced through adverse thermal, mechanical, electrical or chemical stimuli. Ultimately, we will examine the neuronal subpopulations involved in mediating escape reflexes in planarians and how they are functionally restored during regeneration, thereby gaining mechanistic insight into the neuronal circuits required for specific behaviors. Supported by BWF CASI and Sloan Foundation.

  9. Gene expression time-series analysis of Camptothecin effects in U87-MG and DBTRG-05 glioblastoma cell lines

    Directory of Open Access Journals (Sweden)

    Serra Roberto

    2008-08-01

    and mitosis and to the up-regulation of cell growth inhibition and DNA damage. Furthermore, the down-regulation of MYC and DP1 genes, which act as key transcription factors in cell growth control, together with the inhibition of BUB1, BUB3 and MAD2 mRNAs, which are known to be involved in the spindle checkpoint pathway, were specifically associated with the execution of senescence in U87-MG cells and addressed as critical factors that could drive the choice between different CPT-inducible effectors programs. In U87-MG cells we also found inflammation response and IL1-beta induction, as late transcriptional effects of Topo I treatment but these changes were only partially involved in the senescence development, as shown by IL1-beta gene silencing. Conclusion By comparing the transcription profile of two glioblastoma cell lines treated with camptothecin, we were able to identify the common cellular pathways activated upon Topo I inhibition. Moreover, our results helped in identifying some key genes whose expression seemed to be associated with the execution of senescence or apoptosis in U87-MG and DBTRG-05 cells, respectively.

  10. Effects of breast cancer resistance protein inhibitors and pharmaceutical excipients on decreasing gastrointestinal toxicity of camptothecin analogs

    Institute of Scientific and Technical Information of China (English)

    Xin-xin ZHANG; Wei-san PAN; Li GAN; Chun-liu ZHU; Yong GAN

    2008-01-01

    Aim: To investigate the effect of breast cancer resistance protein (BCRP) inhibitors and pharmaceutical excipients on reducing the biliary excretion of camptothecins (CPT), ameliorating delayed-type diarrhea and intestinal mucosa damage induced by CPT. Methods: The cumulative biliary excretion of irinotecan (CPT-11) and hydroxycamptothecin (HCPT) with or without BCRP inhibitors and excipients was investigated in rats. The gastrointestinal toxicity, assessed as the diarrheal score, body weight change and microscopic pathological damage was also determined in rats. Results: Breast cancer resistance protein (BCRP) exhibited important effects on the biliary excretion of CPT. Coadministration of BCRP inhibitors such as GF120918 and cyclosporin A reduced the biliary excretion of CPT-11 and HCPT. Pharmaceutical excipients such as Pluronic F68 and PEG 2000 stearate also showed inhibitory effects on BCRP and similarly reduced CPT biliary excretion. The observed gastrointestinal toxicity was ameliorated by coadministration of BCRP inhibitors and excipients compared with injection of CPT-11 and HCPT alone. Conclusion:The use of excipients as inhibitors of BCRP is safe and relatively non-toxic, and may lead to important pharmacotherapeutic benefits by decreasing the gastrointestinal toxicity of CPT.

  11. Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors.

    Science.gov (United States)

    Tomicic, Maja T; Kaina, Bernd

    2013-01-01

    Topoisomerase I (TOP1) inhibitors applied in cancer therapy such as topotecan and irinotecan are derivatives of the natural alkaloid camptothecin (CPT). The mechanism of CPT poisoning of TOP1 rests on inhibition of the re-ligation function of the enzyme resulting in the stabilization of the TOP1-cleavable complex. In the presence of CPTs this enzyme-DNA complex impairs transcription and DNA replication, resulting in fork stalling and the formation of DNA double-strand breaks (DSB) in proliferating cells. As with most chemotherapeutics, intrinsic and acquired drug resistance represents a hurdle that limits the success of CPT therapy. Preclinical data indicate that resistance to CPT-based drugs might be caused by factors such as (a) poor drug accumulation in the tumor, (b) high rate of drug efflux, (c) mutations in TOP1 leading to failure in CPT docking, or (d) altered signaling triggered by the drug-TOP1-DNA complex, (e) expression of DNA repair proteins, and (f) failure to activate cell death pathways. This review will focus on the issues (d-f). We discuss degradation of TOP1 as part of the repair pathway in the processing of TOP1 associated DNA damage, give a summary of proteins involved in repair of CPT-induced replication mediated DSB, and highlight the role of p53 and inhibitors of apoptosis proteins (IAPs), particularly XIAP and survivin, in cancer cell resistance to CPT-like chemotherapeutics.

  12. Dynamics of immune escape during HIV/SIV infection.

    Directory of Open Access Journals (Sweden)

    Christian L Althaus

    Full Text Available Several studies have shown that cytotoxic T lymphocytes (CTLs play an important role in controlling HIV/SIV infection. Notably, the observation of escape mutants suggests a selective pressure induced by the CTL response. However, it remains difficult to assess the definite role of the cellular immune response. We devise a computational model of HIV/SIV infection having a broad cellular immune response targeting different viral epitopes. The CTL clones are stimulated by viral antigen and interact with the virus population through cytotoxic killing of infected cells. Consequently, the virus population reacts through the acquisition of CTL escape mutations. Our model provides realistic virus dynamics and describes several experimental observations. We postulate that inter-clonal competition and immunodominance may be critical factors determining the sequential emergence of escapes. We show that even though the total killing induced by the CTL response can be high, escape rates against a single CTL clone are often slow and difficult to estimate from infrequent sequence measurements. Finally, our simulations show that a higher degree of immunodominance leads to more frequent escape with a reduced control of viral replication but a substantially impaired replicative capacity of the virus. This result suggests two strategies for vaccine design: Vaccines inducing a broad CTL response should decrease the viral load, whereas vaccines stimulating a narrow but dominant CTL response are likely to induce escape but may dramatically reduce the replicative capacity of the virus.

  13. An escape from crowding.

    Science.gov (United States)

    Freeman, Jeremy; Pelli, Denis G

    2007-10-26

    Crowding occurs when nearby flankers jumble the appearance of a target object, making it hard to identify. Crowding is feature integration over an inappropriately large region. What determines the size of that region? According to bottom-up proposals, the size is that of an anatomically determined isolation field. According to top-down proposals, the size is that of the spotlight of attention. Intriligator and Cavanagh (2001) proposed the latter, but we show that their conclusion rests on an implausible assumption. Here we investigate the role of attention in crowding using the change blindness paradigm. We measure capacity for widely and narrowly spaced letters during a change detection task, both with and without an interstimulus cue. We find that standard crowding manipulations-reducing spacing and adding flankers-severely impair uncued change detection but have no effect on cued change detection. Because crowded letters look less familiar, we must use longer internal descriptions (less compact representations) to remember them. Thus, fewer fit into working memory. The memory limit does not apply to the cued condition because the observer need remember only the cued letter. Cued performance escapes the effects of crowding, as predicted by a top-down account. However, our most parsimonious account of the results is bottom-up: Cued change detection is so easy that the observer can tolerate feature degradation and letter distortion, making the observer immune to crowding. The change detection task enhances the classic partial report paradigm by making the test easier (same/different instead of identifying one of many possible targets), which increases its sensitivity, so it can reveal degraded memory traces.

  14. Escape rates for Gibbs measures

    CERN Document Server

    Ferguson, Andrew

    2010-01-01

    We study the asymptotic behaviour of the escape rate of a Gibbs measure supported on a conformal repeller through a small hole. There are additional applications to the convergence of Hausdorff dimension of the survivor set.

  15. Direction of escape in reindeer

    OpenAIRE

    Baskin, Leonid M.; Terje Skogland

    1997-01-01

    We tested the hypothesis that reindeer prefer to run uphill and upwind when escaping from man. Groups of wild and feral reindeer in Norway, Svalbard and on Wrangel Island were approached and their behaviour and direction of escape were recorded. Two stages of interaction with man were studied: first flight and final withdrawal. First flights proved to be away from man, upwind and uphill. Most final withdrawals were in the direction reindeer were moving when first observed.

  16. Direction of escape in reindeer

    Directory of Open Access Journals (Sweden)

    Leonid M. Baskin

    1997-04-01

    Full Text Available We tested the hypothesis that reindeer prefer to run uphill and upwind when escaping from man. Groups of wild and feral reindeer in Norway, Svalbard and on Wrangel Island were approached and their behaviour and direction of escape were recorded. Two stages of interaction with man were studied: first flight and final withdrawal. First flights proved to be away from man, upwind and uphill. Most final withdrawals were in the direction reindeer were moving when first observed.

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

    Science.gov (United States)

    Kieler-Ferguson, Heidi M; Fréchet, Jean M J; Szoka, Francis C

    2013-01-01

    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.

  18. Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant

    DEFF Research Database (Denmark)

    Arnò, Barbara; D'Annessa, Ilda; Tesauro, Cinzia;

    2013-01-01

    , but it is characterized by a much faster religation rate. The hybrid enzyme is also camptothecin resistant. A 3D structure of the hybrid enzyme has been built and its structural-dynamical properties have been analyzed by molecular dynamics simulation. The analysis indicates that the swapped plasmodial linker samples......A human/plasmodial hybrid enzyme, generated by swapping the human topoisomerase IB linker domain with the corresponding domain of the Plasmodium falciparum enzyme, has been produced and characterized. The hybrid enzyme displays a relaxation activity comparable to the human enzyme...... in the modulation of the topoisomerase IB activity....

  19. Brain delivery of camptothecin by means of solid lipid nanoparticles: Formulation design, in vitro and in vivo studies

    DEFF Research Database (Denmark)

    Martins, S.; Tho, I.; Reimold, I.

    2012-01-01

    to stabilise the lactone ring, which is essential for its antitumour activity, and for avoiding premature loss of drug on the way to target camptothecin to the brain. A multivariate approach was used to assess the influence of the qualitative and quantitative composition on the physicochemical properties...... that fluorescently labelled SLN were detected in the brain after i.v. administration. This study indicates that the camptothecin-loaded SLN are a promising drug brain delivery system worth to explore further for brain tumour therapy. (C) 2012 Elsevier B. V. All rights reserved....

  20. 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.

  1. Submarine Escape Set Test Facilities

    Directory of Open Access Journals (Sweden)

    G.S.N. Murthy

    2009-07-01

    Full Text Available Submarine Escape Set (SES is used by submariners to escape from a sunken submarine. This set caters for breathing needs of the submariner under water, until he reaches the surface. Evaluation of such life-saving equipment is of paramount importance. This paper describes the submarine escape set and various constructional features and schedules of operation of test facilities designed indegenously and which can evaluate the SES. The test facility is divided into two parts: the reducer test facility, and the breathing bag test facility. The equipment has been rigorously tested and accepted by Indian Navy. Two such test facilities have been developed, one of which is installed at INS Satavahana, Visakhapatnam, and are working satisfactorily.

  2. An Approach to New Water-soluble Oligo(ethylene glycol) Camptothecin Analogues by 1,3-Dipolar Cycloaddition

    Institute of Scientific and Technical Information of China (English)

    Chun Yan XU; Ming Zhi HUANG

    2006-01-01

    Combined with an effective copper-catalyzed triazole-forming reaction, a series of novel camptothecin derivatives were synthesized. Incorporating oligo(ethylene glycol) chains into the derivatives enhanced their water-solubility when compared to the parent compound (up to 55-fold).

  3. Immunosuppressive cells in tumor immune escape and metastasis.

    Science.gov (United States)

    Liu, Yang; Cao, Xuetao

    2016-05-01

    Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy.

  4. DYNAMICS OF THE ESCAPE RESPONSE.

    Science.gov (United States)

    requirements. It has been shown that force is a lawful response measure under positive reinforcement (Notterman and Mintz, 1965). Subjects will adjust...concluded that response force in an escape situation is a lawful response measure, and that it operates in a manner similar to force under positive reinforcement .

  5. 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.

  6. 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.

  7. 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.

  8. New class of squalene-based releasable nanoassemblies of paclitaxel, podophyllotoxin, camptothecin and epothilone A.

    Science.gov (United States)

    Borrelli, Stella; Christodoulou, Michael S; Ficarra, Ilaria; Silvani, Alessandra; Cappelletti, Graziella; Cartelli, Daniele; Damia, Giovanna; Ricci, Francesca; Zucchetti, Massimo; Dosio, Franco; Passarella, Daniele

    2014-10-06

    The present study reports the preparation of a novel class of squalene conjugates with paclitaxel, podophyllotoxin, camptothecin and epothilone A. The obtained compounds are characterized by a squalene tail that makes them able to self-assemble in water, and by a drug unit connected via a disulfide-containing linker to secure the release inside the cell. All the obtained compounds were effectively able to self-assemble and to release the parent drug in vitro. Disulfide-containing paclitaxel-squalene derivative showed a similar biological activity when compared to the free drug. Immunofluorescence assay shows that this squalene conjugate enters A549 cells and stain microtubule bundles. The results described herein pave the way for different classes of squalene-based releasable nanoassemblies.

  9. Breast cancer cell line MCF7 escapes from G1/S arrest induced by proteasome inhibition through a GSK-3β dependent mechanism.

    Science.gov (United States)

    Gavilán, Elena; Giráldez, Servando; Sánchez-Aguayo, Inmaculada; Romero, Francisco; Ruano, Diego; Daza, Paula

    2015-05-05

    Targeting the ubiquitin proteasome pathway has emerged as a rational approach in the treatment of human cancers. Autophagy has been described as a cytoprotective mechanism to increase tumor cell survival under stress conditions. Here, we have focused on the role of proteasome inhibition in cell cycle progression and the role of autophagy in the proliferation recovery. The study was performed in the breast cancer cell line MCF7 compared to the normal mammary cell line MCF10A. We found that the proteasome inhibitor MG132 induced G1/S arrest in MCF10A, but G2/M arrest in MCF7 cells. The effect of MG132 on MCF7 was reproduced on MCF10A cells in the presence of the glycogen synthase kinase 3β (GSK-3β) inhibitor VII. Similarly, MCF7 cells overexpressing constitutively active GSK-3β behaved like MCF10A cells. On the other hand, MCF10A cells remained arrested after MG132 removal while MCF7 recovered the proliferative capacity. Importantly, this recovery was abolished in the presence of the autophagy inhibitor 3-methyladenine (3-MA). Thus, our results support the relevance of GSK-3β and autophagy as two targets for controlling cell cycle progression and proliferative capacity in MCF7, highlighting the co-treatment of breast cancer cells with 3-MA to synergize the effect of the proteasome inhibition.

  10. Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives.

    Science.gov (United States)

    Song, Zi-Long; Wang, Mei-Juan; Li, Lanlan; Wu, Dan; Wang, Yu-Han; Yan, Li-Ting; Morris-Natschke, Susan L; Liu, Ying-Qian; Zhao, Yong-Long; Wang, Chih-Ya; Liu, Huanxiang; Goto, Masuo; Liu, Heng; Zhu, Gao-Xiang; Lee, Kuo-Hsiung

    2016-06-10

    In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure-activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π-π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.

  11. Mechanism of E1A-mediated escape from ras-induced senescence in human fibraobIasts%E1A阻断ras诱导人成纤维细胞衰老机制的研究

    Institute of Scientific and Technical Information of China (English)

    李亦蕾; 余乐

    2011-01-01

    Objective To study the effect of binding activities of the NH2 terminus of E1A to the proteins regulating cell growth on ras-induced cell senescence and explore the mechanism of ElA-mediated escape from ras-induced senescence by E1A in human fibroblast. Methods In primary human fibroblasts, the proteins regulating cell growth in association with E1A NH2 terminus, including the Rb family proteins, p300/CBP, and p400, were inactivated or interfered. The effect of alterations in the binding activities of these proteins on cell senescence bypass mediated by E1A was evaluated by cell growth curve. Results Inactivation of Rb family proteins alone was not sufficient to rescue ras-induced cell senescence, whereas inactivation of both the Rb proteins and p300/CBP blocked ras-induced senescence of human fibroblasts. Conclusion Rb and p300/CBP binding activities are both required for E1A to bypass ras-induced senescence in human fibroblasts.%目的 通过研究ElA氨基端细胞生长调节蛋白结合活性对其阻断ras诱导的细胞衰老的影响,以明确在人类成纤维细胞ElA阻断ras诱导的细胞衰老的机制.方法 采用原代培养的人类成纤维细胞,通过灭活或干扰与ElA氨基端相关的细胞生长调节蛋白,包括Rb家族蛋白、p300/CBP、p400,利用细胞生长曲线确定这些蛋白结合活性对于ElA阻断ras诱导的细胞衰老的作用.结果 单纯灭活Rb家族蛋白不能阻断ras诱导的细胞衰老,而同时灭活Rb和p300/CBP即可阻断r弱诱导的细胞衰老.结论 Rb和p300/CBP的结合活性均是EIA阻断ras诱导的人成纤维细胞细胞衰老所必需的.

  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. 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.

  14. Addition of ester enolates to N-alkyl-2-fluoropyridinium salts: total synthesis of (+/-)-20-deoxycamptothecin and (+)-camptothecin.

    Science.gov (United States)

    Bennasar, M-Lluïsa; Zulaica, Ester; Juan, Cecília; Alonso, Yolanda; Bosch, Joan

    2002-10-18

    Several 4-substituted dihydropyridones or 2-pyridones have been prepared by nucleophilic addition of alpha-(methylsulfanyl)ester enolates to N-alkyl-2-fluoropyridinium salts, followed by acid hydrolysis or oxidation with concomitant hydrolysis, of the intermediate 2-fluoro-1,4-dihydropyridine adducts, respectively. Addition of the enolate derived from isopropyl alpha-(methylsulfanyl)butyrate to N-(quinolylmethyl)-2-fluoropyridinium triflate 21 followed by DDQ treatment gave pyridone 29, from which (+/-)-20-deoxycamptothecin (31), a known precursor of camptothecin, was synthesized by a radical cyclization-desulfurization, with subsequent elaboration of the lactone E ring by chemoselective reduction. A similar sequence starting from the enolate of a chiral 2-hydroxybutyric acid derivative (33) provides access to natural (+)-camptothecin (37).

  15. ESCAPE AS REINFORCEMENT AND ESCAPE EXTINCTION IN THE TREATMENT OF FEEDING PROBLEMS

    OpenAIRE

    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 swallowing), escape as reinforcement for mouth clean plus escape extinction (EE), and EE alone as treatment for the food refusal of 5 children. Results were si...

  16. 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.

  17. 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...

  18. Optimization of ultrasound-assisted extraction of camptothecin from Camptotheca acuminata seeds

    Institute of Scientific and Technical Information of China (English)

    JING Li-jia; LI Si-yang; CHANG Zui; WANG Yang; YAN Xiu-feng

    2011-01-01

    Naturally occurring camptothecin (CPT) is an important source of chemotherapeutic agents. The extraction from Camptotheca acuminata is still the main approach to obtain CPT compared with total synthesis. In the present study, ultrasound-assisted extractions (UAE) of CPT from C. acuminata seeds with alkaline solutions were investigated and CPT yield were determined by High Performance Liquid Chromatography. The conditions of alkaline species and concentrations, extraction time, extraction temperature and ultrasonic power were optimized.Results show that both Na3PO4 and Na2CO3 solutions gain good extraction yields, whereas Na3PO4 solution has stronger basicity and need higher concentration than Na2CO3 solution does, thus aqueous Na2CO3 is more beneficial for the extraction. The optimal condition was ultrasonically extracted with 0.5% aqueous Na2CO3 at 50℃ and ultrasonic power of 400 W for 60 min. Comparing with UAE with ethanol, the extraction with 0.5% Na2CO3 solution achieves higher yield. Moreover, aqueous Na2CO3 as a solvent has various advantages including non-toxicity, inflammable, non-corrosive and low cost, which ensure this UAE method is a superior method with high utilizing prospect.

  19. 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.

  20. Preparation, formula optimization and antitumor actions of mannitol coupling camptothecin nanoparticles.

    Science.gov (United States)

    Wang, Zhichao; Li, Qingyong; Zhao, Xiuhua; Sun, Baihe; Zhu, Qiaochu; Gao, Wenqing; Hua, Changlong

    2014-04-25

    The purpose of this work is to prepare a formulation using mannitol coupling Camptothecin (CPT) nanoparticles (CPT-NPs) to circumvent the difficult solubilization practice based on central composite experimental statistical design. CPT-NPs were prepared with a high-pressure homogenization technique method. The independent variables considered for the optimization of CPT-NPs were percentage of CPT in raw material (CPT and mannitol), concentration of CPT in working liquid, cycles numbers and homogenizer pressure for drug loading efficiency, particle size and polydispersity index. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized CPT-NPs showed an appropriate drug loading efficiency (18.09 ± 2.13%), a homogeneous particle size (165.33 ± 37.23 nm) and a low polydispersity index (0.29 ± 0.01). The CPT-NPs group show higher inhibition ratio (79.95%) of H22 tumor growth in vivo compared with TPT and CPT at the same dose. Changes in mice body weight demonstrate CPT-NPs have the lower toxicity. The results of biodistribution studies indicated the obviously superiority of CPT-NPs in increasing the accumulation of CPT within tumor. Overall, CPT-NPs under optimum conditions are considered to be potentially feasible to overcome formulation challenges for drug delivery.

  1. 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.

  2. New polymorphs of 9-nitro-camptothecin prepared using a supercritical anti-solvent process.

    Science.gov (United States)

    Huang, Yinxia; Wang, Hongdi; Liu, Guijin; Jiang, Yanbin

    2015-12-30

    Recrystallization and micronization of 9-nitro-camptothecin (9-NC) has been investigated using the supercritical anti-solvent (SAS) technology in this study. Five operating factors, i.e., the type of organic solvent, the concentration of 9-NC in the solution, the flow rate of 9-NC solution, the precipitation pressure and the temperature, were optimized using a selected OA16 (4(5)) orthogonal array design and a series of characterizations were performed for all samples. The results showed that the processed 9-NC particles exhibited smaller particle size and narrower particle size distribution as compared with 9-NC raw material (Form I), and the optimum micronization conditions for preparing 9-NC with minimum particle size were determined by variance analysis, where the solvent plays the most important role in the formation and transformation of polymorphs. Three new polymorphic forms (Form II, III and IV) of 9-NC, which present different physicochemical properties, were generated after the SAS process. The predicted structures of the 9-NC crystals, which were consistent with the experiments, were performed from their experimental XRD data by the direct space approach using the Reflex module of Materials Studio. Meanwhile, the optimal sample (Form III) was proved to have higher cytotoxicity against the cancer cells, which suggested the therapeutic efficacy of 9-NC is polymorph-dependent.

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

    Directory of Open Access Journals (Sweden)

    Qiaolin Dong

    2016-07-01

    Full Text Available 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.

  4. 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.

  5. Micropropagation and hairy root culture of Ophiorrhiza alata Craib for camptothecin production.

    Science.gov (United States)

    Ya-ut, Pornwilai; Chareonsap, Piyarat; Sukrong, Suchada

    2011-12-01

    An efficient system was developed for the in vitro micropropagation and hairy root culture of Ophiorrhiza alata Craib for camptothecin (CPT) production. Shoot multiplication on leaf and node explants from germinated seeds of O. alata was successful on half-strength Murashige and Skoog medium supplemented with varying amounts of kinetin and α-naphthaleneacetic acid. Node explants grown in vitro were successfully infected by Agrobacterium rhizogenes TISTR 1450 for the establishment of hairy root culture. The amount of CPT in various parts of O. alata was analyzed by HPLC. The accumulation of CPT in transformed hairy roots was twice that in soil-grown plants (785 ± 52 and 388 ± 32 μg/g dry wt, respectively). In the presence of a polystyrene resin (Diaion HP-20) that absorbed CPT, the CPT content in the culture media increased sevenfold compared with controls (1,036 and 151 μg per 250 ml medium, respectively). These results enable the feasible production of CPT of O. alata by means of a cell culture strategy. These measures can help safeguard the plant from extinction.

  6. 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.

  7. 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.

  8. Relationship between DNA damage response, initiated by camptothecin or oxidative stress, and DNA replication, analyzed by quantitative 3D image analysis.

    Science.gov (United States)

    Berniak, K; Rybak, P; Bernas, T; Zarębski, M; Biela, E; Zhao, H; Darzynkiewicz, Z; Dobrucki, J W

    2013-10-01

    A method of quantitative analysis of spatial (3D) relationship between discrete nuclear events detected by confocal microscopy is described and applied in analysis of a dependence between sites of DNA damage signaling (γH2AX foci) and DNA replication (EdU incorporation) in cells subjected to treatments with camptothecin (Cpt) or hydrogen peroxide (H2O2). Cpt induces γH2AX foci, likely reporting formation of DNA double-strand breaks (DSBs), almost exclusively at sites of DNA replication. This finding is consistent with the known mechanism of induction of DSBs by DNA topoisomerase I (topo1) inhibitors at the sites of collisions of the moving replication forks with topo1-DNA "cleavable complexes" stabilized by Cpt. Whereas an increased level of H2AX histone phosphorylation is seen in S-phase of cells subjected to H2O2, only a minor proportion of γH2AX foci coincide with DNA replication sites. Thus, the increased level of H2AX phosphorylation induced by H2O2 is not a direct consequence of formation of DNA lesions at the sites of moving DNA replication forks. These data suggest that oxidative stress induced by H2O2 and formation of the primary H2O2-induced lesions (8-oxo-7,8-dihydroguanosine) inhibits replication globally and triggers formation of γH2AX at various distances from replication forks. Quantitative analysis of a frequency of DNA replication sites and γH2AX foci suggests also that stalling of replicating forks by Cpt leads to activation of new DNA replication origins. © 2013 International Society for Advancement of Cytometry.

  9. Sirt1 attenuates camptothecin-induced apoptosis through caspase-3 pathway in porcine preadipocytes

    Science.gov (United States)

    Adipose tissue is an important energy reservoir, and its over-development results in obesity in humans or body fat over-deposition in livestock. Loss of preadipocytes through apoptosis has been proposed as an alternative way to reduce adipose tissue mass. At present, the effect and regulatory mechan...

  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. 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.

  12. Escaping in Literature. Teaching in the Library.

    Science.gov (United States)

    Hurst, Carol Otis

    1993-01-01

    Explores the "escape" genre of children's literature, and recommends and describes several books that deal with such topics as escape from prison camps, from slavery, from the Holocaust, from war, and from Utopian societies. These books should provoke meaningful classroom discussions and allow children to view their own world from different…

  13. Statin escape phenomenon: Fact or fiction?

    Science.gov (United States)

    Barkas, Fotios; Elisaf, Moses; Klouras, Eleftherios; Dimitriou, Theodora; Tentolouris, Nikolaos; Liberopoulos, Evangelos

    2017-01-01

    AIM To evaluate the presence of the so called “statin escape” phenomenon among hyperlipidemic subjects attending a lipid clinic. METHODS This was a retrospective analysis of 1240 hyperlipidemic individuals followed-up for ≥ 3 years. We excluded those individuals meeting one of the following criteria: Use of statin therapy at baseline visit, discontinuation of statin treatment at most recent visit, change in statin treatment during follow-up and poor compliance to treatment. Statin escape phenomenon was defined as an increase in low-density lipoprotein cholesterol (LDL-C) levels at the most recent visit by > 10% compared with the value at 6 mo following initiation of statin treatment. RESULTS Of 181 eligible subjects, 31% exhibited the statin escape phenomenon. No major differences regarding baseline characteristics were found between statin escapers and non-statin escapers. Both escapers and non-escapers had similar baseline LDL-C levels [174 (152-189) and 177 (152-205) mg/dL, respectively]. In comparison with non-escapers, statin escapers demonstrated lower LDL-C levels at 6 mo after treatment initiation [88 (78-97) mg/dL vs 109 (91-129) mg/dL, P statin-treated individuals. The clinical significance of this phenomenon remains uncertain.

  14. Atmospheric escape, redox evolution, and planetary habitability

    Science.gov (United States)

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

    2011-12-01

    Through the greenhouse effect, the presence and composition of an atmosphere is critical for defining a (conventional) circumstellar habitable zone in terms of planetary surface temperatures suitable for liquid water. Lack of knowledge of planetary atmospheres is likely to frustrate attempts to say with any certainty whether detected terrestrial-sized exoplanets may or may not be habitable. Perhaps an underappreciated role in such considerations is the evolutionary effect of atmospheric escape for determining atmospheric composition or whether an atmosphere exists in the first place. Whether atmospheres exist at all on planets is demonstrably connected to the effect of integrated atmospheric escape. When we observe our own Solar System and transiting exoplanets, the existence of an atmosphere is clearly delineated by a relative vulnerability to thermal escape and impact erosion. The prevalence of thermal escape as a key evolutionary determinant for the presence of planetary atmosphere is shown by a relationship between the relative solar (or stellar) heating and the escape velocity. Those bodies with too much stellar heating and too smaller escape velocity end up devoid of atmospheres. Impact erosion is evident in the relationship between impact velocity and escape velocity. Escape due to impacts is particularly important for understanding the large differences in the atmospheres of giant planet moons, such as Ganymede versus Titan. It is also significant for Mars-sized planets. The oxidation state of atmospheres is important for some theories of the origin of life (where an early reducing atmosphere is helpful for organic synthesis) and the evolution of advanced life (where free molecular oxygen is the best source of high energy metabolism). Surfaces on some relatively small planets and moons are observed to have evolved to an oxidized state, which theory and observation can explain through atmospheric escape. There are several examples in the Solar System where a

  15. A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity.

    Science.gov (United States)

    Seol, Yeonee; Zhang, Hongliang; Pommier, Yves; Neuman, Keir C

    2012-10-02

    Type IB topoisomerases (Top1Bs) relax excessive DNA supercoiling associated with replication and transcription by catalyzing a transient nick in one strand to permit controlled rotation of the DNA about the intact strand. The natural compound camptothecin (CPT) and the cancer chemotherapeutics derived from it, irinotecan and topotecan, are highly specific inhibitors of human nuclear Top1B (nTop1). Previous work on vaccinia Top1B led to an elegant model that describes a straightforward dependence of rotation and religation on the torque caused by supercoiling. Here, we used a single-molecule DNA supercoil relaxation assay to measure the torque dependence of nTop1 and its inhibition by CPT. For comparison, we also examined mitochondrial Top1B and an N-terminal deletion mutant of nTop1. Despite substantial sequence homology in their core domains, nTop1 and mitochondrial Top1B exhibit dramatic differences in sensitivity to torque and CPT, with the N-terminal deletion mutant of nTop1 showing intermediate characteristics. In particular, nTop1 displays nearly torque-independent religation probability, distinguishing it from other Top1B enzymes studied to date. Kinetic modeling reveals a hitherto unobserved torque-independent transition linking the DNA rotation and religation phases of the enzymatic cycle. The parameters of this transition determine the torque sensitivity of religation and the efficiency of CPT binding. This "kinetic clutch" mechanism explains the molecular basis of CPT sensitivity and more generally provides a framework with which to interpret Top1B activity and inhibition.

  16. 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].

  17. Failure of rats to escape from a potentially lethal microwave field

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, D.R.; Levinson, D.M.; Justesen, D.R.; Clarke, R.L.

    1980-01-01

    Ocularly pigmented rats, all mature females of the Long-Evans strain, were repeatedly presented an opportunity to escape from an intense 918-MHz field (whole-body dose rate . 60 mW/g) to a field of lower intensity (40, 30, 20, or 2 mW/g) by performing a simple locomotor response. Other rats could escape 800-microamperemeter faradic shock to the feet and tail by performing the same response in the same milieu, a multimode cavity. None of 20 irradiated rats learned to associate entry into a visually well-demarcated area of the cavity with immediate reduction of dose rate, in spite of field-induced elevations of body temperature to levels that exceeded 41 degrees C and would have been lethal but for a limit on durations of irradiation. In contrast, all of ten rats motivated by faradic shock rapidly learned to escape. The failure of escape learning by irradiated animals probably arose from deficiencies of motivation and, especially, sensory feedback. Whole-body hyperthermia induced by a multipath field may lack the painful or directional sensory properties that optimally promote the motive to escape. Moreover, a decline of body temperature after an escape-response-contingent reduction of field strength will be relatively slow because of the large thermal time constants of mammalian tissues. Without timely sensory feedback, which is an essential element of negative reinforcement, stimulus-response associability would be imparied, which could retard or preclude learning of an escape response.

  18. Quantifying Distributions of Lyman Continuum Escape Fraction

    CERN Document Server

    Cen, Renyue

    2015-01-01

    Simulations have indicated that most of the escaped Lyman continuum photons escape through a minority of solid angles with near complete transparency, with the remaining majority of the solid angles largely opaque, resulting in a very broad and skewed probability distribution function (PDF) of the escape fraction when viewed at different angles. Thus, the escape fraction of Lyman continuum photons of a galaxy observed along a line of sight merely represents the properties of the interstellar medium along that line of sight, which may be an ill-representation of true escape fraction of the galaxy averaged over its full sky. Here we study how Lyman continuum photons escape from galaxies at $z=4-6$, utilizing high-resolution large-scale cosmological radiation-hydrodynamic simulations. We compute the PDF of the mean escape fraction ($\\left$) averaged over mock observational samples, as a function of the sample size, compared to the true mean (had you an infinite sample size). We find that, when the sample size is...

  19. Estimates of N2 narcosis and O2 toxicity during submarine escapes from 600 to 1,000 fsw.

    Science.gov (United States)

    Connor, Christopher W; Ferrigno, Massimo

    2009-01-01

    The U.S. Navy recommends submarine escape for depths down to 600 fsw, with deeper escapes entailing the risks of decompression sickness, nitrogen (N2) narcosis and CNS oxygen (O2) toxicity. However, the escape equipment, including the submarine escape and immersion equipment and the escape trunk, could probably function even at 1,000 fsw. Here we report a theoretical analysis of the risks of both N2 narcosis and CNS O2 toxicity for different escape profiles from 600 to 1,000 fsw. The effect of N2 narcosis, calculated as a function of N2 pressure in the brain using Gas Man software, was expressed as equivalent narcosis depth (END), corresponding to the depth at which the same pressure of N2 would be produced in the brain after five minutes of scuba diving with air. The risk of O2-induced convulsions was estimated using the model developed by Arieli et al. Different dwell times (DTs) at maximal pressure in the escape trunk (from 0 to 60 s) and lungs-to-brain circulation times (10 to 30 s) were included in our analysis. When DT in the escape trunk is very short (e.g., 10 s), the risk of either incapacitating N2 narcosis and/or O2-induced convulsions occurring in the trunk is low, even during escapes from 1,000 fsw.

  20. The escape velocity and Schwarzschild metric

    CERN Document Server

    Murzagalieva, A G; Murzagaliev, G Z

    2002-01-01

    The escape velocity value in the terms of general relativity by means Schwarzschild metric is provided to make of the motion equation with Friedman cosmological model behavior build in the terms of Robertson-Worker metric. (author)

  1. 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

  2. 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

  3. Polymer escape from a confining potential

    Energy Technology Data Exchange (ETDEWEB)

    Mökkönen, Harri, E-mail: harri.mokkonen@aalto.fi [Department of Applied Physics and COMP CoE, Aalto University School of Science, P.O. Box 11100, FIN-00076 Aalto, Espoo (Finland); Faculty of Physical Sciences, University of Iceland, Reykjavík (Iceland); Ikonen, Timo [Department of Applied Physics and COMP CoE, Aalto University School of Science, P.O. Box 11100, FIN-00076 Aalto, Espoo (Finland); VTT Technical Research Centre of Finland, P.O. Box 1000, FI-02044 VTT (Finland); Jónsson, Hannes [Department of Applied Physics and COMP CoE, Aalto University School of Science, P.O. Box 11100, FIN-00076 Aalto, Espoo (Finland); Faculty of Physical Sciences, University of Iceland, Reykjavík (Iceland); Department of Physics, Brown University, Providence, Rhode Island 02912-1843 (United States); Ala-Nissila, Tapio [Department of Applied Physics and COMP CoE, Aalto University School of Science, P.O. Box 11100, FIN-00076 Aalto, Espoo (Finland); Department of Physics, Brown University, Providence, Rhode Island 02912-1843 (United States)

    2014-02-07

    The rate of escape of polymers from a two-dimensionally confining potential well has been evaluated using self-avoiding as well as ideal chain representations of varying length, up to 80 beads. Long timescale Langevin trajectories were calculated using the path integral hyperdynamics method to evaluate the escape rate. A minimum is found in the rate for self-avoiding polymers of intermediate length while the escape rate decreases monotonically with polymer length for ideal polymers. The increase in the rate for long, self-avoiding polymers is ascribed to crowding in the potential well which reduces the free energy escape barrier. An effective potential curve obtained using the centroid as an independent variable was evaluated by thermodynamic averaging and Kramers rate theory then applied to estimate the escape rate. While the qualitative features are well reproduced by this approach, it significantly overestimates the rate, especially for the longer polymers. The reason for this is illustrated by constructing a two-dimensional effective energy surface using the radius of gyration as well as the centroid as controlled variables. This shows that the description of a transition state dividing surface using only the centroid fails to confine the system to the region corresponding to the free energy barrier and this problem becomes more pronounced the longer the polymer is. A proper definition of a transition state for polymer escape needs to take into account the shape as well as the location of the polymer.

  4. 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.

  5. Development and evaluation of lipid nanoparticles for camptothecin de-livery: a comparison of solid lipid nanoparticles, nanostructured lipid car-riers, and lipid emulsion

    Institute of Scientific and Technical Information of China (English)

    Zih-rou HUANG; Shu-chiou HUA; Yueh-lung YANG; Jia-you FANG

    2008-01-01

    Aim:Camptothecin is an anticancer drug that acta against a broad spectrum of tumors. The clinical application of camptothecin is limited by its insolubility, instability, and toxicity problems. The aim of this study was to develop and characterize lipid nanoparticles with different lipid cores which can circumvent these problems. Methods: Lipid nanoparticles made of Precirol (solid lipid nanoparticles; SLN-P), Compritol (SLN-C), Precirol+squalene (nanostructured lipid carriers; NLC), and squalene (a lipid emulsion; LE) as the lipid core ma-terial were prepared. These systems were assessed and compared by evaluat-ing the mean diameter, surface charge, molecular environment, camptothecin release, and cell viability against a melanoma. The safety and storage stability of these systems were also preliminarily examined. Results: The particle size ranged from 190 to 310 nm, with the NLC and LE showing the smallest and largest sizes, respectively. The in vitro drug release occurred in a sustained manner in decreasing order as follows: LE>NLC>SLN-P>SLN-C. It was found that varying the type of inner phase had profound effects on cell viability. The SLN-P generally showed higher cytotoxicity than the free control. The treat-ment of melanomas with the camptothecin-loaded SLN-C and NLC yielded cytotoxicity comparable to that of the free form. The percentage of erythrocyte hemolysis by all nanoparticles was ≤5%, suggesting a good tolerance to lipid nanoparticles. Conclusion: The results collectively suggest that the SLN-P may have the potential to serve as a delivery system for parenteral camptothecin ad-ministration because of the sustained drug release, strong cytotoxicity, limited hemolysis, and good storage stability.

  6. Genes that escape from X inactivation.

    Science.gov (United States)

    Berletch, Joel B; Yang, Fan; Xu, Jun; Carrel, Laura; Disteche, Christine M

    2011-08-01

    To achieve a balanced gene expression dosage between males (XY) and females (XX), mammals have evolved a compensatory mechanism to randomly inactivate one of the female X chromosomes. Despite this chromosome-wide silencing, a number of genes escape X inactivation: in women about 15% of X-linked genes are bi-allelically expressed and in mice, about 3%. Expression from the inactive X allele varies from a few percent of that from the active allele to near equal expression. While most genes have a stable inactivation pattern, a subset of genes exhibit tissue-specific differences in escape from X inactivation. Escape genes appear to be protected from the repressive chromatin modifications associated with X inactivation. Differences in the identity and distribution of escape genes between species and tissues suggest a role for these genes in the evolution of sex differences in specific phenotypes. The higher expression of escape genes in females than in males implies that they may have female-specific roles and may be responsible for some of the phenotypes observed in X aneuploidy.

  7. 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.

  8. Escape statistics for parameter sweeps through bifurcations.

    Science.gov (United States)

    Miller, Nicholas J; Shaw, Steven W

    2012-04-01

    We consider the dynamics of systems undergoing parameter sweeps through bifurcation points in the presence of noise. Of interest here are local codimension-one bifurcations that result in large excursions away from an operating point that is transitioning from stable to unstable during the sweep, since information about these "escape events" can be used for system identification, sensing, and other applications. The analysis is based on stochastic normal forms for the dynamic saddle-node and subcritical pitchfork bifurcations with a time-varying bifurcation parameter and additive noise. The results include formulation and numerical solution for the distribution of escape events in the general case and analytical approximations for delayed bifurcations for which escape occurs well beyond the corresponding quasistatic bifurcation points. These bifurcations result in amplitude jumps encountered during parameter sweeps and are particularly relevant to nano- and microelectromechanical systems, for which noise can play a significant role.

  9. Thermal escape from extrasolar giant planets.

    Science.gov (United States)

    Koskinen, Tommi T; Lavvas, Panayotis; Harris, Matthew J; Yelle, Roger V

    2014-04-28

    The detection of hot atomic hydrogen and heavy atoms and ions at high altitudes around close-in extrasolar giant planets (EGPs) such as HD209458b implies that these planets have hot and rapidly escaping atmospheres that extend to several planetary radii. These characteristics, however, cannot be generalized to all close-in EGPs. The thermal escape mechanism and mass loss rate from EGPs depend on a complex interplay between photochemistry and radiative transfer driven by the stellar UV radiation. In this study, we explore how these processes change under different levels of irradiation on giant planets with different characteristics. We confirm that there are two distinct regimes of thermal escape from EGPs, and that the transition between these regimes is relatively sharp. Our results have implications for thermal mass loss rates from different EGPs that we discuss in the context of currently known planets and the detectability of their upper atmospheres.

  10. Cosmic ray escape from supernova remnants

    CERN Document Server

    Gabici, Stefano

    2011-01-01

    Galactic cosmic rays are believed to be accelerated at supernova remnants via diffusive shock acceleration. Though this mechanism gives fairly robust predictions for the spectrum of particles accelerated at the shock, the spectrum of the cosmic rays which are eventually injected in the interstellar medium is more uncertain and depends on the details of the process of particle escape from the shock. Knowing the spectral shape of these escaping particles is of crucial importance in order to assess the validity of the supernova remnant paradigm for cosmic ray origin. Moreover, after escaping from a supernova remnant, cosmic rays interact with the surrounding ambient gas and produce gamma rays in the vicinity of the remnant itself. The detection of this radiation can be used as an indirect proof of the fact that the supernova remnant was indeed accelerating cosmic rays in the past.

  11. Bacillus anthracis factors for phagosomal escape.

    Science.gov (United States)

    Tonello, Fiorella; Zornetta, Irene

    2012-07-01

    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.

  12. 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

  13. 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.

  14. Do the visual conditions at the point of escape affect European sea bass escape behavior?

    Directory of Open Access Journals (Sweden)

    I.E. PAPADAKIS

    2013-04-01

    Full Text Available European sea bass (Dicentrarchus labrax, an important species for the Mediterranean aquaculture industry, has been reported to escape from sea cage installations. Fish escapes are caused mainly by operational and technical failures that eventually result into a creation of a tear. Escapees may interact with wild stocks through interbreeding, transfer of pathogens and competition for food. The aim of this study was to examine at which extent the presence of a visible obstacle close to a tear on the net have an influence on sea bass propensity to escape. Fish were initially confined into small sea cages, with a tear at one side. The escape behavior was tested under experimental conditions. It is clearly demonstrated that sea bass was able to locate a tear on the net pen, immediately after its appearance. Crossings occurred in all cages, in singles or in a series of up to seven individuals. The presence of an obstacle close to the net tear altered the escape behavior of D. labrax resulting in a delay that eventually reduced the escape rate. Concluding, it is highly recommended that sea bass cages should be kept internally the culture array. Furthermore, the placement of artificial obstacles close to the sea cages could be an efficient practice that mitigates the escape risk after severe environmental conditions.

  15. Net escapement of Antartic krill in trawls

    DEFF Research Database (Denmark)

    Krafft, B.A.; Krag, Ludvig Ahm; Herrmann, Bent;

    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...

  16. 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.

  17. The escape problem for mortal walkers

    CERN Document Server

    Grebenkov, D S

    2016-01-01

    We introduce and investigate the escape problem for random walkers that may eventually die, decay, bleach, or lose activity during their diffusion towards an escape or reactive region on the boundary of a confining domain. In the case of a first-order kinetics (i.e., exponentially distributed lifetimes), we study the effect of the associated death rate onto the survival probability, the exit probability, and the mean first passage time. We derive the upper and lower bounds and some approximations for these quantities. We reveal three asymptotic regimes of small, intermediate and large death rates. General estimates and asymptotics are compared to several explicit solutions for simple domains, and to numerical simulations. These results allow one to account for stochastic photobleaching of fluorescent tracers in bio-imaging, degradation of mRNA molecules in genetic translation mechanisms, or high mortality rates of spermatozoa in the fertilization process. This is also a mathematical ground for optimizing stor...

  18. 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.

  19. 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.

  20. Escaping from a Liquidity Trap and Deflation: The Foolproof Way and Others

    OpenAIRE

    Svensson, Lars E. O.

    2003-01-01

    Existing proposals to escape from a liquidity trap and deflation, including my "Foolproof Way," are discussed in the light of the optimal way to escape. The optimal way involves three elements: (1) an explicit central-bank commitment to a higher future price level; (2) a concrete action that demonstrates the central bank's commitment, induces expectations of a higher future price level and jump-starts the economy; and (3) an exit strategy that specifies when and how to get back to normal. A c...

  1. Dynamical Creation of Channels for Particle Escape in the Solar Corona

    CERN Document Server

    Mahajan, S M; Nikolskaya, K I; Shatashvili, N L; Mahajan, Swadesh M.; Miklaszewski, Riszard; Nikol'skaya, Komunela I.; Shatashvili, Nana L.

    2003-01-01

    It is shown that the connection of sufficiently fast flows with dynamical channels for particle escape in the Solar Corona is rather direct: it depends on their ability to deform (in specific cases to distort) the ambient magnetic field lines to temporarily stretch (shrink, destroy) the closed field lines so that the flow can escape the local region. Using a dissipative two--fluid code in which the flows are treated at par with the currents, we have demonstrated channel creation in a variety of closed--field line structures. This self--induced transparency constitutes the active mode for the formation of the solar wind.

  2. Toxin- and cadmium-induced cell death events in tomato suspension cells resemble features of hypersensitive response

    NARCIS (Netherlands)

    Iakimova, E.T.; Woltering, E.J.; Yordanova, Z.P.

    2007-01-01

    Elicitors of different origin (fumonisin B1, fungal toxin), camptothecin (alkaloid from Camptotheca acuminata), mastoparan (wasp venom) and the heavy metal (cadmium) were tested for their ability to induce programmed cell death (PCD) in a model system of tomato cell culture, line MsK8. By employing

  3. 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.

  4. Sputtering at Mars: MAVEN observations of precipitating and escaping oxygen during nominal and extreme conditions

    Science.gov (United States)

    Curry, Shannon; Luhmann, Janet; Dong, Chuanfei; Ma, Yingjuan; Leblanc, Francois; Modolo, Ronan; Brain, David; Gruesbeck, Jacob; Hara, Takuya; Halekas, Jasper; Dong, Yaxue; Williamson, Hayley N.; Johnson, Robert E.; McFadden, James; Espley, Jared R.; Mitchell, David; Connerney, Jack; Eparvier, Frank; Lillis, Robert J.; Jakosky, Bruce

    2016-10-01

    Sputtering is believed to be one of the dominant escape mechanisms during the early epochs of our solar system when the solar activity and EUV intensities were much higher than the present day. Mars lacks a global dynamo magnetic field, which creates a scenario where the solar wind directly interacts with the upper atmosphere and newly created ions can be picked up and swept away by the background convection electric field. These pick-up ions can directly escape or precipitate back into the atmosphere and induce atmospheric sputtering of neutrals.The MAVEN spacecraft has observed the Mars upper atmosphere, ionosphere, magnetic topology and interactions with the Sun and solar wind during numerous Interplanetary Coronal Mass Ejection (ICME) impacts spanning from March 2015 to June 2016. ICMEs are associated with enhanced solar wind velocities, densities and magnetic field strength, and often drive heavy ion precipitation at much higher rates than during nominal conditions. Thus, ICMEs provide a unique environment for observing sputtering. We will compare MAVEN observations of heavy ion precipitation during nominal conditions as well as during ICMEs. Additionally, we will present global MHD and test particle simulations of the ICMEs in order to calculate sputtering escape rates for oxygen. Finally, we will use the observed and modeled sputtering escape rates to provide an initial estimate of the total sputtered atmospheric escape from Mars over billions of years.

  5. 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.

  6. Ab initio study on the noncovalent adsorption of camptothecin anticancer drug onto graphene, defect modified graphene and graphene oxide.

    Science.gov (United States)

    Saikia, Nabanita; Deka, Ramesh C

    2013-09-01

    The application of graphene and related nanomaterials like boron nitride (BN) nanosheets, BN-graphene hybrid nanomaterials, and graphene oxide (GO) for adsorption of anticancer chemotherapeutic camptothecin (CPT) along with the effect on electronic properties prior to functionalization and after functionalization has been reported using density functional theory (DFT) calculations. The inclusion of dispersion correction to DFT is instrumental in accounting for van der Waals π-π stacking between CPT and the nanomaterial. The adsorption of CPT exhibits significant strain within the nanosheets and noncovalent adsorption of CPT is thermodynamically favoured onto the nanosheets. In case of GO, surface incorporation of functional groups result in significant crumpling along the basal plane and the interaction is basically mediated by H-bonding rather than π-π stacking. Docking studies predict the plausible binding of CPT, CPT functionalized graphene and GO with topoisomerase I (top 1) signifying that CPT interacts through π stacking with AT and GC base pairs of DNA and in presence of nano support, DNA bases preferentially gets bound to the basal plane of graphene and GO rather than the edges. At a theoretical level of understanding, our studies point out the noncovalent interaction of CPT with graphene based nanomaterials and GO for loading and delivery of anticancer chemotherapeutic along with active binding to Top1 protein.

  7. Preparation and characterization of inclusion complexes of antitumor camptothecin with cucurbit[n=7,8]urils

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The slightly water-soluble anticancer drug camptothecin(CPT) and its inclusion complexes with cucurbit[n = 7,8]uril(Q[n](n = 7,8)) were investigated.The formation of 1:2 complexes with Q[n](n = 7,8) in aqueous solution was confirmed by fluorescence spectroscopy and the apparent stability constants were determined to be higher than 3.01 × 1012 L2/mol2.The solid inclusion complexes of CPT and Q[n](n = 7,8) were also prepared by the co-evaporation method and characterized by Fourier transformation-infrared spectroscopy,differential scanning calorimetry and powder X-ray diffraction.Aqueous solubility and dissolution studies indicate that the complexes exhibited significantly increased dissolution rates compared with the pure drug and physical mixtures.The potential of Q[7] or Q[8] for stabilizing lactone modality of CPT was investigated by the High Performance Liquid Chromatography(HPLC) method.The results reveal more than 63% CPT lactone form(active form) in CPT-Q[7] or Q[8] complexes compared to only 36% CPT lactone form in the absence of Q[7] or Q[8] after being incubated in the phosphate buffer solution(pH 7.4 at 37 °C) for 5h.

  8. Influence of Sae-regulated and Agr-regulated factors on the escape of Staphylococcus aureus from human macrophages.

    Science.gov (United States)

    Münzenmayer, Lisa; Geiger, Tobias; Daiber, Ellen; Schulte, Berit; Autenrieth, Stella E; Fraunholz, Martin; Wolz, Christiane

    2016-08-01

    Although Staphylococcus aureus is not a classical intracellular pathogen, it can survive within phagocytes and many other cell types. However, the pathogen is also able to escape from cells by mechanisms that are only partially understood. We analysed a series of isogenic S. aureus mutants of the USA300 derivative JE2 for their capacity to destroy human macrophages from within. Intracellular S. aureus JE2 caused severe cell damage in human macrophages and could efficiently escape from within the cells. To obtain this full escape phenotype including an intermittent residency in the cytoplasm, the combined action of the regulatory systems Sae and Agr is required. Mutants in Sae or mutants deficient in the Sae target genes lukAB and pvl remained in high numbers within the macrophages causing reduced cell damage. Mutants in the regulatory system Agr or in the Agr target gene psmα were largely similar to wild-type bacteria concerning cell damage and escape efficiency. However, these strains were rarely detectable in the cytoplasm, emphasizing the role of phenol-soluble modulins (PSMs) for phagosomal escape. Thus, Sae-regulated toxins largely determine damage and escape from within macrophages, whereas PSMs are mainly responsible for the escape from the phagosome into the cytoplasm. Damage of macrophages induced by intracellular bacteria was linked neither to activation of apoptosis-related caspase 3, 7 or 8 nor to NLRP3-dependent inflammasome activation.

  9. 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.

  10. Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils.

    Science.gov (United States)

    Corleis, Björn; Korbel, Daniel; Wilson, Robert; Bylund, Johan; Chee, Ronnie; Schaible, Ulrich E

    2012-07-01

    Neutrophils enter sites of infection, where they can eliminate pathogenic bacteria in an oxidative manner. Despite their predominance in active tuberculosis lesions, the function of neutrophils in this important human infection is still highly controversial. We observed that virulent Mycobacterium tuberculosis survived inside human neutrophils despite prompt activation of these defence cells' microbicidal effectors. Survival of M. tuberculosis was accompanied by necrotic cell death of infected neutrophils. Necrotic cell death entirely depended on radical oxygen species production since chronic granulomatous disease neutrophils were protected from M. tuberculosis-triggered necrosis. More, importantly, the M. tuberculosis ΔRD1 mutant failed to induce neutrophil necrosis rendering this strain susceptible to radical oxygen species-mediated killing. We conclude that this virulence function is instrumental for M. tuberculosis to escape killing by neutrophils and contributes to pathogenesis in tuberculosis.

  11. Whole-body volume regulation and escape from antidiuresis.

    Science.gov (United States)

    Verbalis, Joseph G

    2006-07-01

    Both individual cells and organs regulate their volume in response to sustained hypo-osmolality via solute and water losses. Similar processes occur in the whole body to regulate the volumes of extracellular fluid (ECF) and intravascular spaces toward normal levels. Body water losses occur via the phenomena "escape from antidiuresis"; solute losses occur through the secondary natriuresis induced by water retention. As a result of resistance to arginine vasopressin (AVP) signaling, escape from antidiuresis is caused by downregulation of kidney aquaporin-2 expression despite high AVP plasma levels. Recent data have implicated downregulation of vasopressin V2R as a potential mechanism of resistance, and suggest that this may be a result of decreased intrarenal angiotensin II signaling in combination with increased intrarenal nitric oxide and prostaglandin E2 signaling. The natriuresis that results in volume regulation of the ECF and vascular spaces is the result of intrarenal hemodynamic changes produced by volume expansion, but the degree to which these effects are modulated by aldosterone secretion and the activity of distal sodium cotransporters and channels remains to be elucidated. The clinical implication of these volume-regulatory processes is that the chronic hyponatremic state is one of water retention and solute losses from intracellular fluid and ECF compartments. The degree to which solute losses versus water retention contribute to hyponatremia will vary in association with many factors, including the etiology of the hyponatremia, the rapidity of development of the hyponatremia, the chronicity of the hyponatremia, the volume of daily water loading, and individual variability. Understanding these volume-regulatory processes allows a better understanding of many aspects of the conundrum of patients with "clinical euvolemia" and dilutional hyponatremia from AVP-induced water retention.

  12. 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

  13. Serial Escape System For Aircraft Crews

    Science.gov (United States)

    Wood, Kenneth E.

    1990-01-01

    Emergency escape system for aircraft and aerospace vehicles ejects up to seven crewmembers, one by one, within 120 s. Intended for emergencies in which disabled craft still in stable flight at no more than 220 kn (113 m/s) equivalent airspeed and sinking no faster than 110 ft/s (33.5 m/s) at altitudes up to 50,000 ft (15.2 km). Ejection rockets load themselves from magazine after each crewmember ejected. Jumpmaster queues other crewmembers and helps them position themselves on egress ramp. Rockets pull crewmembers clear of aircraft structure. Provides orderly, controlled exit and avoids ditching at sea or landing in rough terrain.

  14. Evolutionary escape from the prisoner's dilemma.

    Science.gov (United States)

    Worden, Lee; Levin, Simon A

    2007-04-07

    The classic prisoner's dilemma model of game theory is modified by introducing occasional variations on the options available to players. Mutation and selection of game options reliably change the game matrix, gradually, from a prisoner's dilemma game into a byproduct mutualism one, in which cooperation is stable, and "temptation to defect" is replaced by temptation to cooperate. This result suggests that when there are many different potential ways of interacting, exploring those possibilities may make escape from prisoner's dilemmas a common outcome in the world. A consequence is that persistent prisoner's dilemma structures may be less common than one might otherwise expect.

  15. Fast escaping points of entire functions

    CERN Document Server

    Rippon, P J

    2010-01-01

    Let $f$ be a transcendental entire function and let $A(f)$ denote the set of points that escape to infinity `as fast as possible' under iteration. By writing $A(f)$ as a countable union of closed sets, called `levels' of $A(f)$, we obtain a new understanding of the structure of this set. For example, we show that if $U$ is a Fatou component in $A(f)$, then $\\partial U\\subset A(f)$ and this leads to significant new results and considerable improvements to existing results about $A(f)$. In particular, we study functions for which $A(f)$, and each of its levels, has the structure of an `infinite spider's web'. We show that there are many such functions and that they have a number of strong dynamical properties. This new structure provides an unexpected connection between a conjecture of Baker concerning the components of the Fatou set and a conjecture of Eremenko concerning the components of the escaping set.

  16. Escape of water molecular from Carbon Nanotubes

    Science.gov (United States)

    Li, Jiaxi; Li, Wenfeng; Zhang, Jianwei

    2014-03-01

    Understanding and controlling the transport of water molecules through nanopores have attracted great interest due to potential applications for designing novel nanofluidic devices, machines and sensors. In this work, we theoretically investigate the effects of an external nonuniform electric field on the escape of water molecules through single-walled carbon nanotubes (SWNTs) by using of molecular dynamics (MD) simulations. When polar water molecules are placed in the gradient electric field, the electric force is experienced that can drive the water molecules. Molecular dynamics simulations show that the escape probability of water obeys the Boltzmann distribution. Our results show that energy barrier delta E is independent of temperature which indicates that it is a single-barrier system. From the MD results statistics, the key parameters could be determined such that the relationship between energy barrier delta E and diameter of SWNTs and nozzle distance of the charge r would be revealed that could deepen our current theoretical understanding on transport of water molecular inside SWNTs with the nonuniform electric field.

  17. Uremic escape of renal allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    van Schilfgaarde, R. (Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis); van Breda Vriesman, P.J.C. (Rijksuniversiteit Limburg Maastricht (Netherlands). Dept. of Immunopathology)

    1981-10-01

    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.

  18. Escape from viscosity : the kinematics and hydrodynamics of copepod foraging and escape swimming

    NARCIS (Netherlands)

    van Duren, LA; Videler, JJ

    2003-01-01

    Feeding and escape swimming in adult females of the calanoid copepod. Temora lopgicornis Muller were investigated and compared. Swimming velocities were calculated using a 3-D filming setup., Foraging velocities ranged between 2 and 6 min s(-1), while maximum velocities of up to 80 mm s(-1) were rea

  19. 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.

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

    Science.gov (United States)

    Ünal, Hale; d'Angelo, Ivana; Pagano, Ester; Borrelli, Francesca; Izzo, Angelo; Ungaro, Francesca; Quaglia, Fabiana; Bilensoy, Erem

    2015-01-01

    The objective of this study was to design and in vitro-in vivo evaluate oral nanocapsules prepared from amphiphilic cyclodextrins (CDs) or poly-ɛ-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.

  1. Strong purifying selection at genes escaping X chromosome inactivation.

    Science.gov (United States)

    Park, Chungoo; Carrel, Laura; Makova, Kateryna D

    2010-11-01

    To achieve dosage balance of X-linked genes between mammalian males and females, one female X chromosome becomes inactivated. However, approximately 15% of genes on this inactivated chromosome escape X chromosome inactivation (XCI). Here, using a chromosome-wide analysis of primate X-linked orthologs, we test a hypothesis that such genes evolve under a unique selective pressure. We find that escape genes are subject to stronger purifying selection than inactivated genes and that positive selection does not significantly affect the evolution of these genes. The strength of selection does not differ between escape genes with similar versus different expression levels in males versus females. Intriguingly, escape genes possessing Y homologs evolve under the strongest purifying selection. We also found evidence of stronger conservation in gene expression levels in escape than inactivated genes. We hypothesize that divergence in function and expression between X and Y gametologs is driving such strong purifying selection for escape genes.

  2. Interplay and escape in three-body scattering.

    Science.gov (United States)

    Shebalin, J. V.; Tippens, A. L.

    1996-05-01

    The problem of three gravitationally interacting bodies, with total energy less than zero, is investigated numerically. After introducing the concepts of `periastron graphs' and `composite binaries', time-of-escape and interplay are precisely defined. These definitions are useful in characterizing the complete scattering process: escape to t=-{infinity}, interplay, and escape to t=+{infinity}. These definitions are also useful for the efficient and automatic termination of a numerical simulation of interplay.

  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. The Fastest Saccadic Responses Escape Visual Masking

    DEFF Research Database (Denmark)

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

    2014-01-01

    , 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......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...

  5. 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.

  6. The Origins and Underpinning Principles of E-Scape

    Science.gov (United States)

    Kimbell, Richard

    2012-01-01

    In this article I describe the context within which we developed project e-scape and the early work that laid the foundations of the project. E-scape (e-solutions for creative assessment in portfolio environments) is centred on two innovations. The first concerns a web-based approach to portfolio building; allowing learners to build their…

  7. Green Pea Galaxies Reveal Secrets of Lyα Escape

    Science.gov (United States)

    Yang, Huan; Malhotra, Sangeeta; Gronke, Max; Rhoads, James E.; Dijkstra, Mark; Jaskot, Anne; Zheng, Zhenya; Wang, Junxian

    2016-04-01

    We analyze archival Lyα spectra of 12 “Green Pea” galaxies observed with the Hubble Space Telescope, model their Lyα profiles with radiative transfer models, and explore the dependence of the Lyα escape fraction on various properties. Green Pea galaxies are nearby compact starburst galaxies with [O iii] λ5007 equivalent widths (EWs) of hundreds of Å. All 12 Green Pea galaxies in our sample show Lyα lines in emission, with an Lyα EW distribution similar to high-redshift Lyα emitters. Combining the optical and UV spectra of Green Pea galaxies, we estimate their Lyα escape fractions and find correlations between Lyα escape fraction and kinematic features of Lyα profiles. The escape fraction of Lyα in these galaxies ranges from 1.4% to 67%. We also find that the Lyα escape fraction depends strongly on metallicity and moderately on dust extinction. We compare their high-quality Lyα profiles with single H i shell radiative transfer models and find that the Lyα escape fraction anticorrelates with the derived H i column densities. Single-shell models fit most Lyα profiles well, but not the ones with the highest escape fractions of Lyα. Our results suggest that low H i column density and low metallicity are essential for Lyα escape and make a galaxy an Lyα emitter.

  8. Behavioural asymmetry affects escape performance in a teleost fish

    NARCIS (Netherlands)

    Dadda, Marco; Koolhaas, Wouter H.; Domenici, Paolo

    2010-01-01

    Escape performance is fundamental for survival in fish and most other animals. While previous work has shown that both intrinsic (e.g. size, shape) and extrinsic (e.g. temperature, hypoxia) factors can affect escape performance, the possibility that behavioural asymmetry may affect timing and locomo

  9. 46 CFR 169.313 - Means of escape.

    Science.gov (United States)

    2010-10-01

    ... a hold-back to hold the scuttle in an open position. (e) The required means of escape must not have... escape is acceptable provided that— (1) There is no source of fire in the space, such as a galley stove... back of the ladder; and (4) Except when unavoidable obstructions are encountered, there must be...

  10. How many ions have escaped the Martian atmosphere?

    Science.gov (United States)

    Brain, David; McFadden, James; Halekas, Jasper; Connerney, J. E. P.; Eparvier, Frank; Mitchell, David; Bougher, Stephen W.; Bowers, Charlie; Curry, Shannon; Dong, Chuanfei; Dong, Yaxue; Egan, Hilary; Fang, Xiaohua; Harada, Yuki; Jakosky, Bruce; Lillis, Robert; Luhmann, Janet; Ma, Yingjuan; Modolo, Ronan; Weber, Tristan

    2016-10-01

    The Mars Atmosphere and Volatile EvolutioN (MAVEN) mission has been making science measurements of the Martian upper atmosphere and its escape to space since November 2014. A key part of this effort is the measurement of the escape rates of charged particles (ions) at present and over solar system history. The lack of a global dynamo magnetic field at Mars leaves its upper atmosphere more directly exposed to the impinging solar wind than magnetized planets such as Earth. For this reason it is thought that ion escape at Mars may have played a significant role in long term climate change. MAVEN measures escaping planetary ions directly, with high energy, mass, and time resolution.With nearly two years of observations in hand, we will report the average ion escape rate and the spatial distribution of escaping ions as measured by MAVEN and place them in context with previous measurements of ion loss by other spacecraft (e.g. Phobos 2 and Mars Express). We will then report on the measured variability in ion escape rates with different drivers (e.g. solar EUV, solar wind pressure, etc.). Finally, we will use these results to provide an initial estimate of the total ion escape from Mars over billions of years.

  11. 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...

  12. DDX3 regulates DNA damage-induced apoptosis and p53 stabilization.

    Science.gov (United States)

    Sun, Mianen; Zhou, Tong; Jonasch, Eric; Jope, Richard S

    2013-06-01

    The DEAD box protein family member DDX3 was previously identified as an inhibitor of death receptor-mediated extrinsic apoptotic signaling. However, there had been no studies of the role of DDX3 in regulating the other major type of apoptosis, intrinsic apoptotic signaling, which was examined here. Intrinsic apoptosis was induced in MCF-7 cells by treatment with staurosporine, a general kinase inhibitor, thapsigargin, which induces endoplasmic reticulum (ER) stress, and camptothecin, which causes DNA damage. Each of these treatments caused time-dependent activation of caspase-7, the predominant executioner caspase in these cells. Depletion of DDX3 using shRNA did not alter apoptotic responses to staurosporine or thapsigargin. However, caspase-7 activation induced by camptothecin was regulated by DDX3 in a manner dependent on the functional status of p53. Depletion of DDX3 abrogated camptothecin-induced caspase-7 activation in MCF-7 cells expressing functional wild-type p53, but oppositely potentiated camptothecin-mediated caspase activation in cells expressing mutant or non-functional p53, which was accompanied by increased activation of the extrinsic apoptotic signaling initiator caspase-8. In MCF-7 cells, depletion of DDX3 reduced by more than 50% camptothecin-induced p53 accumulation, and this effect was blocked by inhibition of the proteasome with MG132, indicating that DDX3 regulates p53 not at expression level but rather its stabilization after DNA damage. Co-immunoprecipitation experiments demonstrated that DDX3 associates with p53, and overexpression of DDX3 was sufficient to double the accumulation of p53 in the nucleus after DNA damage. Thus, DDX3 associates with p53, increases p53 accumulation, and positively regulates camptothecin-induced apoptotic signaling in cells expressing functional wild-type p53, whereas in cells expressing mutant or non-functional p53 DDX3 inhibits activation of the extrinsic apoptotic pathway to reduce caspase activation. These

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Effect of N-acetylcysteine on lung and heart injury of rats with a fast floating escape induced decompression sickness%N-乙酰半胱氨酸对快速上浮脱险致减压病大鼠心肺组织的影响

    Institute of Scientific and Technical Information of China (English)

    王芳芳; 方以群; 攸璞; 包晓辰; 马骏; 张师

    2015-01-01

    Objective To investigate the effect of N-acetylcysteine ( NAC) on lung and heart injury of rats with a fast floating escape induced decompression sickness .Methods Eighty male Sprague-Dawley rats were randomly and evenly divided into four groups:control group and three NAC prevention groups .The NAC groups were treated with different doses of NAC(250, 500 or 1000 mg/kg)by intraperitoneal injection 1 h before entrance.In the control group, rats were given an equal volume of saline1h before entrance.The air was pressurized at the 2t/7 exponential rate to 1.5 MPa which was maintained for 4 min and then uniformly decompressed to atmospheric pressure .The extravehicular survival and pathological changes in the lung and heart tissue were detected 0.5 h after rat egress.Results The survival rate of rats treated with NAC 500 mg/kg(90%) was significantly higher than that of those treated with saline (65%)alone (P<0.05).There was large break and fusion in the structure of pulmonary alveolus of control group besides obvious erythrocyte exudation , cardiac muscle fibers edema ,and obvious denaturation and break .Conclusion NAC can play a protective role in rats with a fast floating escape induced decompression sickness by mitigating the injury to and inflammation of lung and heart tissue .%目的:研究N-乙酰半胱氨酸( NAC)对快速上浮脱险致减压病大鼠心肺组织的影响。方法雄性SD大鼠80只,随机分为4组,每组20只。实验组于进舱前1 h通过腹腔注射NAC溶液(注射剂量分别为250、500和1000 mg/kg),对照组于进舱前1 h腹腔注射相同体积生理盐水。压缩空气以指数速率2t/7加压至1.5 MPa,停留4 min后匀速减压至常压出舱。出舱后即观察大鼠行为学表现并统计存活率,出舱后0.5 h活杀大鼠,取心、肺组织,观察其病理变化。结果 NAC 500 mg/kg组大鼠存活率(90%)显著高于对照组(65%)(P<0.05);对照组大鼠肺泡结

  18. The fastest saccadic responses escape visual masking.

    Directory of Open Access Journals (Sweden)

    Sébastien M Crouzet

    Full Text Available 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 under either OSM or backward masking, as they did under the low-contrast condition. This finding supports the hypothesis that masking interferes mostly with reentrant processing at later stages, while leaving early feedforward processing largely intact.

  19. Candida albicans escapes from mouse neutrophils.

    Science.gov (United States)

    Ermert, David; Niemiec, Maria J; Röhm, Marc; Glenthøj, Andreas; Borregaard, Niels; Urban, Constantin F

    2013-08-01

    Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed that murine neutrophils exhibited a significantly lower ability to kill C. albicans than their human counterparts. Strikingly, C. albicans yeast cells formed germ tubes upon internalization by murine neutrophils, eventually rupturing the neutrophil membrane and thereby, killing the phagocyte. On the contrary, growth and subsequent escape of C. albicans are blocked inside human neutrophils. According to our findings, this blockage in human neutrophils might be a result of higher levels of MPO activity and the presence of α-defensins. We therefore outline differences in antifungal immune defense between humans and mouse strains, which facilitates a more accurate interpretation of in vivo results.

  20. Immune Escape Strategies of Malaria Parasites

    Science.gov (United States)

    Gomes, Pollyanna S.; Bhardwaj, Jyoti; Rivera-Correa, Juan; Freire-De-Lima, Celio G.; Morrot, Alexandre

    2016-01-01

    Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins, and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission. PMID:27799922

  1. Efficiently estimating salmon escapement uncertainty using systematically sampled data

    Science.gov (United States)

    Reynolds, Joel H.; Woody, Carol Ann; Gove, Nancy E.; Fair, Lowell F.

    2007-01-01

    Fish escapement is generally monitored using nonreplicated systematic sampling designs (e.g., via visual counts from towers or hydroacoustic counts). These sampling designs support a variety of methods for estimating the variance of the total escapement. Unfortunately, all the methods give biased results, with the magnitude of the bias being determined by the underlying process patterns. Fish escapement commonly exhibits positive autocorrelation and nonlinear patterns, such as diurnal and seasonal patterns. For these patterns, poor choice of variance estimator can needlessly increase the uncertainty managers have to deal with in sustaining fish populations. We illustrate the effect of sampling design and variance estimator choice on variance estimates of total escapement for anadromous salmonids from systematic samples of fish passage. Using simulated tower counts of sockeye salmon Oncorhynchus nerka escapement on the Kvichak River, Alaska, five variance estimators for nonreplicated systematic samples were compared to determine the least biased. Using the least biased variance estimator, four confidence interval estimators were compared for expected coverage and mean interval width. Finally, five systematic sampling designs were compared to determine the design giving the smallest average variance estimate for total annual escapement. For nonreplicated systematic samples of fish escapement, all variance estimators were positively biased. Compared to the other estimators, the least biased estimator reduced bias by, on average, from 12% to 98%. All confidence intervals gave effectively identical results. Replicated systematic sampling designs consistently provided the smallest average estimated variance among those compared.

  2. Lyman-Werner UV escape fractions from primordial haloes

    Science.gov (United States)

    Schauer, Anna T. P.; Whalen, Daniel J.; Glover, Simon C. O.; Klessen, Ralf S.

    2015-12-01

    Population III (Pop III) stars can regulate star formation in the primordial Universe in several ways. They can ionize nearby haloes, and even if their ionizing photons are trapped by their own haloes, their Lyman-Werner (LW) photons can still escape and destroy H2 in other haloes, preventing them from cooling and forming stars. LW escape fractions are thus a key parameter in cosmological simulations of early reionization and star formation but have not yet been parametrized for realistic haloes by halo or stellar mass. To do so, we perform radiation hydrodynamical simulations of LW UV escape from 9-120 M⊙ Pop III stars in 105-107 M⊙ haloes with ZEUS-MP. We find that photons in the LW lines (i.e. those responsible for destroying H2 in nearby systems) have escape fractions ranging from 0 to 85 per cent. No LW photons escape the most massive halo in our sample, even from the most massive star. Escape fractions for photons elsewhere in the 11.18-13.6 eV energy range, which can be redshifted into the LW lines at cosmological distances, are generally much higher, being above 60 per cent for all but the least massive stars in the most massive haloes. We find that shielding of H2 by neutral hydrogen, which has been neglected in most studies to date, produces escape fractions that are up to a factor of 3 smaller than those predicted by H2 self-shielding alone.

  3. Regulation of NHE3, NKCC2, and NCC abundance in kidney during aldosterone escape phenomenon: role of NO.

    Science.gov (United States)

    Turban, Sharon; Wang, Xiao-Yan; Knepper, Mark A

    2003-11-01

    Escape from aldosterone-induced renal NaCl retention is an important homeostatic mechanism in pathophysiological states in which plasma aldosterone levels are inappropriately elevated, e.g., in primary aldosteronism. Our previous studies demonstrated that the escape process occurs largely as a result of a marked suppression of the abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule but have also demonstrated a paradoxical increase in the protein abundance of the apical Na/H exchanger of the proximal tubule (NHE3). In the present study, we confirmed the increase in NHE3 and also showed that a similar increase in NHE3 protein abundance occurs in escape from ANG II-mediated NaCl retention. To investigate the potential role of nitric oxide (NO) in the observed upregulation of NHE3, we repeated the aldosterone escape experiment with a superimposed infusion of a NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME). l-NAME infusion abolished the increase in NHE3 protein abundance. Furthermore, in a different experiment, NO synthase inhibition uncovered an associated decrease in the abundance of the Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb, not seen with simple aldosterone escape. However, NO synthase inhibition did not block the decrease in NCC abundance normally seen with aldosterone escape. Furthermore, l-NAME infusion in aldosterone-treated rats markedly decreased both NHE3 and NKCC2 protein abundance, without changes in the corresponding mRNA levels. We conclude that NHE3 and NKCC2 protein abundances in kidney are positively regulated by NO and that the increase in NHE3 abundance seen in the aldosterone escape phenomenon is NO dependent.

  4. On the large escape of ionizing radiation from GEHRs

    CERN Document Server

    Castellanos, M; Tenorio-Tagle, G

    2001-01-01

    A thorough analysis of well studied giant HII regions on galactic discs for which we know the ionizing stellar population, the gas metallicity and the Wolf-Rayet population, leads to photoionization models which can only match all observed line intensity ratios ([OIII], [OII], [NII], [SII] and [SIII] with respect to the intensity of H$\\beta$), as well as the H$\\beta$ luminosity and equivalent width if one allows for an important escape of energetic ionizing radiation. For the three regions presented here, the fractions of escaping Lyman continuum photons amount to 10 to 73 % and, in all cases, the larger fraction of escaping photons has energies between 13.6 and 24.4 eV. These escaping photons clearly must have an important impact as a source of ionization of the diffuse ionized gas (DIG) found surrounding many galaxies, as well as of the intergalactic medium (IGM).

  5. Behavior of the Escape Rate Function in Hyperbolic Dynamical Systems

    CERN Document Server

    Demers, Mark

    2011-01-01

    For a fixed initial reference measure, we study the dependence of the escape rate on the hole for a smooth or piecewise smooth hyperbolic map. First, we prove the existence and Holder continuity of the escape rate for systems with small holes admitting Young towers. Then we consider general holes for Anosov diffeomorphisms, without size or Markovian restrictions. We prove bounds on the upper and lower escape rates using the notion of pressure on the survivor set and show that a variational principle holds under generic conditions. However, we also show that the escape rate function forms a devil's staircase with jumps along sequences of regular holes and present examples to elucidate some of the difficulties involved in formulating a general theory.

  6. 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.

  7. Oxygen Escape from Venus During High Dynamic Pressure ICMEs

    Science.gov (United States)

    McEnulty, Tess; Luhmann, J. G.; Brain, D. A.; Fedorov, A.; Jian, L. K.; Russell, C. T.; Zhang, T.; Möstl, C.; Futaana, Y.; de Pater, I.

    2013-10-01

    Previous studies using data from Pioneer Venus suggested that oxygen ion escape flux may be enhanced by orders of magnitude during Interplanetary Coronal Mass Ejections. However, this large enhancement has been ambiguous in Venus Express ion data - with some analyses showing no flux enhancement or a small enhancement (within 2 times undisturbed cases). One possible explanation is that high escape flux may be due to high dynamic pressure in the solar wind, and the dynamic pressure has been lower during the VEX time period. So, we focus on ICMEs with the largest dynamic pressure and with VEX sampling of the escaping ions during the sheath of the ICMEs (during which the highest dynamic pressures in the solar wind occur). We will show the characteristics of these large events measured by VEX, and compare them to the largest ICMEs measured by PVO. We will then discuss estimates of the oxygen ion escape flux during these events.

  8. Experimental Analysis and Extinction of Self-Injurious Escape Behavior.

    Science.gov (United States)

    Iwata, Brian A.; And Others

    1990-01-01

    Three studies investigated environmental correlates of self-injurious behavior in seven developmentally disabled children and adolescents which were then later used for treatment. Correlates investigated included positive reinforcement, negative reinforcement, automatic reinforcement, and control. "Escape extinction" was successfully…

  9. 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

  10. Purinergic Inhibition of ENaC Produces Aldosterone Escape

    OpenAIRE

    Stockand, James D.; Mironova, Elena; Bugaj, Vladislav; Rieg, Timo; Insel, Paul A.; Vallon, Volker; Peti-Peterdi, Janos; Pochynyuk, Oleh

    2010-01-01

    The mechanisms underlying “aldosterone escape,” which refers to the excretion of sodium (Na+) during high Na+ intake despite inappropriately increased levels of mineralocorticoids, are incompletely understood. Because local purinergic tone in the aldosterone-sensitive distal nephron downregulates epithelial Na+ channel (ENaC) activity, we tested whether this mechanism mediates aldosterone escape. Here, urinary ATP concentration increased with dietary Na+ intake in mice. Physiologic concentrat...

  11. GREEN PEA GALAXIES REVEAL SECRETS OF Lyα ESCAPE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Huan; Wang, Junxian [CAS Key Laboratory for Research in Galaxies and Cosmology, Department of Astronomy, University of Science and Technology of China (China); Malhotra, Sangeeta; Rhoads, James E. [Arizona State University, School of Earth and Space Exploration (United States); Gronke, Max; Dijkstra, Mark [Institute of Theoretical Astrophysics, University of Oslo (Norway); Jaskot, Anne [Smith College, Northampton, MA (United States); Zheng, Zhenya, E-mail: yanghuan@mail.ustc.edu.cn, E-mail: huan.y@asu.edu, E-mail: Sangeeta.Malhotra@asu.edu, E-mail: James.Rhoads@asu.edu [Pontificia Universidad Católica de Chile, Santiago (Chile)

    2016-04-01

    We analyze archival Lyα spectra of 12 “Green Pea” galaxies observed with the Hubble Space Telescope, model their Lyα profiles with radiative transfer models, and explore the dependence of the Lyα escape fraction on various properties. Green Pea galaxies are nearby compact starburst galaxies with [O iii] λ5007 equivalent widths (EWs) of hundreds of Å. All 12 Green Pea galaxies in our sample show Lyα lines in emission, with an Lyα EW distribution similar to high-redshift Lyα emitters. Combining the optical and UV spectra of Green Pea galaxies, we estimate their Lyα escape fractions and find correlations between Lyα escape fraction and kinematic features of Lyα profiles. The escape fraction of Lyα in these galaxies ranges from 1.4% to 67%. We also find that the Lyα escape fraction depends strongly on metallicity and moderately on dust extinction. We compare their high-quality Lyα profiles with single H i shell radiative transfer models and find that the Lyα escape fraction anticorrelates with the derived H i column densities. Single-shell models fit most Lyα profiles well, but not the ones with the highest escape fractions of Lyα. Our results suggest that low H i column density and low metallicity are essential for Lyα escape and make a galaxy an Lyα emitter.

  12. Group chase and escape with sight-limited chasers

    Science.gov (United States)

    Wang, Huodong; Han, Wenchen; Yang, Junzhong

    2017-01-01

    We study group chase and escape with sight-limited chasers. Two search strategies, random-walk-strategy and relocation-strategy, are introduced for chasers when escapers are out of their fields of vision. There exist two regimes for the group lifetime of escapers. In the narrow sight regime, the group lifetime is a decreasing function of chasers' sight range. In the wide sight regime, the group lifetime stays at a constant when chasers adopting random-walk-strategy while increases with the sight range when chasers adopting relocation-strategy. The impacts of the two search strategies on group chase and escape are studied by investigating the lifetime distribution of all escapers and the dependence of the minimum lifetime on the number of chasers. We also find that, to reach the most efficient and the lowest energy cost chase for chasers, the ratio between the number of chasers and escapers stays at around 6 under random-walk-strategy. However, the optimal number of chasers vanishes and the energy cost monotonically increases with increasing the number of chasers under relocation-strategy.

  13. Lyman-Werner UV Escape Fractions from Primordial Halos

    CERN Document Server

    Schauer, Anna T P; Glover, Simon C O; Klessen, Ralf S

    2015-01-01

    Population III stars can regulate star formation in the primordial Universe in several ways. They can ionize nearby halos, and even if their ionizing photons are trapped by their own halos, their Lyman-Werner (LW) photons can still escape and destroy H$_2$ in other halos, preventing them from cooling and forming stars. LW escape fractions are thus a key parameter in cosmological simulations of early reionization and star formation but have not yet been parametrized for realistic halos by halo or stellar mass. To do so, we perform radiation hydrodynamical simulations of LW UV escape from 9--120 M$_{\\odot}$ Pop III stars in $10^5$ to $10^7$ M$_{\\odot}$ halos with ZEUS-MP. We find that photons in the LW lines (i.e. those responsible for destroying H$_{2}$ in nearby systems) have escape fractions ranging from 0% to 85%. No LW photons escape the most massive halo in our sample, even from the most massive star. Escape fractions for photons elsewhere in the 11.18--13.6~eV energy range, which can be redshifted into t...

  14. Green Pea Galaxies Reveal Secrets of Ly$\\alpha$ Escape

    CERN Document Server

    Yang, Huan; Gronke, Max; Rhoads, James E; Jaskot, Anne; Zheng, Zhenya; Dijkstra, Mark

    2015-01-01

    Star-formation in galaxies generates a lot of Ly$\\alpha$ photons. Understanding the escape of Ly$\\alpha$ photons from galaxies is a key issue in studying high redshift galaxies and probing cosmic reionization with Ly$\\alpha$. To understand Ly$\\alpha$ escape, it is valuable to study analogs of high redshift Ly$\\alpha$ emitters in nearby universe. However, most nearby analogs have too small a Ly$\\alpha$ equivalent width and escape fraction compared to high redshift Ly$\\alpha$ emitters. One different group of nearby analogs are "Green Pea" galaxies, selected by their high equivalent width optical emission lines. Here we show that Green Pea galaxies have strong Ly$\\alpha$ emission lines and high Ly$\\alpha$ escape fraction (see also Henry et al. 2015), providing an opportunity to solve Ly$\\alpha$ escape problem. Green Peas have a Ly$\\alpha$ equivalent width distribution similar to high redshift Ly$\\alpha$ emitters. The Ly$\\alpha$ escape fraction correlates with many quantities of Ly$\\alpha$ profile, especially the...

  15. 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...

  16. STK295900, a dual inhibitor of topoisomerase 1 and 2, induces G(2 arrest in the absence of DNA damage.

    Directory of Open Access Journals (Sweden)

    Sun-Ok Kim

    Full Text Available STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G(2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1 and topoisomerase 2 (Top 2 in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent.

  17. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells.

    Science.gov (United States)

    Barsoum, Ivraym B; Smallwood, Chelsea A; Siemens, D Robert; Graham, Charles H

    2014-02-01

    Immune escape is a fundamental trait of cancer in which mechanistic knowledge is incomplete. Here, we describe a novel mechanism by which hypoxia contributes to tumoral immune escape from cytotoxic T lymphocytes (CTL). Exposure of human or murine cancer cells to hypoxia for 24 hours led to upregulation of the immune inhibitory molecule programmed cell death ligand-1 (PD-L1; also known as B7-H1), in a manner dependent on the transcription factor hypoxia-inducible factor-1α (HIF-1α). In vivo studies also demonstrated cellular colocalization of HIF-1α and PD-L1 in tumors. Hypoxia-induced expression of PD-L1 in cancer cells increased their resistance to CTL-mediated lysis. Using glyceryl trinitrate (GTN), an agonist of nitric oxide (NO) signaling known to block HIF-1α accumulation in hypoxic cells, we prevented hypoxia-induced PD-L1 expression and diminished resistance to CTL-mediated lysis. Moreover, transdermal administration of GTN attenuated tumor growth in mice. We found that higher expression of PD-L1 induced in tumor cells by exposure to hypoxia led to increased apoptosis of cocultured CTLs and Jurkat leukemia T cells. This increase in apoptosis was prevented by blocking the interaction of PD-L1 with PD-1, the PD-L1 receptor on T cells, or by addition of GTN. Our findings point to a role for hypoxia/HIF-1 in driving immune escape from CTL, and they suggest a novel cancer immunotherapy to block PD-L1 expression in hypoxic-tumor cells by administering NO mimetics.

  18. Non-thermal production and escape of OH from the upper atmosphere of Mars

    Science.gov (United States)

    Gacesa, M.; Lewkow, N.; Kharchenko, V.

    2017-03-01

    We present a theoretical analysis of formation and kinetics of hot OH molecules in the upper atmosphere of Mars produced in reactions of thermal molecular hydrogen and energetic oxygen atoms. Two major sources of energetic O considered are the photochemical production, via dissociative recombination of O2+ ions, and energizing collisions with fast atoms produced by the precipitating Solar Wind (SW) ions, mostly H+ and He2+ , and energetic neutral atoms (ENAs) originating in the charge-exchange collisions between the SW ions and atmospheric gases. Energizing collisions of O with atmospheric secondary hot atoms, induced by precipitating SW ions and ENAs, are also included in our consideration. The non-thermal reaction O + H2(v, j) → H + OH(v‧, j‧) is described using recent quantum-mechanical state-to-state cross sections, which allow us to predict non-equilibrium distributions of excited rotational and vibrational states (v‧, j‧) of OH and expected emission spectra. A fraction of produced translationally hot OH is sufficiently energetic to overcome Mars' gravitational potential and escape into space, contributing to the hot corona. We estimate its total escape flux from the dayside of Mars for low solar activity conditions at about 1.1 × 1023 s-1 , or about 0.1% of the total escape rate of atomic O and H. The described non-thermal OH production mechanism is general and expected to contribute to the evolution of atmospheres of the planets, satellites, and exoplanets with similar atmospheric compositions.

  19. Plasma levels of atrial natriuretic peptide (ANP) during mineralocorticoid escape in normal man.

    Science.gov (United States)

    Wambach, G; Götz, S; Suckau, G; Kaufmann, W

    1986-01-01

    A natriuretic factor has long been postulated to play a role in renal mineralocorticoid escape. We therefore investigated changes in plasma levels of atrial natriuretic peptide (ANP) during chronic treatment with 9 alpha-fluorohydrocortisone. Five normal subjects were studied on a constant diet (300 meq Na+ and 72 meq K+ per day) and received 0.8 mg 9 alpha-fluorohydrocortisone for up to 14 days. Sodium balance became positive and body weight increased between 1.0-4.5 kg maximally. Serum aldosterone was suppressed and plasma levels of ANP were stimulated up to 10-fold. Increment in plasma ANP was positively correlated with the gain in body weight (r = 0.666, p less than 0.001). Renormalization of sodium balance was seen in two subjects, however the maximum in plasma ANP did not occur during the time of renal escape. ANP-secretion is stimulated during sodium retention induced by mineralocorticoids, however ANP does not seem to trigger the escape mechanism.

  20. 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.

  1. 78 FR 54585 - Safety Zone; Escape to Miami Triathlon, Biscayne Bay, Miami, FL

    Science.gov (United States)

    2013-09-05

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Escape to Miami Triathlon, Biscayne Bay... during the Publix Escape to Miami Triathlon. The Publix Escape to Miami Triathlon is scheduled to take... of life on navigable waters of the United States during the Publix Escape to Miami Triathlon....

  2. Comparison of spacecraft crew escape systems through dynamic optimization

    Science.gov (United States)

    Hart, William G., III

    Crew escape systems have been a vital component of ensuring safety onboard manned spacecraft. Although there have been only a few aborts involving their use, their operation helps decrease risk in what is known to be a hazardous field. But despite their high reliability, crew escape systems typically suffer from heavy weight, lack of control and hazardous chemical propellants. Hybrid propulsion systems could be a viable solution to all of these problems. With their inert components, ability to throttle and higher specific impulse than solids, hybrids have obtained interest in recent years. This dissertation presents a method that can be used to compare solid and hybrid propulsion systems for the crew escape systems of spacecraft. The concepts of dynamic optimization, Monte Carlo simulation and propulsion system design are combined to produce a tool which can predict the probability of survival for a given abort scenario. The method can also determine the effect of uncertain variables, such as reaction time or the payload of the vehicle, in the safety of the crew. The method is then used to compare crew escape systems for two separate vehicles: a separable crew cabin proposed for the Space Shuttle Launch Vehicle and the Launch Escape System for the Crew Exploration Vehicle scheduled to begin operation in 2012. The effects of uncertain parameters are also studied. The results show the utility of this method and the objective function, and how it could be used in the design process for future space vehicles.

  3. 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...

  4. 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.

  5. 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...

  6. Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics.

    Science.gov (United States)

    Lönn, Peter; Kacsinta, Apollo D; Cui, Xian-Shu; Hamil, Alexander S; Kaulich, Manuel; Gogoi, Khirud; Dowdy, Steven F

    2016-09-08

    Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

  7. Enhancing endosomal escape for nanoparticle mediated siRNA delivery

    Science.gov (United States)

    Ma, Da

    2014-05-01

    Gene therapy with siRNA is a promising biotechnology to treat cancer and other diseases. To realize siRNA-based gene therapy, a safe and efficient delivery method is essential. Nanoparticle mediated siRNA delivery is of great importance to overcome biological barriers for systemic delivery in vivo. Based on recent discoveries, endosomal escape is a critical biological barrier to be overcome for siRNA delivery. This feature article focuses on endosomal escape strategies used for nanoparticle mediated siRNA delivery, including cationic polymers, pH sensitive polymers, calcium phosphate, and cell penetrating peptides. Work has been done to develop different endosomal escape strategies based on nanoparticle types, administration routes, and target organ/cell types. Also, enhancement of endosomal escape has been considered along with other aspects of siRNA delivery to ensure target specific accumulation, high cell uptake, and low toxicity. By enhancing endosomal escape and overcoming other biological barriers, great progress has been achieved in nanoparticle mediated siRNA delivery.

  8. Escape rate and diffusion of a Stochastically Driven particle

    Science.gov (United States)

    Piscitelli, Antonio; Pica Ciamarra, Massimo

    2017-01-01

    The dynamical properties of a tracer repeatedly colliding with heat bath particles can be described within a Langevin framework provided that the tracer is more massive than the bath particles, and that the collisions are frequent. Here we consider the escape of a particle from a potential well, and the diffusion coefficient in a periodic potential, without making these assumptions. We have thus investigated the dynamical properties of a Stochastically Driven particle that moves under the influence of the confining potential in between successive collisions with the heat bath. In the overdamped limit, both the escape rate and the diffusion coefficient coincide with those of a Langevin particle. Conversely, in the underdamped limit the two dynamics have a different temperature dependence. In particular, at low temperature the Stochastically Driven particle has a smaller escape rate, but a larger diffusion coefficient. PMID:28120904

  9. 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 $2M$.

  10. Escape of protists in predator-generated feeding currents

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2002-01-01

    The ciliate Strobilidium sp. and 2 flagellates, Chrysochromulina simplex and Gymnodinium sp., were exposed to predator-generated feeding currents, and their escape responses were quantified using 2- and 3-dimensional video techniques. All 3 studied organisms responded by escaping at a defined...... of Strobilidium sp. to the copepod Temora longicornis. The predicted reaction distance fit closely that measured, When the flagellates were exposed to the flow field of the ciliate Uronema filificum, they both responded up-stream to the feeding current. From the distance at which the flagellates responded...

  11. Escape probability based routing for ad hoc networks

    Institute of Scientific and Technical Information of China (English)

    Zhang Xuanping; Qin Zheng; Li Xin

    2006-01-01

    Routes in an ad hoc network may fail frequently because of node mobility. Stability therefore can be an important element in the design of routing protocols. The node escape probability is introduced to estimate the lifetime and stability of link between neighboring nodes and the escape probability based routing (EPBR) scheme to discover stable routes is proposed. Simulation results show that the EPBR can discover stable routes to reduce the number of route rediscovery, and is applicable for the situation that has highly dynamic network topology with broad area of communication.

  12. Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery

    Science.gov (United States)

    Chu, Zhiqin; Miu, Kaikei; Lung, Pingsai; Zhang, Silu; Zhao, Saisai; Chang, Huan-Cheng; Lin, Ge; Li, Quan

    2015-06-01

    The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristics—quick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds’ escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds’ cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier.

  13. The escaping "pneuma" - gas of ancient earthquake concepts in relation to animal, atmospheric and thermal precursors

    Science.gov (United States)

    Helmut, Tributsch

    2013-04-01

    anomalies matches that of reported unusual animal behaviour. It may indeed be caused by the same geophysical phenomenon, a pressure-change induced liberation of "pneuma" -gas. The latter may simply be understood as the consequence of pressure dependent changes of the chemical equilibrium constants within the condensed phases of the underground. They will be proportional to the reaction molar volume of interfacial and bulk geochemical mechanisms and may lead to the desorption and emission of chemical species, which finally reach the earth surface. The nature of reported animal behaviour is supporting such conclusion. Straightforward experimental strategies will be required for characterization of the escaping gas in terms of chemical and nano- and micro- particle composition. Non-linear irreversible thermodynamic models may be invoked for understanding energy turnover during the geophysical precursor activity.

  14. Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Nielsen, C; Hansen, J E;

    1992-01-01

    The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development of ...... escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection.......The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development...... of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay...

  15. Effect of immune protection of heart allograft in mice induced by immune escape mechanism of trichinella spiralis%旋毛虫免疫逃避机制对诱导小鼠移植心脏免疫保护作用的影响

    Institute of Scientific and Technical Information of China (English)

    邓庚国; 卢新军; 马毅; 廖冰; 陈颖华; 王国栋; 何晓顺

    2015-01-01

    Objective To observe the effect of immune protection of heart allograft in mice induced by immune escape mechanism of trichinella spiralis,and explore new and potential ways against acute rejection in clinic.Methods The heterotopic cardiac transplantation models were divided into three groups:rejection group,treatment group,and isograft group.Mean survival time was measured.Twenty-eight days before transplantation,recipients (C57BL/6) of rejection group were orally infected with 300 muscle larvae,and donors were untreated.Hearts in each group were harvested on the day 7 post-transplantation for pathological observation.Proportion of CD4 +,CD8 + T cells and regulatory T cells (Tregs) was detected by flow cytometry.Results As compared with rejection group (11 days),survival of allografts was significantly prolonged in treatment group (24 days) (P < 0.01),alleviated pathologic signd were observed,and proportion of CD8 + T cells (36.6%) was reduced (48.8%,P < 0.01),but there was no significant difference in CD4 + T cells between treatment group and rejection group.Meanwhile,proportion of Tregs in treatment group (16.9%) was significantly higher than in rejection group (10.8%,P < 0.05).Conclusion Trichinella spiralis infection lowered the proportion of CD8 + T cells,augmented Tregs frequency,and alleviated acute rejection of heterotopic cardiac transplantation in mice,which immunologically protected mice heart allograft.%目的 观察旋毛虫免疫逃避机制对诱导小鼠移植心脏免疫保护作用的影响,探讨可应用于临床的新抗排斥途径.方法 小鼠心脏移植术前28 d,实验组每只受体小鼠(C57 BL/6)以300条旋毛虫肌幼虫经口感染,供体小鼠(BALB/c)未感染,同时设立急性排斥反应组以及同系移植对照组,观察各组移植心脏的存活时间.术后第7天获取供心并观察移植物排斥病理学改变,流式细胞术检测受体脾脏淋巴细胞中CD4+、CD8+T淋巴细胞和调

  16. Spatial and Nonspatial Escape Strategies in the Barnes Maze

    Science.gov (United States)

    Harrison, Fiona E.; Reiserer, Randall S.; Tomarken, Andrew J.; McDonald, Michael P.

    2006-01-01

    The Barnes maze is a spatial memory task that requires subjects to learn the position of a hole that can be used to escape the brightly lit, open surface of the maze. Two experiments assessed the relative importance of spatial (extra-maze) versus proximal visible cues in solving the maze. In Experiment 1, four groups of mice were trained either…

  17. Entrapment and escape of liquid lubricant in metal forming

    DEFF Research Database (Denmark)

    Bech, Jakob Ilsted; Bay, Niels; Eriksen, Morten

    1999-01-01

    with Varying viscosity, speed, reduction, workpiece material, back tension and friction. The mechanisms are influenced by all these parameters in an explicable way. Theoretical models of the escape mechanisms are established combining continuum mechanic analyses of the die pressure distribution with a fluid...

  18. 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)

  19. Brain size as a driver of avian escape strategy.

    Science.gov (United States)

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

    2015-07-03

    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 and natural history traits that correlate with variation in avian escape strategy across a sample of 96 species of birds. Brain mass, body size, habitat structure and group size were the main predictors of escape strategy. The direction of the effect of these traits was consistent with selection for a reduction of monitoring costs. Therefore, attentional costs depend on relative brain size, which determines the ability to monitor the whereabouts of potential predators and the difficulty of this task as reflected by habitat and social complexity. Thus brain size, and the cognitive functions associated with it, constitute a general framework for explaining the effects of body size, habitat structure and sociality identified as determinants of avian escape strategy.

  20. The spectrum of Cosmic Rays escaping from relativistic shocks

    CERN Document Server

    Katz, Boaz; Waxman, Eli

    2010-01-01

    We derive expressions for the time integrated spectrum of Cosmic Rays (CRs) that are accelerated in a decelerating relativistic shock wave and escape ahead of the shock. It is assumed that at any given time the CRs have a power law form, carry a constant fraction of the energy E_tot of the shocked plasma, and escape continuously at the maximal energy attainable. The spectrum of escaping particles is highly sensitive to the instantaneous spectral index due to the fact that the minimal energy, E_min ~ \\Gamma^2 m_pc^2 where \\Gamma is the shock Lorentz factor, changes with time. In particular, the escaping spectrum may be considerably harder than the canonical N(E)\\propto E^-2 spectrum. For a shock expanding into a plasma of density n, a spectral break is expected at the maximal energy attainable at the transition to non relativistic velocities, E ~ 10^19 (\\epsilon_B/0.1)(n/1 cm^-3)^(1/6)(E_tot/10^51 erg)^(1/3) eV where \\epsilon_B is the fraction of the energy flux carried by the magnetic field. If ultra-high ene...

  1. 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 ...

  2. Escaping Embarrassment: Face-Work in the Rap Cipher

    Science.gov (United States)

    Lee, Jooyoung

    2009-01-01

    How do individuals escape embarrassing moments in interaction? Drawing from ethnographic fieldwork, in-depth interviews, and video recordings of weekly street corner ciphers (impromptu rap sessions), this paper expands Goffman's theory of defensive and protective face-work. The findings reveal formulaic and indirect dimensions of face-work. First,…

  3. Purinergic inhibition of ENaC produces aldosterone escape.

    Science.gov (United States)

    Stockand, James D; Mironova, Elena; Bugaj, Vladislav; Rieg, Timo; Insel, Paul A; Vallon, Volker; Peti-Peterdi, Janos; Pochynyuk, Oleh

    2010-11-01

    The mechanisms underlying "aldosterone escape," which refers to the excretion of sodium (Na(+)) during high Na(+) intake despite inappropriately increased levels of mineralocorticoids, are incompletely understood. Because local purinergic tone in the aldosterone-sensitive distal nephron downregulates epithelial Na(+) channel (ENaC) activity, we tested whether this mechanism mediates aldosterone escape. Here, urinary ATP concentration increased with dietary Na(+) intake in mice. Physiologic concentrations of ATP decreased ENaC activity in a dosage-dependent manner. P2Y(2)(-/-) mice, which lack the purinergic receptor, had significantly less increased Na(+) excretion than wild-type mice in response to high-Na(+) intake. Exogenous deoxycorticosterone acetate and deletion of the P2Y(2) receptor each modestly increased the resistance of ENaC to changes in Na(+) intake; together, they markedly increased resistance. Under the latter condition, ENaC could not respond to changes in Na(+) intake. In contrast, as a result of aldosterone escape, wild-type mice had increased Na(+) excretion in response to high-Na(+) intake regardless of the presence of high deoxycorticosterone acetate. These data suggest that control of ENaC by purinergic signaling is necessary for aldosterone escape.

  4. The Dutch approach to the escape from large compartments

    NARCIS (Netherlands)

    Janse, E.W.; Leur, P.H.E. van de

    1999-01-01

    In the Netherlands, the building regulations have no design mies for large fire compartments (over 1000 m2). With respect to the ability of people to escape from a fire in such large spaces, the Centre for Fire Research of TNO Building and Construction Research has developed a guideline that integra

  5. An analog of camptothecin inactive against Topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation.

    Science.gov (United States)

    Bennett, Ryan P; Stewart, Ryan A; Hogan, Priscilla A; Ptak, Roger G; Mankowski, Marie K; Hartman, Tracy L; Buckheit, Robert W; Snyder, Beth A; Salter, Jason D; Morales, Guillermo A; Smith, Harold C

    2016-12-01

    Camptothecin (CPT) is a natural product discovered to be active against various cancers through its ability to inhibit Topoisomerase I (TOP1). CPT analogs also have anti-HIV-1 (HIV) activity that was previously shown to be independent of TOP1 inhibition. We show that a cancer inactive CPT analog (O2-16) inhibits HIV infection by disrupting multimerization of the HIV protein Vif. Antiviral activity depended on the expression of the cellular viral restriction factor APOBEC3G (A3G) that, in the absence of functional Vif, has the ability to hypermutate HIV proviral DNA during reverse transcription. Our studies demonstrate that O2-16 has low cytotoxicity and inhibits Vif-dependent A3G degradation, enabling A3G packaging into HIV viral particles that results in A3G signature hypermutations in viral genomes. This antiviral activity was A3G-dependent and broadly neutralizing against sixteen HIV clinical isolates from groups M (subtypes A-G), N, and O as well as seven single and multi-drug resistant strains of HIV. Molecular modeling predicted binding near the PPLP motif crucial for Vif multimerization and activity. O2-16 also was active in blocking Vif degradation of APOBEC3F (A3F). We propose that CPT analogs not active against TOP1 have novel therapeutic potential as Vif antagonists that enable A3G-dependent hypermutation of HIV.

  6. Restoration of camptothecine production in attenuated endophytic fungus on re-inoculation into host plant and treatment with DNA methyltransferase inhibitor.

    Science.gov (United States)

    Vasanthakumari, M M; Jadhav, S S; Sachin, Naik; Vinod, G; Shweta, Singh; Manjunatha, B L; Kumara, P Mohana; Ravikanth, G; Nataraja, Karaba N; Uma Shaanker, R

    2015-10-01

    Fungal endophytes inhabit living tissues of plants without any apparent symptoms and in many cases are known to produce secondary metabolites similar to those produced by their respective host plants. However on sub-culture, the endophytic fungi gradually attenuate their ability to produce the metabolites. Attenuation has been a major constraint in realizing the potential of endophytic fungi as an alternative source of plant secondary metabolites. In this study, we report attempts to restore camptothecine (CPT) production in attenuated endophytic fungi isolated from CPT producing plants, Nothapodytes nimmoniana and Miquelia dentata when they are passed through their host plant or plants that produce CPT and when treated with a DNA methyl transferase inhibitor. Attenuated endophytic fungi that traversed through their host tissue or plants capable of synthesizing CPT, produced significantly higher CPT compared to the attenuated fungi. Attenuated fungus cultured in the presence of 5-azacytidine, a DNA methyltransferase inhibitor, had an enhanced CPT content compared to untreated attenuated fungus. These results indicate that the attenuation of CPT production in endophytic fungi could in principle be reversed by eliciting some signals from plant tissue, most likely that which prevents the methylation or silencing of the genes responsible for CPT biosynthesis.

  7. 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.

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

    Science.gov (United States)

    Hayashi, Keisuke; Schoonbeek, Henk-Jan; De Waard, Maarten A

    2002-10-01

    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 Camptotheca acuminata and the plant pathogenic fungus Cercospora kikuchii, respectively. Overexpression mutants displayed decreased sensitivity to these compounds and to structurally unrelated fungicides, such as sterol demethylation inhibitors (DMIs). A double-replacement mutant of Bcmfs1 and the ATP-binding cassette (ABC) transporter gene BcatrD was more sensitive to DMI fungicides than a single-replacement mutant of BcatrD, known to encode an important ABC transporter of DMIs. The sensitivity of the wild-type strain and mutants to DMI fungicides correlated with Bcmfs1 expression levels and with the initial accumulation of oxpoconazole by germlings of these isolates. The results indicate that Bcmfs1 is a major facilitator superfamily multidrug transporter involved in protection against natural toxins and fungicides and has a substrate specificity that overlaps with the ABC transporter BcatrD. Bcmfs1 may be involved in protection of B. cinerea against plant defense compounds during the pathogenic phase of growth on host plants and against fungitoxic antimicrobial metabolites during its saprophytic phase of growth.

  9. Escape chambers in the German coal mining industry. Fluchtkammern im deutschen Steinkohlenbergbau

    Energy Technology Data Exchange (ETDEWEB)

    Kock, F.J.; Langer, G. (Bergbau-Forschung G.m.b.H. - Forschungsinstitut des Steinkohlenbergbauvereins, Essen (Germany, F.R.). Hauptstelle fuer das Grubenrettungswesen); Velsen-Zerweck, R. von; Boettcher, K. (Bergbau AG Westfalen, Dortmund (Germany, F.R.). Hauptabteilung Sicherheitswesen)

    1989-08-17

    Escape chambers are used in special cases in German mines for self-rescue of the work force. On the basis of the newly laid down requirements concerning escape chambers a specification for mobile escape chambers was drawn up. The Safety Department of Bergbau AG Westfalen purchased two escape chambers of different manufacturers for 10 persons in each case, which are curently being tested at collieries of Bergbau AG Westfalen. The German coal mining industry thus has escape chambers at its disposal to make self-rescue of the work force even safer in the event of difficult and long escape routes. (orig.).

  10. Formulation of a Cooperative-Confinement-Escape problem of multiple cooperative defenders against an evader escaping from a circular region

    Science.gov (United States)

    Li, Wei

    2016-10-01

    In this paper, we propose and formulate the Cooperative-Confinement-Escape (CCE) problem of multiple cooperative defenders against an evader escaping from a circular region, in which the defenders are moving on the circle with attempt to prevent possible escape of a single evader who is initially located inside the circle. The main contributions are summarized as follows: (1) we first provide an effective formulation of the CCE problem, which is an emphasis of this paper, with design of two nonlinear control strategies for the cooperative defenders and the adversarial evader, respectively. Particularly, we consider to include a proper interaction between each pair of the nearest-neighbor defenders, and an adaptive trajectory prediction mechanism in the strategies of the defenders to increase the chance of successful confinement. (2) For the first attempt on analyzing the CCE dynamics which is unavoidably strongly nonlinear, we analyze the minimum energy of the evader for possible escape. (3) For understanding of the behaviors of the system under different parameters, (i) we illustrate the effectiveness of the confinement strategy using the adaptive trajectory prediction mechanism, and (ii) the physical roles of the system parameters with respect to the system dynamics, some of which may be unexpected or not straightforward. A separate paper will be presented for systematic analysis of the agents' behaviors with respect to the large intervals of the parameter settings.

  11. An Empirical Investigation of Time-Out with and without Escape Extinction to Treat Escape-Maintained Noncompliance

    Science.gov (United States)

    Everett, Gregory E.; Olmi, D. Joe; Edwards, Ron P.; Tingstrom, Daniel H.; Sterling-Turner, Heather E.; Christ, Theodore J.

    2007-01-01

    The present study evaluates the effectiveness of two time-out (TO) procedures in reducing escape-maintained noncompliance of 4 children. Noncompliant behavioral function was established via a functional assessment (FA), including indirect and direct descriptive procedures and brief confirmatory experimental analyses. Following FA, parents were…

  12. Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape.

    Science.gov (United States)

    Peetla, Chiranjeevi; Jin, Shihua; Weimer, Jonathan; Elegbede, Adekunle; Labhasetwar, Vinod

    2014-07-01

    To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs) taken up via endocytic pathways must efficiently transport across the cell membrane and subsequently escape from the secondary endosomes. We hypothesized that the biomechanical and thermodynamic interactions of NPs with plasma and endosomal membrane lipids are involved in these processes. Using model plasma and endosomal lipid membranes, we compared the interactions of cationic NPs composed of poly(D,L-lactide-co-glycolide) modified with the dichain surfactant didodecyldimethylammonium bromide (DMAB) or the single-chain surfactant cetyltrimethylammonium bromide (CTAB) vs anionic unmodified NPs of similar size. We validated our hypothesis in doxorubicin-sensitive (MCF-7, with relatively fluid membranes) and resistant breast cancer cells (MCF-7/ADR, with rigid membranes). Despite their cationic surface charges, DMAB- and CTAB-modified NPs showed different patterns of biophysical interaction: DMAB-modified NPs induced bending of the model plasma membrane, whereas CTAB-modified NPs condensed the membrane, thereby resisted bending. Unmodified NPs showed no effects on bending. DMAB-modified NPs also induced thermodynamic instability of the model endosomal membrane, whereas CTAB-modified and unmodified NPs had no effect. Since bending of the plasma membrane and destabilization of the endosomal membrane are critical biophysical processes in NP cellular uptake and endosomal escape, respectively, we tested these NPs for cellular uptake and drug efficacy. Confocal imaging showed that in both sensitive and resistant cells DMAB-modified NPs exhibited greater cellular uptake and escape from endosomes than CTAB-modified or unmodified NPs. Further, paclitaxel-loaded DMAB-modified NPs induced greater cytotoxicity even in resistant cells than CTAB-modified or unmodified NPs or drug in solution, demonstrating the potential of DMAB-modified NPs to overcome the transport barrier in resistant cells. In

  13. Stream life of spawning pink salmon and the method of escapement enumeration by aerial survey: Draft

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Aerial surveys are currently used as the method tor escapement enumeration of pink salmon throughout Alaska. Other escapement enumeration methods cannot be...

  14. 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.

  15. Escape rate of active particles in the effective equilibrium approach

    Science.gov (United States)

    Sharma, A.; Wittmann, R.; Brader, J. M.

    2017-01-01

    The escape rate of a Brownian particle over a potential barrier is accurately described by the Kramers theory. A quantitative theory explicitly taking the activity of Brownian particles into account has been lacking due to the inherently out-of-equilibrium nature of these particles. Using an effective equilibrium approach [Farage et al., Phys. Rev. E 91, 042310 (2015), 10.1103/PhysRevE.91.042310] we study the escape rate of active particles over a potential barrier and compare our analytical results with data from direct numerical simulation of the colored noise Langevin equation. The effective equilibrium approach generates an effective potential that, when used as input to Kramers rate theory, provides results in excellent agreement with the simulation data.

  16. Partial control of chaotic transients using escape times

    Energy Technology Data Exchange (ETDEWEB)

    Sabuco, Juan; Zambrano, Samuel; Sanjuan, Miguel A F, E-mail: juan.sabuco@urjc.e [Departamento de Fisica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain)

    2010-11-15

    The partial control technique allows one to keep the trajectories of a dynamical system inside a region where there is a chaotic saddle and from which nearly all the trajectories diverge. Its main advantage is that this goal is achieved even if the corrections applied to the trajectories are smaller than the action of environmental noise on the dynamics, a counterintuitive result that is obtained by using certain safe sets. Using the Henon map as a paradigm, we show here the deep relationship between the safe sets and the sets of points with different escape times, the escape time sets. Furthermore, we show that it is possible to find certain extended safe sets that can be used instead of the safe sets in the partial control technique. Numerical simulations confirm our findings and show that in some situations, the use of extended safe sets can be more advantageous.

  17. Behavioral analysis of the escape response in larval zebrafish

    Science.gov (United States)

    Feng, Ruopei; Girdhar, Kiran; Chemla, Yann; Gruebele, Martin

    The behavior of larval zebrafish is of great interest because the limited number of locomotor neurons in larval zebrafish couples with its rich repertoire of movements as a vertebrate animal. Current research uses a priori-selected parameters to describe their swimming behavior while our lab has built a parameter-free model based on singular value decomposition analysis to characterize it. Our previous work has analyzed the free swimming of larval zebrafish and presented a different picture from the current classification of larval zebrafish locomotion. Now we are extending this work to the studies of their escape response to acoustic stimulus. Analysis has shown intrinsic difference in the locomotion between escape response and free swimming.

  18. 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.

  19. 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.

  20. 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.)

  1. Escape Time of Josephson Junctions for Signal Detection

    CERN Document Server

    Addesso, P; Pierro, V

    2014-01-01

    In this Chapter we investigate with the methods of signal detection the response of a Josephson junction to a perturbation to decide if the perturbation contains a coherent oscillation embedded in the background noise. When a Josephson Junction is irradiated by an external noisy source, it eventually leaves the static state and reaches a steady voltage state. The appearance of a voltage step allows to measure the time spent in the metastable state before the transition to the running state, thus defining an escape time. The distribution of the escape times depends upon the characteristics of the noise and the Josephson junction. Moreover, the properties of the distribution depends on the features of the signal (amplitude, frequency and phase), which can be therefore inferred through the appropriate signal processing methods. Signal detection with JJ is interesting for practical purposes, inasmuch as the superconductive elements can be (in principle) cooled to the absolute zero and therefore can add (in practi...

  2. 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.

  3. 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.

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

    OpenAIRE

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

    2011-01-01

    Predator-prey interactions are vital determinants in the natural selection of behavioral traits. However, we have few insights into both the neural mechanisms and the selective advantage of specific 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]. Even though the C. elegans touch response has provided one of the rare examples of how neural ne...

  5. Escape Geography--Developing Middle-School Students' Sense of Place.

    Science.gov (United States)

    Allen, Rodney F.; Molina, Laurie E. S.

    1992-01-01

    Suggests a social studies unit on escaping geography. Examines escape from dangerous places including an airliner, hotel fire, or war zone or from a social situation such as a boring speech or party. Describes historic escapes such as the Underground Railroad and the Berlin Wall. Lists learning strategies such as awareness of space and cognitive…

  6. On the Relative Contributions of Noncontingent Reinforcement and Escape Extinction in the Treatment of Food Refusal

    Science.gov (United States)

    Reed, Gregory K.; Piazza, Cathleen C.; Patel, Meeta R.; Layer, Stacy A.; Bachmeyer, Melanie H.; Bethke, Stephanie D.; Gutshall, Katharine A.

    2004-01-01

    In the current investigation, we evaluated the relative effects of noncontingent reinforcement (NCR), escape extinction, and a combination of NCR and escape extinction as treatment for the feeding problems exhibited by 4 children. For each participant, consumption increased only when escape extinction was implemented, independent of whether NCR…

  7. 46 CFR 56.50-25 - Safety and relief valve escape piping.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Safety and relief valve escape piping. 56.50-25 Section 56.50-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Design Requirements Pertaining to Specific Systems § 56.50-25 Safety and relief valve escape piping. (a) Escape piping...

  8. Crew Escape Technologies (CREST) Mission Area Requirements Study Current and Future Crew Escape Requirements

    Science.gov (United States)

    1992-02-01

    anthropometry and the type and location of the equipment worn by the test suboect. Based upon the data taken In the early nineteen sixties it was...3.1.1 of the CREST Specification describes the system as having -Flow stagnation fence to reduce windblast Induced loads on the head, torso and upper

  9. 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 (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 line with several of them. Total photochemical loss over Mars history is not very useful to

  10. 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.

  11. 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...

  12. [Outline of the ESCAP Regional Post-World Population Conference Consultation Meeting].

    Science.gov (United States)

    Kuroda, T

    1975-01-01

    The ESCAP Regional Post-World Population Conference Consultation was held from January 14th to 20th, 1975, in Bangkok. The Japanese government presented a 5 point statement: 1) recent trends of population in Japan; 2) population policies in the context of social and economic development; 3) outline of government policies and activities; 4) overall coordination machinery; and 5) international cooperation. The agenda were: opening addresses; election of officers; adoption of agenda; review of the world population plan of action; the declaration of a population strategy for development; other guidelines for action in the light of the requirements and conditions of countries of the ESCAP region; proposals for programmes and measures comprising a population strategy for development; implementation of the proposals (including means of incorporation in development planning); international cooperation and coordination; adoption of report; and closing ceremonies. 4 important recommendations were: 1) population increasing rate; 2) legal induced abortion; 3) time limitation for the promotion of family planning; and 4) practical impetus for contraception. Some countries declared the final goal of their population policies: pure reproduction rate 1 (1980) in Singapore, a zero population increasing rate (2)))) in India, and 1.3% (1981) population increasing rate in Korea.

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

    Energy Technology Data Exchange (ETDEWEB)

    Szuecs, Tamas; Bemmerer, Daniel [Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden (Germany)

    2014-07-01

    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.

  14. A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways

    Science.gov (United States)

    Spring, Bryan Q.; Bryan Sears, R.; Zheng, Lei Zak; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E.; Schoenfeld, David A.; Pogue, Brian W.; Pereira, Stephen P.; Villa, Elizabeth; Hasan, Tayyaba

    2016-04-01

    Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)—a multikinase inhibitor—encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities.

  15. 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.

  16. Synthesis and self-assembly of amphiphilic poly(acrylicacid)-poly(ɛ-caprolactone)-poly(acrylicacid) block copolymer as novel carrier for 7-ethyl-10-hydroxy camptothecin.

    Science.gov (United States)

    Djurdjic, Beti; Dimchevska, Simona; Geskovski, Nikola; Petrusevska, Marija; Gancheva, Valerya; Georgiev, Georgi; Petrov, Petar; Goracinova, Katerina

    2015-01-01

    The process of molecular self-assembly plays a crucial role in formulation of polymeric nanoparticulated drug delivery carriers as it creates the possibility for enhanced drug encapsulation and carrier surface engineering. This study aimed to develop a novel self-assembled polymeric micelles for targeted delivery in tumor cells in order to overcome not only various drawbacks of 7-ethyl-10-hydroxy camptothecin (SN-38) but also various reported limitations of other drug delivery systems, especially low drug loading and premature release. Custom synthesized amphiphilic triblock copolymer poly(acrylic acid)-poly(ɛ-caprolactone)-poly(acrylic acid) (PAA(13)-PCL(35)-PAA(13)) was used to prepare kinetically stable micelles by nanoprecipitation and modified nanoprecipitation procedure. Core-shell micelles with diameter of 120-140 nm, negative zeta potential and satisfactory drug loading were produced. The prepared formulations were stable in pH range of 3-12 and in media with NaCl concentration <1 mol/l. Screening mixed level factorial 3 × 2(2) design identified that the process temperature as well as the type of organic solvent has influence upon the efficacy of encapsulation, particle size, dissolution rate and burst release. Fourier transform infrared and differential scanning calorimetry analyses confirmed the entrapment of the active substance into the micelles. The kinetic analysis of dissolution studies revealed that the main mechanism of drug release from the prepared formulations is Fickian diffusion. Growth inhibition studies as well as DNA fragmentation assay performed on SW-480 cell lines clearly demonstrated increased growth inhibition effect and presence of fragmented DNA in cells treated with loaded micelles compared to SN-38 solution. Altogether, these results point out to potential biomedical and clinical application of PAA-PCL-PAA systems in the future.

  17. Synthesis of Marine α-Methoxylated Fatty Acid Analogs that Effectively Inhibit the Topoisomerase IB from Leishmania donovani with a Mechanism Different from that of Camptothecin

    Directory of Open Access Journals (Sweden)

    Rosa M. Reguera

    2013-09-01

    Full Text Available Sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties and in some cases they display enhanced anticancer activities. However, the antiprotozoal properties of the α-methoxylated fatty acids have been less studied. In this work, we describe the total synthesis of (5Z,9Z-(±-2-methoxy-5, 9-eicosadienoic acid (1 and its acetylenic analog (±-2-methoxy-5,9-eicosadiynoic acid (2, and report that they inhibit (EC50 values between 31 and 22 µM the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB. The inhibition of LdTopIB (EC50 = 53 µM by the acid (±-2-methoxy-6-icosynoic acid (12 was studied as well. The potency of LdTopIB inhibition followed the trend 2 > 1 > 12, indicating that the effectiveness of inhibition depends on the degree of unsaturation. All of the studied α-methoxylated fatty acids failed to inhibit the human topoisomerase IB enzyme (hTopIB at 100 µM. However, the α-methoxylated fatty acids were capable of inhibiting an active but truncated LdTopIB with which camptothecin (CPT cannot interact suggesting that the methoxylated fatty acids inhibit LdTopIB with a mechanism different from that of CPT. The diunsaturated fatty acids displayed low cytotoxicity towards Leishmania infantum promastigotes (EC50 values between 260 and 240 µM, but 12 displayed a better cytotoxicity towards Leishmania donovani promastigotes (EC50 = 100 µM and a better therapeutic index.

  18. Development of Guanidine-Bisurea Bifunctional Organocatalyst Bearing Chirality at the Inner and Outer Sides of the Urea Groups, and Application to Enantioselective α-Hydroxylation of Pyranoindolizine Intermediate for Camptothecin Synthesis

    Directory of Open Access Journals (Sweden)

    Minami Odagi

    2015-01-01

    Full Text Available Pyranoindolizine is a tricyclic structure found in various biologically active compounds, such as camptothecin (CPT and its derivatives. In the case of CPTs, the chirality at the α-position in the α-hydroxyl lactone moiety of pyranoindolizine is important for the antitumor activity. This paper deals with enantioselective oxidation of the α-position in pyranoindolizine lactone, which corresponds at C20 in CPT, with cumene hydroperoxide (CHP in the presence of newly synthesized guanidine-bisurea bifunctional organocatalysts bearing chirality on both the inner and outer sides of the urea groups.

  19. 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.

  20. Broad CTL Response in Early HIV Infection Drives Multiple Concurrent CTL Escapes.

    Science.gov (United States)

    Leviyang, Sivan; Ganusov, Vitaly V

    2015-10-01

    Recent studies have highlighted the ability of HIV to escape from cytotoxic T lymphocyte (CTL) responses that concurrently target multiple viral epitopes. Yet, the viral dynamics involved in such escape are incompletely understood. Previous analyses have made several strong assumptions regarding HIV escape from CTL responses such as independent or non-concurrent escape from individual CTL responses. Using experimental data from evolution of HIV half genomes in four patients we observe concurrent viral escape from multiple CTL responses during early infection (first 100 days of infection), providing confirmation of a recent result found in a study of one HIV-infected patient. We show that current methods of estimating CTL escape rates, based on the assumption of independent escapes, are biased and perform poorly when CTL escape proceeds concurrently at multiple epitopes. We propose a new method for analyzing longitudinal sequence data to estimate the rate of CTL escape across multiple epitopes; this method involves few parameters and performs well in simulation studies. By applying our novel method to experimental data, we find that concurrent multiple escapes occur at rates between 0.03 and 0.4 day(-1), a relatively broad range that reflects uncertainty due to sparse sampling and wide ranges of parameter values. However, we show that concurrent escape at rates 0.1-0.2 day(-1) across multiple epitopes is consistent with our patient datasets.

  1. A comparison of positive and negative reinforcement for compliance to treat problem behavior maintained by escape.

    Science.gov (United States)

    Slocum, Sarah K; Vollmer, Timothy R

    2015-09-01

    Previous research has shown that problem behavior maintained by escape can be treated using positive reinforcement. In the current study, we directly compared functional (escape) and nonfunctional (edible) reinforcers in the treatment of escape-maintained problem behavior for 5 subjects. In the first treatment, compliance produced a break from instructions. In the second treatment, compliance produced a small edible item. Neither treatment included escape extinction. Results suggested that the delivery of a positive reinforcer for compliance was effective for treating escape-maintained problem behavior for all 5 subjects, and the delivery of escape for compliance was ineffective for 3 of the 5 subjects. Implications and future directions related to the use of positive reinforcers in the treatment of escape behavior are discussed.

  2. Experimental analysis and extinction of self-injurious escape behavior.

    Science.gov (United States)

    Iwata, B A; Pace, G M; Kalsher, M J; Cowdery, G E; Cataldo, M F

    1990-01-01

    Three studies are presented in which environmental correlates of self-injurious behavior were systematically examined and later used as the basis for treatment. In Study 1, 7 developmentally disabled subjects were exposed to a series of conditions designed to identify factors that maintain self-injurious behavior: attention contingent on self-injurious behavior (positive reinforcement), escape from or avoidance of demands contingent on self-injurious behaviour (negative reinforcement), alone (automatic reinforcement), and play (control). Results of a multielement design showed that each subject's self-injurious behavior occurred more frequently in the demand condition, suggesting that the behavior served an avoidance or escape function. Six of the 7 subjects participated in Study 2. During educational sessions, "escape extinction" was applied as treatment for their self-injurious behavior in a multiple baseline across subjects design. Results showed noticeable reduction or elimination of self-injurious behavior for each subject and an increase in compliance with instructions in all subjects for whom compliance data were taken. The 7th subject, whose self-injurious behavior during Study 1 occurred in response to medical demands (i.e., physical examinations), participated in Study 3. Treatment was comprised of extinction, as in Study 2, plus reinforcement for tolerance of the examination procedure, and was evaluated in a multiple baseline across settings design. Results showed that the treatment was successful in eliminating self-injurious behavior and that its effects transferred across eight new therapists and three physicians. General implications for the design, interpretation, and uses of assessment studies are discussed.

  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. First-passage and escape problems in the Feller process

    Science.gov (United States)

    Masoliver, Jaume; Perelló, Josep

    2012-10-01

    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 have long been well known, 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.

  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. Experimental study of subsonic microjet escaping from a rectangular nozzle

    Science.gov (United States)

    Aniskin, V. M.; Maslov, A. A.; Mukhin, K. A.

    2016-10-01

    The first experiments on the subsonic laminar microjets escaping from the nozzles of rectangular shape are carried out. The nozzle size is 83.3x3823 microns. Reynolds number calculated by the nozzle height and the average flow velocity at the nozzle exit ranged from 58 to 154. The working gas was air at room temperature. The velocity decay and velocity fluctuations along the center line of the jet are determined. The fundamental difference between the laminar microjets characteristics and subsonic turbulent jets of macro size is shown. Based on measurements of velocity fluctuations it is shown the presence of laminar-turbulent transition in microjets and its location is determined.

  7. The mirror of the escaped God – Alejandra Pizarnik

    Directory of Open Access Journals (Sweden)

    Mariano Carou

    2015-04-01

    Full Text Available 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.

  8. 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.

  9. Different virulence of candida albicans is attributed to the ability of escape from neutrophil extracellular traps by secretion of DNase

    Science.gov (United States)

    Zhang, Xiaohuan; Zhao, Sainan; Sun, Luping; Li, Wenqing; Wei, Qiao; Ashman, Robert B; Hu, Yan

    2017-01-01

    Candida albicans is an important opportunistic fungus causing both disseminated and local infections. The discovery of neutrophil extracellular traps (NETs) has presented a new strategy to kill microorganisms in host’s innate immune response. Although it has been reported that NETs can trap and kill both yeast and hyphal forms of C. albicans, the mechanism by which C. albicans escape from NETs has not been fully understood. In this study, the ability of two strains of C. albicans SC5314 and 3683 to escape NETs-mediated killing was compared. It was found that SC5314 induced higher levels of reactive oxygen species (ROS) and expressions of Rac1/2 and more NETs formation by neutrophils, and also generated more deoxyribonucleases (DNase) than 3683 did. However, resistance to neutrophils killing was greater in SC5314 than that of 3683. When extracellular traps were degraded by exogenous DNase I or catalase, and neutrophil phagocytic activity blocked by cytochalasin D, the killing capacity of neutrophils co-cultured with either C. albicans SC5314 or 3683 was significantly decreased. This study indicates that C. albicans can escape from the trapping and killing of NETs by secreting DNase, which offers further insights into the basis for differences in virulence of different strains of C. albicans. PMID:28123633

  10. The mitochondria-mediate apoptosis of Lepidopteran cells induced by azadirachtin.

    Directory of Open Access Journals (Sweden)

    Jingfei Huang

    Full Text Available Mitochondria have been shown to play an important role in apoptosis using mammalian cell lines. However, this seems not to be the case in Drosophila, an insect model organism; thus more in-depth studies of insect cell apoptosis are necessary. In the present study, mitochondrial involvement during azadirachtin- and camptothecin-induced apoptosis in Spodoptera frugiperda Sf9 cells (isolated from Spodoptera frugiperda pupal ovarian tissue was investigated. The results showed that both azadirachtin and camptothecin could induce apoptosis in Sf9 cells. Reactive oxygen species (ROS generation, activation of mitochondrial permeability transition pores (MPTPs and loss of mitochondrial membrane potential (MMP were observed very early during apoptosis and were followed subsequently by the release of cytochrome-c from the mitochondria. Furthermore, the results also revealed that the opening of MPTPs and the loss of MMP induced by azadirachtin could be significantly inhibited by the permeability transition pore (PTP inhibitor cyclosporin A (CsA, which was used to identify the key role of mitochondria in the apoptosis of Sf9 cells. However, in camptothecin-treated Sf9 cells, CsA could not suppress the opening of MPTPs and the loss of MMP when apoptosis was induced. The data from caspase-3 and caspase-9 activity assays and detection of apoptosis by morphological observation and flow cytometry also uncovered the different effect of CsA on the two botanical apoptosis inducers. Although different mechanisms of apoptosis induction exist, our study revealed that mitochondria play a crucial role in insect cell line apoptosis.

  11. Escape of Hydrogen from the Exosphere of Mars

    Science.gov (United States)

    Bhattacharyya, Dolon; Clarke, John T.; Bertaux, Jean-Loup; Chaufray, Jean-Yves; Mayyasi-Matta, Majd A.

    2016-10-01

    After decades of exploration, the martian neutral hydrogen exosphere has remained largely uncharacterized even today. In my dissertation I have attempted to constrain the characteristics of the martian hydrogen exosphere using Hubble Space Telescope observations obtained during October-November 2007 and 2014. These observations reveal short-term seasonal changes exhibited by the martian hydrogen exosphere that are inconsistent with the diffusion-limited escape scenario. This seasonal behavior adds a new element towards backtracking the history of water loss from Mars. Modeling of the data also indicates the likely presence of a superthermal population of hydrogen created by non-thermal processes at Mars, another key element to understand the present-day escape. Exploration of the latitudinal symmetry of the martian exosphere indicates that it is symmetric above 2.5 martian radii and asymmetric below this altitude, which could be due to temperature differences between the day and night sides. Finally, the large uncertainties in determining the characteristics of the martian exosphere after decades of exploration is due to various assumptions about the intrinsic characteristics of the martian exosphere in the modeling process, degeneracy in the two modeling parameters temperature and density of the hydrogen atoms, unaccounted seasonal effects, and uncertainties introduced from spacecraft instrumentation as well as their viewing geometry.

  12. Random fluctuation leads to forbidden escape of particles.

    Science.gov (United States)

    Rodrigues, Christian S; de Moura, Alessandro P S; Grebogi, Celso

    2010-08-01

    A great number of physical processes are described within the context of Hamiltonian scattering. Previous studies have rather been focused on trajectories starting outside invariant structures, since the ones starting inside are expected to stay trapped there forever. This is true though only for the deterministic case. We show however that, under finitely small random fluctuations of the field, trajectories starting inside Kolmogorov-Arnold-Moser (KAM) islands escape within finite time. The nonhyperbolic dynamics gains then hyperbolic characteristics due to the effect of the random perturbed field. As a consequence, trajectories which are started inside KAM curves escape with hyperboliclike time decay distribution, and the fractal dimension of a set of particles that remain in the scattering region approaches that for hyperbolic systems. We show a universal quadratic power law relating the exponential decay to the amplitude of noise. We present a random walk model to relate this distribution to the amplitude of noise, and investigate these phenomena with a numerical study applying random maps.

  13. 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.

  14. Slow and Fast Escape for Open Intermittent Maps

    Science.gov (United States)

    Demers, Mark F.; Todd, Mike

    2017-04-01

    If a system mixes too slowly, putting a hole in it can completely destroy the richness of the dynamics. Here we study this instability for a class of intermittent maps with a family of slowly mixing measures. We show that there are three regimes: (1) standard hyperbolic-like behavior where the rate of mixing is faster than the rate of escape through the hole, there is a unique limiting absolutely continuous conditionally invariant measure (accim) and there is a complete thermodynamic description of the dynamics on the survivor set; (2) an intermediate regime, where the rate of mixing and escape through the hole coincide, limiting accims exist, but much of the thermodynamic picture breaks down; (3) a subexponentially mixing regime where the slow mixing means that mass simply accumulates on the parabolic fixed point. We give a complete picture of the transitions and stability properties (in the size of the hole and as we move through the family) in this class of open systems. In particular, we are able to recover a form of stability in the third regime above via the dynamics on the survivor set, even when no limiting accim exists.

  15. 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

    2011-08-09

    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.

  16. Tectonic escape in the evolution of the continental crust

    Science.gov (United States)

    Burke, K.; Sengor, C.

    1986-01-01

    The continental crust originated by processes similar to those operating today and continents consist of material most of which originated long ago in arc-systems that have later been modified, especially at Andean margins and in continental collisions where crustal thickening is common. Collision-related strike-slip motion is a general process in continental evolution. Because buoyant continental (or arc) material generally moves during collision toward a nearby oceanic margin where less buoyant lithosphere crops out, the process of major strike-slip dominated motion toward a 'free-face' is called 'tectonic escape'. Tectonic escape is and has been an element in continental evolution throughout recorded earth-history. It promotes: (1) rifting and the formation of rift-basins with thinning of thickened crust; (2) pervasive strike-slip faulting late in orogenic history which breaks up mountain belts across strike and may juxtapose unrelated sectors in cross-section; (3) localized compressional mountains and related foreland-trough basins.

  17. Vaccination and timing influence SIV immune escape viral dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Liyen Loh

    2008-01-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTL can be effective at controlling HIV-1 in humans and SIV in macaques, but their utility is partly offset by mutational escape. The kinetics of CTL escape and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help us understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. Traditional methods for following CTL escape and reversion are, however, insensitive to minor viral quasispecies. We developed sensitive quantitative real-time PCR assays to track the viral load of SIV Gag164-172 KP9 wild-type (WT and escape mutant (EM variants in pigtail macaques. Rapid outgrowth of EM virus occurs during the first few weeks of infection. However, the rate of escape plateaued soon after, revealing a prolonged persistence of WT viremia not detectable by standard cloning and sequencing methods. The rate of escape of KP9 correlated with levels of vaccine-primed KP9-specific CD8+ T cells present at that time. Similarly, when non-KP9 responder (lacking the restricting Mane-A*10 allele macaques were infected with SHIVmn229 stock containing a mixture of EM and WT virus, rapid reversion to WT was observed over the first 2 weeks following infection. However, the rate of reversion to WT slowed dramatically over the first month of infection. The serial quantitation of escape mutant viruses evolving during SIV infection shows that rapid dynamics of immune escape and reversion can be observed in early infection, particularly when CD8 T cells are primed by vaccination. However, these early rapid rates of escape and reversion are transient and followed by a significant slowing in these rates later during infection, highlighting that the rate of escape is significantly influenced by the timing of its occurrence.

  18. On the relative contributions of positive reinforcement and escape extinction in the treatment of food refusal.

    OpenAIRE

    Piazza, Cathleen C; Patel, Meeta R; Gulotta, Charles S; Sevin, Bari M; Layer, Stacy A

    2003-01-01

    We compared the effects of positive reinforcement alone, escape extinction alone, and positive reinforcement with escape extinction in the treatment of the food and fluid refusal of 4 children who had been diagnosed with a pediatric feeding disorder. Consumption did not increase when positive reinforcement was implemented alone. By contrast, consumption increased for all participants when escape extinction was implemented, independent of the presence or absence of positive reinforcement. Howe...

  19. Momentum versus extinction effects in the treatment of self-injurious escape behavior.

    OpenAIRE

    Zarcone, J R; Iwata, B A; Hughes, C.E; Vollmer, T R

    1993-01-01

    An individual's self-injurious escape behavior was treated using a high-probability instructional sequence with and without extinction. When presented alone, the high-probability sequence did not reduce self-injurious behavior. When escape extinction was implemented either alone or in combination with the high-probability sequence, self-injury decreased and compliance increased, suggesting that extinction may be a necessary component of the treatment for behavior problems maintained by escape.

  20. Characterization of escape times of Josephson junctions for signal detection.

    Science.gov (United States)

    Addesso, Paolo; Filatrella, Giovanni; Pierro, Vincenzo

    2012-01-01

    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 use of standard signal processing tools can be prohibitive due to the extreme weakness of the source or to the huge amount of data. In this paper we show that the prescriptions for the experimental setup and some physical behaviors depend on the detection strategy. More specifically, by exploitation of the sample mean of escape times to perform detection, two resonant regions are identified. At low frequencies there is a stochastic resonance or activation phenomenon, while near the plasma frequency a geometric resonance appears. Furthermore, detection performance in the geometric resonance region is maximized at the prescribed value of the bias current. 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 is essentially limited by measurement electronics. The behavior of the likelihood ratio and sample mean detector for different values of incoming signal to noise ratio is discussed, and a relationship with the error probability is found. Detectors based on the likelihood ratio test could be employed also to estimate unknown parameters in the applied input signal. As a prototypical example we study the phase estimation problem of a sinusoidal current, which is accomplished by using the filter bank approach. Finally we show that for a physically feasible detector the performances are found to be very close to the Cramer-Rao theoretical bound. Applications might be found, for example, in some astronomical detection problems (where the all-sky gravitational and/or radio wave search for pulsars requires the analysis of nearly sinusoidal

  1. The role of endosomal escape and mitogen-activated protein kinases in adenoviral activation of the innate immune response.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Smith

    Full Text Available Adenoviral vectors (AdV activate multiple signaling pathways associated with innate immune responses, including mitogen-activated protein kinases (MAPKs. In this study, we investigated how systemically-injected AdVs activate two MAPK pathways (p38 and ERK and the contribution of these kinases to AdV-induced cytokine and chemokine responses in mice. Mice were injected intravenously either with a helper-dependent Ad2 vector that does not express viral genes or transgenes, or with the Ad2 mutant ts1, which is defective in endosomal escape. We found that AdV induced rapid phosphorylation of p38 and ERK as well as a significant cytokine response, but ts1 failed to activate p38 or ERK and induced only a limited cytokine response. These results demonstrate that endosomal escape of virions is a critical step in the induction of these innate pathways and responses. We then examined the roles of p38 and ERK pathways in the innate cytokine response by administering specific kinase inhibitors to mice prior to AdV. The cytokine and chemokine response to AdV was only modestly suppressed by a p38 inhibitor, while an ERK inhibitor has mixed effects, lowering some cytokines and elevating others. Thus, even though p38 and ERK are rapidly activated after i.v. injection of AdV, cytokine and chemokine responses are mostly independent of these kinases.

  2. Effects of ionizing radiation on fixed-ratio escape performance in rats

    Energy Technology Data Exchange (ETDEWEB)

    Mele, P.C.; Franz, C.G.; Harrison, J.R. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1990-07-01

    Adult male rats pressed a lever to terminate scrambled footshock according to a fixed-ratio 20 schedule (FR escape). Separate groups of rats received a single whole-body exposure to 4.5 or 7.5 Gray (Gy) of gamma photon radiation or were sham irradiated. The first postirradiation test session began 5 min after the end of the irradiation. The 4.5 Gy dose failed to produce any significant changes in performance over six weeks of testing after exposure. In contrast, response rates after irradiation with 7.5 Gy were decreased over the first four weeks postexposure. Reductions in response rate were due to both an increase in the latency to the first response of a ratio and to a reduction in running response rate. Performance recovered to preirradiation control levels during weeks 5-6 after exposure to 7.5 Gy. Body weights were decreased dose-dependently to a minimum of 91% of preirradiation control values during the third week after exposure to 7.5 Gy. A significant positive correlation existed for changes in the weekly average response rates and body weights at this dose. When a total dose of 7.5 Gy was delivered as 1.5 Gy per day for five consecutive days (dose fractionation), there were no significant changes in performance over eight weeks of testing although reversible decreases in response rates occurred in three of six rats. By comparison with previous studies these results demonstrate that FR escape performance may provide a more sensitive index of radiation-induced behavioral disruption than performance maintained by several other schedules of negative reinforcement.

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

    Directory of Open Access Journals (Sweden)

    Meyer Detlef

    2010-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic

  4. On the relative contributions of positive reinforcement and escape extinction in the treatment of food refusal.

    Science.gov (United States)

    Piazza, Cathleen C; Patel, Meeta R; Gulotta, Charles S; Sevin, Bari M; Layer, Stacy A

    2003-01-01

    We compared the effects of positive reinforcement alone, escape extinction alone, and positive reinforcement with escape extinction in the treatment of the food and fluid refusal of 4 children who had been diagnosed with a pediatric feeding disorder. Consumption did not increase when positive reinforcement was implemented alone. By contrast, consumption increased for all participants when escape extinction was implemented, independent of the presence or absence of positive reinforcement. However, the addition of positive reinforcement to escape extinction was associated with beneficial effects (e.g., greater decreases in negative vocalizations and inappropriate behavior) for some participants.

  5. Experiment for Development of Simple Escape Countermeasures for Frogs Falling into Concrete Canals

    Science.gov (United States)

    Watabe, Keiji; Mori, Atsushi; Koizumi, Noriyuki; Takemura, Takeshi; Park, Myeong Soo

    Three prototype escape countermeasures for frogs that can be easily installed in U-shaped canals with widths of 30-50 cm and depths of 30-50 cm were experimentally produced because frogs cannot escape from agricultural canals with deep concrete walls after falling into the canal. The differences of effectiveness of the 3 prototypes in places for the countermeasures (1 and 2) and flow conditions (dry and water running) were investigated for 2 frog species (Tokyo Daruma Pond Frog and Japanese Brown Frog). The brown frogs escaped from the canals more easily than the pond frogs. The brown frogs escaped regardless of their body size, but the small pond frogs escaped more easily than the large pond frogs. The prototype with slopes beside both canal walls and a net spread across the center line of the canal enabled frogs to escape from the canal more easily than the prototypes with only slopes or nets beside both canal walls. Increasing the number of places for the countermeasures enhanced frog escape. The differences in frog escape between dry canals and canals with water running were not significant. Therefore, the prototypes were confirmed sufficient as escape countermeasures that is inexpensive and can be easily placed in and removed from agricultural canals.

  6. Improving escape panel selectivity in Nephrops directed fisheries by actively stimulating fish behaviour

    DEFF Research Database (Denmark)

    Krag, Ludvig Ahm; Herrmann, Bent; Feekings, Jordan P.

    2016-01-01

    with it. To increase the efficiency of such panels, the contact probability needs to be improved. In this study, we investigate to what extent the efficiency of escape panels can be improved by actively stimulating the escape behaviour of fish. The performance of two identical panel sections was compared...... in a twin-trawl system, one with and one without a stimulation device. A new coupled analysis method was used to explicitly quantify the improvements in contact probability and release efficiency for the escape panel. The results demonstrate that by actively stimulating escape behaviour, the contact...

  7. The structure of spider's web fast escaping sets

    CERN Document Server

    Osborne, J W

    2010-01-01

    Building on recent work by Rippon and Stallard, we explore the intricate structure of the spider's web fast escaping sets associated with certain transcendental entire functions. Our results are expressed in terms of the components of the complement of the set (the 'holes' in the web). We describe the topology of such components and give a characterisation of their possible orbits under iteration. We show that there are uncountably many components having each of a number of orbit types, and we prove that components with bounded orbits are quasiconformally homeomorphic to components of the filled Julia set of a polynomial. We also show that there are singleton periodic components and that these are dense in the Julia set.

  8. 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.

  9. 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.

  10. Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mauricio P. Pinto

    2016-09-01

    Full Text Available Tumor angiogenesis is widely recognized as one of the “hallmarks of cancer”. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1 upregulation of compensatory/alternative pathways for angiogenesis; (2 vasculogenic mimicry; and (3 vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.

  11. On Escaping a Galaxy Cluster in an Accelerating Universe

    CERN Document Server

    Stark, Alejo; Gifford, Daniel

    2016-01-01

    We derive the escape velocity profile for an Einasto density field in an accelerating universe and demonstrate its physical viability by comparing theoretical expectations to both light-cone data generated from N-body simulations and archival data on 20 galaxy clusters. We demonstrate that the projection function ($g(\\beta )$) is deemed physically viable only for the theoretical expectation that includes a cosmology-dependent term. Using simulations, we show that the inferred velocity anisotropy is more than 6{\\sigma} away from the expected value for the theoretical profile that ignores the acceleration of the universe. In the archival data, we constrain the average velocity anisotropy parameter of a sample of 20 clusters to be $\\beta ={0.248}_{-0.360}^{+0.164}$ at the 68% confidence level. Lastly, we briefly discuss how our analytic model may be used as a novel cosmological probe based on galaxy clusters.

  12. An Introduction to Survival, Evasion, Resistance, and Escape (SERE) Medicine.

    Science.gov (United States)

    Smith, Michael B

    2013-01-01

    When an individual finds himself/herself in a survival, evasion, resistance, or escape (SERE) scenario, the ability to treat injuries/illnesses can be the difference between life and death. SERE schools are responsible for preparing military members for these situations, but the concept of SERE medicine is not particularly well defined. To provide a comprehensive working description of SERE medicine, operational and training components were examined. Evidence suggests that SERE medicine is diverse, injury/illness patterns are situationally dependent, and treatment options often differ from conventional clinical medicine. Ideally, medical lessons taught in SERE training are based on actual documented events. Unfortunately, the existing body of literature is dated and does not appear to be expanding. In this article, four distinct facets of SERE medicine are presented to establish a basis for future discussion and research. Recommendations to improve SERE medical curricula and data-gathering processes are also provided.

  13. 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%.

  14. Novel Anti-Melanoma Immunotherapies: Disarming Tumor Escape Mechanisms

    Directory of Open Access Journals (Sweden)

    Sivan Sapoznik

    2012-01-01

    Full Text Available The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles.

  15. Fast Escape from Quantum Mazes in Integrated Photonics

    CERN Document Server

    Caruso, Filippo; Ciriolo, Anna Gabriella; Sciarrino, Fabio; Osellame, Roberto

    2015-01-01

    Escaping from a complex maze, by exploring different paths with several decision-making branches in order to reach the exit, has always been a very challenging and fascinating task. Wave field and quantum objects may explore a complex structure in parallel by interference effects, but without necessarily leading to more efficient transport. Here, inspired by recent observations in biological energy transport phenomena, we demonstrate how a quantum walker can efficiently reach the output of a maze by partially suppressing the presence of interference. In particular, we show theoretically an unprecedented improvement in transport efficiency for increasing maze size with respect to purely quantum and classical approaches. In addition, we investigate experimentally these hybrid transport phenomena, by mapping the maze problem in an integrated waveguide array, probed by coherent light, hence successfully testing our theoretical results. These achievements may lead towards future bio-inspired photonics technologies...

  16. Escaped and Trapped Emission of Organic Light-Emitting Diodes

    Institute of Scientific and Technical Information of China (English)

    LIANG Shi-Xiong; WU Zhao-Xin; ZHAO Xuan-Ke; HOU Xun

    2012-01-01

    By locating the emitters around the first and second antinode of the metal electrode, the escaped and trapped emission of small molecule based bottom emission organic light-emitting diodes is investigated by using an integrating sphere, a fiber spectrometer and a glass hemisphere. It is found that the external coupling ratio by locating the emitters at the second antinode (at a distance of 220 nm from the cathode) is 70%, which is higher than that of an emitter at the first antinode (60 nm from the cathode) in theory and experiment. Extending the "half-space" dipole model by taking the dipole radiation pattern into account, we also calculate the optical coupling efficiency for the emitter at both the first and second antinode. Our experimental and theoretical results will benefit the optimization of device structures for the higher out-coupling efficiency.%By locating the emitters around the first and second antinode of the metal electrode,the escaped and trapped emission of small molecule based bottom emission organic light-emitting diodes is investigated by using an integrating sphere,a fiber spectrometer and a glass hemisphere.It is found that the external coupling ratio by locating the emitters at the second antinode (at a distance of 220 nm from the cathode) is 70%,which is higher than that of an emitter at the first antinode (60nm from the cathode) in theory and experiment.Extending the "half-space" dipole model by taking the dipole radiation pattern into account,we also calculate the optical coupling efficiency for the emitter at both the first and second antinode.Our experimental and theoretical results will benefit the optimization of device structures for the higher out-coupling efficiency.

  17. 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.

  18. Initiating a watch list for Ebola virus antibody escape mutations

    Directory of Open Access Journals (Sweden)

    Craig R. Miller

    2016-02-01

    Full Text Available The 2014 Ebola virus (EBOV outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  19. 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.

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

    Science.gov (United States)

    Hanifin, Charles T; Brodie, Edmund D; Brodie, Edmund D

    2008-03-11

    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.

  1. 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.

  2. 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.

  3. Spoon Distance Fading with and without Escape Extinction as Treatment for Food Refusal

    Science.gov (United States)

    Rivas, Kristi D.; Piazza, Cathleen C.; Patel, Meeta R.; Bachmeyer, Melanie H.

    2010-01-01

    Little is known about the characteristics of meals that serve as motivating operations (MOs) for escape behavior. In the current investigation, we showed that the distance at which a therapist held a spoon from a child's lips served as an MO for escape behavior. Based on these results, we implemented spoon distance fading, compared fading with and…

  4. Hepatitis A Virus Vaccine Escape Variants and Potential New Serotype Emergence

    Science.gov (United States)

    Pérez-Sautu, Unai; Costafreda, M. Isabel; Caylà, Joan; Tortajada, Cecilia; Lite, Josep; Bosch, Albert

    2011-01-01

    Six hepatitis A virus antigenic variants that likely escaped the protective effect of available vaccines were isolated, mostly from men who have sex with men. The need to complete the proper vaccination schedules is critical, particularly in the immunocompromised population, to prevent the emergence of vaccine-escaping variants. PMID:21470474

  5. 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…

  6. Treatment of Escape-Maintained Behavior with Positive Reinforcement: The Role of Reinforcement Contingency and Density

    Science.gov (United States)

    Ingvarsson, Einar T.; Hanley, Gregory P.; Welter, Katherine M.

    2009-01-01

    Functional analyses suggested that the disruptive behavior of three preschool children was maintained by escape from demands. While keeping the escape contingency intact, we conducted (a) a density analysis in which the children earned preferred items for task completion according to two schedules that varied in reinforcement density, and (b) a…

  7. 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…

  8. Competing Contingencies for Escape Behavior: Effects of Negative Reinforcement Magnitude and Quality

    Science.gov (United States)

    Hammond, Jennifer L.

    2009-01-01

    Previous research has shown that problem behavior maintained by social-negative reinforcement can be treated without escape extinction by enhancing the quality of positive reinforcement for an appropriate alternative response such as compliance. By contrast, negative reinforcement (escape) for compliance generally has been ineffective in the…

  9. Hepatitis A Virus Vaccine Escape Variants and Potential New Serotype Emergence

    OpenAIRE

    Pérez-Sautu, Unai; Costafreda, M. Isabel; Caylà, Joan; Tortajada, Cecilia; Lite, Josep; Bosch, Albert; Pintó, Rosa M.

    2011-01-01

    Six hepatitis A virus antigenic variants that likely escaped the protective effect of available vaccines were isolated, mostly from men who have sex with men. The need to complete the proper vaccination schedules is critical, particularly in the immunocompromised population, to prevent the emergence of vaccine-escaping variants.

  10. Identification of genes escaping X inactivation by allelic expression analysis in a novel hybrid mouse model.

    Science.gov (United States)

    Berletch, Joel B; Ma, Wenxiu; Yang, Fan; Shendure, Jay; Noble, William S; Disteche, Christine M; Deng, Xinxian

    2015-12-01

    X chromosome inactivation (XCI) is a female-specific mechanism that serves to balance gene dosage between the sexes whereby one X chromosome in females is inactivated during early development. Despite this silencing, a small portion of genes escape inactivation and remain expressed from the inactive X (Xi). Little is known about the distribution of escape from XCI in different tissues in vivo and about the mechanisms that control tissue-specific differences. Using a new binomial model in conjunction with a mouse model with identifiable alleles and skewed X inactivation we are able to survey genes that escape XCI in vivo. We show that escape from X inactivation can be a common feature of some genes, whereas others escape in a tissue specific manner. Furthermore, we characterize the chromatin environment of escape genes and show that expression from the Xi correlates with factors associated with open chromatin and that CTCF co-localizes with escape genes. Here, we provide a detailed description of the experimental design and data analysis pipeline we used to assay allele-specific expression and epigenetic characteristics of genes escaping X inactivation. The data is publicly available through the GEO database under ascension numbers GSM1014171, GSE44255, and GSE59779. Interpretation and discussion of these data are included in a previously published study (Berletch et al., 2015) [1].

  11. Escape from transcriptional shutoff during poliovirus infection: NF-κB-responsive genes IκBa and A20.

    Science.gov (United States)

    Doukas, Tammy; Sarnow, Peter

    2011-10-01

    It has been known for a long time that infection of cultured cells with poliovirus results in the overall inhibition of transcription of most host genes. We examined whether selected host genes can escape transcriptional inhibition by thiouridine marking newly synthesized host mRNAs during viral infection. Using cDNA microarrays hybridized to cDNAs made from thiolated mRNAs, a small set of host transcripts was identified and their expression verified by quantitative PCR and Northern and Western blot analyses. These transcripts were synthesized from genes that displayed enrichment for NF-κB binding sites in their promoter regions, suggesting that some NF-κB-regulated promoters can escape the virus-induced inhibition of transcription. In particular, two negative regulators of NF-κB, IκBa and A20, were upregulated during viral infection. Depletion of A20 enhanced viral RNA abundance and viral yield, arguing that cells respond to virus infection by counteracting NF-κB-induced proviral effects.

  12. Modeling the endosomal escape of cell-penetrating peptides using a transmembrane pH gradient.

    Science.gov (United States)

    Madani, Fatemeh; Abdo, Rania; Lindberg, Staffan; Hirose, Hisaaki; Futaki, Shiroh; Langel, Ulo; Gräslund, Astrid

    2013-04-01

    Cell-penetrating peptides (CPPs) can internalize into cells with covalently or non-covalently bound biologically active cargo molecules, which by themselves are not able to pass the cell membrane. Direct penetration and endocytosis are two main pathways suggested for the cellular uptake of CPPs. Cargo molecules which have entered the cell via an endocytotic pathway must be released from the endosome before degradation by enzymatic processes and endosomal acidification. Endosomal entrapment seems to be a major limitation in delivery of these molecules into the cytoplasm. Bacteriorhodopsin (BR) asymmetrically introduced into large unilamellar vesicles (LUVs) was used to induce a pH gradient across the lipid bilayer. By measuring pH outside the LUVs, we observed light-induced proton pumping mediated by BR from the outside to the inside of the LUVs, creating an acidic pH inside the LUVs, similar to the late endosomes in vivo. Here we studied the background mechanism(s) of endosomal escape. 20% negatively charged LUVs were used as model endosomes with incorporated BR into the membrane and fluorescein-labeled CPPs entrapped inside the LUVs, together with a fluorescence quencher. The translocation of different CPPs in the presence of a pH gradient across the membrane was studied. The results show that the light-induced pH gradient induced by BR facilitates vesicle membrane translocation, particularly for the intermediately hydrophobic CPPs, and much less for hydrophilic CPPs. The presence of chloroquine inside the LUVs or addition of pyrenebutyrate outside the LUVs destabilizes the vesicle membrane, resulting in significant changes of the pH gradient across the membrane.

  13. Farming-up coastal fish assemblages through a massive aquaculture escape event.

    Science.gov (United States)

    Toledo-Guedes, Kilian; Sanchez-Jerez, Pablo; Benjumea, María E; Brito, Alberto

    2014-07-01

    We investigated the changes on the mean trophic level of fish assemblages across different spatiotemporal scales, before and after a massive escape event occurred off La Palma (Canary Islands), which resulted in the release of 1.5 million fish (mostly Dicentrarchus labrax) into the wild. The presence of escaped fish altered significantly the mean trophic level of fish assemblages in shallow coastal waters. This alteration was exacerbated by the massive escape. A nearby marine protected area buffered the changes in mean trophic level but exhibited the same temporal patterns as highly fished areas. Moreover, escaped fish exploited natural resources according to their total length and possibly, time since escapement. New concerns arise as a "farming up" process is detected in shallow coastal fish assemblages where marine aquaculture is established.

  14. 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.

  15. Complex Economies Have a Lateral Escape from the Poverty Trap

    Science.gov (United States)

    Pugliese, Emanuele; Chiarotti, Guido L.; Zaccaria, Andrea; Pietronero, Luciano

    2017-01-01

    We analyze the decisive role played by the complexity of economic systems at the onset of the industrialization process of countries over the past 50 years. Our analysis of the input growth dynamics, considering a further dimension through a recently introduced measure of economic complexity, reveals that more differentiated and more complex economies face a lower barrier (in terms of GDP per capita) when starting the transition towards industrialization. As a consequence, we can extend the classical concept of a one-dimensional poverty trap, by introducing a two-dimensional poverty trap: a country will start the industrialization process if it is rich enough (as in neo-classical economic theories), complex enough (using this new dimension and laterally escaping from the poverty trap), or a linear combination of the two. This naturally leads to the proposal of a Complex Index of Relative Development (CIRD) which shows, when analyzed as a function of the growth due to input, a shape of an upside down parabola similar to that expected from the standard economic theories when considering only the GDP per capita dimension. PMID:28072867

  16. Modified guidance laws to escape microbursts with turbulence

    Directory of Open Access Journals (Sweden)

    Atilla Dogan

    2002-01-01

    Full Text Available This paper introduces Modified Altitude- and Dive-Guidance laws for escaping a microburst with turbulence. The goal is to develop a procedure to estimate the highest altitude at which an aircraft can fly through a microburst without running into stall. First, a new metric is constructed that quantifies the aircraft upward force capability in a microburst encounter. In the absence of turbulence, the metric is shown to be a decreasing function of altitude. This suggests that descending to a low altitude may improve safety in the sense that the aircraft will have more upward force capability to maintain its altitude. In the presence of stochastic turbulence, the metric is treated as a random variable and its probability distribution function is analytically approximated as a function of altitude. This approximation allows us to determine the highest safe altitude at which the aircraft may descend, hence avoiding to descend too low. This highest safe altitude is used as the commanded altitude in Modified Altitude- and Dive-Guidance. Monte Carlo simulations show that these Modified Altitude- and Dive-Guidance strategies can decrease the probability of minimum altitude being lower than a given value without significantly increasing the probability of crash.

  17. 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...

  18. 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.

  19. 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

  20. 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.

  1. Breakdown of the escape dynamics in Josephson junctions

    Science.gov (United States)

    Massarotti, D.; Stornaiuolo, D.; Lucignano, P.; Galletti, L.; Born, D.; Rotoli, G.; Lombardi, F.; Longobardi, L.; Tagliacozzo, A.; Tafuri, F.

    2015-08-01

    We have identified anomalous behavior of the escape rate out of the zero-voltage state in Josephson junctions with a high critical current density Jc. For this study we have employed YBa2Cu3O7 -x grain boundary junctions, which span a wide range of Jc and have appropriate electrodynamical parameters. Such high Jc junctions, when hysteretic, do not switch from the superconducting to the normal state following the expected stochastic Josephson distribution, despite having standard Josephson properties such as a Fraunhofer magnetic field pattern. The switching current distributions (SCDs) are consistent with nonequilibrium dynamics taking place on a local rather than a global scale. This means that macroscopic quantum phenomena seem to be practically unattainable for high Jc junctions. We argue that SCDs are an accurate means to measure nonequilibrium effects. This transition from global to local dynamics is of relevance for all kinds of weak links, including the emergent family of nanohybrid Josephson junctions. Therefore caution should be applied in the use of such junctions in, for instance, the search for Majorana fermions.

  2. Fast-starting after a breath: air-breathing motions are kinematically similar to escape responses in the catfish Hoplosternum littorale

    Directory of Open Access Journals (Sweden)

    Paolo Domenici

    2014-12-01

    Full Text Available Fast-starts are brief accelerations commonly observed in fish within the context of predator–prey interactions. In typical C-start escape responses, fish react to a threatening stimulus by bending their body into a C-shape during the first muscle contraction (i.e. stage 1 which provides a sudden acceleration away from the stimulus. Recently, similar C-starts have been recorded in fish aiming at a prey. Little is known about C-starts outside the context of predator–prey interactions, though recent work has shown that escape response can also be induced by high temperature. Here, we test the hypothesis that air-breathing fish may use C-starts in the context of gulping air at the surface. Hoplosternum littorale is an air-breathing freshwater catfish found in South America. Field video observations reveal that their air-breathing behaviour consists of air-gulping at the surface, followed by a fast turn which re-directs the fish towards the bottom. Using high-speed video in the laboratory, we compared the kinematics of the turn immediately following air-gulping performed by H. littorale in normoxia with those of mechanically-triggered C-start escape responses and with routine (i.e. spontaneous turns. Our results show that air-breathing events overlap considerably with escape responses with a large stage 1 angle in terms of turning rates, distance covered and the relationship between these rates. Therefore, these two behaviours can be considered kinematically comparable, suggesting that air-breathing in this species is followed by escape-like C-start motions, presumably to minimise time at the surface and exposure to avian predators. These findings show that C-starts can occur in a variety of contexts in which fish may need to get away from areas of potential danger.

  3. Review of One Illness Away: Why People Become Poor and How They Escape Poverty

    OpenAIRE

    Afia B. Yamoah

    2011-01-01

    Afia B. Yamoah reviews One Illness Away: Why People Become Poor and How They Escape Poverty, by Anirudh Krishna. Krishna argues that poverty policy needs to address reasons why people become poor and how they can escape poverty.

  4. Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration.

    Directory of Open Access Journals (Sweden)

    Ji-Hye Choi

    Full Text Available BACKGROUND: Dendritic cells (DCs are the most potent antigen-presenting cells that link innate and adaptive immune responses, playing a pivotal role in triggering antigen-specific immunity. Antigen uptake by DCs induces maturational changes that include increased surface expression of major histocompatibility complex (MHC and costimulatory molecules. In addition, DCs actively migrate to regional lymph nodes and activate antigen-specific naive T cells after capturing antigens. We characterize the functional changes of DCs infected with Orientia tsutsugamushi, the causative agent of scrub typhus, since there is limited knowledge of the role played by DCs in O. tsutsugamushi infection. METHODOLOGY/PRINCIPAL FINDING: O. tsutsugamushi efficiently infected bone marrow-derived DCs and induced surface expression of MHC II and costimulatory molecules. In addition, O. tsutsugamushi induced autophagy activation, but actively escaped from this innate defense system. Infected DCs also secreted cytokines and chemokines such as IL-6, IL-12, MCP5, MIP-1α, and RANTES. Furthermore, in vitro migration of DCs in the presence of a CCL19 gradient within a 3D collagen matrix was drastically impaired when infected with O. tsutsugamushi. The infected cells migrated much less efficiently into lymphatic vessels of ear dermis ex vivo when compared to LPS-stimulated DCs. In vivo migration of O. tsutsugamushi-infected DCs to regional lymph nodes was significantly impaired and similar to that of immature DCs. Finally, we found that MAP kinases involved in chemotactic signaling were differentially activated in O. tsutsugamushi-infected DCs. CONCLUSION/SIGNIFICANCE: These results suggest that O. tsutsugamushi can target DCs to exploit these sentinel cells as replication reservoirs and delay or impair the functional maturation of DCs during the bacterial infection in mammals.

  5. Reporter assay for endo/lysosomal escape of toxin-based therapeutics.

    Science.gov (United States)

    Gilabert-Oriol, Roger; Thakur, Mayank; von Mallinckrodt, Benedicta; Bhargava, Cheenu; Wiesner, Burkhard; Eichhorst, Jenny; Melzig, Matthias F; Fuchs, Hendrik; Weng, Alexander

    2014-05-22

    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, (Alexa)saporin 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 (Alexa)saporin 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.

  6. H Escape Rates Inferred from MAVEN/IUVS Observations of the Mars Hydrogen Corona

    Science.gov (United States)

    Chaffin, Michael S.; Chaufray, Jean-Yves; Deighan, Justin; Schneider, Nicholas M.; McClintock, William; Stewart, A. Ian F.; Thiemann, E. M.; Clarke, John T.; Holsclaw, Gregory; Jain, Sonal Kumar; Crismani, Matteo; Stiepen, Arnaud; Montmessin, Franck; Eparvier, Francis; Jakosky, Bruce

    2016-10-01

    H escape oxidizes and dessicates the Mars atmosphere and surface, providing a key control on the present-day chemistry and long-term evolution of the planet. Recently, large variations in the escape rate of H as a function of season have been reported by several studies, making continued observation of the variation a high priority. We present escape rates derived from Mars Atmosphere and Volatile EvolutioN (MAVEN) mission Imaging UltraViolet Spectrograph (IUVS) observations of the extended atmosphere of Mars at H Lyman alpha (121.6 nm), which must be interpreted with a coupled density/radiative transfer model owing to the optically thick nature of the emission and the small fraction of H present in the corona on escaping trajectories. We recover densities, temperatures, and escape rates under the assumption of spherical symmetry for multiple periods across MAVEN's mission so far, beginning in December 2014 (escape rates ~4e8/cm2/s). We describe the observed variation and compare it with previously observed seasonal variation in retrieved H escape rates, providing a necessary input for future photochemical modeling studies and estimates of water loss from Mars over its history.

  7. 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.

  8. Do malaria parasites manipulate the escape behaviour of their avian hosts? An experimental study.

    Science.gov (United States)

    Garcia-Longoria, Luz; Møller, Anders P; Balbontín, Javier; de Lope, Florentino; Marzal, Alfonso

    2015-12-01

    Escape behaviour is the behaviour that birds and other animals display when already caught by a predator. An individual exhibiting higher intensity of such anti-predator behaviour could have greater probabilities of escape from predators. Parasites are known to affect different aspects of host behaviour to increase their own fitness. Vector-transmitted parasites such as malaria parasites should gain by manipulating their hosts to enhance the probability of transmission. Several studies have shown that malaria parasites can manipulate their vectors leading to increased transmission success. However, little is known about whether malaria parasites can manipulate escape behaviour of their avian hosts thereby increasing the spread of the parasite. Here we used an experimental approach to explore if Plasmodium relictum can manipulate the escape behaviour of one of its most common avian hosts, the house sparrow Passer domesticus. We experimentally tested whether malaria parasites manipulate the escape behaviour of their avian host. We showed a decrease in the intensity of biting and tonic immobility after removal of infection with anti-malaria medication compared to pre-experimental behaviour. These outcomes suggest that infected sparrows performed more intense escape behaviour, which would increase the likelihood of individuals escaping from predators, but also benefit the parasite by increasing its transmission opportunities.

  9. Quantifying the impact of human immunodeficiency virus-1 escape from cytotoxic T-lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ulrich D Kadolsky

    Full Text Available HIV-1 escape from the cytotoxic T-lymphocyte (CTL response leads to a weakening of viral control and is likely to be detrimental to the patient. To date, the impact of escape on viral load and CD4(+ T cell count has not been quantified, primarily because of sparse longitudinal data and the difficulty of separating cause and effect in cross-sectional studies. We use two independent methods to quantify the impact of HIV-1 escape from CTLs in chronic infection: mathematical modelling of escape and statistical analysis of a cross-sectional cohort. Mathematical modelling revealed a modest increase in log viral load of 0.051 copies ml(-1 per escape event. Analysis of the cross-sectional cohort revealed a significant positive association between viral load and the number of "escape events", after correcting for length of infection and rate of replication. We estimate that a single CTL escape event leads to a viral load increase of 0.11 log copies ml(-1 (95% confidence interval: 0.040-0.18, consistent with the predictions from the mathematical modelling. Overall, the number of escape events could only account for approximately 6% of the viral load variation in the cohort. Our findings indicate that although the loss of the CTL response for a single epitope results in a highly statistically significant increase in viral load, the biological impact is modest. We suggest that this small increase in viral load is explained by the small growth advantage of the variant relative to the wildtype virus. Escape from CTLs had a measurable, but unexpectedly low, impact on viral load in chronic infection.

  10. 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.

  11. The Cell Wall Lipid PDIM Contributes to Phagosomal Escape and Host Cell Exit of Mycobacterium tuberculosis

    Science.gov (United States)

    Quigley, Jeff; Hughitt, V. Keith; Velikovsky, Carlos A.; Mariuzza, Roy A.

    2017-01-01

    ABSTRACT The cell wall of Mycobacterium tuberculosis is composed of unique lipids that are important for pathogenesis. Indeed, the first-ever genetic screen in M. tuberculosis identified genes involved in the biosynthesis and transport of the cell wall lipid PDIM (phthiocerol dimycocerosates) as crucial for the survival of M. tuberculosis in mice. Here we show evidence for a novel molecular mechanism of the PDIM-mediated virulence in M. tuberculosis. We characterized the DNA interaction and the regulon of Rv3167c, a transcriptional repressor that is involved in virulence regulation of M. tuberculosis, and discovered that it controls the PDIM operon. A loss-of-function genetic approach showed that PDIM levels directly correlate with the capacity of M. tuberculosis to escape the phagosome and induce host cell necrosis and macroautophagy. In conclusion, our study attributes a novel role of the cell wall lipid PDIM in intracellular host cell modulation, which is important for host cell exit and dissemination of M. tuberculosis. PMID:28270579

  12. 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...

  13. Distinct effects of endosomal escape and inhibition of endosomal trafficking on gene delivery via electrotransfection

    Science.gov (United States)

    Chang, Chun-Chi; Wang, Liangli; Yuan, Fan

    2017-01-01

    A recent theory suggests that endocytosis is involved in uptake and intracellular transport of electrotransfected plasmid DNA (pDNA). The goal of the current study was to understand if approaches used previously to improve endocytosis of gene delivery vectors could be applied to enhancing electrotransfection efficiency (eTE). Results from the study showed that photochemically induced endosomal escape, which could increase poly-L-lysine (PLL)-mediated gene delivery, decreased eTE. The decrease could not be blocked by treatment of cells with endonuclease inhibitors (aurintricarboxylic acid and zinc ion) or antioxidants (L-glutamine and ascorbic acid). Chemical treatment of cells with an endosomal trafficking inhibitor that blocks endosome progression, bafilomycin A1, resulted in a significant decrease in eTE. However, treatment of cells with lysosomotropic agents (chloroquine and ammonium chloride) had little effects on eTE. These data suggested that endosomes played important roles in protecting and intracellular trafficking of electrotransfected pDNA. PMID:28182739

  14. Turning pain into cues for goal-directed behavior : Implementation intentions reduce escape-avoidance behavior on a painful task

    NARCIS (Netherlands)

    Karsdorp, P.A.; Geenen, R.; Kroese, F.M.; Vlaeyen, J.W.S.

    2016-01-01

    Pain automatically elicits escape-avoidance behavior to avert bodily harm. In patients with chronic pain, long-term escape-avoidance behavior may increase the risk of chronic disability. The aim of the presents study was to examine whether implementation intentions reduce escape-avoidance behavior d

  15. Optimal search and ambush for a hider who can escape the search region

    OpenAIRE

    Alpern, Steve; Fokkink, Robbert; Simanjuntak, Martin

    2016-01-01

    Search games for a mobile or immobile hider traditionally have the hider permanently confined to a compact ‘search region’ making eventual capture inevitable. Hence the payoff can be taken as time until capture. However in many real life search problems it is possible for the hider to escape an area in which he was known to be located (e.g. Bin Laden from Tora Bora) or for a prey animal to escape a predator’s hunting territory. We model and solve such continuous time problems with escape wher...

  16. Mean Exit Time and Escape Probability for a Tumor Growth System under Non-Gaussian Noise

    CERN Document Server

    Ren, Jian; Gao, Ting; Kan, Xingye; Duan, Jinqiao

    2011-01-01

    Effects of non-Gaussian $\\alpha-$stable L\\'evy noise on the Gompertz tumor growth model are quantified by considering the mean exit time and escape probability of the cancer cell density from inside a safe or benign domain. The mean exit time and escape probability problems are formulated in a differential-integral equation with a fractional Laplacian operator. Numerical simulations are conducted to evaluate how the mean exit time and escape probability vary or bifurcates when $\\alpha$ changes. Some bifurcation phenomena are observed and their impacts are discussed.

  17. 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.

  18. CD147 stimulates hepatoma cells escaping from immune surveillance of T cells by interaction with Cyclophilin A.

    Science.gov (United States)

    Ren, Yi-Xin; Wang, Shu-Jing; Fan, Jian-Hui; Sun, Shi-Jie; Li, Xia; Padhiar, Arshad Ahmed; Zhang, Jia-Ning

    2016-05-01

    T cells play an important role in tumor immune surveillance. CD147 is a member of immunoglobulin superfamily present on the surface of many tumor cells and mediates malignant cell behaviors. Cyclophilin A (CypA) is an intracellular protein promoting inflammation when released from cells. CypA is a natural ligand for CD147. In this study, CD147 specific short hairpin RNAs (shRNA) were transfected into murine hepatocellular carcinoma Hepa1-6 cells to assess the effects of CD147 on hepatoma cells escaping from immune surveillance of T cells. We found extracellular CypA stimulated cell proliferation through CD147 by activating ERK1/2 signaling pathway. Downregulation of CD147 expression on Hepa1-6 cells significantly suppressed tumor progression in vivo, and decreased cell viability when co-cultured with T cells in vitro. Importantly, knockdown of CD147 on Hepa1-6 cells resulted in significantly increased T cells chemotaxis induced by CypA both in vivo and in vitro. These findings provide novel mechanisms how tumor cells escaping from immune surveillance of T cells. We provide a potential therapy for hepatocellular carcinoma by targeting CD147 or CD147-CypA interactions.

  19. 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...... 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-dependent to a large extent...

  20. Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA∗008 to Escape Elimination by NK Cells

    Directory of Open Access Journals (Sweden)

    Einat Seidel

    2015-02-01

    Full Text Available Natural killer (NK cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV. NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA∗008, is considered to be an HCMV-resistant “escape variant” that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA∗008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host allele illustrates the dynamic co-evolution of host and pathogen.

  1. 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.

  2. Escape dynamics in collinear atomic-like three mass point systems

    CERN Document Server

    Pasca, Daniel; Stoica, Cristina

    2009-01-01

    The present paper studies the escape mechanism in collinear three point mass systems with small-range-repulsive/large-range-attractive pairwise-interaction. Specifically, we focus on systems with non-negative total energy. We show that on the zero energy level set, most of the orbits lead to binary escape configurations and the set of initial conditions leading to escape configurations where all three separations infinitely increase as $t \\to \\infty 1$ has zero Lebesgue measure. We also give numerical evidence of the existence of a periodic orbit for the case when the two outer masses are equal. For positive energies, we prove that the set of initial conditions leading to escape configurations where all three separations infinitely increase as $t \\to \\infty$ has positive Lebesgue measure. Keywords: linear three point

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

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Andersen, Anders Peter; Langlois, Vincent J.;

    2010-01-01

    estimate the force and power output needed to accelerate and overcome drag. Both are very high compared with those of other organisms, as are the escape velocities in comparison to startle velocities of other aquatic animals. Thus, the maximum weight-specific force, which for muscle motors of other animals...... has been found to be near constant at 57 N (kg muscle)−1, is more than an order of magnitude higher for the escaping copepods. We argue that this is feasible because most copepods have different systems for steady propulsion (feeding appendages) and intensive escapes (swimming legs), with the muscular...... arrangement of the latter probably adapted for high force production during short-lasting bursts. The resulting escape velocities scale with body length to power 0.65, different from the size-scaling of both similar sized and larger animals moving at constant velocity, but similar to that found for startle...

  4. 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.

  5. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure.

    Science.gov (United States)

    Oka, Takafumi; Hikoso, Shungo; Yamaguchi, Osamu; Taneike, Manabu; Takeda, Toshihiro; Tamai, Takahito; Oyabu, Jota; Murakawa, Tomokazu; Nakayama, Hiroyuki; Nishida, Kazuhiko; Akira, Shizuo; Yamamoto, Akitsugu; Komuro, Issei; Otsu, Kinya

    2012-05-10

    Heart failure is a leading cause of morbidity and mortality in industrialized countries. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure. However, the mechanisms responsible for initiating and integrating inflammatory responses within the heart remain poorly defined. Mitochondria are evolutionary endosymbionts derived from bacteria and contain DNA similar to bacterial DNA. Mitochondria damaged by external haemodynamic stress are degraded by the autophagy/lysosome system in cardiomyocytes. Here we show that mitochondrial DNA that escapes from autophagy cell-autonomously leads to Toll-like receptor (TLR) 9-mediated inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy. Cardiac-specific deletion of lysosomal deoxyribonuclease (DNase) II showed no cardiac phenotypes under baseline conditions, but increased mortality and caused severe myocarditis and dilated cardiomyopathy 10 days after treatment with pressure overload. Early in the pathogenesis, DNase II-deficient hearts showed infiltration of inflammatory cells and increased messenger RNA expression of inflammatory cytokines, with accumulation of mitochondrial DNA deposits in autolysosomes in the myocardium. Administration of inhibitory oligodeoxynucleotides against TLR9, which is known to be activated by bacterial DNA, or ablation of Tlr9 attenuated the development of cardiomyopathy in DNase II-deficient mice. Furthermore, Tlr9 ablation improved pressure overload-induced cardiac dysfunction and inflammation even in mice with wild-type Dnase2a alleles. These data provide new perspectives on the mechanism of genesis of chronic inflammation in failing hearts.

  6. Influence of throat configuration and fish density on escapement of channel catfish from hoop nets

    Science.gov (United States)

    Porath, Mark T.; Pape, Larry D.; Richters, Lindsey K.

    2011-01-01

    In recent years, several state agencies have adopted the use of baited, tandemset hoop nets to assess lentic channel catfish Ictalurus punctatus populations. Some level of escapement from the net is expected because an opening exists in each throat of the net, although factors influencing rates of escapement from hoop nets have not been quantified. We conducted experiments to quantify rates of escapement and to determine the influence of throat configuration and fish density within the net on escapement rates. An initial experiment to determine the rate of escapement from each net compartment utilized individually tagged channel catfish placed within the entrance (between the two throats) and cod (within the second throat) compartments of a single hoop net for overnight sets. From this experiment, the mean rate (±SE) of channel catfish escaping was 4.2% (±1.5) from the cod (cod throat was additionally restricted from the traditionally manufactured product), and 74% (±4.2) from the entrance compartments. In a subsequent experiment, channel catfish were placed only in the cod compartment with different throat configurations (restricted or unrestricted) and at two densities (low [6 fish per net] and high [60 fish per net]) for overnight sets to determine the influence of fish density and throat configuration on escapement rates. Escapement rates between throat configurations were doubled at low fish density (13.3 ± 5.4% restricted versus 26.7 ± 5.6% unrestricted) and tripled at high fish density (14.3 ± 4.9% restricted versus 51.9 ± 5.0% unrestricted). These results suggest that retention efficiency is high from cod compartments with restricted throat entrances. However, managers and researchers need to be aware that modification to the cod throats (restrictions) is needed for hoop nets ordered from manufacturers. Managers need to be consistent in their use and reporting of cod end throat configurations when using this gear.

  7. Solution of the boundary value problem for optimal escape in continuous stochastic systems and maps.

    OpenAIRE

    S; Beri; Mannella, R.; Luchinsky, Dmitry G.; Silchenko, A. N.; McClintock, Peter V. E.

    2005-01-01

    Topologies of invariant manifolds and optimal trajectories are investigated in stochastic continuous systems and maps. A topological method is introduced that simplifies the solution of boundary value problems: The activation energy is calculated as a function of a set of parameters characterizing the initial conditions of the escape path. The method is applied explicitly to compute the optimal escape path and the activation energy for a variety of dynamical systems and maps.

  8. Choices between positive and negative reinforcement during treatment for escape-maintained behavior.

    Science.gov (United States)

    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 preference for positive reinforcement to an unstable selection pattern.

  9. THE EFFECTS OF FIXED-TIME ESCAPE ON INAPPROPRIATE AND APPROPRIATE CLASSROOM BEHAVIOR

    OpenAIRE

    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 substantial decrease in disruptive behavior and an increase in time engaged in tasks for both participants.

  10. 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...

  11. 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

  12. Quantifying the Escape Mortality of Trawl Caught Antarctic Krill (Euphausia superba)

    Science.gov (United States)

    Krafft, Bjørn A.; Krag, Ludvig A.; Engås, Arill; Nordrum, Sigve; Bruheim, Inge; Herrmann, Bent

    2016-01-01

    Antarctic krill (Euphausia superba) is an abundant fishery resource, the harvest levels of which are expected to increase. However, many of the length classes of krill can escape through commonly used commercial trawl mesh sizes. A vital component of the overall management of a fishery is to estimate the total fishing mortality and quantify the mortality rate of individuals that escape from fishing gear. The methods for determining fishing mortality in krill are still poorly developed. We used a covered codend sampling technique followed by onboard observations made in holding tanks to monitor mortality rates of escaped krill. Haul duration, hydrological conditions, maximum fishing depth and catch composition all had no significant effect on mortality of krill escaping 16 mm mesh size nets, nor was any further mortality associated with the holding tank conditions. A non- parametric Kaplan-Meier analysis was used to model the relationship between mortality rates of escapees and time. There was a weak tendency, though not significant, for smaller individuals to suffer higher mortality than larger individuals. The mortality of krill escaping the trawl nets in our study was 4.4 ± 4.4%, suggesting that krill are fairly tolerant of the capture-and-escape process in trawls. PMID:27622510

  13. Escape of Mars' CO2 atmosphere by suprathermal atoms during the past 4 Gyrs

    Science.gov (United States)

    Amerstorfer, Ute; Gröller, Hannes; Lichtenegger, Herbert; Lammer, Helmut; Tian, Feng

    2016-04-01

    The escape of atmospheric particles plays a crucial role in the evolution of the atmosphere of Mars. Especially, the escape of oxygen and carbon is thought to have influenced its amount of CO2. With a Monte-Carlo model we investigate the escape of hot oxygen and carbon from the martian atmosphere for three points in time in its history corresponding to 3, 10, and 20 times the present EUV level. We study and discuss different possible sources of hot oxygen and carbon atoms in the thermosphere and their changing importance with the EUV flux. We find that the escape due to photodissociation increases with increasing EUV level, as is a commonly assumed opinion. However, for the escape via other reactions, e.g. dissociative recombination, this is only true until the EUV level reaches 10 times the present EUV flux, but then the rates start to decrease. Our results thus suggest that some escape mechanisms related to the loss of CO2 are less important than previously thought for atmospheres exposed to higher EUV radiation. This work receives funding from the Austrian Science Fund (FWF): P 24247-N16.

  14. Hot oxygen escape from Mars: Simple scaling with solar EUV irradiance

    Science.gov (United States)

    Cravens, T. E.; Rahmati, A.; Fox, Jane L.; Lillis, R.; Bougher, S.; Luhmann, J.; Sakai, S.; Deighan, J.; Lee, Yuni; Combi, M.; Jakosky, B.

    2017-01-01

    The evolution of the atmosphere of Mars and the loss of volatiles over the lifetime of the solar system is a key topic in planetary science. An important loss process for atomic species, such as oxygen, is ionospheric photochemical escape. Dissociative recombination of O2+ ions (the major ion species) produces fast oxygen atoms, some of which can escape from the planet. Many theoretical hot O models have been constructed over the years, although a number of uncertainties are present in these models, particularly concerning the elastic cross sections of O atoms with CO2. Recently, the Mars Atmosphere and Volatile Evolution mission has been rapidly improving our understanding of the upper atmosphere and ionosphere of Mars and its interaction with the external environment (e.g., solar wind), allowing a new assessment of this important loss process. The purpose of the current paper is to take a simple analytical approach to the oxygen escape problem in order to (1) study the role that variations in solar radiation or solar wind fluxes could have on escape in a transparent fashion and (2) isolate the effects of uncertainties in oxygen cross sections on the derived oxygen escape rates. In agreement with several more elaborate numerical models, we find that the escape flux is directly proportional to the incident solar extreme ultraviolet irradiance and is inversely proportional to the backscatter elastic cross section. The amount of O lost due to ion transport in the topside ionosphere is found to be about 5-10% of the total.

  15. Lobelia siphilitica plants that escape herbivory in time also have reduced latex production.

    Directory of Open Access Journals (Sweden)

    Amy L Parachnowitsch

    Full Text Available Flowering phenology is an important determinant of a plant's reproductive success. Both assortative mating and niche construction can result in the evolution of correlations between phenology and other reproductive, functional, and life history traits. Correlations between phenology and herbivore defence traits are particularly likely because the timing of flowering can allow a plant to escape herbivory. To test whether herbivore escape and defence are correlated, we estimated phenotypic and genetic correlations between flowering phenology and latex production in greenhouse-grown Lobelia siphilitica L. (Lobeliaceae. Lobelia siphilitica plants that flower later escape herbivory by a specialist pre-dispersal seed predator, and thus should invest fewer resources in defence. Consistent with this prediction, we found that later flowering was phenotypically and genetically correlated with reduced latex production. To test whether herbivore escape and latex production were costly, we also measured four fitness correlates. Flowering phenology was negatively genetically correlated with three out of four fitness estimates, suggesting that herbivore escape can be costly. In contrast, we did not find evidence for costs of latex production. Generally, our results suggest that herbivore escape and defence traits will not evolve independently in L. siphilitica.

  16. CD4 binding site broadly neutralizing antibody selection of HIV-1 escape mutants.

    Science.gov (United States)

    Dreja, Hanna; Pade, Corinna; Chen, Lei; McKnight, Áine

    2015-07-01

    All human immunodeficiency virus type-1 (HIV-1) viruses use CD4 to enter cells. Consequently, the viral envelope CD4-binding site (CD4bs) is relatively conserved, making it a logical neutralizing antibody target. It is important to understand how CD4-binding site variation allows for escape from neutralizing antibodies. Alanine scanning mutagenesis identifies residues in antigenic sites, whereas escape mutant selection identifies viable mutants. We selected HIV-1 to escape CD4bs neutralizing mAbs b12, A12 and HJ16. Viruses that escape from A12 and b12 remained susceptible to HJ16, VRC01 and J3, whilst six different viruses that escape HJ16 remained sensitive to A12, b12 and J3. In contrast, their sensitivity to VRC01 was variable. Triple HJ16/A12/b12-resistant virus proved that HIV-1 could escape multiple broadly neutralizing monoclonal antibodies, but still retain sensitivity to VRC01 and the llama-derived J3 nanobody. This antigenic variability may reflect that occurring in circulating viruses, so studies like this can predict immunologically relevant antigenic forms of the CD4bs for inclusion in HIV-1 vaccines.

  17. 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...

  18. Escape-Route Planning of Underground Coal Mine Based on Improved Ant Algorithm

    Directory of Open Access Journals (Sweden)

    Guangwei Yan

    2013-01-01

    Full Text Available When a mine disaster occurs, to lessen disaster losses and improve survival chances of the trapped miners, good escape routes need to be found and used. Based on the improved ant algorithm, we proposed a new escape-route planning method of underground mines. At first, six factors which influence escape difficulty are evaluated and a weight calculation model is built to form a weighted graph of the underground tunnels. Then an improved ant algorithm is designed and used to find good escape routes. We proposed a tunnel network zoning method to improve the searching efficiency of the ant algorithm. We use max-min ant system method to optimize the meeting strategy of ants and improve the performance of the ant algorithm. In addition, when a small part of the mine tunnel network changes, the system may fix the optimal routes and avoid starting a new processing procedure. Experiments show that the proposed method can find good escape routes efficiently and can be used in the escape-route planning of large and medium underground coal mines.

  19. Fundamental Experiment to Determine Escape Countermeasures for Frogs Falling into Agricultural Canals

    Science.gov (United States)

    Watabe, Keiji; Mori, Atsushi; Koizumi, Noriyuki; Takemura, Takeshi

    Frogs often drown in agricultural canals with deep concrete walls, which are installed commonly in paddy fields after land improvement projects in Japan, because they cannot escape after falling into the canal. Therefore, countermeasures that enable frogs to escape from canals are required in some rural areas. An experimental canal with partially sloped walls was used as an escape countermeasure to investigate the preferable angle of slope for the walls, water depth and flow velocity that enables Tokyo Daruma Pond Frogs (Rana porosa porosa), which have no adhesive discs, to easily escape. Walls with slopes of 30-45 degrees allowed 50-60% of frogs to escape from the experimental canals, frogs especially easily climbed the 30 degree sloped walls. When the water depth was 5 cm or flow velocity was greater than 20 cm/s, approximately 80% of the frogs moved downstream and reached the sloped walls because the frogs' toes did not reach the bottom of the canal. However, if the depth was 2 cm and the flow velocity was 5 cm/s, only 4% of the frogs climbed the sloped walls because they could move freely. The frogs appeared to not be good at long-distance swimming and could not remain a long-time under running water. Therefore, walls sloped less than 30 degrees and control of both water depth and flow velocity appears important for enabling frogs to easily escape from canals.

  20. Chaotic escape from an open vase-shaped cavity. I. Numerical and experimental results

    Science.gov (United States)

    Novick, Jaison; Keeler, Matthew L.; Giefer, Joshua; Delos, John B.

    2012-01-01

    We present part I in a two-part study of an open chaotic cavity shaped as a vase. The vase possesses an unstable periodic orbit in its neck. Trajectories passing through this orbit escape without return. For our analysis, we consider a family of trajectories launched from a point on the vase boundary. We imagine a vertical array of detectors past the unstable periodic orbit and, for each escaping trajectory, record the propagation time and the vertical detector position. We find that the escape time exhibits a complicated recursive structure. This recursive structure is explored in part I of our study. We present an approximation to the Helmholtz equation for waves escaping the vase. By choosing a set of detector points, we interpolate trajectories connecting the source to the different detector points. We use these interpolated classical trajectories to construct the solution to the wave equation at a detector point. Finally, we construct a plot of the detector position versus the escape time and compare this graph to the results of an experiment using classical ultrasound waves. We find that generally the classical trajectories organize the escaping ultrasound waves.

  1. Chaotic escape from an open vase-shaped cavity. II. Topological theory.

    Science.gov (United States)

    Novick, Jaison; Delos, John B

    2012-01-01

    We present part II of a study of chaotic escape from an open two-dimensional vase-shaped cavity. A surface of section reveals that the chaotic dynamics is controlled by a homoclinic tangle, the union of stable and unstable manifolds attached to a hyperbolic fixed point. Furthermore, the surface of section rectifies escape-time graphs into sequences of escape segments; each sequence is called an epistrophe. Some of the escape segments (and therefore some of the epistrophes) are forced by the topology of the dynamics of the homoclinic tangle. These topologically forced structures can be predicted using the method called homotopic lobe dynamics (HLD). HLD takes a finite length of the unstable manifold and a judiciously altered topology and returns a set of symbolic dynamical equations that encode the folding and stretching of the unstable manifold. We present three applications of this method to three different lengths of the unstable manifold. Using each set of dynamical equations, we compute minimal sets of escape segments associated with the unstable manifold, and minimal sets associated with a burst of trajectories emanating from a point on the vase's boundary. The topological theory predicts most of the early escape segments that are found in numerical computations.

  2. Camptothecin and 10-Hydroxycamptothecin Accumulate Differentially Under Specific Developmental Control in Camptotheca acuminata%喜树碱和10-羟基喜树碱受喜树生长发育调控的不同特点

    Institute of Scientific and Technical Information of China (English)

    祖元刚; 唐中华; 于景华; 赵春建

    2003-01-01

    Camptotheca acuminata Decaisne is a tree unique to China, producing terpenoid indole alkaloid (TIA), camptothecin (CPT), and 10-hydroxycamptothecin (HCPT), which possesses strong anti-cancer bioactivity. The dynamics of HCPT and CPT during seed maturation, seed germination, postgerminative development and daily growth were measured by High Performance Liquid Chromatography (HPLC). This article provides some evidence for presenting the theory that each characteristic of HCPT and CPT accumulation is under developmental regulation and then attempt to elucidate the metabolic relationships between them. HCPT accumulates particularly in young tissues and organs and is relatively unstable, while the distribution of CPT is more ubiquitous and stable. Their different distribution properties suggest that HCPT and CPT are differentially regulated and play distinct roles during development.%为了揭示喜树碱(camptothecin, CPT)和10-羟基喜树碱(10-hydroxycamptothecin, HCPT)在喜树(Camptotheca acuminata Decaisne)体内代谢的生理调控机制及这两种类似物之间的关系和作用,运用高效液相色谱技术对种子形成、成熟、萌发和幼苗生长过程中喜树碱和10-羟基喜树碱的代谢动态进行了全面的研究.结果表明,喜树碱相对稳定地存在于成熟和幼嫩的组织中;10-羟基喜树碱特异性地积累在乳熟期的种子、种芽的子叶、幼嫩的真叶等幼嫩组织中,随着组织的进一步发育和成熟,其含量快速减少,成熟组织中积累极少,并且这两种生物碱的代谢在时间和数量上都呈现出相互消长的特点,由此推断,这两种生物碱不同程度地受生长发育调控的特点可能与喜树的化学防御策略密切相关,并且,它们之间可以相互转化以充分利用有限的氮素资源.

  3. Two cases of atmospheric escape in the Solar System: Titan and Earth

    Science.gov (United States)

    Dandouras, I.

    2012-01-01

    Escape into space of the constituents of a planetary upper atmosphere can occur either in the form of neutral gas (thermal escape or non-thermal escape), or in the form of plasma. The long-term stability of an atmosphere results from the balance between source and escape rates. Two cases will be examined: Titan and Earth. Titan is the second largest planetary satellite in the Solar System and is the only one that has an atmosphere as substantial as that of the Earth. Titan's nitrogen rich atmosphere is embedded within Saturn's magnetosphere, and is directly bombarded by energetic ions due to Titan's lack of a significant intrinsic magnetic field. In addition to thermal escape, energy input from Saturn's magnetosphere and from Solar UV radiation can drive several non-thermal escape mechanisms in Titan's upper atmosphere: sputtering, dissociation and dissociative ionization of molecular nitrogen producing pick-up ions, photochemical production of fast neutrals etc. Earth also constantly loses matter, mostly in the form of H+ and O+ ions, through various outflow processes from the upper atmosphere and ionosphere. Most of the ions are low-energy (plasma reservoir is the plasmasphere, which is a toroidal region encircling the Earth and containing cold and dense plasma. Plasma plumes, forming in the outer plasmasphere and released outwards, constitute a well-established mode for plasmaspheric material release to the magnetosphere. They are associated to geomagnetically active periods and the related electric field change. In 1992 Lemaire and Shunk proposed the existence of an additional mode for plasmaspheric material release and escape: a plasmaspheric wind, steadily transporting cold plasmaspheric plasma outwards across the geomagnetic field lines. This has been proposed on a theoretical basis. Direct detection of this wind has, however, eluded observation in the past. Analysis of ion measurements, acquired in the outer plasmasphere by the CIS experiment onboard the

  4. 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.

  5. Modeling the endosomal escape of cell-penetrating peptides: transmembrane pH gradient driven translocation across phospholipid bilayers.

    Science.gov (United States)

    Magzoub, Mazin; Pramanik, Aladdin; Gräslund, Astrid

    2005-11-15

    Cell-penetrating peptides (CPPs) are able to mediate the efficient cellular uptake of a wide range of cargoes. Internalization of a number of CPPs requires uptake by endocytosis, initiated by binding to anionic cell surface heparan sulfate (HS), followed by escape from endosomes. To elucidate the endosomal escape mechanism, we have modeled the process for two CPPs: penetratin (pAntp) and the N-terminal signal peptide of the unprocessed bovine prion protein (bPrPp). Large unilamellar phospholipid vesicles (LUVs) were produced encapsulating either peptide, and an ionophore, nigericin, was used to create a transmembrane pH gradient (DeltapH(mem), inside acidic) similar to the one arising in endosomes in vivo. In the absence of DeltapH(mem), no pAntp escape from the LUVs is observed, while a fraction of bPrPp escapes. In the presence of DeltapH(mem), a significant amount of pAntp escapes and an even higher degree of bPrPp escape takes place. These results, together with the differences in kinetics of escape, indicate different escape mechanisms for the two peptides. A minimum threshold peptide concentration exists for the escape of both peptides. Coupling of the peptides to a cargo reduces the fraction escaping, while complexation with HS significantly hinders the escape. Fluorescence correlation spectroscopy results show that during the escape process the LUVs are intact. Taken together, these results suggest a model for endosomal escape of CPPs: DeltapH(mem)-mediated mechanism, following dissociation from HS of the peptides, above a minimum threshold peptide concentration, in a process that does not involve lysis of the vesicles.

  6. Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches

    Directory of Open Access Journals (Sweden)

    Cristina eBottino

    2014-02-01

    Full Text Available 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

  7. Role of AmiA in the morphological transition of Helicobacter pylori and in immune escape.

    Directory of Open Access Journals (Sweden)

    Catherine Chaput

    2006-09-01

    Full Text Available The human gastric pathogen Helicobacter pylori is responsible for peptic ulcers and neoplasia. Both in vitro and in the human stomach it can be found in two forms, the bacillary and coccoid forms. The molecular mechanisms of the morphological transition between these two forms and the role of coccoids remain largely unknown. The peptidoglycan (PG layer is a major determinant of bacterial cell shape, and therefore we studied H. pylori PG structure during the morphological transition. The transition correlated with an accumulation of the N-acetyl-D-glucosaminyl-beta(1,4-N-acetylmuramyl-L-Ala-D-Glu (GM-dipeptide motif. We investigated the molecular mechanisms responsible for the GM-dipeptide motif accumulation, and studied the role of various putative PG hydrolases in this process. Interestingly, a mutant strain with a mutation in the amiA gene, encoding a putative PG hydrolase, was impaired in accumulating the GM-dipeptide motif and transforming into coccoids. We investigated the role of the morphological transition and the PG modification in the biology of H. pylori. PG modification and transformation of H. pylori was accompanied by an escape from detection by human Nod1 and the absence of NF-kappaB activation in epithelial cells. Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric epithelial cells. amiA is, to our knowledge, the first genetic determinant discovered to be required for this morphological transition into the coccoid forms, and therefore contributes to modulation of the host response and participates in the chronicity of H. pylori infection.

  8. Extinction Correction Significantly Influences the Estimate of the Lyα Escape Fraction

    Science.gov (United States)

    An, Fang Xia; Zheng, Xian Zhong; Hao, Cai-Na; Huang, Jia-Sheng; Xia, Xiao-Yang

    2017-02-01

    The Lyα escape fraction is a key measure to constrain the neutral state of the intergalactic medium and then to understand how the universe was fully reionized. We combine deep narrowband imaging data from the custom-made filter NB393 and the {{{H}}}2S1 filter centered at 2.14 μm to examine the Lyα emitters and Hα emitters at the same redshift z = 2.24. The combination of these two populations allows us to determine the Lyα escape fraction at z = 2.24. Over an area of 383 arcmin2 in the Extended Chandra Deep Field South (ECDFS), 124 Lyα emitters are detected down to NB393 = 26.4 mag at the 5σ level, and 56 Hα emitters come from An et al. Of these, four have both Lyα and Hα emissions (LAHAEs). We also collect the Lyα emitters and Hα emitters at z = 2.24 in the COSMOS field from the literature, and increase the number of LAHAEs to 15 in total. About one-third of them are AGNs. We measure the individual/volumetric Lyα escape fraction by comparing the observed Lyα luminosity/luminosity density to the extinction-corrected Hα luminosity/luminosity density. We revisit the extinction correction for Hα emitters using the Galactic extinction law with color excess for nebular emission. We also adopt the Calzetti extinction law together with an identical color excess for stellar and nebular regions to explore how the uncertainties in extinction correction affect the estimate of individual and global Lyα escape fractions. In both cases, an anti-correlation between the Lyα escape fraction and dust attenuation is found among the LAHAEs, suggesting that dust absorption is responsible for the suppression of the escaping Lyα photons. However, the estimated Lyα escape fraction of individual LAHAEs varies by up to ∼3 percentage points between the two methods of extinction correction. We find the global Lyα escape fraction at z = 2.24 to be (3.7 ± 1.4)% in the ECDFS. The variation in the color excess of the extinction causes a discrepancy of ∼1 percentage

  9. 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 ...

  10. How Hospitable Are Space Weather Affected Habitable Zones? The Role of Ion Escape

    Science.gov (United States)

    Airapetian, Vladimir S.; Glocer, Alex; Khazanov, George V.; Loyd, R. O. P.; France, Kevin; Sojka, Jan; Danchi, William C.; Liemohn, Michael W.

    2017-02-01

    Atmospheres of exoplanets in the habitable zones around active young G-K-M stars are subject to extreme X-ray and EUV (XUV) fluxes from their host stars that can initiate atmospheric erosion. Atmospheric loss affects exoplanetary habitability in terms of surface water inventory, atmospheric pressure, the efficiency of greenhouse warming, and the dosage of the UV surface irradiation. Thermal escape models suggest that exoplanetary atmospheres around active K-M stars should undergo massive hydrogen escape, while heavier species including oxygen will accumulate forming an oxidizing atmosphere. Here, we show that non-thermal oxygen ion escape could be as important as thermal, hydrodynamic H escape in removing the constituents of water from exoplanetary atmospheres under supersolar XUV irradiation. Our models suggest that the atmospheres of a significant fraction of Earth-like exoplanets around M dwarfs and active K stars exposed to high XUV fluxes will incur a significant atmospheric loss rate of oxygen and nitrogen, which will make them uninhabitable within a few tens to hundreds of Myr, given a low replenishment rate from volcanism or cometary bombardment. Our non-thermal escape models have important implications for the habitability of the Proxima Centauri’s terrestrial planet.

  11. Escape from Telomere-Driven Crisis Is DNA Ligase III Dependent

    Directory of Open Access Journals (Sweden)

    Rhiannon E. Jones

    2014-08-01

    Full Text Available Short dysfunctional telomeres are capable of fusion, generating dicentric chromosomes and initiating breakage-fusion-bridge cycles. Cells that escape the ensuing cellular crisis exhibit large-scale genomic rearrangements that drive clonal evolution and malignant progression. We demonstrate that there is an absolute requirement for fully functional DNA ligase III (LIG3, but not ligase IV (LIG4, to facilitate the escape from a telomere-driven crisis. LIG3- and LIG4-dependent alternative (A and classical (C nonhomologous end-joining (NHEJ pathways were capable of mediating the fusion of short dysfunctional telomeres, both displaying characteristic patterns of microhomology and deletion. Cells that failed to escape crisis exhibited increased proportions of C-NHEJ-mediated interchromosomal fusions, whereas those that escaped displayed increased proportions of intrachromosomal fusions. We propose that the balance between inter- and intrachromosomal telomere fusions dictates the ability of human cells to escape crisis and is influenced by the relative activities of A- and C-NHEJ at short dysfunctional telomeres.

  12. EFFECT OF ESCAPE DEVICE FOR SUBMERGED FLOATING TUNNEL (SFT) ON HYDRODYNAMIC LOADS APPLIED TO SFT

    Institute of Scientific and Technical Information of China (English)

    DONG Man-sheng; MIAO Guo-ping; YONG Long-chang; NIU Zhong-rong; PANG Huan-ping; HOU Chao-qun

    2012-01-01

    This paper presents a potential approach to settle the problem of surviving major safety accidents in Submerged Floating Tunnel (SFT) that detachable emergency escape devices are set up outside SFT.The Computational Fluid Dynamics (CFD)technology is used to investigate the effect of emergency escape devices on the hydrodynamic load acting on SFT in uniform and oscillatory flows and water waves by numerical test.The governing equations,i.e.,the Reynolds-Averaged Navier-Stokes (RANS)equations and k - ε standard turbulence equations,are solved by the Finite Volume Method (FVM).Analytic solutions for the Airy wave are applied to set boundary conditions to generate water wave.The VOF method is used to trace the free surface.In uniform flow,hydrodynamic loads,applied to SFT with emergency escape device,reduce obviously.But,in oscillatory flow,it has little influence on hydrodynamic loads acting on SFT.Horizontal and vertical wave loads of SFT magnify to some extend due to emergency escape devices so that the influence of emergency escape devices on hydrodynamic loads of SFT should be taken into consideration when designed.

  13. Selectivity of escape-hole size in tube traps for whitespotted conger Conger myriaster

    Institute of Scientific and Technical Information of China (English)

    YANG Bingzhong; TANG Yanli; LIANG Zhenlin

    2011-01-01

    Comparative fishing experiments were carried out in 2010 using tube traps with five hole diameters (8,15,18,20 and 22 mm) to establish the size selectivity of escape holes for white-spotted conger.Selectivity and split parameters of the SELECT model were calculated using the estimated-split and equal-spilt model.From likelihood ratio tests and AIC (Akaike's Information Criterion) values,the estimated-split model was selected as the best-fit model.Size selectivity of escape holes in the tube traps was expressed as a logistic curve,similar to mesh selectivity.The 50% selection length of white-spotted conger in the estimated-split model was 28.26,33.35,39.31 and 47.30 cm for escape-hole diameters of 15,18,20 and 22 mm,respectively.The optimum escape-hole size is discussed with respect to management of the white-spotted conger fishery.The results indicate that tube traps with escape holes of 18 mm in diameter would benefit this fishery.

  14. Inter- vs intra-individual variation and temporal repeatability of escape responses in the coral reef fish Amblyglyphidodon curacao

    Directory of Open Access Journals (Sweden)

    Maïwenn Jornod

    2015-11-01

    Full Text Available Fast-start escape responses are critical behaviours used by fishes during predator-prey encounters and some interactions with hetero- and conspecifics. In experimental studies, escape responses are often measured once per individual and considered representative of maximum performance. However, few studies have compared variability and repeatability in escape performances within and among individuals. Using the tropical damselfish Amblyglyphidodon curacao, we quantified inter- and intra-individual variation in behavioural and kinematic components of escape performance during repeated presentations of a stimulus at 15 min intervals. Individual maximum escape performance was repeatable through time, but there was considerable variation in the magnitude of responses both among and within fish. We found no evidence of habituation or fatigue due to repeated stimulations, suggesting that fish can be stimulated multiple times to ensure that an accurate estimate of maximum escape performance is obtained.

  15. 3D Simulations of the variability of the atmospheric escape at Mars with the EUV solar flux

    Science.gov (United States)

    Chaufray, J.-Y.; Leblanc, F.; Modolo, R.; Gonzalez-Galindo, F.; Lopez-Valverde, M.; Forget, F.

    2014-04-01

    The exosphere is the collisionless region surrounding a planetary atmosphere. The exosphere of Mars is an important region to characterize the escape processes. It is mainly formed from processes responsible of the atmospheric escape in the underlying atmosphere/ionosphere. The Martian exosphere is mainly composed of atomic hydrogen, molecular hydrogen and atomic oxygen. Atomic and molecular hydrogen escape is dominated by the thermal escape while the oxygen escape is dominated by the O2+ dissociative recombination in the Martian upper ionosphere. Therefore their escape rates are expected to vary strongly with the EUV solar flux which is the main driver of the heating and ionization of the Martian upper atmosphere. In this presentation, we will present simulations obtained from a 3D Martian exospheric model, coupled to the 3D GCM-LMD model for different solar UV conditions representative of current and past conditions.

  16. Fast-starting after a breath: air-breathing motions are kinematically similar to escape responses in the catfish Hoplosternum littorale

    DEFF Research Database (Denmark)

    Domenici, Paolo; Norin, Tommy; Bushnell, Peter G.;

    2015-01-01

    acceleration away from the stimulus. Recently, similar C-starts have been recorded in fish aiming at a prey. Little is known about C-starts outside the context of predator–prey interactions, though recent work has shown that escape response can also be induced by high temperature. Here, we test the hypothesis...... that air-breathing fish may use C-starts in the context of gulping air at the surface. Hoplosternum littorale is an air-breathing freshwater catfish found in South America. Field video observations reveal that their air-breathing behaviour consists of air-gulping at the surface, followed by a fast turn...

  17. Mathematical modeling of the heat treatment and combustion of a coal particle. III. Volatile escape stage

    Science.gov (United States)

    Enkhjargal, Kh.; Salomatov, V. V.

    2011-05-01

    The present paper is a continuation of previous publications of the authors in this journal in which two phases of the multistage process of combustion of a coal particle were considered in detail with the help of mathematical modeling: its radiation-convection heating and drying. In the present work, the escape dynamics of volatiles is investigated. The physico-mathematical model of the thermodestruction of an individual coal particle with a dominant influence of endothermal effects has been formulated. Approximate-analytical solutions of this model that are of paramount importance for detailed analysis of the influence of the physical and regime parameters on the escape dynamics of volatiles have been found. The results obtained form the basis for engineering calculations of the volatile escape stage and can be used successfully in the search for effective regimes of burning of various solid fuels, in particular, Shivé-Ovoos coal of Mongolia.

  18. Intermittent cold water swim stress increases immobility and interferes with escape performance in rat.

    Science.gov (United States)

    Christianson, John P; Drugan, Robert C

    2005-11-30

    The behavioral consequences of intermittent, 5 s cold-water swims (15 degrees C) or confinement were assessed 24 h after stress in a 5 min forced swim test or an instrumental swim escape test (SET). The SET was conducted with temporal and instrumental parameters similar to the shock-motivated shuttle escape test. The tests detected significantly increased immobility in the forced swim test and increased latency to escape in the SET. These results extend previous findings with intermittent swim stress and provide evidence that intermittent swim stress produces behavioral deficits similar to other stress models. This new model may be a useful tool for exploring the physiological mechanisms underlying the stress response.

  19. 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...

  20. Studying Lyman-alpha escape and reionization in Green Pea galaxies

    Science.gov (United States)

    Yang, Huan; Malhotra, Sangeeta; Rhoads, James E.; Gronke, Max; Leitherer, Claus; Wofford, Aida; Dijkstra, Mark

    2017-01-01

    Green Pea galaxies are low-redshift galaxies with extreme [OIII]5007 emission line. We built the first statistical sample of Green Peas observed by HST/COS and used them as analogs of high-z Lyman-alpha emitters to study Ly-alpha escape and Ly-alpha sizes. Using the HST/COS 2D spectra, we found that Ly-alpha sizes of Green Peas are larger than the UV continuum sizes. We found many correlations between Ly-alpha escape fraction and galactic properties -- dust extinction, Ly-alpha kinematic features, [OIII]/[OII] ratio, and gas outflow velocities. We fit an empirical relation to predict Ly-alpha escape fraction from dust extinction and Ly-alpha red-peak velocity. In the JWST era, we can use this relation to derive the IGM HI column density along the line of sight of each high-z Ly-alpha emitter and probe the reionization process.

  1. Towards Curative Cancer Immunotherapy: Overcoming Posttherapy Tumor Escape

    Directory of Open Access Journals (Sweden)

    Gang Zhou

    2012-01-01

    Full Text Available The past decade has witnessed the evolvement of cancer immunotherapy as an increasingly effective therapeutic modality, evidenced by the approval of two immune-based products by the FDA, that is, the cancer vaccine Provenge (sipuleucel-T for prostate cancer and the antagonist antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4 ipilimumab for advanced melanoma. In addition, the clinical evaluations of a variety of promising immunotherapy drugs are well under way. Benefiting from more efficacious immunotherapeutic agents and treatment strategies, a number of recent clinical studies have achieved unprecedented therapeutic outcomes in some patients with certain types of cancers. Despite these advances, however, the efficacy of most cancer immunotherapies currently under clinical development has been modest. A recurring scenario is that therapeutic maneuvers initially led to measurable antitumor immune responses in cancer patients but ultimately failed to improve patient outcomes. It is increasingly recognized that tumor cells can antagonize therapy-induced immune attacks through a variety of counterregulation mechanisms, which represent a fundamental barrier to the success of cancer immunotherapy. Herein we summarize the findings from some recent preclinical and clinical studies, focusing on how tumor cells advance their survival and expansion by hijacking therapy-induced immune effector mechanisms that would otherwise mediate their destruction.

  2. 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.

  3. Entire functions for which the escaping set is a spider's web

    Science.gov (United States)

    Sixsmith, D. J.

    2011-11-01

    We construct several new classes of transcendental entire functions, f, such that both the escaping set, I(f), and the fast escaping set, A(f), have a structure known as a spider's web. We show that some of these classes have a degree of stability under changes in the function. We show that new examples of functions for which I(f) and A(f) are spiders' webs can be constructed by composition, by differentiation, and by integration of existing examples. We use a property of spiders' webs to give new results concerning functions with no unbounded Fatou components.

  4. Entire functions for which the escaping set is a spider's web

    CERN Document Server

    Sixsmith, D J

    2010-01-01

    We construct several new classes of transcendental entire functions, f, such that both the escaping set, I(f), and the fast escaping set, A(f), have a structure known as a spider's web. We show that some of these classes have a degree of stability under changes in the function. We show that new examples of functions for which I(f) and A(f) are spiders' webs can be constructed by composition, by differentiation, and by integration of existing examples. We use a property of spiders' webs to give new results concerning functions with no unbounded Fatou components.

  5. Carrier transfer and thermal escape in CdTe/ZnTe quantum dots.

    Science.gov (United States)

    Man, Minh Tan; Lee, Hong Seok

    2014-02-24

    We report on the carrier transfer and thermal escape in CdTe/ZnTe quantum dots (QDs) grown on a GaAs substrate. The significant emission-energy-dependent decay time at high excitation intensity (35 W/cm2) is attributed to the lateral transfer of carriers in the QDs. At low temperature (thermally activated transition occurs between two different states separated by approximately 9 meV, while the main contribution to nonradiative processes is the thermal escape from QDs that is assisted by carrier scattering via the emission of longitudinal phonons through the excited QD states at high temperature, with energies of approximately 19 meV.

  6. Escape from intermittent repellers: periodic orbit theory for crossover from exponential to algebraic decay.

    Science.gov (United States)

    Dahlqvist, P

    1999-12-01

    We apply periodic orbit theory to study the asymptotic distribution of escape times from an intermittent map. The dynamical zeta function exhibits a branch point which is associated with an asymptotic power law escape. By an analytic continuation technique we compute a pair of complex conjugate zeroes beyond the branch point, associated with a preasymptotic exponential decay. The crossover time from an exponential to a power law is also predicted. The theoretical predictions are confirmed by numerical simulation. Applications to conductance fluctuations in quantum dots are discussed.

  7. 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 $\\mathcal{S}_p$.

  8. Quantifying the escape mortality of trawl caught Antarctic krill (Euphausia superba)

    DEFF Research Database (Denmark)

    Krafft, Bjørn A; Krag, Ludvig Ahm; Engås, Arill;

    2016-01-01

    Antarctic krill (Euphausia superba) is an abundant fishery resource, the harvest levels of which are expected to increase. However, many of the length classes of krill can escape through commonly used commercial trawl mesh sizes. A vital component of the overall management of a fishery is to esti......Antarctic krill (Euphausia superba) is an abundant fishery resource, the harvest levels of which are expected to increase. However, many of the length classes of krill can escape through commonly used commercial trawl mesh sizes. A vital component of the overall management of a fishery...

  9. Escape of DNA from a weakly biased thin nanopore: Experimental evidence for a universal diffusive behavior

    Science.gov (United States)

    Hoogerheide, David P.; Albertorio, Fernando; Golovchenko, Jene A.

    2014-01-01

    We report experimental escape time distributions of double-stranded DNA (dsDNA) molecules initially threaded halfway through a thin solid-state nanopore. We find a universal behavior of the escape time distributions consistent with a one-dimensional first passage formulation notwithstanding the geometry of the experiment and the potential role of complex molecule-liquid-pore interactions. Diffusion constants that depend on the molecule length and pore size are determined. Also discussed are the practical implications of long time diffusive molecule trapping in the nanopore. PMID:24483704

  10. Stellar wind interaction and pick-up ion escape of the Kepler-11 "super-Earths"

    Science.gov (United States)

    Kislyakova, Kristina; Johnstone, Colin; Odert, Petra; Erkaev, Nikolai; Lammer, Helmut; Lüftinger, Theresa; Holmstöm, Mats; Khodachenko, Maxim; Güdel, Manuel

    2014-05-01

    We present the results of modeling of the interactions between stellar wind and the extended hydrogen-dominated upper atmospheres of planets and estimate the resulting escape of planetary pick-up ions from the 5 «super-Earths» in the compact Kepler-11 system. We compare the escape rates with the efficiency of the thermal escape of neutral hydrogen atoms. Assuming the stellar wind of Kepler-11 is similar to the solar wind, we used a polytropic 1D hydrodynamic wind model to estimate the wind properties at the planetary orbits. We applied a Direct Simulation Monte Carlo Model to model the hydrogen coronae and the stellar wind plasma interaction around Kepler-11b-f planets within a realistic expected heating efficiency range of 15-40%. The same model was used to estimate the ion pick-up escape from the XUV heated and hydrodynamically extended upper atmospheres of Kepler-11b-f. Modeling clarifies the influence of possible magnetic moments on escape processes and allows to estimate the charge exchange and photoionization production rates of planetary ions as well as the loss rates of pick-up H+ ions for all five planets. This study presents also the comparison of the results between the five 'super-Earths' and in a more general sense also with the thermal escape rates of the neutral planetary hydrogen atoms. Our results show that for all Kepler-11b-f exoplanets, a huge neutral hydrogen corona is formed around the planet. The non-symmetric form of the corona changes from planet to planet and is defined mostly by radiation pressure, charge-exchange and gravitational effects. According to our estimates, nonthermal escape rates of pick-up ionized hydrogen atoms for Kepler-11 «super-Earths» vary between ~ 6.4 × 1030 s-1 and ~ 4.1 × 1031 s-1 depending on the planet's orbital location and assumed heating efficiency. These values correspond to non-thermal mass loss rates of ~ 1.07 × 107 g·s-1 and ~ 6.8 × 107 g·s-1 respectively, which is a few percent of the thermal

  11. "We are free, you are slaves. Come on, let's run away": Escape from Constantia, 1712.

    OpenAIRE

    Paulse, Michele

    2014-01-01

    Slaves were imported to the Cape from 1658 to 1808. The majority of the captives lived in Cape Town and many other slaves lived on farms. Added to this captive population were political exiles. In 1712, 23 slaves and exiles gathered at Constantia, a renowned wine farm, to run away. Since the holding was an important homestead, one would expect that this escape would have been reconstructed in the histories of the farm and slavery at the Cape. At the time, the escape raised s...

  12. Antarctic krill; assessment of mesh size selectivity and escape mortality from trawls

    DEFF Research Database (Denmark)

    Krafft, Bjørn A.; Krag, Ludvig Ahm; Herrmann, Bent;

    2015-01-01

    This working paper presents the aims and methodology for a three-year-project (commenced in 2015) assessing size selectivity and escape mortality of Antarctic krill from trawl nets. The project is widely based on acquired experiences from a completed study Net Escapement of Antarctic krill...... in Trawls (NEAT), presented in WG-EMM 2012/24, WGEMM 2013/34, WG-EMM 2014/14 and WG-EMM 2014/16. Funding is provided by the Norwegian Research Council and ship-time for executing the field-experiments is offered free-of-charge by two Norwegian commercial fishing companies; Olympic Seafood AS and Aker Bio...

  13. 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;

    2008-01-01

    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 suppression of MMR...

  14. Resveratrol-3-O-glucuronide and resveratrol-4’-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin

    Science.gov (United States)

    Resveratrol has been reported to inhibit or induce DNA damage depending upon the type of cell and experimental conditions. Dietary resveratrol is present in the body mostly as metabolites and little is known about the activities of these metabolic products. We evaluated physiologically obtainable ...

  15. 喜树碱在二甲亚砜和甲醇(或乙醇)混合溶剂中溶解度的测定和关联%Measurement and Correlation of Camptothecine Solubility in Dimethylsulfoxide-Methanol/Ethanol Mixed Solvents

    Institute of Scientific and Technical Information of China (English)

    支娟娟; 徐家阔; 刘琼; 李涛; 任保增

    2016-01-01

    Camptothecine solubility in dimethylsulfoxide-methanol/ethanol mixed solvents was measured over temperature range of 274.50~326.00 K under atmospheric pressure. The experimental results show that the solubility of camptothecine in the mixed solvents increases with the increase of temperature and dimethylsulfoxide mole fraction. The experimental solubility data are well correlated with a modified Apelblat equation, λh equation and ideal equation, respectively. The Akaike’s Information Criterion (AIC) was used to select the best model for correlation. The dissolution enthalpy, entropy and Gibbs free energy change of camptothecine are calculated using the measured solubility.%采用重量法测定了喜树碱(camptothecine,CPT)在二甲亚砜(dimethylsulfoxide, DMSO)+甲醇(或乙醇)混合溶剂中的溶解度,温度范围是274.50~326.00 K。在混合溶剂中CPT的溶解度随温度的升高而增大,随混合溶剂中DMSO摩尔分数含量的增大而增大。分别用修正Apelblat方程、λh方程和理想状态方程进行关联,关联效果令人满意,获得了相关模型参数。相对而言,λh方程关联的效果较好。根据溶解度数据和修正的Apelblat方程计算出溶解焓、溶解熵和吉布斯自由能。

  16. 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.

  17. 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

  18. 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.

  19. Antigen Loss Variants: Catching Hold of Escaping Foes

    Science.gov (United States)

    Vyas, Maulik; Müller, Rolf; Pogge von Strandmann, Elke

    2017-01-01

    Since mid-1990s, the field of cancer immunotherapy has seen steady growth and selected immunotherapies are now a routine and preferred therapeutic option of certain malignancies. Both active and passive cancer immunotherapies exploit the fact that tumor cells express specific antigens on the cell surface, thereby mounting an immune response specifically against malignant cells. It is well established that cancer cells typically lose surface antigens following natural or therapy-induced selective pressure and these antigen-loss variants are often the population that causes therapy-resistant relapse. CD19 and CD20 antigen loss in acute lymphocytic leukemia and chronic lymphocytic leukemia, respectively, and lineage switching in leukemia associated with mixed lineage leukemia (MLL) gene rearrangements are well-documented evidences in this regard. Although increasing number of novel immunotherapies are being developed, majority of these do not address the control of antigen loss variants. Here, we review the occurrence of antigen loss variants in leukemia and discuss the therapeutic strategies to tackle the same. We also present an approach of dual-targeting immunoligand effectively retargeting NK cells against antigen loss variants in MLL-associated leukemia. Novel immunotherapies simultaneously targeting more than one tumor antigen certainly hold promise to completely eradicate tumor and prevent therapy-resistant relapses. PMID:28286501

  20. Self-consciousness and binge eating in college women : an escape from rumination?

    NARCIS (Netherlands)

    Dalley, Simon; Donofrio, Stacey

    2014-01-01

    Background: Binge-eating is a highly distressing symptom that has been found to co-occur with other symptoms of eating disorders such as bulimia nervosa. One perspective of binge eating is that it is an attempt to escape high levels of aversive self-consciousness. A primary aim of this study is to e

  1. 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.

  2. Improving the effectiveness of escape windows in directed Norway lobster Nephrops norvegicus trawl fisheries

    DEFF Research Database (Denmark)

    Madsen, Niels; Holst, René; Frandsen, Rikke

    2012-01-01

    A substantial improvement in the bycatch selectivity of Norway lobster Nephrops norvegicus trawls is required, particularly with respect to cod Gadus morhua , whose stocks are at low levels in several areas. Conventional escape windows are not adequate to properly release cod and other bycatch sp...

  3. Escape from Harm’s Way: The Experiences of Southeast Asian Elders and their Families

    Directory of Open Access Journals (Sweden)

    Daniel F. Detzner

    2009-01-01

    Full Text Available This study uses a life history approach to understand the lived experiences of 40 Southeast Asian elderly refugees who fled from their home countries and resettled in the United States in the late 1970’s and 1980’s. The focus is concentrated on the elders’ narratives of escape. Their experiences are consolidated into motivational elements leading to flight; six dichotomous dimensions of the leave taking; and complicating factors affecting the escape. The results indicate that escapes: (a are motivated by a multiplicity of overlapping factors; (b appear to have an impact on health after resettlement; and (c are complex events where the same generational cohort fleeing from the same conflict, during the same time period, may arrive in the same destination with very different levels of distress. This study aims to develop a framework for understanding the escape narratives of elderly refugees as a way to understand the nature and sources of individual, family, and community distress that often hinders successful integration of refugee populations.

  4. Increased transcapillary escape rate of albumin in type 1 (insulin-dependent) diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B

    1986-01-01

    The transcapillary escape rate, intravascular mass and outflux of albumin were measured in 75 Type 1 (insulin-dependent) diabetic patients. The groups were defined as: group 1: normal urinary albumin excretion, less than 30 mg/24 h (n = 21); group 2: microalbuminuria, 30-300 mg/24 h (n = 36); group...

  5. The interaction between Aegean back-arc extension and Anatolia escape since Middle Miocene

    NARCIS (Netherlands)

    Philippon, M.; Brun, J.-P.; Gueydan, F.; Sokoutis, D.

    2014-01-01

    The Aegean domain is a key area for understanding the processes of back-arc extension. Observed deformation pattern and present day kinematics result from the interaction between the southward retreat of the Hellenic trench and the westward escape of Anatolia. Lithosphere-scale analogue models were

  6. Escape from Management Hell: 12 Tales of Horror, Humor, and Heroism.

    Science.gov (United States)

    Gilbreath, Robert D.

    This book offers a set of stories in which corporate executives demonstrate the folly and futility of their own business practices. In the stories, 12 executives are trying to escape from a hell of their own making. The tales provide insights into the management woes with which people at all levels deal on a daily basis. Topics include: the…

  7. Queer(y)ing and Recrafting Agency: Moving Away from a Model of Coercion versus Escape

    Science.gov (United States)

    Gowlett, Christina

    2014-01-01

    This paper applies a Butlerian-inspired "queer(y)ing" methodology to disrupt the utility of agency being framed within the binary of escape and coercion. In particular, it uses Butler's concept of performative resignification to analyse how Simon, a 16-year-old white male student, maneouvres his way through the social conventions of…

  8. The effects of differential negative reinforcement of other behavior and noncontingent escape on compliance.

    OpenAIRE

    Kodak, Tiffany; Miltenberger, Raymond G; Romaniuk, Cathryn

    2003-01-01

    The present study evaluated the effects of noncontingent escape and differential negative reinforcement of other behavior in reducing problem behaviors and increasing compliance in 2 children with disabilities. Results showed that both methods reduced problem behavior and increased compliance for both children.

  9. The use of noncontingent escape to reduce disruptive behaviors in children with speech delays.

    OpenAIRE

    Coleman, C. L.; Holmes, P A

    1998-01-01

    Noncontingent escape (NCE) was used to reduce disruptive behavior in 3 children during regularly scheduled speech therapy sessions. Results showed rapid decreases in disruptive behavior and accompanying increases in compliance across children. Findings suggest that speech therapists with little expertise in behavior analysis can effectively implement NCE.

  10. Queer(y)ing and Recrafting Agency: Moving Away from a Model of Coercion versus Escape

    Science.gov (United States)

    Gowlett, Christina

    2014-01-01

    This paper applies a Butlerian-inspired "queer(y)ing" methodology to disrupt the utility of agency being framed within the binary of escape and coercion. In particular, it uses Butler's concept of performative resignification to analyse how Simon, a 16-year-old white male student, maneouvres his way through the social conventions of…

  11. 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...

  12. Slow Down or Speed Up? Lowering Periapsis versus Escaping from a Circular Orbit

    Science.gov (United States)

    Blanco, Philip

    2017-01-01

    Paul Hewitt's "Figuring Physics" in the Feb. 2016 issue asked whether it would take a larger velocity change to stop a satellite in a circular orbit or to cause it to escape. An extension of this problem asks: What "minimum" velocity change is required to crash a satellite into the planet, and how does that compare with the…

  13. Escape fraction of ionizing photons during reionization: effects due to supernova feedback and runaway OB stars

    CERN Document Server

    Kimm, Taysun

    2014-01-01

    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 feedback and runaway OB stars) on the escape fraction (f_esc) at the epoch of reionization (z>7). We implement a new, physically motivated supernova 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 supernova feedback. Consequently, the photon number-weighted mean escape fraction for dwarf galaxies in halos of mass 10^8-10^10.5 Msun is found to be ~11%, although instantaneous values of f...

  14. 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...

  15. Using Stimulus Fading without Escape Extinction to Increase Compliance with Toothbrushing in Children with Autism

    Science.gov (United States)

    Bishop, Michele R.; Kenzer, Amy L.; Coffman, Christine M.; Tarbox, Courtney M.; Tarbox, Jonathan; Lanagan, Taira M.

    2013-01-01

    Routine toothbrushing is an essential part of good oral hygiene. This study investigated the use of stimulus fading without escape extinction to increase compliance with toothbrushing with three children with autism spectrum disorder (ASD). A 30-step stimulus fading hierarchy was implemented; gradually increasing the proximity of the toothbrush to…

  16. Hot Oxygen and Carbon Escape from the Early Atmosphere of Mars

    Science.gov (United States)

    Amerstorfer, U.; Gröller, H.; Lichtenegger, H.; Lammer, H.; Tian, F.

    2015-12-01

    Nowadays, the atmosphere of Mars is commonly assumed to be much different than in the early times of its evolution. Especially, the escape of water and carbon dioxide is thought to have formed its shape during millions of years. Also the Sun emitted a higher EUV flux in former times, influencing the particle environment around Mars.We study the escape of oxygen and carbon from the early Martian atmosphere for different EUV fluxes with a Monte-Carlo model. We consider different possible sources of hot oxygen and carbon atoms in the thermosphere, e.g. dissociative recombination of O2+ , CO+ and CO2+ , photodissociation of O2 and CO, and other reactions like charge transfer. From the calculated production rate profiles we can get insights into the importance of the different source reactions. The resulting energy distribution functions at the exobase level are used to study the exospheric densities and the escape of hot oxygen and carbon. We discuss the escape rates of those atoms and the importance of different source processes compared to the present situation at Mars.This work receives funding from the Austrian Science Fund (FWF): P 24247.

  17. Molecular pathology of mismatch repair deficient tumours with emphasis on immune escape mechanisms

    NARCIS (Netherlands)

    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 tumou

  18. Optogenetics Based Rat-Robot Control: Optical Stimulation Encodes "Stop" and "Escape" Commands.

    Science.gov (United States)

    Chen, SiCong; Zhou, Hong; Guo, SongChao; Zhang, JiaCheng; Qu, Yi; Feng, ZhouYan; Xu, KeDi; Zheng, XiaoXiang

    2015-08-01

    Electric brain stimulation is frequently used in bio-robot control. However, one possible limitation of electric stimulation is the resultant wide range of influences that may lead to unexpected side-effects. Although there has been prior research done towards optogenetics based brain activation, there has not been much development regarding the comparisons between electric and optical methods of brain activation. In this study, we first encode "Stop" and "Escape" commands by optical stimulation in the dorsal periaqueductal grey (dPAG). The rats behavioral comparisons are then noted down under these two methods. The dPAG neural activity recorded during optical stimulation suggests rate and temporal coding mechanisms in behavioral control. The behavioral comparisons show that rats exhibit anxiety under the "Stop" command conveyed through both optical and electric methods. However, rats are able to recover more quickly from freezing only under optical "Stop" command. Under "Escape" commands, also conveyed through optical means, the rat would move with lessened urgency but the results are more stable. Moreover, c-Fos study shows the optical stimulation activates restricted range in midbrain: the optical stimulation affected only dPAG and its downstreams but electric stimulation activates both the upstream and downstream circuits, in which the glutamatergic neurons are largely occupied and play important role in "Stop" and "Escape" behavior controls. We conclude that optical stimulation is more suited for encoding "Stop" and "Escape" commands for rat-robot control.

  19. Stellar wind interaction and pick-up ion escape of the Kepler-11 "super-Earths"

    CERN Document Server

    Kislyakova, K G; Odert, P; Erkaev, N V; Lammer, H; üftinger, T L; Holmström, M; Khodachenko, M L; üdel, M G

    2013-01-01

    We study the interactions between stellar wind and the extended hydrogen-dominated upper atmospheres of planets and the resulting escape of planetary pick-up ions from the 5 "super-Earths" in the compact Kepler-11 system and compare the escape rates with the efficiency of the thermal escape of neutral hydrogen atoms. Assuming the stellar wind of Kepler-11 is similar to the solar wind, we use a polytropic 1D hydrodynamic wind model to estimate the wind properties at the planetary orbits. We apply a Direct Simulation Monte Carlo Model to model the hydrogen coronae and the stellar wind plasma interaction around Kepler-11b-f within a realistic expected heating efficiency range of 15-40%. The same model is used to estimate the ion pick-up escape from the XUV heated and hydrodynamically extended upper atmospheres of Kepler-11b-f. From the interaction model we study the influence of possible magnetic moments, calculate the charge exchange and photoionization production rates of planetary ions and estimate the loss r...

  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. Optimal escape from potential wells-patterns of regular and chaotic bifurcation

    Science.gov (United States)

    Stewart, H. B.; Thompson, J. M. T.; Ueda, Y.; Lansbury, A. N.

    The patterns of bifurcation governing the escape of periodically forced oscillations from a potential well over a smooth potential barrier are studied by numerical simulation. Both the generic asymmetric single-well cubic potential and the symmetric twin-well potential Duffing oscillator are surveyed by varying three parameters: forcing frequency, forcing amplitude, and damping coefficient. The close relationship between optimal escape and nonlinear resonance within the well is confirmed over a wide range of damping. Subtle but significant differences are observed at higher damping ratios. The possibility of indeterminate outcomes of jumps to and from resonance near optimal escape is cmppletely suppressed above a critical level of the damping ratio (about 0.12 for the asymmetric single-well oscillator). Coincidentally, at almost the same level of damping, the optimal escape condition becomes distinct from the apex in the (ω, F) plane of the bistable regime; this corresponds to the appearance of chaotic attractors which subsume both resonant and non-resonant motions within one well. At higher damping levels, further changes occur involving conversions from chaotic-saddle to regular-saddle bifurcations. These changes in optimal escape phenomena correspond to codimension three bifurcations at exceptional points in the space of three parameters. These bifurcations are described in terms of homoclinic and heteroclinic structures of invariant manifolds, and changes in accessible boundary orbits. The same sequence of codimension three bifurcations is observed in both the twin-well Duffing oscillator and the asymmetric single-well escape equation. Within the codimension three bifurcation patterns governing escape, one particular codimension two global bifurcation involves a chaotic attractor explosion, or interior crisis, compounded with a blue sky catastrophe or boundary crisis of the exploded attractor. This codimension two bifurcation has structure containing a form of

  2. 76 FR 26957 - Special Conditions: Boeing, Model 747-8 Series Airplanes; Door 1 Extendable Length Escape Slide

    Science.gov (United States)

    2011-05-10

    ...; Door 1 Extendable Length Escape Slide AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... extendable length escape slide. The applicable airworthiness regulations do not contain adequate or... unusual design features: The 747-8 design offers seating capacity on two separate decks, the main...

  3. Comparing Effective Treatments for Attention-Maintained and Escape- Maintained Behaviors in Children with Behavior Disorders: Brief Review and Analysis

    OpenAIRE

    Lauren Worcester; T. F. McLaughlin

    2013-01-01

    This literature review compares treatment for attention-maintainedversus escape maintained aberrant behavior in children with behavior disorders. Specifically, studies utilizing time out procedures, differential reinforcement procedures, noncontingent reinforcement, and functional communication training are discussed. It was found that these are effective treatments for attention-maintained behaviors; while escape extinction, positive and negative reinforcement, functional communication trai...

  4. 77 FR 50165 - Escape and Evacuation Plans for Surface Coal Mines, Surface Facilities and Surface Work Areas of...

    Science.gov (United States)

    2012-08-20

    ... Administration. Title: Escape and Evacuation Plans for Surface Coal Mines, Surface Facilities ] and Surface Work... Safety and Health Administration Escape and Evacuation Plans for Surface Coal Mines, Surface Facilities and Surface Work Areas of Underground Coal Mines AGENCY: Mine Safety and Health Administration,...

  5. Energetic Particle Diagnostics for Transport Analysis 3.Escaping Fast Ion Diagnostics for the Fast Particle Transport Analysis

    Science.gov (United States)

    Isobe, Mitsutaka; Shinohara, Kouji

    Escaping energetic ion diagnostics in magnetically confined plasma experiments are described in this lecture note. Experimental results from escaping energetic ion diagnostics in TFTR, JFT-2M, CHS and W7-AS are shown. In addition to mechanism of energetic ion loss from a viewpoint of particle orbit, effect of MHD activity on energetic particle transport is reviewed.

  6. HIV-1 resistance to neutralizing antibodies: Determination of antibody concentrations leading to escape mutant evolution.

    Science.gov (United States)

    Magnus, Carsten; Reh, Lucia; Trkola, Alexandra

    2016-06-15

    Broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) are considered vital components of novel therapeutics and blueprints for vaccine research. Yet escape to even the most potent of these antibodies is imminent in natural infection. Measures to define antibody efficacy and prevent mutant selection are thus urgently needed. Here, we derive a mathematical framework to predict the concentration ranges for which antibody escape variants can outcompete their viral ancestors, referred to as mutant selection window (MSW). When determining the MSW, we focus on the differential efficacy of neutralizing antibodies against HIV-1 in two canonical infection routes, free-virus infection and cell-cell transmission. The latter has proven highly effective in vitro suggesting its importance for both in vivo spread as well as for escaping targeted intervention strategies. We observed a range of MSW patterns that highlight the potential of mutants to arise in both transmission pathways and over wide concentration ranges. Most importantly, we found that only when the arising mutant has both, residual sensitivity to the neutralizing antibody and reduced infectivity compared to the parental virus, antibody dosing outside of the MSW to restrict mutant selection is possible. Emergence of mutants that provide complete escape and have no considerable fitness loss cannot be prevented by adjusting antibody doses. The latter may in part explain the ubiquitous resistance to neutralizing antibodies observed in natural infection and antibody treatment. Based on our findings, combinations of antibodies targeting different epitopes should be favored for antibody-based interventions as this may render complete resistance less likely to occur and also increase chances that multiple escapes result in severe fitness loss of the virus making longer-term antibody treatment more feasible.

  7. 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.

  8. 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.

  9. 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.

  10. A convergent and essential interneuron pathway for Mauthner-cell-mediated escapes.

    Science.gov (United States)

    Lacoste, Alix M B; Schoppik, David; Robson, Drew N; Haesemeyer, Martin; Portugues, Ruben; Li, Jennifer M; Randlett, Owen; Wee, Caroline L; Engert, Florian; Schier, Alexander F

    2015-06-01

    The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By in vivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits.

  11. The general circulation of Titan and the topside escape rates of N2, CH4, and H2

    Science.gov (United States)

    Bell, J. M.; Waite, J. H.; Magee, B. A.; Gell, D.; Westlake, J. H.; Mandt, K. E.

    2009-12-01

    The general circulation of the atmosphere can have a significant impact on the escape of species from the upper atmospheres of planets (cf. Hartle and Mayer [1976]). Recently, Bell et al. [2009] used a one-dimensional (1-D) model to constrain mass loss rates from Titan’s upper atmosphere for both CH4 and H2. We report on the impacts of the 3-D circulation of Titan on the estimated escape fluxes of nitrogen, methane, and hydrogen. We present two scenarios for CH4 escape from Titan’s upper atmosphere: (1) a hydrodynamic escape scenario (Strobel [2009]) and (2) a low escape scenario (Bell et al [2009]). The composition, dynamics, and energetics of these two configurations will be discussed within the context of recent INMS measurements in the thermosphere and recent magnetospheric carbon ion measurements.

  12. 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

  13. Germ line transmission of the Cdk4(R24C) mutation facilitates tumorigenesis and escape from cellular senescence.

    Science.gov (United States)

    Rane, Sushil G; Cosenza, Stephen C; Mettus, Richard V; Reddy, E Premkumar

    2002-01-01

    Mutations in CDK4 and its key kinase inhibitor p16(INK4a) have been implicated in the genesis and progression of familial human melanoma. The importance of the CDK4 locus in human cancer first became evident following the identification of a germ line CDK4-Arg24Cys (R24C) mutation, which abolishes the ability of CDK4 to bind to p16(INK4a). To determine the role of the Cdk4(R24C) germ line mutation in the genesis of other cancer types, we introduced the R24C mutation in the Cdk4 locus of mice by using Cre-loxP-mediated "knock-in" technology. Cdk4(R24C/R24C) mouse embryo fibroblasts (MEFs) displayed increased Cdk4 kinase activity resulting in hyperphosphorylation of all three members of the Rb family, pRb, p107, and p130. MEFs derived from Cdk4(R24C/R24C) mice displayed decreased doubling times, escape from replicative senescence, and escape sensitivity to contact-induced growth arrest. These MEFs also exhibited a high degree of susceptibility to oncogene-induced transformation, suggesting that the Cdk4(R24C) mutation can serve as a primary event in the progression towards a fully transformed phenotype. In agreement with the in vitro data, homozygous Cdk4(R24C/R24C) mice developed tumors of various etiology within 8 to 10 months of their life span. The majority of these tumors were found in the pancreas, pituitary, brain, mammary tissue, and skin. In addition, Cdk4(R24C/R24C) mice showed extraordinary susceptibility to carcinogens and developed papillomas within the first 8 to 10 weeks following cutaneous application of the carcinogens 9,10-di-methyl-1,2-benz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). This report formally establishes that the activation of Cdk4 is sufficient to promote cancer in many tissues. The observation that a wide variety of tumors develop in mice harboring the Cdk4(R24C) mutation offers a genetic proof that Cdk4 activation may constitute a central event in the genesis of many types of cancers in addition to melanoma.

  14. MAPK14/p38α confers irinotecan resistance to TP53-defective cells by inducing survival autophagy.

    Science.gov (United States)

    Paillas, Salome; Causse, Annick; Marzi, Laetitia; de Medina, Philippe; Poirot, Marc; Denis, Vincent; Vezzio-Vie, Nadia; Espert, Lucile; Arzouk, Hayat; Coquelle, Arnaud; Martineau, Pierre; Del Rio, Maguy; Pattingre, Sophie; Gongora, Céline

    2012-07-01

    Recently we have shown that the mitogen-activated protein kinase (MAPK) MAPK14/p38α is involved in resistance of colon cancer cells to camptothecin-related drugs. Here we further investigated the cellular mechanisms involved in such drug resistance and showed that, in HCT116 human colorectal adenocarcinoma cells in which TP53 was genetically ablated (HCT116-TP53KO), overexpression of constitutively active MAPK14/p38α decreases cell sensitivity to SN-38 (the active metabolite of irinotecan), inhibits cell proliferation and induces survival-autophagy. Since autophagy is known to facilitate cancer cell resistance to chemotherapy and radiation treatment, we then investigated the relationship between MAPK14/p38α, autophagy and resistance to irinotecan. We demonstrated that induction of autophagy by SN38 is dependent on MAPK14/p38α activation. Finally, we showed that inhibition of MAPK14/p38α or autophagy both sensitizes HCT116-TP53KO cells to drug therapy. Our data proved that the two effects are interrelated, since the role of autophagy in drug resistance required the MAPK14/p38α. Our results highlight the existence of a new mechanism of resistance to camptothecin-related drugs: upon SN38 induction, MAPK14/p38α is activated and triggers survival-promoting autophagy to protect tumor cells against the cytotoxic effects of the drug. Colon cancer cells could thus be sensitized to drug therapy by inhibiting either MAPK14/p38 or autophagy.

  15. 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

  16. Non-thermal escape of H2 and OH from the upper atmosphere of Mars

    Science.gov (United States)

    Gacesa, Marko; Kharchenko, Vasili

    2016-10-01

    Two major sources of energetic O atoms in the upper atmosphere of Mars are photochemical production, via dissociative recombination (DR) of O2+ and CO2+ molecular ions, and energizing collisions with fast energetic neutral atoms (ENA) produced by the precipitating solar wind ions. The non-thermal O atoms can either directly escape to space, forming a hot oxygen corona, or participate in collisions with background thermal atmospheric gases, such as H2. In this study we present a theoretical analysis of formation and kinetics of hot OH molecules in the upper atmosphere of Mars, produced in reactions of thermal molecular hydrogen and suprathermal oxygen atoms energized by both DR and ENAs. The non-thermal chemical reaction O + H2(v',j') → H + OH(v',j') is described using recent quantum-mechanical state-to-state cross sections[1], which allow us to predict non-equilibrium distributions of excited rotational and vibrational states (v',j') of OH and expected emission spectra for different geometry and solar activity conditions. A potential consequence is appearance or enhancement of faint Meinel bands in the upper atmosphere of Mars. Moreover, a fraction of produced translationally hot H2 and OH are sufficiently energetic to overcome Mars' gravitational potential and escape into space, contributing to the hot corona. The described non-thermal mechanisms produce estimated total escape fluxes of OH and H2 from dayside of Mars, for low solar activity conditions, equal to about 5×1022 s-1 for OH, or about 0.1% of the total escape rate of atomic O and H, and 1023 s-1 for H2 [2]. If HD molecules are considered instead of H2, the non-thermal mechanisms are about 30 times more efficient than Jeans escape, contribute about 5-10% of the total D escape rate, potentially of interest in atmospheric models of water evolution on Mars.[1] M. Gacesa and V. Kharchenko, J. Chem. Phys. 141, 4324 (2014)[2] M. Gacesa, P. Zhang, V. Kharchenko, Geophys. Res. Lett. 39, L10203 (2012).

  17. 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...

  18. 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...

  19. Escape of Lyα and continuum photons from star-forming galaxies

    Science.gov (United States)

    Yajima, Hidenobu; Li, Yuexing; Zhu, Qirong; Abel, Tom; Gronwall, Caryl; Ciardullo, Robin

    2014-05-01

    A large number of high-redshift galaxies have been discovered via their narrow-band Lyα line or broad-band continuum colours in recent years. The nature of the escaping process of photons from these early galaxies is crucial to understand galaxy evolution and the cosmic reionization. Here, we investigate the escape of Lyα, non-ionizing UV-continuum (λ = 1300-1600 Å in rest frame), and ionizing photons (λ emissivity of Lyman Alpha Emitters (LAEs). By combining this relation with the observed luminosity functions of LAEs at different redshift, we estimate the contribution from LAEs to the reionization of intergalactic medium (IGM). Our result suggests that ionizing photons from LAEs alone are not sufficient to ionize IGM at z ≳ 6, but they can maintain the ionization of IGM at z ˜ 0-5.

  20. 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.

  1. An evaluation of two differential reinforcement procedures with escape extinction to treat food refusal.

    Science.gov (United States)

    Patel, Meeta R; Piazza, Cathleen C; Martinez, Cheryl J; Volkert, Valerie M; Christine, M Santana

    2002-01-01

    Consumption of solids and liquids occurs as a chain of behaviors that may include accepting, swallowing, and retaining the food or drink. In the current investigation, we evaluated the relative effectiveness of differential reinforcement of the first behavior in the chain (acceptance) versus differential reinforcement for the terminal behavior in the chain (mouth clean). Three children who had been diagnosed with a feeding disorder participated. Acceptance remained at zero when differential reinforcement contingencies were implemented for acceptance or mouth clean. Acceptance and mouth clean increased for all 3 participants once escape extinction was added to the differential reinforcement procedures, independent of whether reinforcement was provided for acceptance or for mouth clean. Maintenance was observed in 2 children when escape extinction was removed from the treatment package. The mechanism by which consumption increased is discussed in relation to positive and negative reinforcement contingencies.

  2. Escape from the Besieged Fortress -An Analysis of Alice Munro's "Runaway"

    Institute of Scientific and Technical Information of China (English)

    王琴; 除晓娜

    2011-01-01

    Alice Munro is one of the famous Canadian writers and is renowned above all for the astonishing subtlety of her short stories.Her theme has often been the dilemmas of the female coming to terms with family,friends in a small town.This paper attempts to make a brief introduction about the stories of Alice Munro's Runaway and explores the protagonist's choices in the dilemma situation,and then exposes the cruelty of reality is that they cannot get rid of the ineluctable reality of life.Escape is only a temporary action which cannot save them from endless triviality of life.What they should do is not to escape from life,but to adapt to the reality of life.

  3. 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

    . 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......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...... 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 (diabetic patients with nephropathy (urinary...

  4. MINING SECURITY PIPE© (TSM© WITH UNDERGROUND GPS GLOBAL© (RSPG© ESCAPE SECURITY DEVICE IN UNDERGROUND MINING

    Directory of Open Access Journals (Sweden)

    Rafael Barrionuevo GIMÉNEZ

    2016-04-01

    Full Text Available TSM is escape pipe in case of collapse of terrain. The TSM is a passive security tool placed underground to connect the work area with secure area (mining gallery mainly. TSM is light and hand able pipe made with aramid (Kevlar, carbon fibre, or other kind of new material. The TSM will be placed as a pipe line network with many in/out entrances/exits to rich and connect problem work areas with another parts in a safe mode. Different levels of instrumentation could be added inside such as micro-led escape way suggested, temperature, humidity, level of oxygen, etc.. The open hardware and software like Arduino will be the heart of control and automation system.

  5. Immunomodulation in trichinellosis: does Trichinella really escape the host immune system?

    Science.gov (United States)

    Bruschi, Fabrizio; Chiumiento, Lorena

    2012-03-01

    This review describes different aspects of the host immune response to Trichinella. The role of antibodies, T cells, mast cells, eosinophils and neutrophils in immune reaction to this nematode is considered, in the light of the recent data derived from experimental models, both in in vivo and in vitro. The knowledge of immune response mechanisms against Trichinella is fundamental to understand how the parasite can escape such mechanisms. The principal evasion mechanisms of host immune response occurring in trichinellosis are described, some of which are shared by other parasites, some others are peculiar of this parasite, but particular attention is focused on immunomodulation and the possibilities to exploit this parasite ability to verify the effects on immuno-mediated diseases. In conclusion, some considerations on the actual ability to escape the host immune response by the parasite are discussed, taking into account the recent data that shows that the parasite might rather drive immune system of the host towards a less dangerous response.

  6. Prior individual training and self-organized queuing during group emergency escape of mice from water pool.

    Directory of Open Access Journals (Sweden)

    Caesar Saloma

    Full Text Available We study the impact of prior individual training during group emergency evacuation using mice that escape from an enclosed water pool to a dry platform via any of two possible exits. Experimenting with mice avoids serious ethical and legal issues that arise when dealing with unwitting human participants while minimizing concerns regarding the reliability of results obtained from simulated experiments using 'actors'. First, mice were trained separately and their individual escape times measured over several trials. Mice learned quickly to swim towards an exit-they achieved their fastest escape times within the first four trials. The trained mice were then placed together in the pool and allowed to escape. No two mice were permitted in the pool beforehand and only one could pass through an exit opening at any given time. At first trial, groups of trained mice escaped seven and five times faster than their corresponding control groups of untrained mice at pool occupancy rate ρ of 11.9% and 4%, respectively. Faster evacuation happened because trained mice: (a had better recognition of the available pool space and took shorter escape routes to an exit, (b were less likely to form arches that blocked an exit opening, and (c utilized the two exits efficiently without preference. Trained groups achieved continuous egress without an apparent leader-coordinator (self-organized queuing-a collective behavior not experienced during individual training. Queuing was unobserved in untrained groups where mice were prone to wall seeking, aimless swimming and/or blind copying that produced circuitous escape routes, biased exit use and clogging. The experiments also reveal that faster and less costly group training at ρ = 4%, yielded an average individual escape time that is comparable with individualized training. However, group training in a more crowded pool (ρ = 11.9% produced a longer average individual escape time.

  7. Escape of X-linked miRNA genes from meiotic sex chromosome inactivation.

    Science.gov (United States)

    Sosa, Enrique; Flores, Luis; Yan, Wei; McCarrey, John R

    2015-11-01

    Past studies have indicated that transcription of all X-linked genes is repressed by meiotic sex chromosome inactivation (MSCI) during the meiotic phase of spermatogenesis in mammals. However, more recent studies have shown an increase in steady-state levels of certain X-linked miRNAs in pachytene spermatocytes, suggesting that either synthesis of these miRNAs increases or that degradation of these miRNAs decreases dramatically in these cells. To distinguish between these possibilities, we performed RNA-FISH to detect nascent transcripts from multiple miRNA genes in various spermatogenic cell types. Our results show definitively that Type I X-linked miRNA genes are subject to MSCI, as are all or most X-linked mRNA genes, whereas Type II and III X-linked miRNA genes escape MSCI by continuing ongoing, active transcription in primary spermatocytes. We corroborated these results by co-localization of RNA-FISH signals with both a corresponding DNA-FISH signal and an immunofluorescence signal for RNA polymerase II. We also found that X-linked miRNA genes that escape MSCI locate non-randomly to the periphery of the XY body, whereas genes that are subject to MSCI remain located within the XY body in pachytene spermatocytes, suggesting that the mechanism of escape of X-linked miRNA genes from MSCI involves their relocation to a position outside of the repressive chromatin domain associated with the XY body. The fact that Type II and III X-linked miRNA genes escape MSCI suggests an immediacy of function of the encoded miRNAs specifically required during the meiotic stages of spermatogenesis.

  8. New constraints on the escape of ionizing photons from starburst galaxies using ionization-parameter mapping

    Energy Technology Data Exchange (ETDEWEB)

    Zastrow, Jordan; Oey, M. S. [Department of Astronomy, University of Michigan, 500 Church Street, 830 Dennison, Ann Arbor, MI 48109-1042 (United States); Veilleux, Sylvain [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); McDonald, Michael, E-mail: jazast@umich.edu [Kavli Institute for Astrophysics and Space Research, MIT, Cambridge, MA 02139 (United States)

    2013-12-10

    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.

  9. Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1.

    Science.gov (United States)

    Dutta, Sheetij; Dlugosz, Lisa S; Clayton, Joshua W; Pool, Christopher D; Haynes, J David; Gasser, Robert A; Batchelor, Adrian H

    2010-02-01

    Antibodies against apical membrane antigen 1 (AMA1) inhibit invasion of Plasmodium merozoites into red cells, and a large number of single nucleotide polymorphisms on AMA1 allow the parasite to escape inhibitory antibodies. The availability of a crystal structure makes it possible to test protein engineering strategies to develop a monovalent broadly reactive vaccine. Previously, we showed that a linear stretch of polymorphic residues (amino acids 187 to 207), localized within the C1 cluster on domain 1, conferred the highest level of escape from inhibitory antibodies, and these were termed antigenic escape residues (AER). Here we test the hypothesis that immunodampening the C1 AER will divert the immune system toward more conserved regions. We substituted seven C1 AER of the FVO strain Plasmodium falciparum AMA1 with alanine residues (ALA). The resulting ALA protein was less immunogenic than the native protein in rabbits. Anti-ALA antibodies contained a higher proportion of cross-reactive domain 2 and domain 3 antibodies and had higher avidity than anti-FVO. No overall enhancement of cross-reactive inhibitory activity was observed when anti-FVO and anti-ALA sera were compared for their ability to inhibit invasion. Alanine mutations at the C1 AER had shifted the immune response toward cross-strain-reactive epitopes that were noninhibitory, refuting the hypothesis but confirming the importance of the C1 cluster as an inhibitory epitope. We further demonstrate that naturally occurring polymorphisms that fall within the C1 cluster can predict escape from cross-strain invasion inhibition, reinforcing the importance of the C1 cluster genotype for antigenic categorization and allelic shift analyses in future phase 2b trials.

  10. Symmetry Breaking on Density in Escaping Ants: Experiment and Alarm Pheromone Model

    OpenAIRE

    Geng Li; Di Huan; Bertrand Roehner; Yijuan Xu; Ling Zeng; Zengru Di; Zhangang Han

    2014-01-01

    International audience; 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 collectiv...

  11. 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.

  12. Role of RNA secondary structure in emergence of compartment specific hepatitis B virus immune escape variants

    OpenAIRE

    Datta, Sibnarayan; Chakravarty, Runu

    2016-01-01

    AIM To investigate the role of subgenotype specific RNA secondary structure in the compartment specific selection of hepatitis B virus (HBV) immune escape mutations. METHODS This study was based on the analysis of the specific observation of HBV subgenotype A1 in the serum/plasma, while subgenotype A2 with G145R mutation in the peripheral blood leukocytes (PBLs). Genetic variability found among the two subgenotypes was used for prediction and comparison of the full length pregenomic RNA (pgRN...

  13. 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.

  14. mPGES-1 deletion impairs aldosterone escape and enhances sodium appetite

    OpenAIRE

    Jia, Zhanjun; Aoyagi, Toshinori; Kohan, Donald E.; Yang, Tianxin

    2010-01-01

    Aldosterone (Aldo) is a major sodium-retaining hormone that reduces renal sodium excretion and also stimulates sodium appetite. In the face of excess Aldo, the sodium-retaining action of this steroid is overridden by an adaptive regulatory mechanism, a phenomenon termed Aldo escape. The underlying mechanism of this phenomenon is not well defined but appeared to involve a number of natriuretic factors such prostaglandins (PGs). Here, we investigated the role of microsomal prostaglandin E synth...

  15. Plasma volume, intravascular albumin and its transcapillary escape rate in patients with extensive skin disease

    DEFF Research Database (Denmark)

    Parving, H H; Worm, A M; Rossing, N

    1976-01-01

    less than 0-001). The transcapillary escape rate of albumin (TER alb) was significantly elevated, mean 8-6 +/- 1-1 (s.d.) % X h-1, as compared to normal subjects, mean 5-6 +/- 1-1 (s.d.) % X h-1, (+54%, P less than 0-001). The same patients were studied again after a 1-week treatment with prednisone...

  16. 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.

  17. Vector bosons escaping from the brane: $e^+e^- \\to \\gamma +$ nothing

    OpenAIRE

    Astakhov, D. I.; Kirpichnikov, D. V.

    2010-01-01

    We consider phenomenological consequences of RS2-n model with infinite extra dimension, namely, the production, in high energy collisions, of a photon or Z-boson escaping from our brane in association with a photon remaining on the brane. This would show up as process $e^+e^-\\rightarrow \\gamma +$nothing. We compare the signal with the Standard Model background coming from $e^+e^- \\rightarrow \\gamma \\bar{\

  18. 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 3 mm 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.

  19. The great escape: the role of self-esteem and self-related cognition in terror management

    OpenAIRE

    2015-01-01

    Integrating terror management theory and objective self-awareness theory, we propose the\\ud existential escape hypothesis, which states that people with low self-esteem should be\\ud especially prone to escaping self-awareness as a distal response to thoughts of death. This is\\ud because they lack the means to bolster the self as a defense, and the propensity to bolster the\\ud self reduces the motivation to escape from self-awareness. Five studies supported this\\ud hypothesis. Individuals low,...

  20. Many X-linked microRNAs escape meiotic sex chromosome inactivation.

    Science.gov (United States)

    Song, Rui; Ro, Seungil; Michaels, Jason D; Park, Chanjae; McCarrey, John R; Yan, Wei

    2009-04-01

    Meiotic sex chromosome inactivation (MSCI) during spermatogenesis is characterized by transcriptional silencing of genes on both the X and Y chromosomes in mid-to-late pachytene spermatocytes. MSCI is believed to result from meiotic silencing of unpaired DNA because the X and Y chromosomes remain largely unpaired throughout first meiotic prophase. However, unlike X-chromosome inactivation in female embryonic cells, where 25-30% of X-linked structural genes have been reported to escape inactivation, previous microarray- and RT-PCR-based studies of expression of >364 X-linked mRNA-encoding genes during spermatogenesis have failed to reveal any X-linked gene that escapes the silencing effects of MSCI in primary spermatocytes. Here we show that many X-linked miRNAs are transcribed and processed in pachytene spermatocytes. This unprecedented escape from MSCI by these X-linked miRNAs suggests that they may participate in a critical function at this stage of spermatogenesis, including the possibility that they contribute to the process of MSCI itself, or that they may be essential for post-transcriptional regulation of autosomal mRNAs during the late meiotic and early postmeiotic stages of spermatogenesis.

  1. 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.

  2. Crossover of the thermal escape problem in annular spatially distributed systems.

    Science.gov (United States)

    Fedorov, Kirill G; Pankratov, Andrey L

    2009-12-31

    The computer simulations of fluctuational dynamics of an annular system governed by the sine-Gordon model with a white noise source are performed. It is demonstrated that the mean escape time (MET) of a phase string for an annular structure can be much larger than for a linear one and has a strongly pronounced maximum as a function of system's length. The location of the MET maximum roughly equals the size of the kink-antikink pair, which leads to evidence of a spatial crossover between two dynamical regimes: when the phase string escapes over the potential barrier as a whole and when the creation of kink-antikink pairs is the main mechanism of the escape process. For large lengths and in the limit of small noise intensity gamma, for both MET and inverse concentration of kinks, we observe the same dependence versus the kink energy E(k): approximately exp(2E(k)/gamma) for the annular structure and approximately exp(E(k)/gamma) for the linear one.

  3. 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.

  4. Time-Dependent Corrections to the Ly-alpha Escape Probability During Cosmological Hydrogen Recombination

    CERN Document Server

    Chluba, J

    2008-01-01

    In this paper we consider the effects connected with the detailed radiative transfer during the epoch of cosmological recombination on the ionization history of our Universe. We focus on the escape of photons from the hydrogen Lyman-alpha resonance at redshifts 600<~z<~2000, one of two key mechanisms defining the rate of cosmological recombination. We approach this problem within the standard formulation, and corrections due to two-photon interactions are deferred to another paper. As a main result we show here that within a non-stationary approach to the escape problem the resulting correction in the free electron fraction, N_e, is about ~1.6-1.8% in the redshift range 800<~z<~1200. Therefore the discussed process results in one of the biggest modification to the ionization history close to the maximum of Thomson-visibility function at z~1100 considered sofar. We prove our results both numerically and analytically, deriving the escape probability, and considering both Lyman-alpha line-emission an...

  5. Mechanism of escape, extrasystolic, and parasystolic arrhythmias. Study on an electrical analogue.

    Science.gov (United States)

    Sideris, D A

    1976-01-01

    A simple analogue of the heart consisting of a system of neon relaxation oscillators is presented. The analogue may display rhythm patterns similar to sinus rhythm, escape rhythm, isorrhythmic dissociation with synchronization, atrial extrasystoles, ventricular extrasystoles, and parasystole. The strict rules followed by these arrhythmias, as well as the deviations from the rules commonly followed by the equivalent heart arrhythmias, may be easily reproduced on the analogue. Such features are the Treppe phenomenon and captured beats in escape rhythm, fixed coupling intervals in extrasystoles, partial or complete atrioventricular block in very premature atrial extrasystoles, prolongation of the period following an atrial extrasystole, interpolated premature beats, complete compensatory pause and the rule of bigeminy in ventricular extrasystoles, slight instability of the parasystolic period, multiple length parasystolic periods slightly different from the exact multiples of the parasystolic idioperiod, preference of the parasystoles for certain phase in the sinus cycle, synchronization at a phase difference and fluctuation repeatedly and without interruption from a parasystolic to an extrasystolic rhythm and synchronization in escape rhythm with isorrhythmic dissociation. The mechanisms involved in these phenomena are discussed in detail. The striking similarity between the properties of the cardiac pacemakers and those of the relaxation oscillators on the one hand and betwen the rhythm patterns of the heart and those of the analogue on the other may permit the hypothesis that the mechanisms operating in the analogue may be used in analyzing and understanding heart arrhythmias.

  6. 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.

  7. Symmetry breaking on density in escaping ants: experiment and alarm pheromone model.

    Science.gov (United States)

    Li, Geng; Huan, Di; Roehner, Bertrand; Xu, Yijuan; Zeng, Ling; Di, Zengru; Han, Zhangang

    2014-01-01

    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.

  8. The Impact of Unresolved Turbulence on the Escape Fraction of Lyman Continuum Photons

    Science.gov (United States)

    Safarzadeh, M.; Scannapieco, E.

    2016-11-01

    We investigate the relation between the turbulent Mach number ({ M }) and the escape fraction of Lyman continuum photons ({f}{esc}) in high-redshift galaxies. Approximating the turbulence as isothermal and isotropic, we show that the increase in the variance in column densities from { M }=1 to { M }=10 causes {f}{esc} to increase by ≈ 25%, and the increase from { M }=1 to { M }=20 causes {f}{esc} to increases by ≈ 50% for a medium with opacity τ ≈ 1. At a fixed Mach number, the correction factor for escape fraction relative to a constant column density case scales exponentially with the opacity in the cell, which has a large impact for simulated star-forming regions. Furthermore, in simulations of isotropic turbulence with full atomic/ionic cooling and chemistry, the fraction of HI drops by a factor of ≈ 2.5 at { M }≈ 10 even when the mean temperature is ≈ 5× {10}3 {{K}}. If turbulence is unresolved, these effects together enhance {f}{esc} by a factor \\gt 3 at Mach numbers above 10. Such Mach numbers are common at high redshifts where vigorous turbulence is driven by supernovae, gravitational instabilities, and merger activity, as shown both by numerical simulations and observations. These results, if implemented in the current hydrodynamical cosmological simulations to account for unresolved turbulence, can boost the theoretical predictions of the Lyman Continuum photon escape fraction and further constrain the sources of reionization.

  9. 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...

  10. TAP-independent self-peptides enhance T cell recognition of immune-escaped tumors

    Science.gov (United States)

    Doorduijn, Elien M.; Sluijter, Marjolein; Querido, Bianca J.; Oliveira, Cláudia C.; Achour, Adnane; Ossendorp, Ferry; van der Burg, Sjoerd H.; van Hall, Thorbald

    2016-01-01

    Tumor cells frequently escape from CD8+ T cell recognition by abrogating MHC-I antigen presentation. Deficiency in processing components, like the transporter associated with antigen processing (TAP), results in strongly decreased surface display of peptide/MHC-I complexes. We previously identified a class of hidden self-antigens known as T cell epitopes associated with impaired peptide processing (TEIPP), which emerge on tumor cells with such processing defects. In the present study, we analyzed thymus selection and peripheral behavior of T cells with specificity for the prototypic TEIPP antigen, the “self” TRH4 peptide/Db complex. TEIPP T cells were efficiently selected in the thymus, egressed with a naive phenotype, and could be exploited for immunotherapy against immune-escaped, TAP-deficient tumor cells expressing low levels of MHC-I (MHC-Ilo). In contrast, overt thymus deletion and functionally impaired TEIPP T cells were observed in mice deficient for TAP1 due to TEIPP antigen presentation on all body cells in these mice. Our results strongly support the concept that TEIPPs derive from ubiquitous, nonmutated self-antigens and constitute a class of immunogenic neoantigens that are unmasked during tumor immune evasion. These data suggest that TEIPP-specific CD8+ T cells are promising candidates in the treatment of tumors that have escaped from conventional immunotherapies. PMID:26784543

  11. New Constraints on the Lyman Continuum Escape Fraction at z~1.3

    CERN Document Server

    Siana, Brian; Colbert, James; Ferguson, Henry C; Dickinson, Mark; Brown, Thomas M; Conselice, Christopher J; de Mello, Duilia F; Gardner, Jonathan P; Giavalisco, Mauro; Menanteau, Felipe

    2007-01-01

    We examine deep far-ultraviolet (1600 Angstrom) imaging of the Hubble Deep Field-North (HDFN) and the Hubble Ultra Deep Field (HUDF) to search for leaking Lyman continuum radiation from starburst galaxies at z~1.3. There are 21 (primarily sub-L*) galaxies with spectroscopic redshifts between 1.1escape fractions. We show that previous high-redshift studies may have underestimated the amplitude of the Lyman Break, and thus the relative escape fraction, by a factor of ~2. Once the starburst age and intergalactic HI absorption are accounted for, 18 galaxies in our sample have limits to the relative escape fraction, f_esc,rel < 1.0 with some limits as low as f_esc,rel < 0.10 and a sta...

  12. Suppressing escape events in maps of the unit interval with demographic noise

    Science.gov (United States)

    Parra-Rojas, César; Challenger, Joseph D.; Fanelli, Duccio; McKane, Alan J.

    2016-11-01

    We explore the properties of discrete-time stochastic processes with a bounded state space, whose deterministic limit is given by a map of the unit interval. We find that, in the mesoscopic description of the system, the large jumps between successive iterates of the process can result in probability leaking out of the unit interval, despite the fact that the noise is multiplicative and vanishes at the boundaries. By including higher-order terms in the mesoscopic expansion, we are able to capture the non-Gaussian nature of the noise distribution near the boundaries, but this does not preclude the possibility of a trajectory leaving the interval. We propose a number of prescriptions for treating these escape events, and we compare the results with those obtained for the metastable behavior of the microscopic model, where escape events are not possible. We find that, rather than truncating the noise distribution, censoring this distribution to prevent escape events leads to results which are more consistent with the microscopic model. The addition of higher moments to the noise distribution does not increase the accuracy of the final results, and it can be replaced by the simpler Gaussian noise.

  13. Extinction Correction Significantly Influences the Estimate of Ly$\\alpha$ Escape Fraction

    CERN Document Server

    An, Fangxia; HAO, Cai-Na; Huang, Jia-Sheng; Xia, Xiao-Yang

    2016-01-01

    The Ly$\\alpha$ escape fraction is a key measure to constraining the neutral state of the inter-galactic medium and then to understanding how the universe was fully reionized. We combine deep narrow-band imaging data through the custom-made filter NB393 and the $H_{2}S$1 filter centered at 2.14 $\\mu$m to examine the Ly$\\alpha$ emitters and H$\\alpha$ emitters at the same redshift $z=2.24$. The combination of two populations allows us to determine the Ly$\\alpha$ escape fraction at $z=2.24$. Over an area of 383 arcmin$^{2}$ in the Extended Chandra Deep Field (ECDFS), 124 Ly$\\alpha$ emitters are detected down to NB393 = 26.4 mag at the 5$\\sigma$ level and 56 H$\\alpha$ emitters from An14. Of them, four have both Ly$\\alpha$ and H$\\alpha$ emissions (LAHAEs). We measure the individual/volumetric Ly$\\alpha$ escape fraction by comparing the observed Ly$\\alpha$ luminosity/luminosity density to extinction-corrected H$\\alpha$ luminosity/luminosity density. We revisit the extinction correction for H$\\alpha$ emitters using t...

  14. Dependence of O+ escape rate from the Venusian upper atmosphere on IMF directions

    Science.gov (United States)

    Masunaga, K.; Futaana, Y.; Stenberg, G.; Barabash, S.; Zhang, T. L.; Fedorov, A.; Okano, S.; Terada, N.

    2013-09-01

    We investigate the dependence of the O+ escape rate from the Venusian upper atmosphere on the upstream interplanetary magnetic field (IMF) direction. Using the data obtained from the Analyser of Space Plasma and Energetic Atoms (ASPERA-4) instrument and the magnetometer (MAG) onboard Venus Express, O+ fluxes observed in the night side region is statistically calculated. The data is classified into two cases: the perpendicular IMF case and the parallel IMF case, where IMF is nearly perpendicular to the solar wind velocity and nearly parallel to it. In the period between June 21 2006 and May 31, 2010, the O+ escape rates of (5.8 ± 2.9) × 10^24 s^-1 (perpendicular IMF case) and (4.9 ± 2.2) × 10^24 s^-1 (parallel IMF case) are obtained. Since these values are not significantly different, we conclude that the IMF direction does not affect the total amount of O+ outflow from Venus. Several acceleration mechanisms must balance each other in order to keep the escape rate constant.

  15. 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...

  16. Alternative strategies of seed predator escape by early-germinating oaks in Asia and North America.

    Science.gov (United States)

    Yi, Xianfeng; Yang, Yueqin; Curtis, Rachel; Bartlow, Andrew W; Agosta, Salvatore J; Steele, Michael A

    2012-03-01

    Early germination of white oaks is widely viewed as an evolutionary strategy to escape rodent predation; yet, the mechanism by which this is accomplished is poorly understood. We report that chestnut oak Quercus montana (CO) and white oak Q. alba (WO) (from North America), and oriental cork oak Q. variabilis (OO) and Mongolian oak Q. mongolica (MO) (from Asia) can escape predation and successfully establish from only taproots. During germination in autumn, cotyledonary petioles of acorns of CO and WO elongate and push the plumule out of the cotyledons, whereas OO and MO extend only the hypocotyls and retain the plumule within the cotyledons. Experiments showed that the pruned taproots (>6 cm) of CO and WO acorns containing the plumule successfully germinated and survived, and the pruned taproots (≥12 cm) of OO and MO acorns without the plumule successfully regenerated along with the detached acorns, thus producing two seedlings. We argue that these two distinct regeneration morphologies reflect alternative strategies for escaping seed predation.

  17. The Relationship between Endorsing Gambling as an Escape and the Display of Gambling Problems

    Directory of Open Access Journals (Sweden)

    Jeffrey N. Weatherly

    2013-01-01

    Full Text Available 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. Endorsing gambling as an escape on the GFA-R was again predictive of SOGS scores. The function of one’s gambling was also predictive of the respondents’ PGSI scores, but whether gambling for positive reinforcement or as an escape was the significant predictor differed between male and female respondents. Scores on the GFA-R subscales also accounted for a significant amount of variance in PGSI scores above and beyond that accounted for by SOGS scores. The present results support the idea that both practitioners and researchers should be interested in the function of an individual’s gambling as well as the presence or the absence of pathology. They also suggest that differences in the function of gambling might also exist between the sexes.

  18. The evolution of drought escape and avoidance in natural herbaceous populations.

    Science.gov (United States)

    Kooyers, Nicholas J

    2015-05-01

    While the functional genetics and physiological mechanisms controlling drought resistance in crop plants have been intensely studied, less research has examined the genetic basis of adaptation to drought stress in natural populations. Drought resistance adaptations in nature reflect natural rather than human-mediated selection and may identify novel mechanisms for stress tolerance. Adaptations conferring drought resistance have historically been divided into alternative strategies including drought escape (rapid development to complete a life cycle before drought) and drought avoidance (reducing water loss to prevent dehydration). Recent studies in genetic model systems such as Arabidopsis, Mimulus, and Panicum have begun to elucidate the genes, expression profiles, and physiological changes responsible for ecologically important variation in drought resistance. Similar to most crop plants, variation in drought escape and avoidance is complex, underlain by many QTL of small effect, and pervasive gene by environment interactions. Recently identified major-effect alleles point to a significant role for genetic constraints in limiting the concurrent evolution of both drought escape and avoidance strategies, although these constraints are not universally found. This progress suggests that understanding the mechanistic basic and fitness consequences of gene by environment interactions will be critical for crop improvement and forecasting population persistence in unpredictable environments.

  19. Ultra Violet Escape Fractions from Giant Molecular Clouds During Early Cluster Formation

    CERN Document Server

    Howard, Corey S; Klessen, Ralf S

    2016-01-01

    The UV photon escape fraction from molecular clouds is a key parameter for understanding the ionization of the Interstellar Medium (ISM), and extragalactic processes, such as cosmic reionization. We present the ionizing photon flux and the corresponding photon escape fraction (f$_{esc}$) arising as a consequence of star cluster formation in a turbulent, 10$^6$ M$_{\\odot}$ GMC, simulated using the code FLASH. We make use of sink particles to represent young, star-forming clusters coupled with a radiative transfer scheme to calculate the emergent UV flux. We find that the ionizing photon flux across the cloud boundary is highly variable in time and space due to the turbulent nature of the intervening gas. The escaping photon fraction remains at $\\sim$5% for the first 2.5 Myr, followed by two pronounced peaks at 3.25 and 3.8 Myr with a maximum f$_{esc}$ of 30% and 37%, respectively. These peaks are due to the formation of large HII regions, that expand into regions of lower density and some of which reach the cl...

  20. 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

    2016-06-01

    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.

  1. 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.

  2. Neurological effects on startle response and escape from predation by medaka exposed to organic chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, R.; Drummond, R.; Hammermeister, D.; Bradbury, S. [Environmental Protection Agency, Duluth, MN (United States). Environmental Research Lab.

    1995-12-31

    Simultaneous electrophysiological and behavioral studies were performed on juvenile Japanese medaka (Oryzias latipes) exposed to representative neurotoxic organic chemicals at sublethal concentrations. Non-invasive recordings were made of the electrical impulses generated within giant neuronal Mauthner cells, associated interneurons or motoneurons, and musculature, all of which initiate the startle or escape response in fish. Timing in milliseconds between these electrical sequelae was measured for each fish before and at 24 and 48 hours exposure to a chemical. Also noted was the number of startle responses to number of stimuli ratio (R/S). Other groups of medaka were fed to bluegills and consumption times recorded to assess their ability to escape predation. These results were compared to neurophysiological effect levels. Phenol, 2,4-dinitrophenol, chlorpyrifos, fenvalerate, and 1-octanol impaired the ability of medaka to escape predation at all concentrations. Medaka were more susceptible to predation in high concentrations of carbaryl and strychnine, but less susceptible at low concentrations, whereas the reverse was true for endosulfan. The variety of neurological effects detected at these concentrations suggest that different mechanisms may be responsible. Phenol and strychnine affected Mauthner cell to motoneuron transmission, chlorpyrifos and carbaryl showed neuromuscular effects, and R/S was affected by most chemicals. Although a variety of neurotoxic mechanisms were examined, the exposure threshold for significant effects for each specific compound was found to be consistent for both the neurophysiological and behavioral endpoints.

  3. Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias.

    Science.gov (United States)

    Dunford, Andrew; Weinstock, David M; Savova, Virginia; Schumacher, Steven E; Cleary, John P; Yoda, Akinori; Sullivan, Timothy J; Hess, Julian M; Gimelbrant, Alexander A; Beroukhim, Rameen; Lawrence, Michael S; Getz, Gad; Lane, Andrew A

    2017-01-01

    There is a striking and unexplained male predominance across many cancer types. A subset of X-chromosome genes can escape X-inactivation, which would protect females from complete functional loss by a single mutation. To identify putative 'escape from X-inactivation tumor-suppressor' (EXITS) genes, we examined somatic alterations from >4,100 cancers across 21 tumor types for sex bias. Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes (ATRX, CNKSR2, DDX3X, KDM5C, KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males (based on a false discovery rate genes (Fisher's exact P genes that escape X-inactivation were observed in combined analysis across many cancers and in several individual tumor types, suggesting a generalized phenomenon. We conclude that biallelic expression of EXITS genes in females explains a portion of the reduced cancer incidence in females as compared to males across a variety of tumor types.

  4. Constraints on Bounded Motion and Mutual Escape for the Full 3-Body Problem

    CERN Document Server

    Scheeres, D J

    2016-01-01

    When gravitational aggregates are spun to fission they can undergo complex dynamical evolution, including escape and reconfiguration. Previous work has shown that a simple analysis of the full 2-body problem provides physically relevant insights for whether a fissioned system can lead to escape of the components and the creation of asteroid pairs. In this paper we extend the analysis to the full 3-body problem, utilizing recent advances in the understanding of fission mechanics of these systems. Specifically, we find that the full 3-body problem can eject a body with as much as 0.31 of the total system mass, significantly larger than the 0.17 mass limit previously calculated for the full 2-body problem. This paper derives rigorous limits on a fissioned 3-body system with regards to whether fissioned system components can physically escape from each other and what other stable relative equilibria they could settle in. We explore this question with a narrow focus on the Spherical Full Three Body Problem studied...

  5. 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.

  6. Mutation or loss of Wilms' tumor gene 1 (WT1 are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination

    Directory of Open Access Journals (Sweden)

    Ochsenreither Sebastian

    2010-01-01

    Full Text Available Abstract Background Efficacy of cancer vaccines may be limited due to immune escape mechanisms like loss or mutation of target antigens. Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML for loss or mutations of the WT1 epitope or epitope flanking sequences that may abolish proper T cell recognition or epitope presentation. Methods All patients had been enrolled in a WT1 peptide phase II vaccination trial (NCT00153582 and ultimately progressed despite induction of a WT1 specific T cell response. Blood and bone marrow samples prior to vaccination and during progression were analyzed for mRNA expression level of WT1. Base exchanges within the epitope sequence or flanking regions (10 amino acids N- and C-terminal of the epitope were assessed with melting point analysis and sequencing. HLA class I expression and WT1 protein expression was analyzed by flow cytometry. Results Only in one patient, downregulation of WT1 mRNA by 1 log and loss of WT1 detection on protein level at time of disease progression was observed. No mutation leading to a base exchange within the epitope sequence or epitope flanking sequences could be detected in any patient. Further, no loss of HLA class I expression on leukemic blasts was observed. Conclusion Defects in antigen presentation caused by loss or mutation of WT1 or downregulation of HLA molecules are not the major basis for escape from the immune response induced by WT1 peptide vaccination.

  7. Indirect Evidence for Escaping Lyman Continuum Photons in Local Lyman Break Galaxy Analogs

    Science.gov (United States)

    Alexandroff, Rachael; Heckman, Timothy M.; Borthakur, Sanchayeeta; Overzier, Roderik

    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, however, what conditions and physical processes would enable a significant fraction of the ionizing photons to escape from these gas-rich galaxies. In addition, studies of high redshift galaxies have yet to uncover a large sample of galaxies with the required high escape fraction of ionizing photons.We have uncovered a sample of local analogs to high-redshift, star-forming Lyman Break Galaxies (LBGs) called Lyman Break Analogs (LBAs) by matching the Sloan Digital Sky Survey (SDSS) and Galaxy Evolution Explorer (GALEX) catalogs. These galaxies are remarkably similar to LBGs in their properties-- morphology, size, UV luminosity, SFR, mass, velocity dispersion, metallicity and dust content. We obtained HST COS far-UV spectroscopy plus ancillary multi-waveband data of a sample of 22 LBAs to look for indirect evidence of escaping ionizing radiation (leakiness).We measure three parameters: (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 blue-shifted Lyman alpha 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 [SII] optical emission lines that trace matter-bounded HII regions. We find all three diagnostics agree well with one another. Finally, we find the strongest correlation between these leakiness indicators and both the compactness of the galactic star-forming region (size and star formation rate/area) and the speed of the galactic outflow. This suggests that extreme feedback- a high intensity of ionizing radiation and strong pressure from both radiation and a hot galactic wind- combines to create significant holes in the neutral gas. These results not only shed new light on the physical

  8. The Connection Between Reddening, Gas Covering Fraction, and the Escape of Ionizing Radiation at High Redshift

    Science.gov (United States)

    Reddy, Naveen A.; Steidel, Charles C.; Pettini, Max; Bogosavljević, Milan; Shapley, Alice E.

    2016-09-01

    Using a large sample of spectroscopically confirmed z∼ 3 galaxies, we establish an empirical relationship between reddening (E(B-V)), neutral gas covering fraction ({f}{{cov}}({{H}} {{I}})), and the escape of ionizing (Lyman continuum, LyC) photons. Our sample includes 933 galaxies at z∼ 3,121 of which have deep spectroscopic observations (≳ 7 hr) at 850≲ {λ }{{rest}}≲ 1300 Å with the Low Resolution Imaging Spectrograph on Keck. The high covering fraction of outflowing optically thick {{H}} {{I}} indicated by the composite spectra of these galaxies implies that photoelectric absorption, rather than dust attenuation, dominates the depletion of LyC photons. By modeling the composite spectra as the combination of an unattenuated stellar spectrum including nebular continuum emission with one that is absorbed by {{H}} {{I}} and reddened by a line-of-sight extinction, we derive an empirical relationship between E(B-V) and {f}{{cov}}({{H}} {{I}}). Galaxies with redder UV continua have larger covering fractions of {{H}} {{I}} characterized by higher line-of-sight extinctions. We develop a model which connects the ionizing escape fraction with E(B-V), and which may be used to estimate the ionizing escape fraction for an ensemble of galaxies. Alternatively, direct measurements of the escape fraction for our sample allow us to constrain the intrinsic LyC-to-UV flux density ratio to be }{{int}}≳ 0.20, a value that favors stellar population models that include weaker stellar winds, a flatter initial mass function, and/or binary evolution. Last, we demonstrate how the framework discussed here may be used to assess the pathways by which ionizing radiation escapes from high-redshift galaxies. Based on data obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA, and was made possible by the generous financial support of the W.M. Keck Foundation.

  9. Infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors : A potential virus escape mechanism?

    NARCIS (Netherlands)

    Zandberg, Mariet; van Son, Willem J.; Harmsen, Martin C.; Bakker, Winston W.

    2007-01-01

    Background. Human cytomegalovirus (CMV) uses different strategies to escape from human host defense reactions. Previously we have observed that infection of endothelial cells with CMV in vitro leads to enhanced activity of endothelial ectonucleotidases. These ectoenzymes are responsible for hydrolys

  10. [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).

  11. Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes

    NARCIS (Netherlands)

    T.M. Bestebroer (Theo); N.J. Nieuwkoop; R.A.M. Fouchier (Ron); G.F. Rimmelzwaan (Guus); J.T.M. Voeten; A.D.M.E. Osterhaus (Ab)

    2000-01-01

    textabstractViruses exploit different strategies to escape immune surveillance, including the introduction of mutations in cytotoxic T-lymphocyte (CTL) epitopes. The sequence of these epitopes is critical for their binding to major histocompatibility complex (MHC) class I molecules

  12. Akt and SHIP modulate Francisella escape from the phagosome and induction of the Fas-mediated death pathway.

    Directory of Open Access Journals (Sweden)

    Murugesan V S Rajaram

    Full Text Available Francisella tularensis infects macrophages and escapes phago-lysosomal fusion to replicate within the host cytosol, resulting in host cell apoptosis. Here we show that the Fas-mediated death pathway is activated in infected cells and correlates with escape of the bacterium from the phagosome and the bacterial burden. Our studies also demonstrate that constitutive activation of Akt, or deletion of SHIP, promotes phago-lysosomal fusion and limits bacterial burden in the host cytosol, and the subsequent induction of Fas expression and cell death. Finally, we show that phagosomal escape/intracellular bacterial burden regulate activation of the transcription factors sp1/sp3, leading to Fas expression and cell death. These data identify for the first time host cell signaling pathways that regulate the phagosomal escape of Francisella, leading to the induction of Fas and subsequent host cell death.

  13. The effects of variable-time delivery of food items and praise on problem behavior reinforced by escape.

    Science.gov (United States)

    Lomas, Joanna E; Fisher, Wayne W; Kelley, Michael E

    2010-01-01

    Prior research indicates that reinforcement of an appropriate response (e.g., compliance) can produce concomitant reductions in problem behavior reinforced by escape when problem behavior continues to produce negative reinforcement (e.g., Lalli et al., 1999). These effects may be due to a preference for positive over negative reinforcement or to positive reinforcement acting as an abolishing operation, rendering demands less aversive and escape from demands less effective as negative reinforcement. In the current investigation, we delivered a preferred food item and praise on a variable-time 15-s schedule while providing escape for problem behavior on a fixed-ratio 1 schedule in a demand condition for 3 participants with problem behavior maintained by negative reinforcement. Results for all 3 participants showed that variable-time delivery of preferred edible items reduced problem behavior even though escape continued to be available for these responses. These findings are discussed in the context of motivating operations.

  14. 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...

  15. 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.

  16. Androgen inhibits the growth of carcinoma cell lines established from prostate cancer xenografts that escape androgen treatment.

    Science.gov (United States)

    Joly-Pharaboz, Marie-Odile; Kalach, Jean-Jacques; Pharaboz, Julie; Chantepie, Jacqueline; Nicolas, Brigitte; Baille, Marie-Laurence; Ruffion, Alain; Benahmed, Mohamed; André, Jean

    2008-07-01

    Most prostate cancers escape endocrine therapy by diverse mechanisms. One of them might be growth repression by androgen. We reported that androgen represses the growth in culture of MOP cells (a sub-line of LNCaP cells) and that of MOP cell xenografts, although tumor growth becomes androgen-independent (AI). Here we explore whether AI tumors contain androgen-responsive cells. ME carcinoma cells were established from AI tumors. The responses to androgen were examined by cell counting, DAPI labeling, flow cytometry, PSA immunoassay and tumor size follow-up. Androgen receptors (AR) were analyzed by western blotting and DNA sequencing. The pattern of responses of these cells to androgen was compared to that of MOP cells and that of JAC cells established from LNCaP-like MOP cells. R1881, a synthetic androgen: (1) repressed the growth of all the six ME cell lines obtained, MOP and JAC cells, (2) augmented the secretion of PSA, (3) induced spectacular cell bubbling/fragmentation and (4) blocked the cell cycle and induced a modest increase of apoptosis. All the androgen-repressed cells expressed the same level of mutated AR as LNCaP cells. In nude mice, the growth of ME-2 cell xenografts displayed transient androgen repression similar to that of MOP cells. In culture neither fibroblasts nor extra-cellular matrix altered the effects of R1881 on cell proliferation. These results demonstrate that androgen-independent tumors contain androgen-responsive cells. The apparent discrepancy between the responses to androgen of tumors and those of carcinoma cells in culture suggests that microenvironmental factors contribute to the androgen responsiveness of tumor cells in vivo. These modifications, albeit unspecified, could be suitable targets for restoring the androgen responsiveness of AI tumors.

  17. HER2 Oncogenic Function Escapes EGFR Tyrosine Kinase Inhibitors via Activation of Alternative HER Receptors in Breast Cancer Cells

    Science.gov (United States)

    Kong, Anthony; Calleja, Véronique; Leboucher, Pierre; Harris, Adrian; Parker, Peter J.; Larijani, Banafshé

    2008-01-01

    Background The response rate to EGFR tyrosine kinase inhibitors (TKIs) may be poor and unpredictable in cancer patients with EGFR expression itself being an inadequate response indicator. There is limited understanding of the mechanisms underlying this resistance. Furthermore, although TKIs suppress the growth of HER2-overexpressing breast tumor cells, they do not fully inhibit HER2 oncogenic function at physiological doses. Methodology and Principal Findings Here we have provided a molecular mechanism of how HER2 oncogenic function escapes TKIs' inhibition via alternative HER receptor activation as a result of autocrine ligand release. Using both Förster Resonance Energy Transfer (FRET) which monitors in situ HER receptor phosphorylation as well as classical biochemical analysis, we have shown that the specific tyrosine kinase inhibitors (TKIs) of EGFR, AG1478 and Iressa (Gefitinib) decreased EGFR and HER3 phosphorylation through the inhibition of EGFR/HER3 dimerization. Consequent to this, we demonstrate that cleavage of HER4 and dimerization of HER4/HER2 occur together with reactivation of HER3 via HER2/HER3, leading to persistent HER2 phosphorylation in the now resistant, surviving cells. These drug treatment–induced processes were found to be mediated by the release of ligands including heregulin and betacellulin that activate HER3 and HER4 via HER2. Whereas an anti-betacellulin antibody in combination with Iressa increased the anti-proliferative effect in resistant cells, ligands such as heregulin and betacellulin rendered sensitive SKBR3 cells resistant to Iressa. Conclusions and Significance These results demonstrate the role of drug-induced autocrine events leading to the activation of alternative HER receptors in maintaining HER2 phosphorylation and in mediating resistance to EGFR tyrosine kinase inhibitors (TKIs) in breast cancer cells, and hence specify treatment opportunities to overcome resistance in patients. PMID:18682844

  18. Expression of Fas ligand and Caspase-3 contributes to formation of immune escape in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Hua-Chuan Zheng; Jin-llin Sun; Zheng-Li Wei; Xue-Fei Yang; Yin-Chang Zhang; Yan Xin

    2003-01-01

    AIM: To study the role of Fas ligand (FasL) and Caspase-3expression in carcinogenesis and progression of gastric cancer and molecular mechanisms of relevant immune escape.METHODS: FasL and Caspase-3 expression was studied in adjacent epithelial cells, cancer cells and lymphocytes of primary foci, and cancer cells of metastatic foci from 113 cases of gastric cancer by streptavidin-biotin-peroxidase (S-P) immunohistochemistry. Expression of both proteins in cancer cells of primary foci was compared with clinicopathological features of gastric cancer. The relationship between FasL expression in cancer cells and Caspase-3expression in cancer cells or infiltrating lymphocytes of primary foci was investigated.RESULTS: Cancer cells of primary foci expressed FasL in 53.98 % (61/113) of gastric cancers, more than their adjacent epithelial cells (34.51%, 39/113) (P=0.003, X2=8.681), while the expression of Caspase-3 in cancer cells of primary foci was detected in 32.74 % (37/113) of gastric cancers, less than in the adjacent epithelial cells (50.44 %, 57/113)(P=0.007, X2=7.286). Infiltrating lymphocytes of the primary foci showed positive immunoreactivity to Caspase-3 in 70.80 % (80/113) of gastric cancers, more than their corresponding adjacent epithelial cells (P=0.001, X2=10.635)or cancer cells of primary foci (P=0.000, X2=32.767). FasL was less expressed in cancer cells of metastases (51.16 %,22/43) than in those of the corresponding primary foci (81.58 %, 31/38) (P=0.003, X2=9.907). Conversely,Caspase-3 was more expressed in cancer cells of metastases (58.14 %, 25/43) than in those of the corresponding primary foci (34.21%, 13/38) (P=0.031, X2=4.638). FasL expression was significantly correlated with tumor size (P=0.035,rs=0.276), invasive depth (P=0.039, rs=0.195), metastasis (P=0.039, rs=0.195), differentiation (P=0.015, rs=0.228)and Lauren′s classification (P=0.038, rs=0.196), but not with age or gender of patients, growth pattern or TNM staging of gastric cancer

  19. A COMPARISON OF VARIOUS FORMS OF REINFORCEMENT WITH AND WITHOUT EXTINCTION AS TREATMENT FOR ESCAPE-MAINTAINED PROBLEM BEHAVIOR

    OpenAIRE

    Carter, Stacy L

    2010-01-01

    The present investigation compared the effects of reinforcing compliance with either positive or negative reinforcement for a participant who displayed escape-maintained problem behavior. The results indicated that positive reinforcement in the form of a highly preferred edible or leisure item produced higher levels of compliance and lower levels of problem behavior when compared to negative reinforcement in the form of escape from demands. In addition, an extinction procedure was unnecessary...

  20. 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.