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Sample records for great escape viral

  1. Viral escape from antisense RNA.

    PubMed

    Bull, J J; Jacobson, A; Badgett, M R; Molineux, I J

    1998-05-01

    RNA coliphage SP was propagated for several generations on a host expressing an inhibitory antisense RNA complementary to bases 31-270 of the positive-stranded genome. Phages evolved that escaped inhibition. Typically, these escape mutants contained 3-4 base substitutions, but different sequences were observed among different isolates. The mutations were located within three different types of structural features within the predicted secondary structure of SP genomic RNA: (i) hairpin loops; (ii) hairpin stems; and (iii) the 5' region of the phage genome complementary to the antisense molecule. Computer modelling of the mutant genomic RNAs showed that all of the substitutions within hairpin stems improved the Watson-Crick pairing of the stem. No major structural rearrangements were predicted for any of the mutant genomes, and most substitutions in coding regions did not alter the amino acid sequence. Although the evolved phage populations were polymorphic for substitutions, many substitutions appeared independently in two selected lines. The creation of a new, perfect, antisense RNA against an escape mutant resulted in the inhibition of that mutant but not of other escape mutants nor of the ancestral, unevolved phage. Thus, at least in this system, a population of viruses that evolved to escape from a single antisense RNA would require a cocktail of several antisense RNAs for inhibition. PMID:9643550

  2. [Interferon : antiviral mechanisms and viral escape].

    PubMed

    Espert, Lucile; Gongora, Céline; Mechti, Nadir

    2003-02-01

    15 % of human cancers have virus origin, meaning that viruses are the second cause of cancers after tabagism. The knowledge of antiviral mechanisms is essential for treatment and prevention of infection evolution towards cancers. Interferons (IFNs) are a large family of multifunctional cytokines. They are involved in regulation of cell growth and modulation of immune response. But, all these functions seem to converge toward the most important of them : the antiviral activity. IFN secretion is the first event induced by viral infection, and will act on specific receptors on neighbour cells and prevent their infection by inducing numbers of antiviral genes. Although few of them are well known like the PKR, the 2-5OAS/RNase L pathway and the Mx proteins, many others need extensive studies to understand the wide range of IFN effect. Viruses have evolved to circumvent the IFN antiviral activity, and are able not only to divert the cellular machinery but also to lure the antiviral mechanisms of the host cell. The purpose of this review is to describe the many antiviral pathways and proteins induced by IFNs and to summarize the strategies of viral escape. PMID:12660132

  3. Viral escape mechanisms--escapology taught by viruses.

    PubMed

    Lucas, M; Karrer, U; Lucas, A; Klenerman, P

    2001-10-01

    Viruses have 'studied' immunology over millions of years of coevolution with their hosts. During this ongoing education they have developed countless mechanisms to escape from the host's immune system. To illustrate the most common strategies of viral immune escape we have focused on two murine models of persistent infection, lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV). LCMV is a fast replicating small RNA virus with a genome prone to mutations. Therefore, LCMV escapes from the immune system mainly by two strategies: 'speed' and 'shape change'. At the opposite extreme, MCMV is a large, complex DNA virus with a more rigid genome and thus the strategies used by LCMV are no option. However, MCMV has the coding capacity for additional genes which interfere specifically with the immune response of the host. These escape strategies have been described as 'camouflage' and 'sabotage'. Using these simple concepts we describe the spectrum of viral escapology, giving credit not only to the researchers who uncovered this fascinating area of immunology but also to the viruses themselves, who still have a few lessons to teach.

  4. Viral Escape Mutant Epitope Maintains TCR Affinity for Antigen yet Curtails CD8 T Cell Responses

    PubMed Central

    Shorter, Shayla K.; Schnell, Frederick J.; McMaster, Sean R.; Pinelli, David F.; Andargachew, Rakieb; Evavold, Brian D.

    2016-01-01

    T cells have the remarkable ability to recognize antigen with great specificity and in turn mount an appropriate and robust immune response. Critical to this process is the initial T cell antigen recognition and subsequent signal transduction events. This antigen recognition can be modulated at the site of TCR interaction with peptide:major histocompatibility (pMHC) or peptide interaction with the MHC molecule. Both events could have a range of effects on T cell fate. Though responses to antigens that bind sub-optimally to TCR, known as altered peptide ligands (APL), have been studied extensively, the impact of disrupting antigen binding to MHC has been highlighted to a lesser extent and is usually considered to result in complete loss of epitope recognition. Here we present a model of viral evasion from CD8 T cell immuno-surveillance by a lymphocytic choriomeningitis virus (LCMV) escape mutant with an epitope for which TCR affinity for pMHC remains high but where the antigenic peptide binds sub optimally to MHC. Despite high TCR affinity for variant epitope, levels of interferon regulatory factor-4 (IRF4) are not sustained in response to the variant indicating differences in perceived TCR signal strength. The CD8+ T cell response to the variant epitope is characterized by early proliferation and up-regulation of activation markers. Interestingly, this response is not maintained and is characterized by a lack in IL-2 and IFNγ production, increased apoptosis and an abrogated glycolytic response. We show that disrupting the stability of peptide in MHC can effectively disrupt TCR signal strength despite unchanged affinity for TCR and can significantly impact the CD8+ T cell response to a viral escape mutant. PMID:26915099

  5. RNA Viruses and RNAi: Quasispecies Implications for Viral Escape

    PubMed Central

    Presloid, John B.; Novella, Isabel S.

    2015-01-01

    Due to high mutation rates, populations of RNA viruses exist as a collection of closely related mutants known as a quasispecies. A consequence of error-prone replication is the potential for rapid adaptation of RNA viruses when a selective pressure is applied, including host immune systems and antiviral drugs. RNA interference (RNAi) acts to inhibit protein synthesis by targeting specific mRNAs for degradation and this process has been developed to target RNA viruses, exhibiting their potential as a therapeutic against infections. However, viruses containing mutations conferring resistance to RNAi were isolated in nearly all cases, underlining the problems of rapid viral evolution. Thus, while promising, the use of RNAi in treating or preventing viral diseases remains fraught with the typical complications that result from high specificity of the target, as seen in other antiviral regimens. PMID:26102581

  6. Enhancement of viral escape in HIV-1 Nef by STEP vaccination

    PubMed Central

    Park, Sung Yong; Mack, Wendy J.; Lee, Ha Y.

    2016-01-01

    Objective: Properly priming cytotoxic T-lymphocyte (CTL) responses is an important task in HIV-1 vaccination. However, the STEP trial showed no efficacy even though the vaccine elicited HIV-specific CTL responses. Our study is to investigate whether or not the STEP vaccine enhanced viral escape in infected volunteers. Methods: The signature of viral escape, the presence of multiple escape variants, could be falsely represented by the existence of multiple founder viruses. Therefore, we use a mathematical model to designate STEP study patients with infections from a single founder virus. We then conduct permutation tests on each of 9988 Gag, Pol, and Nef overlapping peptides to identify epitopes with significant differences in diversity between the vaccine and placebo groups using previously published STEP trial sequence data. Results: We identify signatures of vaccine-enhanced viral escape within HIV-1 Nef from the STEP trial. Vaccine-treated patients showed a greater level of epitope diversity in one of the immunodomiant epitopes, EVGFPVRPQVPL (Nef65–76), compared with placebo-treated patients (P = 0.0038). In the other three Nef epitopes, there is a marginally significant difference in the epitope diversity between the vaccine and placebo group (P < 0.1). This greater epitope diversity was neither due to any difference in infection duration nor overall nef gene diversity between the two groups, suggesting that the increase in viral escape was likely mediated by vaccine-induced T-cell responses. Conclusion: Viral escape in Nef is elevated preferentially in STEP vaccine-treated individuals, suggesting that vaccination primarily modulated initial CTL responses. Our observations provide important insights into improving vaccine-primed first immune control. PMID:27427874

  7. Synthesizing within-host and population-level selective pressures on viral populations: the impact of adaptive immunity on viral immune escape

    PubMed Central

    Volkov, Igor; Pepin, Kim M.; Lloyd-Smith, James O.; Banavar, Jayanth R.; Grenfell, Bryan T.

    2010-01-01

    The evolution of viruses to escape prevailing host immunity involves selection at multiple integrative scales, from within-host viral and immune kinetics to the host population level. In order to understand how viral immune escape occurs, we develop an analytical framework that links the dynamical nature of immunity and viral variation across these scales. Our epidemiological model incorporates within-host viral evolutionary dynamics for a virus that causes acute infections (e.g. influenza and norovirus) with changes in host immunity in response to genetic changes in the virus population. We use a deterministic description of the within-host replication dynamics of the virus, the pool of susceptible host cells and the host adaptive immune response. We find that viral immune escape is most effective at intermediate values of immune strength. At very low levels of immunity, selection is too weak to drive immune escape in recovered hosts, while very high levels of immunity impose such strong selection that viral subpopulations go extinct before acquiring enough genetic diversity to escape host immunity. This result echoes the predictions of simpler models, but our formulation allows us to dissect the combination of within-host and transmission-level processes that drive immune escape. PMID:20335194

  8. Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance.

    PubMed

    Groth, Ariane; Klöss, Stephan; von Strandmann, Elke Pogge; Koehl, Ulrike; Koch, Joachim

    2011-01-01

    Human natural killer (NK) cells recognize and efficiently eliminate MHC class I low or negative malignant targets and virally infected host cells, without requirement for prior sensitization. However, viruses and various tumor cells display elaborate adaptations to evade and overcome immunosurveillance. The current review focuses on escape mechanisms of viruses and malignantly transformed 'stressed' cells to evade from NK cell cytotoxicity. A general overview of recent clinical studies using allogeneic donor NK cells is given, summarizing first data about a possible benefit for patients suffering from high-risk leukemia and solid tumors. Finally, the review discusses the future perspectives and hypotheses aiming to improve therapeutic NK cell strategies against tumor immune escape mechanisms.

  9. Human Papillomavirus L2 facilitates viral escape from late endosomes via Sorting Nexin 17

    PubMed Central

    Marušič, Martina Bergant; Ozbun, Michelle A; Campos, Samuel K; Myers, Michael P; Banks, Lawrence

    2011-01-01

    The Human Papillomavirus (HPV) L2 capsid protein plays an essential role during the early stages of viral infection, but the molecular mechanisms underlying its mode of action remain obscure. Using a proteomic approach we have identified the adaptor protein, Sorting Nexin 17 (SNX17) as a strong interacting partner of HPV L2. This interaction occurs through a highly conserved SNX17 consensus binding motif, which is present in the majority of HPV L2 proteins analysed. Using mutants of L2 defective for SNX17 interaction, or siRNA ablation of SNX17 expression we demonstrate that the interaction between L2 and SNX17 is essential for viral infection. Furthermore, loss of the L2-SNX17 interaction results in enhanced turnover of the L2 protein and decreased stability of the viral capsids, and concomitantly there is a dramatic decrease in the efficiency with which viral genomes transit to the nucleus. Indeed, using a range of endosomal and lysosomal markers we show that capsids defective in their capacity to bind SNX17 transit much more rapidly to the lysosomal compartment. These results demonstrate that the L2-SNX17 interaction is essential for viral infection and facilitates the escape of the L2-DNA complex from the late endosomal/lysosomal compartments. PMID:22151726

  10. Can the Bacterial Community of a High Arctic Glacier Surface Escape Viral Control?

    PubMed Central

    Rassner, Sara M. E.; Anesio, Alexandre M.; Girdwood, Susan E.; Hell, Katherina; Gokul, Jarishma K.; Whitworth, David E.; Edwards, Arwyn

    2016-01-01

    Glacial ice surfaces represent a seasonally evolving three-dimensional photic zone which accumulates microbial biomass and potentiates positive feedbacks in ice melt. Since viruses are abundant in glacial systems and may exert controls on supraglacial bacterial production, we examined whether changes in resource availability would promote changes in the bacterial community and the dynamics between viruses and bacteria of meltwater from the photic zone of a Svalbard glacier. Our results indicated that, under ambient nutrient conditions, low estimated viral decay rates account for a strong viral control of bacterial productivity, incurring a potent viral shunt of a third of bacterial carbon in the supraglacial microbial loop. Moreover, it appears that virus particles are very stable in supraglacial meltwater, raising the prospect that viruses liberated in melt are viable downstream. However, manipulating resource availability as dissolved organic carbon, nitrogen, and phosphorous in experimental microcosms demonstrates that the photic zone bacterial communities can escape viral control. This is evidenced by a marked decline in virus-to-bacterium ratio (VBR) concomitant with increased bacterial productivity and number. Pyrosequencing shows a few bacterial taxa, principally Janthinobacterium sp., dominate both the source meltwater and microcosm communities. Combined, our results suggest that viruses maintain high VBR to promote contact with low-density hosts, by the manufacture of robust particles, but that this necessitates a trade-off which limits viral production. Consequently, dominant bacterial taxa appear to access resources to evade viral control. We propose that a delicate interplay of bacterial and viral strategies affects biogeochemical cycling upon glaciers and, ultimately, downstream ecosystems. PMID:27446002

  11. Can the Bacterial Community of a High Arctic Glacier Surface Escape Viral Control?

    PubMed

    Rassner, Sara M E; Anesio, Alexandre M; Girdwood, Susan E; Hell, Katherina; Gokul, Jarishma K; Whitworth, David E; Edwards, Arwyn

    2016-01-01

    Glacial ice surfaces represent a seasonally evolving three-dimensional photic zone which accumulates microbial biomass and potentiates positive feedbacks in ice melt. Since viruses are abundant in glacial systems and may exert controls on supraglacial bacterial production, we examined whether changes in resource availability would promote changes in the bacterial community and the dynamics between viruses and bacteria of meltwater from the photic zone of a Svalbard glacier. Our results indicated that, under ambient nutrient conditions, low estimated viral decay rates account for a strong viral control of bacterial productivity, incurring a potent viral shunt of a third of bacterial carbon in the supraglacial microbial loop. Moreover, it appears that virus particles are very stable in supraglacial meltwater, raising the prospect that viruses liberated in melt are viable downstream. However, manipulating resource availability as dissolved organic carbon, nitrogen, and phosphorous in experimental microcosms demonstrates that the photic zone bacterial communities can escape viral control. This is evidenced by a marked decline in virus-to-bacterium ratio (VBR) concomitant with increased bacterial productivity and number. Pyrosequencing shows a few bacterial taxa, principally Janthinobacterium sp., dominate both the source meltwater and microcosm communities. Combined, our results suggest that viruses maintain high VBR to promote contact with low-density hosts, by the manufacture of robust particles, but that this necessitates a trade-off which limits viral production. Consequently, dominant bacterial taxa appear to access resources to evade viral control. We propose that a delicate interplay of bacterial and viral strategies affects biogeochemical cycling upon glaciers and, ultimately, downstream ecosystems.

  12. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape.

    PubMed

    Hütter, Gero; Bodor, Josef; Ledger, Scott; Boyd, Maureen; Millington, Michelle; Tsie, Marlene; Symonds, Geoff

    2015-07-27

    Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  13. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

    PubMed Central

    Hütter, Gero; Bodor, Josef; Ledger, Scott; Boyd, Maureen; Millington, Michelle; Tsie, Marlene; Symonds, Geoff

    2015-01-01

    Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape. PMID:26225991

  14. A Bioinformatics Pipeline for the Analyses of Viral Escape Dynamics and Host Immune Responses during an Infection

    PubMed Central

    Bull, Rowena; Lloyd, Andrew; Luciani, Fabio

    2014-01-01

    Rapidly mutating viruses, such as hepatitis C virus (HCV) and HIV, have adopted evolutionary strategies that allow escape from the host immune response via genomic mutations. Recent advances in high-throughput sequencing are reshaping the field of immuno-virology of viral infections, as these allow fast and cheap generation of genomic data. However, due to the large volumes of data generated, a thorough understanding of the biological and immunological significance of such information is often difficult. This paper proposes a pipeline that allows visualization and statistical analysis of viral mutations that are associated with immune escape. Taking next generation sequencing data from longitudinal analysis of HCV viral genomes during a single HCV infection, along with antigen specific T-cell responses detected from the same subject, we demonstrate the applicability of these tools in the context of primary HCV infection. We provide a statistical and visual explanation of the relationship between cooccurring mutations on the viral genome and the parallel adaptive immune response against HCV. PMID:25013771

  15. Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness.

    PubMed

    Uebelhoer, Luke; Han, Jin-Hwan; Callendret, Benoit; Mateu, Guaniri; Shoukry, Naglaa H; Hanson, Holly L; Rice, Charles M; Walker, Christopher M; Grakoui, Arash

    2008-01-01

    Mechanisms by which hepatitis C virus (HCV) evades cellular immunity to establish persistence in chronically infected individuals are not clear. Mutations in human leukocyte antigen (HLA) class I-restricted epitopes targeted by CD8(+) T cells are associated with persistence, but the extent to which these mutations affect viral fitness is not fully understood. Previous work showed that the HCV quasispecies in a persistently infected chimpanzee accumulated multiple mutations in numerous class I epitopes over a period of 7 years. During the acute phase of infection, one representative epitope in the C-terminal region of the NS3/4A helicase, NS3(1629-1637), displayed multiple serial amino acid substitutions in major histocompatibility complex (MHC) anchor and T cell receptor (TCR) contact residues. Only one of these amino acid substitutions at position 9 (P9) of the epitope was stable in the quasispecies. We therefore assessed the effect of each mutation observed during in vivo infection on viral fitness and T cell responses using an HCV subgenomic replicon system and a recently developed in vitro infectious virus cell culture model. Mutation of a position 7 (P7) TCR-contact residue, I1635T, expectedly ablated the T cell response without affecting viral RNA replication or virion production. In contrast, two mutations at the P9 MHC-anchor residue abrogated antigen-specific T cell responses, but additionally decreased viral RNA replication and virion production. The first escape mutation, L1637P, detected in vivo only transiently at 3 mo after infection, decreased viral production, and reverted to the parental sequence in vitro. The second P9 variant, L1637S, which was stable in vivo through 7 years of follow-up, evaded the antigen-specific T cell response and did not revert in vitro despite being less optimal in virion production compared to the parental virus. These studies suggest that HCV escape mutants emerging early in infection are not necessarily stable, but are

  16. Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape.

    PubMed

    Landolfo, Santo; De Andrea, Marco; Dell'Oste, Valentina; Gugliesi, Francesca

    2016-08-12

    Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed "restriction factors" (RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus (HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell's intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16 (IFI16) (a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and hDaxx; the latter three being the keys elements of nuclear domain 10 (ND10). IFI16 inhibits the synthesis of virus DNA by down-regulating UL54 transcription - a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65 (pUL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents. PMID:27563536

  17. Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape

    PubMed Central

    Landolfo, Santo; De Andrea, Marco; Dell’Oste, Valentina; Gugliesi, Francesca

    2016-01-01

    Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed “restriction factors” (RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus (HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell’s intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16 (IFI16) (a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and hDaxx; the latter three being the keys elements of nuclear domain 10 (ND10). IFI16 inhibits the synthesis of virus DNA by down-regulating UL54 transcription - a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65 (pUL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents. PMID:27563536

  18. Viral CTL Escape Mutants Are Generated in Lymph Nodes and Subsequently Become Fixed in Plasma and Rectal Mucosa during Acute SIV Infection of Macaques

    PubMed Central

    Vanderford, Thomas H.; Bleckwehl, Chelsea; Engram, Jessica C.; Dunham, Richard M.; Klatt, Nichole R.; Feinberg, Mark B.; Garber, David A.; Betts, Michael R.; Silvestri, Guido

    2011-01-01

    SIVmac239 infection of rhesus macaques (RMs) results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL) response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitudinally assessed the presence of CTL escape variants in two MamuA*01-restricted immunodominant epitopes (Tat-SL8 and Gag-CM9) in the plasma, PBMCs, lymph nodes (LN), and rectal biopsies (RB) of fifteen SIVmac239-infected RMs. As expected, Gag-CM9 did not exhibit signs of escape before day 84 post infection. In contrast, Tat-SL8 escape mutants were apparent in all tissues by day 14 post infection. Interestingly LNs and plasma exhibited the highest level of escape at day 14 and day 28 post infection, respectively, with the rate of escape in the RB remaining lower throughout the acute infection. The possibility that CTL escape occurs in LNs before RBs is confirmed by the observation that the specific mutants found at high frequency in LNs at day 14 post infection became dominant at day 28 post infection in plasma, PBMC, and RB. Finally, the frequency of escape mutants in plasma at day 28 post infection correlated strongly with the level Tat-SL8-specific CD8 T cells in the LN and PBMC at day 14 post infection. These results indicate that LNs represent the primary source of CTL escape mutants during the acute phase of SIVmac239 infection, suggesting that LNs are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants. PMID:21625590

  19. The great escape: An intra-Messinian gas system in the eastern Mediterranean

    NASA Astrophysics Data System (ADS)

    Lazar, Michael; Schattner, Uri; Reshef, Moshe

    2012-10-01

    This study explores, for the first time, the response of the Mediterranean seafloor to desiccation and its affect on climate during the Messinian lowstand. New high-resolution 3-D pre-stack depth migrated seismic reflection data show evidence for gas outflow stemming from pre-Messinian sources. Our results indicate that giant pockmarks formed during this lowstand. Emission continued throughout the Messinian and persisted after it ended as evident by pockmark arrays on the then-seafloor. High reflectivity between the top-Messinian and overlying Pliocene sediments indicates significant gas accumulation immediately below the latter. Attribute analysis show minor chaotic paths through the Plio-Pleistocene, which do not reach the present-day seafloor. Our data indicate that as long as sea level was low there was massive gas escape to the shallow sea and atmosphere. We suggest that this probably resulted in the mid-Messinian climatic shift. Major emissions identified here indicate an indirect cause to negative climatic feedback during this period.

  20. Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals.

    PubMed

    Rast, Luke I; Rouzine, Igor M; Rozhnova, Ganna; Bishop, Lisa; Weinberger, Ariel D; Weinberger, Leor S

    2016-05-01

    The rapid evolution of RNA-encoded viruses such as HIV presents a major barrier to infectious disease control using conventional pharmaceuticals and vaccines. Previously, it was proposed that defective interfering particles could be developed to indefinitely control the HIV/AIDS pandemic; in individual patients, these engineered molecular parasites were further predicted to be refractory to HIV's mutational escape (i.e., be 'resistance-proof'). However, an outstanding question has been whether these engineered interfering particles-termed Therapeutic Interfering Particles (TIPs)-would remain resistance-proof at the population-scale, where TIP-resistant HIV mutants may transmit more efficiently by reaching higher viral loads in the TIP-treated subpopulation. Here, we develop a multi-scale model to test whether TIPs will maintain indefinite control of HIV at the population-scale, as HIV ('unilaterally') evolves toward TIP resistance by limiting the production of viral proteins available for TIPs to parasitize. Model results capture the existence of two intrinsic evolutionary tradeoffs that collectively prevent the spread of TIP-resistant HIV mutants in a population. First, despite their increased transmission rates in TIP-treated sub-populations, unilateral TIP-resistant mutants are shown to have reduced transmission rates in TIP-untreated sub-populations. Second, these TIP-resistant mutants are shown to have reduced growth rates (i.e., replicative fitness) in both TIP-treated and TIP-untreated individuals. As a result of these tradeoffs, the model finds that TIP-susceptible HIV strains continually outcompete TIP-resistant HIV mutants at both patient and population scales when TIPs are engineered to express >3-fold more genomic RNA than HIV expresses. Thus, the results provide design constraints for engineering population-scale therapies that may be refractory to the acquisition of antiviral resistance. PMID:27152856

  1. Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals

    PubMed Central

    Rast, Luke I.; Rouzine, Igor M.; Rozhnova, Ganna; Bishop, Lisa; Weinberger, Ariel D.; Weinberger, Leor S.

    2016-01-01

    The rapid evolution of RNA-encoded viruses such as HIV presents a major barrier to infectious disease control using conventional pharmaceuticals and vaccines. Previously, it was proposed that defective interfering particles could be developed to indefinitely control the HIV/AIDS pandemic; in individual patients, these engineered molecular parasites were further predicted to be refractory to HIV’s mutational escape (i.e., be ‘resistance-proof’). However, an outstanding question has been whether these engineered interfering particles—termed Therapeutic Interfering Particles (TIPs)—would remain resistance-proof at the population-scale, where TIP-resistant HIV mutants may transmit more efficiently by reaching higher viral loads in the TIP-treated subpopulation. Here, we develop a multi-scale model to test whether TIPs will maintain indefinite control of HIV at the population-scale, as HIV (‘unilaterally’) evolves toward TIP resistance by limiting the production of viral proteins available for TIPs to parasitize. Model results capture the existence of two intrinsic evolutionary tradeoffs that collectively prevent the spread of TIP-resistant HIV mutants in a population. First, despite their increased transmission rates in TIP-treated sub-populations, unilateral TIP-resistant mutants are shown to have reduced transmission rates in TIP-untreated sub-populations. Second, these TIP-resistant mutants are shown to have reduced growth rates (i.e., replicative fitness) in both TIP-treated and TIP-untreated individuals. As a result of these tradeoffs, the model finds that TIP-susceptible HIV strains continually outcompete TIP-resistant HIV mutants at both patient and population scales when TIPs are engineered to express >3-fold more genomic RNA than HIV expresses. Thus, the results provide design constraints for engineering population-scale therapies that may be refractory to the acquisition of antiviral resistance. PMID:27152856

  2. Emergence of viral hemorrhagic septicemia virus in the North American Great Lakes region is associated with low viral genetic diversity

    USGS Publications Warehouse

    Thompson, T.M.; Batts, W.N.; Faisal, M.; Bowser, P.; Casey, J.W.; Phillips, K.; Garver, K.A.; Winton, J.; Kurath, G.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a fish rhabdovirus that causes disease in a broad range of marine and freshwater hosts. The known geographic range includes the Northern Atlantic and Pacific Oceans, and recently it has invaded the Great Lakes region of North Ame­rica. The goal of this work was to characterize genetic diversity of Great Lakes VHSV isolates at the early stage of this viral emergence by comparing a partial glycoprotein (G) gene sequence (669 nt) of 108 isolates collected from 2003 to 2009 from 31 species and at 37 sites. Phylogenetic analysis showed that all isolates fell into sub-lineage IVb within the major VHSV genetic group IV. Among these 108 isolates, genetic diversity was low, with a maximum of 1.05% within the 669 nt region. There were 11 unique sequences, designated vcG001 to vcG011. Two dominant sequence types, vcG001 and vcG002, accounted for 90% (97 of 108) of the isolates. The vcG001 isolates were most widespread. We saw no apparent association of sequence type with host or year of isolation, but we did note a spatial pattern, in which vcG002 isolates were more prevalent in the easternmost sub-regions, including inland New York state and the St. Lawrence Seaway. Different sequence types were found among isolates from single disease outbreaks, and mixtures of types were evident within 2 isolates from ­individual fish. Overall, the genetic diversity of VHSV in the Great Lakes region was found to be extremely low, consistent with an introduction of a new virus into a geographic region with ­previously naïve host populations.

  3. The “Cheshire Cat” escape strategy of the coccolithophore Emiliania huxleyi in response to viral infection

    PubMed Central

    Frada, Miguel; Probert, Ian; Allen, Michael J.; Wilson, William H.; de Vargas, Colomban

    2008-01-01

    The coccolithophore Emiliania huxleyi is one of the most successful eukaryotes in modern oceans. The two phases in its haplodiploid life cycle exhibit radically different phenotypes. The diploid calcified phase forms extensive blooms, which profoundly impact global biogeochemical equilibria. By contrast, the ecological role of the noncalcified haploid phase has been completely overlooked. Giant phycodnaviruses (Emiliania huxleyi viruses, EhVs) have been shown to infect and lyse diploid-phase cells and to be heavily implicated in the regulation of populations and the termination of blooms. Here, we demonstrate that the haploid phase of E. huxleyi is unrecognizable and therefore resistant to EhVs that kill the diploid phase. We further show that exposure of diploid E. huxleyi to EhVs induces transition to the haploid phase. Thus we have clearly demonstrated a drastic difference in viral susceptibility between life cycle stages with different ploidy levels in a unicellular eukaryote. Resistance of the haploid phase of E. huxleyi provides an escape mechanism that involves separation of meiosis from sexual fusion in time, thus ensuring that genes of dominant diploid clones are passed on to the next generation in a virus-free environment. These “Cheshire Cat” ecological dynamics release host evolution from pathogen pressure and thus can be seen as an opposite force to a classic “Red Queen” coevolutionary arms race. In E. huxleyi, this phenomenon can account for the fact that the selective balance is tilted toward the boom-and-bust scenario of optimization of both growth rates of calcifying E. huxleyi cells and infectivity of EhVs. PMID:18824682

  4. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells.

    PubMed

    Weiler, Andrea M; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L; Scheef, Elizabeth A; Reed, Jason S; Panganiban, Antonito T; Sacha, Jonah B; Rakasz, Eva G; Friedrich, Thomas C; Maness, Nicholas J

    2016-02-01

    Nef-specific CD8(+) T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165-173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication. PMID:26637459

  5. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells.

    PubMed

    Weiler, Andrea M; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L; Scheef, Elizabeth A; Reed, Jason S; Panganiban, Antonito T; Sacha, Jonah B; Rakasz, Eva G; Friedrich, Thomas C; Maness, Nicholas J

    2015-12-04

    Nef-specific CD8(+) T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165-173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication.

  6. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells

    PubMed Central

    Weiler, Andrea M.; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L.; Scheef, Elizabeth A.; Reed, Jason S.; Panganiban, Antonito T.; Sacha, Jonah B.; Rakasz, Eva G.; Friedrich, Thomas C.

    2015-01-01

    Nef-specific CD8+ T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165–173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication. PMID:26637459

  7. Protruding Features of Viral Capsids Are Clustered on Icosahedral Great Circles.

    PubMed

    Wilson, David P

    2016-01-01

    Spherical viruses are remarkably well characterized by the Triangulation (T) number developed by Casper and Klug. The T-number specifies how many viral capsid proteins are required to cover the virus, as well as how they are further subdivided into pentamer and hexamer subunits. The T-number however does not constrain the orientations of these proteins within the subunits or dictate where the proteins should place their protruding features. These protrusions often take the form of loops, spires and helices, and are significant because they aid in stability of the capsid as well as recognition by the host organism. Until now there has be no overall understanding of the placement of protrusions for spherical viruses, other than they have icosahedral symmetry. We constructed a set of gauge points based upon the work affine extensions of Keef and Twarock, which have fixed relative angular locations with which to measure the locations of these features. This work adds a new element to our understanding of the geometric arrangement of spherical viral capsid proteins; chiefly that the locations of protruding features are not found stochastically distributed in an icosahedral manner across the viral surface, but instead these features are found only in specific locations along the 15 icosahedral great circles. We have found that this result holds true as the T number and viral capsids size increases, suggesting an underlying geometric constraint on their locations. This is in spite of the fact that the constraints on the pentamers and hexamer orientations change as a function of T-number, as you need to accommodate more hexamers in the same solid angle between pentamers. The existence of this angular constraint of viral capsids suggests that there is a fitness or energetic benefit to the virus placing its protrusions in this manner. This discovery may have profound impacts on identifying and eliminating viral pathogens, understanding evolutionary constraints as well as

  8. Protruding Features of Viral Capsids Are Clustered on Icosahedral Great Circles

    PubMed Central

    Wilson, David P.

    2016-01-01

    Spherical viruses are remarkably well characterized by the Triangulation (T) number developed by Casper and Klug. The T-number specifies how many viral capsid proteins are required to cover the virus, as well as how they are further subdivided into pentamer and hexamer subunits. The T-number however does not constrain the orientations of these proteins within the subunits or dictate where the proteins should place their protruding features. These protrusions often take the form of loops, spires and helices, and are significant because they aid in stability of the capsid as well as recognition by the host organism. Until now there has be no overall understanding of the placement of protrusions for spherical viruses, other than they have icosahedral symmetry. We constructed a set of gauge points based upon the work affine extensions of Keef and Twarock, which have fixed relative angular locations with which to measure the locations of these features. This work adds a new element to our understanding of the geometric arrangement of spherical viral capsid proteins; chiefly that the locations of protruding features are not found stochastically distributed in an icosahedral manner across the viral surface, but instead these features are found only in specific locations along the 15 icosahedral great circles. We have found that this result holds true as the T number and viral capsids size increases, suggesting an underlying geometric constraint on their locations. This is in spite of the fact that the constraints on the pentamers and hexamer orientations change as a function of T-number, as you need to accommodate more hexamers in the same solid angle between pentamers. The existence of this angular constraint of viral capsids suggests that there is a fitness or energetic benefit to the virus placing its protrusions in this manner. This discovery may have profound impacts on identifying and eliminating viral pathogens, understanding evolutionary constraints as well as

  9. Molecular characterization of the Great Lakes viral hemorrhagic septicemia virus (VHSV) isolate from USA

    PubMed Central

    Ammayappan, Arun; Vakharia, Vikram N

    2009-01-01

    Background Viral hemorrhagic septicemia virus (VHSV) is a highly contagious viral disease of fresh and saltwater fish worldwide. VHSV caused several large scale fish kills in the Great Lakes area and has been found in 28 different host species. The emergence of VHS in the Great Lakes began with the isolation of VHSV from a diseased muskellunge (Esox masquinongy) caught from Lake St. Clair in 2003. VHSV is a member of the genus Novirhabdovirus, within the family Rhabdoviridae. It has a linear single-stranded, negative-sense RNA genome of approximately 11 kbp, with six genes. VHSV replicates in the cytoplasm and produces six monocistronic mRNAs. The gene order of VHSV is 3'-N-P-M-G-NV-L-5'. This study describes molecular characterization of the Great Lakes VHSV strain (MI03GL), and its phylogenetic relationships with selected European and North American isolates. Results The complete genomic sequences of VHSV-MI03GL strain was determined from cloned cDNA of six overlapping fragments, obtained by RT-PCR amplification of genomic RNA. The complete genome sequence of MI03GL comprises 11,184 nucleotides (GenBank GQ385941) with the gene order of 3'-N-P-M-G-NV-L-5'. These genes are separated by conserved gene junctions, with di-nucleotide gene spacers. The first 4 nucleotides at the termini of the VHSV genome are complementary and identical to other novirhadoviruses genomic termini. Sequence homology and phylogenetic analysis show that the Great Lakes virus is closely related to the Japanese strains JF00Ehi1 (96%) and KRRV9822 (95%). Among other novirhabdoviruses, VHSV shares highest sequence homology (62%) with snakehead rhabdovirus. Conclusion Phylogenetic tree obtained by comparing 48 glycoprotein gene sequences of different VHSV strains demonstrate that the Great Lakes VHSV is closely related to the North American and Japanese genotype IVa, but forms a distinct genotype IVb, which is clearly different from the three European genotypes. Molecular characterization of the

  10. Viral Escape from Neutralizing Antibodies in Early Subtype A HIV-1 Infection Drives an Increase in Autologous Neutralization Breadth

    PubMed Central

    Murphy, Megan K.; Yue, Ling; Pan, Ruimin; Boliar, Saikat; Sethi, Anurag; Tian, Jianhui; Pfafferot, Katja; Karita, Etienne; Allen, Susan A.; Cormier, Emmanuel; Goepfert, Paul A.; Borrow, Persephone; Robinson, James E.; Gnanakaran, S.; Hunter, Eric; Kong, Xiang-Peng; Derdeyn, Cynthia A.

    2013-01-01

    Antibodies that neutralize (nAbs) genetically diverse HIV-1 strains have been recovered from a subset of HIV-1 infected subjects during chronic infection. Exact mechanisms that expand the otherwise narrow neutralization capacity observed during early infection are, however, currently undefined. Here we characterized the earliest nAb responses in a subtype A HIV-1 infected Rwandan seroconverter who later developed moderate cross-clade nAb breadth, using (i) envelope (Env) glycoproteins from the transmitted/founder virus and twenty longitudinal nAb escape variants, (ii) longitudinal autologous plasma, and (iii) autologous monoclonal antibodies (mAbs). Initially, nAbs targeted a single region of gp120, which flanked the V3 domain and involved the alpha2 helix. A single amino acid change at one of three positions in this region conferred early escape. One immunoglobulin heavy chain and two light chains recovered from autologous B cells comprised two mAbs, 19.3H-L1 and 19.3H-L3, which neutralized the founder Env along with one or three of the early escape variants carrying these mutations, respectively. Neither mAb neutralized later nAb escape or heterologous Envs. Crystal structures of the antigen-binding fragments (Fabs) revealed flat epitope contact surfaces, where minimal light chain mutation in 19.3H-L3 allowed for additional antigenic interactions. Resistance to mAb neutralization arose in later Envs through alteration of two glycans spatially adjacent to the initial escape signatures. The cross-neutralizing nAbs that ultimately developed failed to target any of the defined V3-proximal changes generated during the first year of infection in this subject. Our data demonstrate that this subject's first recognized nAb epitope elicited strain-specific mAbs, which incrementally acquired autologous breadth, and directed later B cell responses to target distinct portions of Env. This immune re-focusing could have triggered the evolution of cross-clade antibodies and

  11. Molecular epidemiology of viral hemorrhagic septicemia virus in the Great Lakes region

    USGS Publications Warehouse

    Winton, James; Kurath, Gael; Batts, William

    2008-01-01

    Viral hemorrhagic septicemia virus (VHSV) is considered by many nations and international organizations to be one of the most important viral pathogens of finfish (Office International des Epizooties 2007). For several decades following its initial characterization in the 1950s, VHSV was thought to be limited to Europe where it was regarded as an endemic pathogen of freshwater fish that was especially problematic for farmed rainbow trout, an introduced species (Wolf 1988; Smail 1999). Subsequently, it was shown that VHSV was present among many species of marine and anadromous fishes in both the Pacific and Atlantic Oceans where it has been associated with substantial mortality among both wild and cultured fish (Meyers and Winton 1995; Skall et al. 2005).

  12. Distribution of an invasive aquatic pathogen (viral hemorrhagic septicemia virus) in the Great Lakes and its relationship to shipping

    USGS Publications Warehouse

    Bain, Mark B.; Cornwell, Emily R.; Hope, Kristine M.; Eckerlin, Geofrey E.; Casey, Rufina N.; Groocock, Geoffrey H.; Getchell, Rodman G.; Bowser, Paul R.; Winton, James R.; Batts, William N.; Cangelosi, Allegra; Casey, James W.

    2010-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus found in fish from oceans of the northern hemisphere and freshwaters of Europe. It has caused extensive losses of cultured and wild fish and has become established in the North American Great Lakes. Large die-offs of wild fish in the Great Lakes due to VHSV have alarmed the public and provoked government attention on the introduction and spread of aquatic animal pathogens in freshwaters. We investigated the relations between VHSV dispersion and shipping and boating activity in the Great Lakes by sampling fish and water at sites that were commercial shipping harbors, recreational boating centers, and open shorelines. Fish and water samples were individually analyzed for VHSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell culture assays. Of 1,221 fish of 17 species, 55 were VHSV positive with highly varied qRT-PCR titers (1 to 5,950,000 N gene copies). The detections of VHSV in fish and water samples were closely associated and the virus was detected in 21 of 30 sites sampled. The occurrence of VHSV was not related to type of site or shipping related invasion hotspots. Our results indicate that VHSV is widely dispersed in the Great Lakes and is both an enzootic and epizootic pathogen. We demonstrate that pathogen distribution information could be developed quickly and is clearly needed for aquatic ecosystem conservation, management of affected populations, and informed regulation of the worldwide trade of aquatic organisms.

  13. Distribution of an Invasive Aquatic Pathogen (Viral Hemorrhagic Septicemia Virus) in the Great Lakes and Its Relationship to Shipping

    PubMed Central

    Bain, Mark B.; Cornwell, Emily R.; Hope, Kristine M.; Eckerlin, Geofrey E.; Casey, Rufina N.; Groocock, Geoffrey H.; Getchell, Rodman G.; Bowser, Paul R.; Winton, James R.; Batts, William N.; Cangelosi, Allegra; Casey, James W.

    2010-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus found in fish from oceans of the northern hemisphere and freshwaters of Europe. It has caused extensive losses of cultured and wild fish and has become established in the North American Great Lakes. Large die-offs of wild fish in the Great Lakes due to VHSV have alarmed the public and provoked government attention on the introduction and spread of aquatic animal pathogens in freshwaters. We investigated the relations between VHSV dispersion and shipping and boating activity in the Great Lakes by sampling fish and water at sites that were commercial shipping harbors, recreational boating centers, and open shorelines. Fish and water samples were individually analyzed for VHSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell culture assays. Of 1,221 fish of 17 species, 55 were VHSV positive with highly varied qRT-PCR titers (1 to 5,950,000 N gene copies). The detections of VHSV in fish and water samples were closely associated and the virus was detected in 21 of 30 sites sampled. The occurrence of VHSV was not related to type of site or shipping related invasion hotspots. Our results indicate that VHSV is widely dispersed in the Great Lakes and is both an enzootic and epizootic pathogen. We demonstrate that pathogen distribution information could be developed quickly and is clearly needed for aquatic ecosystem conservation, management of affected populations, and informed regulation of the worldwide trade of aquatic organisms. PMID:20405014

  14. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

    USGS Publications Warehouse

    Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-ΔNV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-ΔNV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-ΔNV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

  15. Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa

    PubMed Central

    Jimenez Cruz, Camilo A.; Garcia-Beltran, Wilfredo F.; Carlson, Jonathan M.; van Teijlingen, Nienke H.; Mann, Jaclyn K.; Jaggernath, Manjeetha; Kang, Seung-gu; Körner, Christian; Chung, Amy W.; Schafer, Jamie L.; Evans, David T.; Alter, Galit; Walker, Bruce D.; Goulder, Philip J.; Carrington, Mary; Hartmann, Pia; Pertel, Thomas; Zhou, Ruhong; Ndung’u, Thumbi; Altfeld, Marcus

    2015-01-01

    Background Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure. Methods and Findings Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I—presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control. Conclusions These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades

  16. Escape of Sierra Nevada-Great Valley Block Motion Contributes to Upper-Plate Contraction Within the Southern Cascadia Margin Near Humboldt Bay, CA.

    NASA Astrophysics Data System (ADS)

    Williams, T. B.; Kelsey, H. M.; Freymueller, J. T.

    2002-12-01

    Recent GPS-derived site velocities (1993-2002) in northwestern California reveal that an additional mechanism other than subduction is in part accountable for observed upper plate contraction north of the migrating Mendocino triple junction. Sites at and near Cape Mendocino are moving approximately 30 mm/yr and are consistently oriented approximately N 10° W, sub-parallel to the southern Cascadia trench. Sites just north of latitude 40.4° N begin to be oriented east of north, sub-parallel to the Gorda-North America plate convergence direction. The transition from west-of-north to east-of-north site azimuths occurs 20 km north of the Mendocino Fault. The change in site azimuths is abrupt, with an eastward swing of 25°-30° occurring over a distance of approximately 8 km across the Eel River valley. North and east of Cape Mendocino, sites 50-300 km inland have velocities oriented west of north, consistent with the direction of northern Sierra Nevada-Great Valley (SNGV) block and Pacific-North America (P-NA) relative motion. Northern SNGV block motion is 11 mm/yr directed to the northwest. This velocity persists northwestward to within 50 km of the coast at the latitude of Humboldt Bay. Approximately 20 mm/yr of distributed P-NA motion occurs inland of Cape Mendocino across the northern projections of the Ma'acama and Bartlett Springs fault zones, and continues northward into the Humboldt Bay region. The direction of observed SNGV motion is obliquely convergent to the P-NA relative motion direction. The observed convergence between SNGV and the Coast Ranges begins approximately 130 km inland of the coast near Weaverville, CA. We observe 3-6 mm/yr of roughly east-west contraction in that area, which is near the location of the highest topography in the northern Coast Ranges. Near Humboldt Bay, NE-SW convergence of 16+/-2 mm/yr occurs from the coast to approximately 50 km inland. After removing an estimate of the interseismic subduction zone signal from the

  17. Conservation of Total Escape from Hydrodynamic Planetary Atmospheres

    NASA Astrophysics Data System (ADS)

    Tian, F.

    2013-12-01

    Atmosphere escape is one key process controlling the evolution of planets. However, estimating the escape rate in any detail is difficult because there are many physical processes contributing to the total escape rate. Here we show that as a result of energy conservation the total escape rate from hydrodynamic planetary atmospheres where the outflow remains subsonic is nearly constant under the same stellar XUV photon flux when increasing the escape efficiency from the exobase level, consistent with the energy limited escape approximation. Thus the estimate of atmospheric escape in a planet's evolution history can be greatly simplified.

  18. Gene Diversification of an Emerging Pathogen: A Decade of Mutation in a Novel Fish Viral Hemorrhagic Septicemia (VHS) Substrain since Its First Appearance in the Laurentian Great Lakes

    PubMed Central

    Leaman, Douglas W.; Niner, Megan D.; Shepherd, Brian S.

    2015-01-01

    Viral Hemorrhagic Septicemia virus (VHSv) is an RNA rhabdovirus, which causes one of the world's most serious fish diseases, infecting >80 freshwater and marine species across the Northern Hemisphere. A new, novel, and especially virulent substrain—VHSv-IVb—first appeared in the Laurentian Great Lakes about a decade ago, resulting in massive fish kills. It rapidly spread and has genetically diversified. This study analyzes temporal and spatial mutational patterns of VHSv-IVb across the Great Lakes for the novel non-virion (Nv) gene that is unique to this group of novirhabdoviruses, in relation to its glycoprotein (G), phosphoprotein (P), and matrix (M) genes. Results show that the Nv-gene has been evolving the fastest (k = 2.0x10-3 substitutions/site/year), with the G-gene at ~1/7 that rate (k = 2.8x10-4). Most (all but one) of the 12 unique Nv- haplotypes identified encode different amino acids, totaling 26 changes. Among the 12 corresponding G-gene haplotypes, seven vary in amino acids with eight total changes. The P- and M- genes are more evolutionarily conserved, evolving at just ~1/15 (k = 1.2x10-4) of the Nv-gene’s rate. The 12 isolates contained four P-gene haplotypes with two amino acid changes, and six M-gene haplotypes with three amino acid differences. Patterns of evolutionary changes coincided among the genes for some of the isolates, but appeared independent in others. New viral variants were discovered following the large 2006 outbreak; such differentiation may have been in response to fish populations developing resistance, meriting further investigation. Two 2012 variants were isolated by us from central Lake Erie fish that lacked classic VHSv symptoms, having genetically distinctive Nv-, G-, and M-gene sequences (with one of them also differing in its P-gene); they differ from each other by a G-gene amino acid change and also differ from all other isolates by a shared Nv-gene amino acid change. Such rapid evolutionary differentiation may

  19. Gene Diversification of an Emerging Pathogen: A Decade of Mutation in a Novel Fish Viral Hemorrhagic Septicemia (VHS) Substrain since Its First Appearance in the Laurentian Great Lakes.

    PubMed

    Stepien, Carol A; Pierce, Lindsey R; Leaman, Douglas W; Niner, Megan D; Shepherd, Brian S

    2015-01-01

    Viral Hemorrhagic Septicemia virus (VHSv) is an RNA rhabdovirus, which causes one of the world's most serious fish diseases, infecting >80 freshwater and marine species across the Northern Hemisphere. A new, novel, and especially virulent substrain-VHSv-IVb-first appeared in the Laurentian Great Lakes about a decade ago, resulting in massive fish kills. It rapidly spread and has genetically diversified. This study analyzes temporal and spatial mutational patterns of VHSv-IVb across the Great Lakes for the novel non-virion (Nv) gene that is unique to this group of novirhabdoviruses, in relation to its glycoprotein (G), phosphoprotein (P), and matrix (M) genes. Results show that the Nv-gene has been evolving the fastest (k = 2.0 x 10-3 substitutions/site/year), with the G-gene at ~1/7 that rate (k = 2.8 x 10-4). Most (all but one) of the 12 unique Nv- haplotypes identified encode different amino acids, totaling 26 changes. Among the 12 corresponding G-gene haplotypes, seven vary in amino acids with eight total changes. The P- and M- genes are more evolutionarily conserved, evolving at just ~1/15 (k = 1.2 x 10-4) of the Nv-gene's rate. The 12 isolates contained four P-gene haplotypes with two amino acid changes, and six M-gene haplotypes with three amino acid differences. Patterns of evolutionary changes coincided among the genes for some of the isolates, but appeared independent in others. New viral variants were discovered following the large 2006 outbreak; such differentiation may have been in response to fish populations developing resistance, meriting further investigation. Two 2012 variants were isolated by us from central Lake Erie fish that lacked classic VHSv symptoms, having genetically distinctive Nv-, G-, and M-gene sequences (with one of them also differing in its P-gene); they differ from each other by a G-gene amino acid change and also differ from all other isolates by a shared Nv-gene amino acid change. Such rapid evolutionary differentiation may

  20. Complications and Great Escapes: Equipment and Techniques

    PubMed Central

    McPherson, Rory; Buckenham, Timothy

    2014-01-01

    All endovascular procedures have the potential for complications. The primary aims should always be avoidance of preventable complications and to minimize the impact of any complication. The core principles of an effective preventive strategy are: involving the interventional and clinical teams in a clear outline of the procedure and its potential adverse outcomes; ensuring an adequate inventory of required and backup equipment; the use of “time-out” to minimize wrong patient/wrong side adverse events; and an active audit program to identify areas of improvement. In the event of an adverse outcome there are many strategies that can be employed to rectify the situation or minimize the iatrogenic injury. This article provides a case-based discussion highlighting some of these techniques and how they can be used in a clinical setting. PMID:25435662

  1. Comparative susceptibility among three stocks of yellow perch, Perca flavescens (Mitchill), to viral haemorrhagic septicaemia virus strain IVb from the Great Lakes.

    PubMed

    Olson, W; Emmenegger, E; Glenn, J; Winton, J; Goetz, F

    2013-08-01

    The Great Lakes strain of viral haemorrhagic septicaemia virus IVb (VHSV-IVb) is capable of infecting a wide number of naive species and has been associated with large fish kills in the Midwestern United States since its discovery in 2005. The yellow perch, Perca flavescens (Mitchill), a freshwater species commonly found throughout inland waters of the United States and prized for its high value in sport and commercial fisheries, is a species documented in several fish kills affiliated with VHS. In the present study, differences in survival after infection with VHSV IVb were observed among juvenile fish from three yellow perch broodstocks that were originally derived from distinct wild populations, suggesting innate differences in susceptibility due to genetic variance. While all three stocks were susceptible upon waterborne exposure to VHS virus infection, fish derived from the Midwest (Lake Winnebago, WI) showed significantly lower cumulative % survival compared with two perch stocks derived from the East Coast (Perquimans River, NC and Choptank River, MD) of the United States. However, despite differences in apparent susceptibility, clinical signs did not vary between stocks and included moderate-to-severe haemorrhages at the pelvic and pectoral fin bases and exophthalmia. After the 28-day challenge was complete, VHS virus was analysed in subsets of whole fish that had either survived or succumbed to the infection using both plaque assay and quantitative PCR methodologies. A direct correlation was identified between the two methods, suggesting the potential for both methods to be used to detect virus in a research setting. PMID:23305522

  2. Comparative susceptibility among three stocks of yellow perch, Perca flavescens (Mitchill), to viral haemorrhagic septicaemia virus strain IVb from the Great Lakes

    USGS Publications Warehouse

    Olson, W.; Emmenegger, E.; Glenn, J.; Winton, J.; Goetz, F.

    2013-01-01

    The Great Lakes strain of viral haemorrhagic septicaemia virus IVb (VHSV-IVb) is capable of infecting a wide number of naive species and has been associated with large fish kills in the Midwestern United States since its discovery in 2005. The yellow perch, Perca flavescens (Mitchill), a freshwater species commonly found throughout inland waters of the United States and prized for its high value in sport and commercial fisheries, is a species documented in several fish kills affiliated with VHS. In the present study, differences in survival after infection with VHSV IVb were observed among juvenile fish from three yellow perch broodstocks that were originally derived from distinct wild populations, suggesting innate differences in susceptibility due to genetic variance. While all three stocks were susceptible upon waterborne exposure to VHS virus infection, fish derived from the Midwest (Lake Winnebago, WI) showed significantly lower cumulative % survival compared with two perch stocks derived from the East Coast (Perquimans River, NC and Choptank River, MD) of the United States. However, despite differences in apparent susceptibility, clinical signs did not vary between stocks and included moderate-to-severe haemorrhages at the pelvic and pectoral fin bases and exophthalmia. After the 28-day challenge was complete, VHS virus was analysed in subsets of whole fish that had either survived or succumbed to the infection using both plaque assay and quantitative PCR methodologies. A direct correlation was identified between the two methods, suggesting the potential for both methods to be used to detect virus in a research setting.

  3. Characteristics of Foot-and-Mouth Disease Viral Strains Circulating at the Wildlife/livestock Interface of the Great Limpopo Transfrontier Conservation Area.

    PubMed

    Jori, F; Caron, A; Thompson, P N; Dwarka, R; Foggin, C; de Garine-Wichatitsky, M; Hofmeyr, M; Van Heerden, J; Heath, L

    2016-02-01

    Foot-and-mouth disease (FMD) inflicts severe economic losses within infected countries and is arguably the most important trade-restricting livestock disease in the world. In southern Africa, infected African buffaloes (Syncerus caffer) are the major reservoir of the South African Territories (SAT) types of the virus. With the progressive expansion of transfrontier conservation areas (TFCAs), the risk of FMD outbreaks is expected to increase due to a higher probability of buffalo/livestock contacts. To investigate the dynamics of FMD within and around the Great Limpopo TFCA (GLTFCA), 5 herds of buffaloes were sampled in June 2010 to characterize circulating viruses in South Africa and Zimbabwe. Three SAT-2 and three SAT-3 viral strains were isolated in both countries, including one that was genetically linked with a recent SAT-2 outbreak in Mozambique in 2011. In addition, two groups of unvaccinated cattle (n = 192) were serologically monitored for 1 year at the wildlife/livestock interface of Gonarezhou National Park (GNP) in Zimbabwe between April 2009 and January 2010, using the liquid-phase blocking ELISA (LPBE) and a test for antibodies directed against non-structural proteins (NSP). Neither clinical signs nor vaccination of cattle were reported during the study, yet a high proportion of the monitored cattle showed antibody responses against SAT-3 and SAT-1. Antibodies against NSP were also detected in 10% of the monitored cattle. The results of this study suggest that cattle grazing in areas adjacent to the GLTFCA can be infected by buffalo or other infected livestock and that cattle trade movements can act as efficient disseminators of FMD viruses to areas several hundred kilometres from the virus source. Current methods of surveillance of FMD at the GLTFCA interface seem insufficient to control for FMD emergence and dissemination and require urgent reassessment and regional coordination.

  4. Structured Observations Reveal Slow HIV-1 CTL Escape

    PubMed Central

    Roberts, Hannah E.; Hurst, Jacob; Robinson, Nicola; Brown, Helen; Flanagan, Peter; Vass, Laura; Fidler, Sarah; Weber, Jonathan; Babiker, Abdel; Phillips, Rodney E.; McLean, Angela R.; Frater, John

    2015-01-01

    The existence of viral variants that escape from the selection pressures imposed by cytotoxic T-lymphocytes (CTLs) in HIV-1 infection is well documented, but it is unclear when they arise, with reported measures of the time to escape in individuals ranging from days to years. A study of participants enrolled in the SPARTAC (Short Pulse Anti-Retroviral Therapy at HIV Seroconversion) clinical trial allowed direct observation of the evolution of CTL escape variants in 125 adults with primary HIV-1 infection observed for up to three years. Patient HLA-type, longitudinal CD8+ T-cell responses measured by IFN-γ ELISpot and longitudinal HIV-1 gag, pol, and nef sequence data were used to study the timing and prevalence of CTL escape in the participants whilst untreated. Results showed that sequence variation within CTL epitopes at the first time point (within six months of the estimated date of seroconversion) was consistent with most mutations being transmitted in the infecting viral strain rather than with escape arising within the first few weeks of infection. Escape arose throughout the first three years of infection, but slowly and steadily. Approximately one third of patients did not drive any new escape in an HLA-restricted epitope in just under two years. Patients driving several escape mutations during these two years were rare and the median and modal numbers of new escape events in each patient were one and zero respectively. Survival analysis of time to escape found that possession of a protective HLA type significantly reduced time to first escape in a patient (p = 0.01), and epitopes escaped faster in the face of a measurable CD8+ ELISpot response (p = 0.001). However, even in an HLA matched host who mounted a measurable, specific, CD8+ response the average time before the targeted epitope evolved an escape mutation was longer than two years. PMID:25642847

  5. Structured observations reveal slow HIV-1 CTL escape.

    PubMed

    Roberts, Hannah E; Hurst, Jacob; Robinson, Nicola; Brown, Helen; Flanagan, Peter; Vass, Laura; Fidler, Sarah; Weber, Jonathan; Babiker, Abdel; Phillips, Rodney E; McLean, Angela R; Frater, John

    2015-02-01

    The existence of viral variants that escape from the selection pressures imposed by cytotoxic T-lymphocytes (CTLs) in HIV-1 infection is well documented, but it is unclear when they arise, with reported measures of the time to escape in individuals ranging from days to years. A study of participants enrolled in the SPARTAC (Short Pulse Anti-Retroviral Therapy at HIV Seroconversion) clinical trial allowed direct observation of the evolution of CTL escape variants in 125 adults with primary HIV-1 infection observed for up to three years. Patient HLA-type, longitudinal CD8+ T-cell responses measured by IFN-γ ELISpot and longitudinal HIV-1 gag, pol, and nef sequence data were used to study the timing and prevalence of CTL escape in the participants whilst untreated. Results showed that sequence variation within CTL epitopes at the first time point (within six months of the estimated date of seroconversion) was consistent with most mutations being transmitted in the infecting viral strain rather than with escape arising within the first few weeks of infection. Escape arose throughout the first three years of infection, but slowly and steadily. Approximately one third of patients did not drive any new escape in an HLA-restricted epitope in just under two years. Patients driving several escape mutations during these two years were rare and the median and modal numbers of new escape events in each patient were one and zero respectively. Survival analysis of time to escape found that possession of a protective HLA type significantly reduced time to first escape in a patient (p = 0.01), and epitopes escaped faster in the face of a measurable CD8+ ELISpot response (p = 0.001). However, even in an HLA matched host who mounted a measurable, specific, CD8+ response the average time before the targeted epitope evolved an escape mutation was longer than two years.

  6. Anticipating and blocking HIV-1 escape by second generation antiviral shRNAs

    PubMed Central

    2010-01-01

    Background RNA interference (RNAi) is an evolutionary conserved gene silencing mechanism that mediates the sequence-specific breakdown of target mRNAs. RNAi can be used to inhibit HIV-1 replication by targeting the viral RNA genome. However, the error-prone replication machinery of HIV-1 can generate RNAi-resistant variants with specific mutations in the target sequence. For durable inhibition of HIV-1 replication the emergence of such escape viruses must be controlled. Here we present a strategy that anticipates HIV-1 escape by designing 2nd generation short hairpin RNAs (shRNAs) that form a complete match with the viral escape sequences. Results To block the two favorite viral escape routes observed when the HIV-1 integrase gene sequence is targeted, the original shRNA inhibitor was combined with two 2nd generation shRNAs in a single lentiviral expression vector. We demonstrate in long-term viral challenge experiments that the two dominant viral escape routes were effectively blocked. Eventually, virus breakthrough did however occur, but HIV-1 evolution was skewed and forced to use new escape routes. Conclusion These results demonstrate the power of the 2nd generation RNAi concept. Popular viral escape routes are blocked by the 2nd generation RNAi strategy. As a consequence viral evolution was skewed leading to new escape routes. These results are of importance for a deeper understanding of HIV-1 evolution under RNAi pressure. PMID:20529316

  7. Light weight escape capsule for fighter aircraft

    NASA Technical Reports Server (NTRS)

    Robert, James A.

    1988-01-01

    Emergency crew escape capabilities have been less than adequate for fighter aircraft since before WW II. From the over-the-side bailout of those days through the current ejection seat with a rocket catapult, escaping from a disabled aircraft has been risky at best. Current efforts are underway toward developing a high-tech, smart ejection seat that will give fighter pilots more room to live in the sky, but an escape capsule is needed to meet current and future fighter envelopes. Escape capsules have a bad reputation due to past examples of high weight, poor performance and great complexity. However, the advantages available demand that a capsule be developed. This capsule concept will minimize the inherent disavantages and incorporate the benefits while integrating all aspects of crew station design. The resulting design is appropriate for a crew station of the year 2010 and includes improved combat acceleration protection, chemical or biological combat capability, improved aircraft to escape system interaction, and the highest level of escape performance achievable. The capsule is compact, which can allow a reduced aircraft size and weighs only 1200 lb. The escape system weight penalty is only 120 lb higher than that for the next ejection seat and the capsule has a corresponding increase in performance.

  8. Genetic diversification of an emerging pathogen: A decade of mutation by the fish Viral Hemorrhagic Septicemia (VHS) virus in the Laurentian Great Lakes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Viral Hemorrhagic Septicemia virus (VHSv) is an RNA rhabdovirus, which causes one of the world's most serious fish diseases, infecting >80 freshwater and marine species across the Northern Hemisphere. A new, novel, and especially virulent substrain - VHSv-IVb - first appeared in the Laurentian Gre...

  9. THERMALLY DRIVEN ATMOSPHERIC ESCAPE

    SciTech Connect

    Johnson, Robert E.

    2010-06-20

    Accurately determining the escape rate from a planet's atmosphere is critical for determining its evolution. A large amount of Cassini data is now available for Titan's upper atmosphere and a wealth of data is expected within the next decade on escape from Pluto, Mars, and extra-solar planets. Escape can be driven by upward thermal conduction of energy deposited well below the exobase, as well as by nonthermal processes produced by energy deposited in the exobase region. Recent applications of a model for escape driven by upward thermal conduction, called the slow hydrodynamic escape model, have resulted in surprisingly large loss rates for the atmosphere of Titan, Saturn's largest moon. Based on a molecular kinetic simulation of the exobase region, these rates appear to be orders of magnitude too large. Therefore, the slow hydrodynamic model is evaluated here. It is shown that such a model cannot give a reliable description of the atmospheric temperature profile unless it is coupled to a molecular kinetic description of the exobase region. Therefore, the present escape rates for Titan and Pluto must be re-evaluated using the atmospheric model described here.

  10. [Viral hepatitis: from A to G viruses].

    PubMed

    Figueroa Barrios R, R

    1996-01-01

    Great advances has been achieved in the last 10 years in the study of acute and chronic viral hepatitis. The enigma of non-A non-B viral hepatitis was disclosed when C virus was identified and later when E virus was isolated. New viruses has been searched to explain non-A to non-E viral hepatitis, being reported recently G virus. Epidemiology and clinical aspects has been reviewed identifying unusual clinical forms: choletasic and relapsing hepatitis in HAV infection; escape mutants B virus hepatitis in HVB infection; and the silent evolution to chronicity in more than 70% of cases in HVC infection. Diagnostic techniques has been developed to asses serum antibodies and the virus itself. It is important to quantitate the viral particles in the serum before treatment. PCR technique has been used with good results. A and E virus do not remain in the host and permanent inmunity is obtained after infection is resolved. 10% of B and 80% of C viral hepatitis goes to chronicity. So far, the only drug used to treat chronic viral B, D and C hepatitis is interferon alfa, obtaining good response en 40%. Combinations with Rivabirin and increasing the dose, frequency and duration of interferon treatment are in study. lt is a recomendation to treat acute HCV infection with Interferon alfa to prevent chronicity. Vaccines against A and B virus are used, being included in childhood vaccination programs. No HVC vaccine has developed probably to constant virus mutancy. New chalenges are present in this field and in the identification of new hepatitis viruses. PMID:12165788

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

    PubMed

    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.

  12. Woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis B?

    PubMed

    Taffon, Stefania; Kondili, Loreta A; Giuseppetti, Roberto; Ciccaglione, Anna Rita; Pulimanti, Barbara; Attili, Adolfo F; Rapicetta, Maria; D'Ugo, Emilio

    2015-04-01

    Marmota monax and its natural infection by woodchuck hepatitis virus (WHV) could be used as a predictive model for evaluating mechanisms of viral persistence during chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the presence of viral variants in the core gene of chronically WHV-infected woodchucks that showed two different patterns of peripheral blood mononuclear cells' (PBMCs') responses after stimulation with a specific WHV core peptide. Sequences' analysis of the WHV core region from eight WHV chronically infected woodchucks have been performed after in vitro stimulation with an immunodominant epitope of the WHV core protein (amino acids [aa] 96-110). Following this stimulation, positive PBMC responses at each point of follow-up were observed for four animals (group A), and weak immune responses at one or a few points of follow-up were observed for the remaining four animals (group B). The WHV core gene sequences contained amino acid deletions (aa 84-126, aa 84-113) in three of four group A animals and in none of group B animals. In the group A animals, the same deletions were observed in liver specimens and in two of four tumor specimens. Hepatocellular carcinoma (HCC) was diagnosed in all group A animals and in one group B animal. In conclusion, internal deletions in the core region correlated with a sustained PBMC response to the immunogenic peptide (96-110) of the core protein. A possible role of this relationship in hepatocarcinogenesis could be hypothesized; however, this needs to be investigated in patients with chronic HBV infection. The evaluation of virus-specific T-cell responses and T-cell epitopes that are possibly related to the mechanisms of viral evasion should be further investigated in order to design combined antiviral and immune approaches to control chronic HBV infection. PMID:25666197

  13. Spacecraft crew escape

    NASA Astrophysics Data System (ADS)

    Miller, B. A.

    Safe crew escape from spacecraft is extremely difficult to engineer and has large cost and vehicle payload penalties. Because of these factors calculated risks have apparently been taken and only the most rudimentary means of crew protecion have been provided for space programs. Although designed for maximum reliability and safety a calculated risk is taken that on-balance it is more acceptable to risk the loss of possibly some or all occupants than introduce the mass, cost and complexity of an escape system. This philosophy was accepted until the Challenger tragedy. It is now clear that the use of this previously acceptable logic is invalid and that provisions must be made for spacecraft crew escape in the event of a catastrophic accident. This paper reviews the funded studies and subsequent proposals undertaken by Martin-Baker for the use of both encapsullated and open ejection seats for the Hermes Spaceplane. The technical difficulties, special innovations and future applications are also discussed.

  14. Escape and rescue model

    NASA Astrophysics Data System (ADS)

    Alvord, D.; Nelson, H. E.

    The Escape and Rescue model is a discrete-event simulation program written in Simscript. It was developed to simulate the emergency movement involved in escape and/or rescue of people from a Board and Care Home housing a group of persons with varying degrees of physical or mental disabilities along with a small live-in staff. It may, however, be used in a much more general setting. It can reasonably handle a building with up to 100 residents and 100 rooms.

  15. Expression kinetics of key genes in the early innate immune response to Great Lakes viral hemorrhagic septicemia virus IVb infection in yellow perch (Perca flavescens)

    USGS Publications Warehouse

    Olson, Wendy; Emmenegger, Eveline; Glenn, Jolene; Simchick, Crystal; Winton, Jim; Goetz, Frederick

    2013-01-01

    The recently discovered strain of viral hemorrhagic septicemia virus, VHSV-IVb, represents an example of the introduction of an extremely pathogenic rhabdovirus capable of infecting a wide variety of new fish species in a new host-environment. The goal of the present study was to delineate the expression kinetics of key genes in the innate immune response relative to the very early stages of VHSV-IVb infection using the yellow perch (Perca flavescens) as a model. Administration of VHSV-IVb by IP-injection into juvenile yellow perch resulted in 84% cumulative mortality, indicating their high susceptibility to this disease. In fish sampled in the very early stages of infection, a significant up-regulation of Mx gene expression in the liver, as well as IL-1β and SAA activation in the head kidney, spleen, and liver was directly correlated to viral load. The potential down-regulation of Mx in the hematopoietic tissues, head kidney and spleen, may represent a strategy utilized by the virus to increase replication.

  16. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  17. Titan impacts and escape

    NASA Astrophysics Data System (ADS)

    Korycansky, D. G.; Zahnle, Kevin J.

    2011-01-01

    We report on hydrodynamic calculations of impacts of large (multi-kilometer) objects on Saturn's moon Titan. We assess escape from Titan, and evaluate the hypothesis that escaping ejecta blackened the leading hemisphere of Iapetus and peppered the surface of Hyperion. We carried out two- and three-dimensional simulations of impactors ranging in size from 4 to 100 km diameter, impact velocities between 7 and 15 km s -1, and impact angles from 0° to 75° from the vertical. We used the ZEUSMP2 hydrocode for the calculations. Simulations were made using three different geometries: three-dimensional Cartesian, two-dimensional axisymmetric spherical polar, and two-dimensional plane polar. Three-dimensional Cartesian geometry calculations were carried out over a limited domain (e.g. 240 km on a side for an impactor of size di = 10 km), and the results compared to ones with the same parameters done by Artemieva and Lunine (2005); in general the comparison was good. Being computationally less demanding, two-dimensional calculations were possible for much larger domains, covering global regions of the satellite (from 800 km below Titan's surface to the exobase altitude 1700 km above the surface). Axisymmetric spherical polar calculations were carried out for vertical impacts. Two-dimensional plane-polar geometry calculations were made for both vertical and oblique impacts. In general, calculations among all three geometries gave consistent results. Our basic result is that the amount of escaping material is less than or approximately equal to the impactor mass even for the most favorable cases. Amounts of escaping material scaled most strongly as a function of velocity, with high-velocity impacts generating the largest amount, as expected. Dependence of the relative amount of escaping mass fesc = mesc/ Mi on impactor diameter di was weak. Oblique impacts (impact angle θi > 45°) were more effective than vertical or near-vertical impacts; ratios of mesc/ Mi ˜ 1-2 were

  18. Spacecraft Escape Capsule

    NASA Technical Reports Server (NTRS)

    Robertson, Edward A.; Charles, Dingell W.; Bufkin, Ann L.; Rodriggs, Liana M.; Peterson, Wayne; Cuthbert, Peter; Lee, David E.; Westhelle, Carlos

    2006-01-01

    A report discusses the Gumdrop capsule a conceptual spacecraft that would enable the crew to escape safely in the event of a major equipment failure at any time from launch through atmospheric re-entry. The scaleable Gumdrop capsule would comprise a command module (CM), a service module (SM), and a crew escape system (CES). The CM would contain a pressurized crew environment that would include avionic, life-support, thermal control, propulsive attitude control, and recovery systems. The SM would provide the primary propulsion and would also supply electrical power, life-support resources, and active thermal control to the CM. The CES would include a solid rocket motor, embedded within the SM, for pushing the CM away from the SM in the event of a critical thermal-protection-system failure or loss of control. The CM and SM would normally remain integrated with each other from launch through recovery, but could be separated using the CES, if necessary, to enable the safe recovery of the crew in the CM. The crew escape motor could be used, alternatively, as a redundant means of de-orbit propulsion for the CM in the event of a major system failure in the SM.

  19. Retrospective detection by negative contrast electron microscopy of faecal viral particles in free-living wild red squirrels (Sciurus vulgaris) with suspected enteropathy in Great Britain.

    PubMed

    Everest, D J; Stidworthy, M F; Milne, E M; Meredith, A L; Chantrey, J; Shuttleworth, C; Blackett, T; Butler, H; Wilkinson, M; Sainsbury, A W

    2010-12-25

    Transmission electron microscopy identified adenovirus particles in 10 of 70 (14.3 per cent) samples of large intestinal content collected at postmortem examination from free-living wild red squirrels (Sciurus vulgaris) across Great Britain between 2000 and 2009. Examination was limited to cases in which an enteropathy was suspected on the basis of predetermined macroscopic criteria such as semi-solid or diarrhoeic faeces, suspected enteritis or the presence of intussusception. In most cases, meaningful histological examination of enteric tissue was not possible due to pronounced autolysis. Two (2.9 per cent) of the samples were negative for adenovirus but were found to contain rotavirus particles, a novel finding in this species.

  20. Viral pneumonia.

    PubMed

    Greenberg, S B

    1991-09-01

    Viral pneumonias are common in infants and young children but rare in adults. Respiratory syncytial virus (RSV) and para-influenza viruses are the most frequent viral pathogens in infants and children. Influenza virus types A and B account for over one half of viral pneumonias in adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus (CMV) and other herpesviruses, as well as rubeola and adenovirus. Diagnosis of viral pneumonia depends on appropriate viral cultures and acute and convalescent sera for specific antibodies. Superinfection with bacteria is common in adults. Anti-viral therapy is available for several respiratory viruses. Ribavirin, amantadine/rimantadine, interferon alpha, and acyclovir are antiviral drugs that may be of benefit in treatment and prophylaxis. Prevention of viral pneumonia will depend upon improved viral immunization practices.

  1. Escape of a knot from a DNA molecule in flow

    NASA Astrophysics Data System (ADS)

    Renner, Benjamin; Doyle, Patrick

    2014-03-01

    Macroscale knots are an everyday occurrence when trying to unravel an unorganized flexible string (e.g. an iPhone cord taken out of your pocket). In nature, knots are found in proteins and viral capsid DNA, and the properties imbued by their topologies are thought to have biological significance. Unlike their macroscale counterparts, thermal fluctuations greatly influence the dynamics of polymer knots. Here, we use Brownian Dynamics simulations to study knot diffusion along a linear polymer chain. The model is parameterized to dsDNA, a model polymer used in previous simulation and experimental studies of knot dynamics. We have used this model to study the process of knot escape and transport along a dsDNA strand extended by an elongational flow. For a range of knot topologies and flow strengths, we show scalings that result in collapse of the data onto a master curve. We show a topologically mediated mode of transport coincides with observed differences in rates of knot transport, and we provide a simple mechanistic explanation for its effect. We anticipate these results will build on the growing body of fundamental studies of knotted polymers and inform future experimental study. This work is supported by the Singapore-MIT Alliance for Research and Technology (SMART) and National Science Foundation (NSF) grant CBET-0852235.

  2. Great Minds? Great Lakes!

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Chicago, IL. Great Lakes National Program Office.

    This book contains lesson plans that provide an integrated approach to incorporating Great Lakes environmental issues into elementary subjects. The book is divided into three subject areas: (1) History, which includes the origins of the Great Lakes, Great Lakes people, and shipwrecks; (2) Social Studies, which covers government, acid rain as a…

  3. Viral pneumonia

    MedlinePlus

    ... Names Pneumonia - viral; "Walking pneumonia" - viral Images Lungs Respiratory system References Lee FE, Treanor J. Viral infections. In: Mason RJ, VC Broaddus, Martin TR, et al, eds. Murray and Nadel’s Textbook of Respiratory Medicine . 5th ed. Philadelphia, PA: Saunders Elsevier; 2010: ...

  4. Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response.

    PubMed

    Jones, Nicola A; Wei, Xiping; Flower, Darren R; Wong, Mailee; Michor, Franziska; Saag, Michael S; Hahn, Beatrice H; Nowak, Martin A; Shaw, George M; Borrow, Persephone

    2004-11-15

    CD8+ cytotoxic T lymphocytes (CTLs) play an important role in containment of virus replication in primary human immunodeficiency virus (HIV) infection. HIV's ability to mutate to escape from CTL pressure is increasingly recognized; but comprehensive studies of escape from the CD8 T cell response in primary HIV infection are currently lacking. Here, we have fully characterized the primary CTL response to autologous virus Env, Gag, and Tat proteins in three patients, and investigated the extent, kinetics, and mechanisms of viral escape from epitope-specific components of the response. In all three individuals, we observed variation beginning within weeks of infection at epitope-containing sites in the viral quasispecies, which conferred escape by mechanisms including altered peptide presentation/recognition and altered antigen processing. The number of epitope-containing regions exhibiting evidence of early CTL escape ranged from 1 out of 21 in a subject who controlled viral replication effectively to 5 out of 7 in a subject who did not. Evaluation of the extent and kinetics of HIV-1 escape from >40 different epitope-specific CD8 T cell responses enabled analysis of factors determining escape and suggested that escape is restricted by costs to intrinsic viral fitness and by broad, codominant distribution of CTL-mediated pressure on viral replication.

  5. Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response.

    PubMed

    Jones, Nicola A; Wei, Xiping; Flower, Darren R; Wong, Mailee; Michor, Franziska; Saag, Michael S; Hahn, Beatrice H; Nowak, Martin A; Shaw, George M; Borrow, Persephone

    2004-11-15

    CD8+ cytotoxic T lymphocytes (CTLs) play an important role in containment of virus replication in primary human immunodeficiency virus (HIV) infection. HIV's ability to mutate to escape from CTL pressure is increasingly recognized; but comprehensive studies of escape from the CD8 T cell response in primary HIV infection are currently lacking. Here, we have fully characterized the primary CTL response to autologous virus Env, Gag, and Tat proteins in three patients, and investigated the extent, kinetics, and mechanisms of viral escape from epitope-specific components of the response. In all three individuals, we observed variation beginning within weeks of infection at epitope-containing sites in the viral quasispecies, which conferred escape by mechanisms including altered peptide presentation/recognition and altered antigen processing. The number of epitope-containing regions exhibiting evidence of early CTL escape ranged from 1 out of 21 in a subject who controlled viral replication effectively to 5 out of 7 in a subject who did not. Evaluation of the extent and kinetics of HIV-1 escape from >40 different epitope-specific CD8 T cell responses enabled analysis of factors determining escape and suggested that escape is restricted by costs to intrinsic viral fitness and by broad, codominant distribution of CTL-mediated pressure on viral replication. PMID:15545352

  6. Reconstructing the Alcatraz escape

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  7. Hydrodynamic escape from planetary atmospheres

    NASA Astrophysics Data System (ADS)

    Tian, Feng

    Hydrodynamic escape is an important process in the formation and evolution of planetary atmospheres. Due to the existence of a singularity point near the transonic point, it is difficult to find transonic steady state solutions by solving the time-independent hydrodynamic equations. In addition to that, most previous works assume that all energy driving the escape flow is deposited in one narrow layer. This assumption not only results in less accurate solutions to the hydrodynamic escape problem, but also makes it difficult to include other chemical and physical processes in the hydrodynamic escape models. In this work, a numerical model describing the transonic hydrodynamic escape from planetary atmospheres is developed. A robust solution technique is used to solve the time dependent hydrodynamic equations. The method has been validated in an isothermal atmosphere where an analytical solution is available. The hydrodynamic model is applied to 3 cases: hydrogen escape from small orbit extrasolar planets, hydrogen escape from a hydrogen rich early Earth's atmosphere, and nitrogen/methane escape from Pluto's atmosphere. Results of simulations on extrasolar planets are in good agreement with the observations of the transiting extrasolar planet HD209458b. Hydrodynamic escape of hydrogen from other hypothetical close-in extrasolar planets are simulated and the influence of hydrogen escape on the long-term evolution of these extrasolar planets are discussed. Simulations on early Earth suggest that hydrodynamic escape of hydrogen from a hydrogen rich early Earth's atmosphere is about two orders magnitude slower than the diffusion limited escape rate. A hydrogen rich early Earth's atmosphere could have been maintained by the balance between the hydrogen escape and the supply of hydrogen into the atmosphere by volcanic outgassing. Origin of life may have occurred in the organic soup ocean created by the efficient formation of prebiotic molecules in the hydrogen rich early

  8. Escape of atmospheres and loss of water

    NASA Technical Reports Server (NTRS)

    Hunten, D. M.; Donahue, T. M.; Walker, J. C. G.; Kasting, J. F.

    1989-01-01

    The properties and limitations of several loss processes for atmospheric gases are presented and discussed. They include thermal loss (Jeans and hydrodynamic); nonthermal loss (all processes involve charged particles); and impact erosion, including thermal escape from a molten body heated by rapid accretion. Hydrodynamic escape, or 'blowoff', is of particular interest because it offers the prospect of processing large quantities of gas and enriching the remainder in heavy elements and isotopes. In a second part, the water budgets and likely evolutionary histories of Venus, Earth and Mars are assessed. Although it is tempting to associate the great D/H enrichment on Venus with loss of a large initial endowment, a steady state with juvenile water (perhaps from comets) is equally probable.

  9. Great Lakes: Great Gardening.

    ERIC Educational Resources Information Center

    New York Sea Grant Inst., Albany, NY.

    This folder contains 12 fact sheets designed to improve the quality of gardens near the Great Lakes. The titles are: (1) "Your Garden and the Great Lakes"; (2) "Organic Gardening"; (3) "Fruit and Vegetable Gardening"; (4) "Composting Yard Wastes"; (5) "Herbicides and Water Quality"; (6) "Watering"; (7) "Soil Erosion by Water"; (8) "Soil…

  10. Viral infection

    PubMed Central

    Puigdomènech, Isabel; de Armas-Rillo, Laura; Machado, José-David

    2011-01-01

    Viruses have developed different survival strategies in host cells by crossing cell-membrane compartments, during different steps of their viral life cycle. In fact, the non-regenerative viral membrane of enveloped viruses needs to encounter the dynamic cell-host membrane, during early steps of the infection process, in which both membranes fuse, either at cell-surface or in an endocytic compartment, to promote viral entry and infection. Once inside the cell, many viruses accomplish their replication process through exploiting or modulating membrane traffic, and generating specialized compartments to assure viral replication, viral budding and spreading, which also serve to evade the immune responses against the pathogen. In this review, we have attempted to present some data that highlight the importance of membrane dynamics during viral entry and replicative processes, in order to understand how viruses use and move through different complex and dynamic cell-membrane structures and how they use them to persist. PMID:21966556

  11. THERMALLY DRIVEN ATMOSPHERIC ESCAPE: TRANSITION FROM HYDRODYNAMIC TO JEANS ESCAPE

    SciTech Connect

    Volkov, Alexey N.; Johnson, Robert E.; Tucker, Orenthal J.; Erwin, Justin T.

    2011-03-10

    Thermally driven escape from planetary atmospheres changes in nature from an organized outflow (hydrodynamic escape) to escape on a molecule-by-molecule basis (Jeans escape) with increasing Jeans parameter, {lambda}, the ratio of the gravitational to thermal energy of the atmospheric molecules. This change is described here for the first time using the direct simulation Monte Carlo method. When heating is predominantly below the lower boundary of the simulation region, R{sub 0}, and well below the exobase of a single-component atmosphere, the nature of the escape process changes over a surprisingly narrow range of Jeans parameters, {lambda}{sub 0}, evaluated at R{sub 0}. For an atomic gas, the transition occurs over {lambda}{sub 0} {approx} 2-3, where the lower bound, {lambda}{sub 0} {approx} 2.1, corresponds to the upper limit for isentropic, supersonic outflow. For {lambda}{sub 0} > 3 escape occurs on a molecule-by-molecule basis and we show that, contrary to earlier suggestions, for {lambda}{sub 0} > {approx}6 the escape rate does not deviate significantly from the familiar Jeans rate. In a gas composed of diatomic molecules, the transition shifts to {lambda}{sub 0} {approx} 2.4-3.6 and at {lambda}{sub 0} > {approx}4 the escape rate increases a few tens of percent over that for the monatomic gas. Scaling by the Jeans parameter and the Knudsen number, these results can be applied to thermally induced escape of the major species from solar and extrasolar planets.

  12. Escape from Vela X

    SciTech Connect

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

    2012-02-15

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

  13. ESCAPE FROM VELA X

    SciTech Connect

    Hinton, J. A.; Ohm, S.; Funk, S.; Parsons, R. D.

    2011-12-10

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

  14. An escape from crowding.

    PubMed

    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.

  15. Viral meningitis.

    PubMed

    Chadwick, David R

    2005-01-01

    Viruses probably account for most cases of acute meningitis. Viral meningitis is often assumed to be a largely benign disease. For the commonest pathogens causing meningitis, enteroviruses, this is usually the case; however, for many of the other pathogens causing viral meningitis, and for common pathogens in the immunocompromised or infants, viral meningitis is frequently associated with substantial neurological complications and a significant mortality. Diagnostic methods for rapid and accurate identification of pathogens have improved over recent years, permitting more precise and earlier diagnoses. There have been fewer developments in therapies for viral meningitis, and there remain no effective therapies for most pathogens, emphasising the importance of prevention and early diagnosis. This review focuses on the presentation, diagnosis and management of viral meningitis and also covers the prevention of meningitis for pathogens where effective vaccines are available. PMID:16474042

  16. Viral meningitis.

    PubMed

    Chadwick, David R

    2005-01-01

    Viruses probably account for most cases of acute meningitis. Viral meningitis is often assumed to be a largely benign disease. For the commonest pathogens causing meningitis, enteroviruses, this is usually the case; however, for many of the other pathogens causing viral meningitis, and for common pathogens in the immunocompromised or infants, viral meningitis is frequently associated with substantial neurological complications and a significant mortality. Diagnostic methods for rapid and accurate identification of pathogens have improved over recent years, permitting more precise and earlier diagnoses. There have been fewer developments in therapies for viral meningitis, and there remain no effective therapies for most pathogens, emphasising the importance of prevention and early diagnosis. This review focuses on the presentation, diagnosis and management of viral meningitis and also covers the prevention of meningitis for pathogens where effective vaccines are available.

  17. [Pathology and viral metagenomics, a recent history].

    PubMed

    Bernardo, Pauline; Albina, Emmanuel; Eloit, Marc; Roumagnac, Philippe

    2013-05-01

    Human, animal and plant viral diseases have greatly benefited from recent metagenomics developments. Viral metagenomics is a culture-independent approach used to investigate the complete viral genetic populations of a sample. During the last decade, metagenomics concepts and techniques that were first used by ecologists progressively spread into the scientific field of viral pathology. The sample, which was first for ecologists a fraction of ecosystem, became for pathologists an organism that hosts millions of microbes and viruses. This new approach, providing without a priori high resolution qualitative and quantitative data on the viral diversity, is now revolutionizing the way pathologists decipher viral diseases. This review describes the very last improvements of the high throughput next generation sequencing methods and discusses the applications of viral metagenomics in viral pathology, including discovery of novel viruses, viral surveillance and diagnostic, large-scale molecular epidemiology, and viral evolution.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27604151

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

    PubMed

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

    2016-01-01

    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. PMID:27604151

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

    PubMed

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

    2015-09-01

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

  1. Great Minds? Great Lakes!

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Chicago, IL. Great Lakes National Program Office.

    This booklet introduces an environmental curriculum for use in a variety of elementary subjects. The lesson plans provide an integrated approach to incorporating Great Lakes environmental issues into the subjects of history, social studies, and environmental sciences. Each of these sections contains background information, discussion points, and a…

  2. Viral Gastroenteritis

    MedlinePlus

    ... stomach, small intestine, and large intestine. Several different viruses can cause viral gastroenteritis, which is highly contagious ... and last for 1 to 3 days. Some viruses cause symptoms that last longer. [ Top ] What are ...

  3. Viral arthritis

    MedlinePlus

    Infectious arthritis - viral ... Ohl CA, Forster D. Infectious arthritis of native joints. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious ...

  4. Plasma Escape from Unmagnetized Bodies

    NASA Technical Reports Server (NTRS)

    Hartle, R. E.; Grebowsky, J. M.; Intriligator, D. S.

    1998-01-01

    A considerable fraction of atmospheric loss at Venus and Titan is in the form of plasma escape. This is due in part to the fact that the ionospheres of these unmagnetized bodies interact directly with the high speed plasmas flowing around them. The similarities of the interactions help reinforce interpretations of measurements made at each body, especially when instruments and measurement sites differ. For example, it is well established through this method that ions born in the exospheres above the ionopauses are picked up and carried away by the solar wind at Venus and the rotating plasma in Saturn's magnetosphere. On the other hand, it is more difficult to relate the observations associated with escape of cooler ionospheric plasma down the ionotails of each body. A clear example of ionospheric plasma escaping Titan was observed as it flowed down its ionotail (1). Measurements at Venus have not as yet clearly distinguished between ionospheric and pickup ion escape in the ionotail; however, cold ions detected in the distant wake at 1 AU by the CELIAS/CTOF instrument on SOHO have been interpreted as ionospheric in origin (2). An algorithm to determine ionospheric flow from Pioneer Venus aeronomical measurements is used to show that escape of cold ionospheric plasma is likely to occur. These results along with plasma flow measurements made in the ionotail of Venus are combined and compared to the corresponding flow at Titan.

  5. Viral proteases as targets for drug design.

    PubMed

    Skoreński, Marcin; Sieńczyk, Marcin

    2013-01-01

    In order to productively infect a host, viruses must enter the cell and force host cell replication mechanisms to produce new infectious virus particles. The success of this process unfortunately results in disease progression and, in the case of infection with many viral species, may cause mortality. The discoveries of Louis Pasteur and Edward Jenner led to one of the greatest advances in modern medicine - the development of vaccines that generate long-lasting memory immune responses to combat viral infection. Widespread use of vaccines has reduced mortality and morbidity associated with viral infection and, in some cases, has completely eradicated virus from the human population. Unfortunately, several viral species maintain a significant ability to mutate and "escape" vaccine-induced immune responses. Thus, novel anti-viral agents are required for treatment and prevention of viral disease. Targeting proteases that are crucial in the viral life cycle has proven to be an effective method to control viral infection, and this avenue of investigation continues to generate anti-viral treatments. Herein, we provide the reader with a brief history as well as a comprehensive review of the most recent advances in the design and synthesis of viral protease inhibitors. PMID:23016690

  6. Enhancing endosomal escape for nanoparticle mediated siRNA delivery

    NASA Astrophysics Data System (ADS)

    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.

  7. Viral arthritis

    PubMed Central

    Marks, Michael; Marks, Jonathan L

    2016-01-01

    Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy. PMID:27037381

  8. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    SciTech Connect

    Ganusov, Vitaly V; Korber, Bette M; Perelson, Alan S

    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.

  9. Lise Meitner's escape from Germany

    NASA Astrophysics Data System (ADS)

    Sime, Ruth Lewin

    1990-03-01

    Lise Meitner (1878-1968) achieved prominence as a nuclear physicist in Germany; although of Jewish origin, her Austrian citizenship exempted her from Nazi racial laws until the annexation of Austria in 1938 precipitated her dismissal. Forbidden to emigrate, she narrowly escaped to the Netherlands with the help of concerned friends in the international physics community.

  10. Mechanisms of Ionospheric Mass Escape

    NASA Technical Reports Server (NTRS)

    Moore, T. E.; Khazanov, G. V.

    2010-01-01

    The dependence of ionospheric O+ escape flux on electromagnetic energy flux and electron precipitation into the ionosphere is derived for a hypothetical ambipolar pick-up process, powered the relative motion of plasmas and neutral upper atmosphere, and by electron precipitation, at heights where the ions are magnetized but influenced by photo-ionization, collisions with gas atoms, ambipolar and centrifugal acceleration. Ion pick-up by the convection electric field produces "ring-beam" or toroidal velocity distributions, as inferred from direct plasma measurements, from observations of the associated waves, and from the spectra of incoherent radar echoes. Ring-beams are unstable to plasma wave growth, resulting in rapid relaxation via transverse velocity diffusion, into transversely accelerated ion populations. Ion escape is substantially facilitated by the ambipolar potential, but is only weakly affected by centrifugal acceleration. If, as cited simulations suggest, ion ring beams relax into non-thermal velocity distributions with characteristic speed equal to the local ion-neutral flow speed, a generalized "Jeans escape" calculation shows that the escape flux of ionospheric O+ increases with Poynting flux and with precipitating electron density in rough agreement with observations.

  11. 42 CFR 84.51 - Entry and escape, or escape only; classification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... during entry into a hazardous atmosphere, and for escape from a hazardous atmosphere; or (b) Escape only. Respirators designed and approved for use only during escape from a hazardous atmosphere....

  12. 42 CFR 84.51 - Entry and escape, or escape only; classification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... during entry into a hazardous atmosphere, and for escape from a hazardous atmosphere; or (b) Escape only. Respirators designed and approved for use only during escape from a hazardous atmosphere....

  13. 42 CFR 84.51 - Entry and escape, or escape only; classification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... during entry into a hazardous atmosphere, and for escape from a hazardous atmosphere; or (b) Escape only. Respirators designed and approved for use only during escape from a hazardous atmosphere....

  14. 42 CFR 84.51 - Entry and escape, or escape only; classification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... during entry into a hazardous atmosphere, and for escape from a hazardous atmosphere; or (b) Escape only. Respirators designed and approved for use only during escape from a hazardous atmosphere....

  15. 42 CFR 84.51 - Entry and escape, or escape only; classification.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... during entry into a hazardous atmosphere, and for escape from a hazardous atmosphere; or (b) Escape only. Respirators designed and approved for use only during escape from a hazardous atmosphere....

  16. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  17. Escape Analysis on the Confinement-Escape Problem of a Defender Against an Evader Escaping From a Circular Region.

    PubMed

    Li, Wei

    2016-09-01

    In this paper, we investigate some mathematical properties of the confinement-escape problem of a defender and an evader with respect to a circular region, which was proposed in the author's previous work. Initially, the evader is located inside the circle, the defender patrols on the circle and tries to seal it to prevent the evader' escape; while the evader attempts to escape with avoidance of the defender. Here, we adopt the same control laws of the agents and consider particularly the successful-escape conditions which ensure a monotone-increasing distance (MID) between the defender and the evader as the system evolves, for abbreviation, we call it the escape with the MID to the defender, or simply the MID escape. Then, we: 1) provide some sufficient conditions for the MID escape under different situations; 2) provide the corresponding upper-limit estimations of the escape time; and 3) discuss the characteristics of the analytical results. PMID:27390195

  18. Blue Origin Conducts Pad Escape Test

    NASA Video Gallery

    Blue Origin conducted a successful pad escape test Oct. 19 at the company's West Texas launch site, firing its pusher escape motor and launching a full-scale suborbital crew capsule from a simulate...

  19. Viral fitness: definitions, measurement, and current insights

    USGS Publications Warehouse

    Wargo, Andrew R.; Kurath, Gael

    2012-01-01

    Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.

  20. [Escape Behaviors and Its Underlying Neuronal Circuits].

    PubMed

    Oda, Yoichi

    2015-10-01

    Escape behaviors are crucial to survive predator encounters or aversive stimuli. The neural circuits mediating escape behaviors of different animal species have a common framework to trigger extremely fast and robust movement with minimum delay. Thus, the neuronal escape circuits possibly represent functional architectures that perform the most efficient sensory-motor processing in the brain. Here, I review the escape behaviors and underlying neuronal circuits of several invertebrates and fish by focusing on the Mauthner cells, a pair of giant reticulospinal neurons in the hindbrain, that trigger fast escape behavior in goldfish and zebrafish. PMID:26450070

  1. On ion escape from Venus

    NASA Astrophysics Data System (ADS)

    Jarvinen, Riku

    2011-04-01

    This doctoral thesis is about the solar wind influence on the atmosphere of the planet Venus. A numerical plasma simulation model was developed for the interaction between Venus and the solar wind to study the erosion of charged particles from the Venus upper atmosphere. The developed model is a hybrid simulation where ions are treated as particles and electrons are modelled as a fluid. The simulation was used to study the solar wind induced ion escape from Venus as observed by the European Space Agency's Venus Express and NASA's Pioneer Venus Orbiter spacecraft. Especially, observations made by the ASPERA-4 particle instrument onboard Venus Express were studied. The thesis consists of an introductory part and four peer-reviewed articles published in scientific journals. In the introduction Venus is presented as one of the terrestrial planets in the Solar System and the main findings of the work are discussed within the wider context of planetary physics. Venus is the closest neighbouring planet to the Earth and the most earthlike planet in its size and mass orbiting the Sun. Whereas the atmosphere of the Earth consists mainly of nitrogen and oxygen, Venus has a hot carbon dioxide atmosphere, which is dominated by the greenhouse effect. Venus has all of its water in the atmosphere, which is only a fraction of the Earth's total water supply. Since planets developed presumably in similar conditions in the young Solar System, why Venus and Earth became so different in many respects? One important feature of Venus is that the planet does not have an intrinsic magnetic field. This makes it possible for the solar wind, a continuous stream of charged particles from the Sun, to flow close to Venus and to pick up ions from the planet's upper atmosphere. The strong intrinsic magnetic field of the Earth dominates the terrestrial magnetosphere and deflects the solar wind flow far away from the atmosphere. The region around Venus where the planet's atmosphere interacts with the

  2. On ion escape from Venus

    NASA Astrophysics Data System (ADS)

    Jarvinen, R.

    2011-04-01

    This doctoral thesis is about the solar wind influence on the atmosphere of the planet Venus. A numerical plasma simulation model was developed for the interaction between Venus and the solar wind to study the erosion of charged particles from the Venus upper atmosphere. The developed model is a hybrid simulation where ions are treated as particles and electrons are modelled as a fluid. The simulation was used to study the solar wind induced ion escape from Venus as observed by the European Space Agency's Venus Express and NASA's Pioneer Venus Orbiter spacecraft. Especially, observations made by the ASPERA-4 particle instrument onboard Venus Express were studied. The thesis consists of an introductory part and four peer-reviewed articles published in scientific journals. In the introduction Venus is presented as one of the terrestrial planets in the Solar System and the main findings of the work are discussed within the wider context of planetary physics.Venus is the closest neighbouring planet to the Earth and the most earthlike planet in its size and mass orbiting the Sun. Whereas the atmosphere of the Earth consists mainly of nitrogen and oxygen, Venus has a hot carbon dioxide atmosphere, which is dominated by the greenhouse effect. Venus has all of its water in the atmosphere, which is only a fraction of the Earth's total water supply. Since planets developed presumably in similar conditions in the young Solar System, why Venus and Earth became so different in many respects?One important feature of Venus is that the planet does not have an intrinsic magnetic field. This makes it possible for the solar wind, a continuous stream of charged particles from the Sun, to flow close to Venus and to pick up ions from the planet's upper atmosphere. The strong intrinsic magnetic field of the Earth dominates the terrestrial magnetosphere and deflects the solar wind flow far away from the atmosphere. The region around Venus where the planet's atmosphere interacts with the

  3. Mars atmosphere evolution: Escape to space

    NASA Technical Reports Server (NTRS)

    Luhmann, J. G.

    1992-01-01

    The loss mechanisms and the rates of escape, to space, of Martian atmosphere constituents have changed throughout the history of the solar system. For the first billion years, Mars' atmosphere escape was probably dominated by impact erosion related to the presence of debris left over from the accretionary phase. This loss was further augmented by hydrodynamic outflows related to the presence of an early denser atmosphere and a sun that was brighter in the EUV wavelengths. Following this initial 'catastrophic' phase, during which a large fraction of the original atmosphere was lost but then replaced by volcanism and cometary impact, the 'modern' loss mechanisms which still operate today would have taken over. Those mechanisms that now contribute to escape to space consist of classical thermal or Jeans escape, nonthermal escape due to chemical reaction in the atmosphere, and solar wind-related losses. Both the loss mechanisms and the rates of escape are discussed.

  4. Differential reinforcement of alternative behavior and demand fading in the treatment of escape-maintained destructive behavior.

    PubMed

    Piazza, C C; Moes, D R; Fisher, W W

    1996-01-01

    The escape-maintained destructive behavior of a boy with autism was reduced during instructional sequences with differential reinforcement of compliance (DRA), escape extinction without physical guidance, and demand fading. The procedure decreased destructive behaviors to near-zero levels and greatly increased compliance.

  5. Model of a mechanical clock escapement

    NASA Astrophysics Data System (ADS)

    Moline, David; Wagner, John; Volk, Eugene

    2012-07-01

    The mechanical tower clock originated in Europe during the 14th century to sound hourly bells and later display hands on a dial. An important innovation was the escapement mechanism, which converts stored energy into oscillatory motion for fixed time intervals through the pendulum swing. Previous work has modeled the escapement mechanism in terms of inelastic and elastic collisions. We derive and experimentally verify a theoretical model in terms of impulsive differential equations for the Graham escapement mechanism in a Seth Thomas tower clock. The model offers insight into the clock's mechanical behavior and the functionality of the deadbeat escapement mechanism.

  6. Electronic Escape Trails for Firefighters

    NASA Technical Reports Server (NTRS)

    Jorgensen, Charles; Schipper, John; Betts, Bradley

    2008-01-01

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

  7. Viral Parkinsonism

    PubMed Central

    Jang, Haeman; Boltz, David A.; Webster, Robert G.; Smeyne, Richard Jay

    2015-01-01

    Parkinson's disease is a debilitating neurological disorder characterized that affects 1-2% of the adult population over 55 years of age. For the vast majority of cases, the etiology of this disorder is unknown, although it is generally accepted that there is a genetic susceptibility to any number of environmental agents. One such agent may be viruses. It has been shown that numerous viruses can enter the nervous system, i.e. they are neurotropic, and induce a number of encephalopathies. One of the secondary consequences of these encephalopathies can be parkinsonism, that is both transient as well as permanent. One of the most highlighted and controversial cases of viral parkinsonism is that which followed the 1918 influenza outbreak and the subsequent induction of von Economo's encephalopathy. In this review, we discuss the neurological sequelae of infection by influenza virus as well as that of other viruses known to induce parkinsonism including Coxsackie, Japanese encephalitis B, St. Louis, West Nile and HIV viruses. PMID:18760350

  8. Viral evolution

    PubMed Central

    Nasir, Arshan; Kim, Kyung Mo; Caetano-Anollés, Gustavo

    2012-01-01

    Explaining the origin of viruses remains an important challenge for evolutionary biology. Previous explanatory frameworks described viruses as founders of cellular life, as parasitic reductive products of ancient cellular organisms or as escapees of modern genomes. Each of these frameworks endow viruses with distinct molecular, cellular, dynamic and emergent properties that carry broad and important implications for many disciplines, including biology, ecology and epidemiology. In a recent genome-wide structural phylogenomic analysis, we have shown that large-to-medium-sized viruses coevolved with cellular ancestors and have chosen the evolutionary reductive route. Here we interpret these results and provide a parsimonious hypothesis for the origin of viruses that is supported by molecular data and objective evolutionary bioinformatic approaches. Results suggest two important phases in the evolution of viruses: (1) origin from primordial cells and coexistence with cellular ancestors, and (2) prolonged pressure of genome reduction and relatively late adaptation to the parasitic lifestyle once virions and diversified cellular life took over the planet. Under this evolutionary model, new viral lineages can evolve from existing cellular parasites and enhance the diversity of the world’s virosphere. PMID:23550145

  9. Behavioral analysis of the escape response in larval zebrafish

    NASA Astrophysics Data System (ADS)

    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.

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

    ERIC Educational Resources Information Center

    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. Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome

    PubMed Central

    2012-01-01

    Background A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes (CTL) on viral fitness in the context of the cognate transmitted/founder (T/F) genome, we developed a new competitive fitness assay using molecular clones of T/F genomes lacking exogenous genetic markers and a highly sensitive and precise parallel allele-specific sequencing (PASS) method. Results The T/F and mutant viruses were competed in CD4+ T-cell enriched cultures, relative proportions of viruses were assayed after repeated cell-free passage, and fitness costs were estimated by mathematical modeling. Naturally occurring HLA B57-restricted mutations involving the TW10 epitope in Gag and two epitopes in Tat/Rev and Env were assessed independently and together. Compensatory mutations which restored viral replication fitness were also assessed. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K) in Env and a reversion mutation in the Tat/Rev overlapping region. Conclusions These findings reveal a broad spectrum of fitness costs to CTL escape mutations in T/F viral genomes, similar to recent findings reported for neutralizing antibody escape mutations, and highlight the extraordinary plasticity and adaptive potential of the HIV-1 genome. Analysis of T/F genomes and their evolved progeny is a powerful approach for assessing the impact of composite mutational events on viral fitness. PMID:23110705

  12. Viral hepatitis*

    PubMed Central

    Deinhardt, F.; Gust, I. D.

    1982-01-01

    Three forms of viral hepatitis can be recognized: hepatitis A, hepatitis B, and hepatitis non-A, non-B. Hepatitis A is caused by a picornavirus, is transmitted by the faceal—oral route, does not become chronic, and no chronic virus carriers exist. The virus can be grown in cell cultures, and killed as well as live attenuated virus vaccines are under development. Hepatitis B is caused by an enveloped virus containing a circular, double-stranded form of DNA. The disease is transmitted parenterally through inoculation of blood or blood products containing virus or through close personal contact with a virus-positive person. Hepatitis B becomes chronic in a certain number of cases and can lead to cirrhosis and primary liver cell carcinoma. The blood and certain body secretions of individuals with a persistent or chronic infection may remain infectious for many years. The hepatitis B virus cannot be grown in cell cultures but the entire genome has been sequenced and cloned in bacterial and eukaryotic cells. An inactivated virus vaccine has been prepared from hepatitis B surface antigen present in the plasma of hepatitis B virus carriers and further vaccines are under development. The agents of hepatitis non-A, non-B have not been identified. It is possible to distinguish between a predominantly parenterally transmitted and an orally transmitted form of hepatitis non-A, non-B. The latter is reported to be caused by a picornavirus that does not, however, have any antigenic relationship with hepatitis A virus. PMID:6817933

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  15. Escaping Homelessness: Anticipated and Perceived Facilitators

    ERIC Educational Resources Information Center

    Patterson, Allisha; Tweed, Roger

    2009-01-01

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

  16. Great Apes

    USGS Publications Warehouse

    Sleeman, Jonathan M.; Cerveny, Shannon

    2014-01-01

    Anesthesia of great apes is often necessary to conduct diagnostic analysis, provide therapeutics, facilitate surgical procedures, and enable transport and translocation for conservation purposes. Due to the stress of remote delivery injection of anesthetic agents, recent studies have focused on oral delivery and/or transmucosal absorption of preanesthetic and anesthetic agents. Maintenance of the airway and provision of oxygen is an important aspect of anesthesia in great ape species. The provision of analgesia is an important aspect of the anesthesia protocol for any procedure involving painful stimuli. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are often administered alone, or in combination to provide multi-modal analgesia. There is increasing conservation management of in situ great ape populations, which has resulted in the development of field anesthesia techniques for free-living great apes for the purposes of translocation, reintroduction into the wild, and clinical interventions.

  17. Atmospheric escape, redox evolution, and planetary habitability

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed Central

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

    2016-01-01

    Several recent studies demonstrated that the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 can be used for guide RNA (gRNA)-directed, sequence-specific cleavage of HIV proviral DNA in infected cells. We here demonstrate profound inhibition of HIV-1 replication by harnessing T cells with Cas9 and antiviral gRNAs. However, the virus rapidly and consistently escaped from this inhibition. Sequencing of the HIV-1 escape variants revealed nucleotide insertions, deletions, and substitutions around the Cas9/gRNA cleavage site that are typical for DNA repair by the nonhomologous end-joining pathway. We thus demonstrate the potency of CRISPR-Cas9 as an antiviral approach, but any therapeutic strategy should consider the viral escape implications. PMID:26796669

  19. Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape.

    PubMed

    Walters, Robert W; Freimuth, Paul; Moninger, Thomas O; Ganske, Ingrid; Zabner, Joseph; Welsh, Michael J

    2002-09-20

    Adenovirus binds its receptor (CAR), enters cells, and replicates. It must then escape to the environment to infect a new host. We found that following infection, human airway epithelia first released adenovirus to the basolateral surface. Virus then traveled between epithelial cells to emerge on the apical surface. Adenovirus fiber protein, which is produced during viral replication, facilitated apical escape. Fiber binds CAR, which sits on the basolateral membrane where it maintains tight junction integrity. When fiber bound CAR, it disrupted junctional integrity, allowing virus to filter between the cells and emerge apically. Thus, adenovirus exploits its receptor for two important but distinct steps in its life cycle: entry into host cells and escape across epithelial barriers to the environment.

  20. Escape of magnetic toroids from the Sun

    NASA Technical Reports Server (NTRS)

    Bieber, John W.; Rust, David M.

    1995-01-01

    Analysis of heliospheric magnetic fields at 1 AU shows that 10(exp 24) Mx of net azimuthal flux escapes from the Sun per solar cycle. This rate is consistent with rates derived from other indicators of flux escape, including coronal mass ejections and filament eruptions. The toroidal flux escape rate is compared with the apparent rate of flux emergence at the solar surface, and it is concluded that escaping toroids will remove at least 20% of the emerging flux, and may remove as much as 100% of emerging flux if multiple eruptions occur on the toroids. The data imply that flux escapes the Sun with an efficiency far exceeding Parker's upper limit estimate of 3%. Toroidal flux escape is almost certainly the source of the observed overwinding of the interplanetary magnetic field spiral. Two mechanisms to facilitate net flux escape are discussed: helicity charging to push open the fields and flux transport with reconnection to close them off. We estimate the Sun will shed approximately 2 x 10(exp 45) of magnetic helicity per solar cycle, leading to a mean helicity density of 100 Mx(exp 2)cm(exp -3) at 1 AU, which agrees well with observations.

  1. Interspecific evaluation of octopus escape behavior.

    PubMed

    Wood, James B; Anderson, Roland C

    2004-01-01

    The well-known ability of octopuses to escape enclosures is a behavior that can be fatal and, therefore, is an animal welfare issue. This study obtained survey data from 38 participants-primarily scientists and public aquarists who work with octopuses-on 25 described species of octopus. The study demonstrates that the likeliness to escape is species specific (p =.001). The study gives husbandry techniques to keep captive octopuses contained. This first interspecific study of octopus escape behavior allows readers to make informed species-specific husbandry choices.

  2. Great Comets

    NASA Astrophysics Data System (ADS)

    Burnham, Robert

    2000-05-01

    Spectacular and mysterious objects that come and go in the night sky, comets have dwelt in our popular culture for untold ages. As remnants from the formation of the Solar system, they are objects of key scientific research and space missions. As one of nature's most potent and dramatic dangers, they pose a threat to our safety--and yet they were the origin of our oceans and perhaps even life itself. This beautifully illustrated book tells the story of the biggest and most awe-inspiring of all comets: those that have earned the title "Great." Robert Burnham focuses on the Great comets Hyakutake in 1996 and Hale-Bopp in 1997, which gripped attention worldwide because, for many, they were the first comets ever seen. He places these two recent comets in the context of their predecessors from past ages, among them the famous Comet Halley. Great Comets explains the exciting new discoveries that have come from these magnificent objects and profiles the spaceprobes to comets due for launch in the next few years. The book even takes a peek behind Hollywood's science-fiction fantasies to assess the real risks humanity faces from potential impacts of both comets and asteroids. For everyone interested in astronomy, this exciting book reveals the secrets of the Great Comets and provides essential tools for keeping up to date with comet discoveries in the future. Robert Burnham has been an amateur astronomer since the mid-1950s. He has been a senior editor of Astronomy magazine (1986-88) and is the author of many books and CD-ROMS, including Comet Hale-Bopp: Find and Enjoy the Great Comet and Comet Explorer.

  3. A quantitative quasispecies theory-based model of virus escape mutation under immune selection.

    PubMed

    Woo, Hyung-June; Reifman, Jaques

    2012-08-01

    Viral infections involve a complex interplay of the immune response and escape mutation of the virus quasispecies inside a single host. Although fundamental aspects of such a balance of mutation and selection pressure have been established by the quasispecies theory decades ago, its implications have largely remained qualitative. Here, we present a quantitative approach to model the virus evolution under cytotoxic T-lymphocyte immune response. The virus quasispecies dynamics are explicitly represented by mutations in the combined sequence space of a set of epitopes within the viral genome. We stochastically simulated the growth of a viral population originating from a single wild-type founder virus and its recognition and clearance by the immune response, as well as the expansion of its genetic diversity. Applied to the immune escape of a simian immunodeficiency virus epitope, model predictions were quantitatively comparable to the experimental data. Within the model parameter space, we found two qualitatively different regimes of infectious disease pathogenesis, each representing alternative fates of the immune response: It can clear the infection in finite time or eventually be overwhelmed by viral growth and escape mutation. The latter regime exhibits the characteristic disease progression pattern of human immunodeficiency virus, while the former is bounded by maximum mutation rates that can be suppressed by the immune response. Our results demonstrate that, by explicitly representing epitope mutations and thus providing a genotype-phenotype map, the quasispecies theory can form the basis of a detailed sequence-specific model of real-world viral pathogens evolving under immune selection.

  4. [Viral superantigens].

    PubMed

    Us, Dürdal

    2016-07-01

    , expression of endogenous SAgs leads to thymic deletion of responding T cells (bearing Vβ6-9+ TCR) due to self-tolerance induction during the fetal life, and protects the host against future exogenous MMTV infections. The SAg of rabies virus is the N protein found in nucleocapsid structure and stimulates Vβ8+TCR-bearing T cells. The SAg-induced polyclonal activation of T cells leads to turn-off the specific immune response, to enhance the immunopathogenesis and facilitates viral transmission from the initial site of infection (the muscle tissue) to the nerve endings. In case of EBV-associated SAg that activates Vβ13+TCR-bearing T cells, it was detected that the SAg activity was not encoded by EBV itself, but instead was due to the transactivation of HERV-K18 by EBV latent membrane proteins, whose env gene encodes the SAg (Sutkowski, et al. 2001). It has been denoted that EBV-induced SAg expression plays a role in the long-term persistence and latency of virus in memory B cells, in the development of autoimmune diseases and in the oncogenesis mechanisms. The proteins which are identified as SAgs of HIV are Nef and gp120. It is believed that, the massive activation of CD4+ T cells (selectively with Vβ-12+, Vβ-5.3+ and Vβ-18+ TCRs) in early stages of infection and clonal deletion, anergy and apoptosis of bystander T cells in the late stages may be due to SAg property of Nef protein, as well as the other mechanisms. However there are some studies indicating that Nef does not act as a SAg (Lapatschek, et al. 2001). HIV gp120 glycoprotein is a B-cell SAg that binds to VH3-expressing B cell receptors and causes polyclonal B cell activation. In addition, binding of gp120 to IgE on the surface of basophiles and mast cells causes activation of those cells, secretion of high level proinflammatory mediators leading to allergic reactions and tissue damage. In a recent study, the depletion (anergy or deletion) of T cell populations bearing Vβ12+, Vβ13+ and Vβ17+ TCR have been

  5. Escape of H and D from Mars' Atmosphere and the Evolution of its Crustal Water Reservoirs

    NASA Technical Reports Server (NTRS)

    Hartle, Richard E.; Einaudi, Franco (Technical Monitor)

    2001-01-01

    The evolution of water on Mars involves preferential escape of hydrogen over deuterium, producing its deuterium rich atmosphere with a D/H ratio 5.2 times that of terrestrial water. In the past decade, several estimates have been made of the magnitudes of current and ancient crustal water reservoirs on Mars that freely exchange with its atmosphere. Some of the differences in the magnitudes of the reservoirs are influenced by differences in the following basic parameters: composition of H, D, H2 and HD at the exobase; thermal history of the atmosphere; escape mechanisms; and the D/H ratio of earlier epochs as inferred from meteorites. The dominant escape mechanism used in the estimates is Jeans escape. However, the Jeans escape flux is enhanced considerably when atmospheric winds and rotation are applied at the exobase . This constraint is of particular importance because the enhancement of the D escape flux can be an order of magnitude greater than the enhancement of the H escape flux. This preferential enhancement of the D escape flux over that of H means that a great deal more H must escape (than in the case without winds and rotation) to attain the same D/H ratio in the today's atmosphere. Another new constraint on reservoir magnitudes comes from the recent interpretation of Martian meteorite data, which suggests that the D/H ratio was 2 times that of terrestrial water at the end of the heavy bombardment period (1). These two constraints together lead to larger current and ancient crustal water reservoirs. Applying Rayleigh fractionation, new estimates of the sizes of the water reservoirs are made using the above constraints along with plausible values for hydrogen and deuterium densities, temperatures, wind speeds and rotation rates at the exobase.

  6. Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail.

    PubMed

    Kugelman, Jeffrey R; Kugelman-Tonos, Johanny; Ladner, Jason T; Pettit, James; Keeton, Carolyn M; Nagle, Elyse R; Garcia, Karla Y; Froude, Jeffrey W; Kuehne, Ana I; Kuhn, Jens H; Bavari, Sina; Zeitlin, Larry; Dye, John M; Olinger, Gene G; Sanchez-Lockhart, Mariano; Palacios, Gustavo F

    2015-09-29

    MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape. PMID:26365189

  7. Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail.

    PubMed

    Kugelman, Jeffrey R; Kugelman-Tonos, Johanny; Ladner, Jason T; Pettit, James; Keeton, Carolyn M; Nagle, Elyse R; Garcia, Karla Y; Froude, Jeffrey W; Kuehne, Ana I; Kuhn, Jens H; Bavari, Sina; Zeitlin, Larry; Dye, John M; Olinger, Gene G; Sanchez-Lockhart, Mariano; Palacios, Gustavo F

    2015-09-29

    MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape.

  8. Biogeochemistry: Nocturnal escape route for marsh gas

    NASA Astrophysics Data System (ADS)

    Anthony, Katey Walter; MacIntyre, Sally

    2016-07-01

    A field study of methane emissions from wetlands reveals that more of the gas escapes through diffusive processes than was thought, mostly at night. Because methane is a greenhouse gas, the findings have implications for global warming.

  9. Great Lakes

    USGS Publications Warehouse

    Edsall, Thomas A.; Mac, Michael J.; Opler, Paul A.; Puckett Haecker, Catherine E.; Doran, Peter D.

    1998-01-01

    The wild plants and animals and the natural systems that support them in the Great Lakes region are valuable resources of considerable local, regional, and national interest. They are also, in part, transboundary resources that the U.S. shares with its Canadian neighbors to the north. The way these resources are changing over time is inadequately known and is a concern for resource users and for those charged with managing and protecting these unique and valuable resources. This chapter describes the wild plants and animals and the systems that support them in the Great Lakes region; addresses their condition; and points out the gaps in our knowledge about them that, if filled, would aid in their conservation and appropriate use.

  10. Development of X-15 escape system

    NASA Technical Reports Server (NTRS)

    Hegenwald, J F

    1958-01-01

    The content of this paper is concerned primarily with testing and determining the suitability of such factors as cockpit mobility, escape potential, mechanical reliability, post-separation performance, and airframe compatibility. Integrating the results of the various studies led to the conclusion that the pressure suit in combination with the open ejection seat would best satisfy the X-15 emergency-escape requirements by virtue of elimination of capsule-imposed penalties on aircraft performance and significant reduction in development time.

  11. Great Expectations for "Great Expectations."

    ERIC Educational Resources Information Center

    Ridley, Cheryl

    Designed to make the study of Dickens'"Great Expectations" an appealing and worthwhile experience, this paper presents a unit of study intended to help students gain (1) an appreciation of Dickens' skill at creating realistic human characters; (2) an insight into the problems of a young man confused by false values and unreal ambitions and ways to…

  12. Great Ideas for Great Behavior.

    ERIC Educational Resources Information Center

    Reep, Beverly B.

    1991-01-01

    Describes a South Carolina elementary school principal's program for decreasing discipline referrals and creating a positive school environment. The Great Behavior program involves weekly drawings and prizes for well-behaved students and an end-of-school party and pie-throwing event. Following a first-year 47 percent reduction in discipline…

  13. Viral Skin Diseases.

    PubMed

    Ramdass, Priya; Mullick, Sahil; Farber, Harold F

    2015-12-01

    In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome.

  14. Viral Skin Diseases.

    PubMed

    Ramdass, Priya; Mullick, Sahil; Farber, Harold F

    2015-12-01

    In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome. PMID:26612372

  15. Escape from an effortful situation1

    PubMed Central

    Miller, L. Keith

    1968-01-01

    This experiment investigated the tendency to escape from a situation requiring effortful responding. Five human subjects responded in a situation where the response mechanism required 20-lb force to operate; responses were reinforced according to a variable-interval schedule. A subject escaped from this situation by emitting a vocal response which produced a 60-sec “easy period”. During the easy period the reinforcement contingency was switched to a response mechanism requiring 1 lb to operate. It was found that: (1) Escape responding could be conditioned and maintained by producing the easy period; the easy period did not maintain escape responding when the force requirement in the normal situation was equated with it. (2) The rate of escape responding was a function of the magnitude of the force normally required. (3) When easy periods were scheduled after fixed ratios, pausing from the end of the previous easy period to the first escape response was noted. It was concluded that a situation requiring high-force responding is a negative reinforcer. The pattern of fixed-ratio responding suggests that this reinforcer produces typical schedule control in human subjects. PMID:5749186

  16. Polymer escape from a confining potential

    SciTech Connect

    Mökkönen, Harri; Ikonen, Timo; Jónsson, Hannes; Ala-Nissila, Tapio

    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.

  17. Polymer escape from a confining potential

    NASA Astrophysics Data System (ADS)

    Mökkönen, Harri; Ikonen, Timo; Jónsson, Hannes; Ala-Nissila, Tapio

    2014-02-01

    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.

  18. SUMO-conjugating enzyme E2 UBC9 mediates viral immediate-early protein SUMOylation in crayfish to facilitate reproduction of white spot syndrome virus.

    PubMed

    Chen, An-Jing; Gao, Lu; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing

    2013-01-01

    Successful viruses have evolved superior strategies to escape host defenses or exploit host biological pathways. Most of the viral immediate-early (ie) genes are essential for viral infection and depend solely on host proteins; however, the molecular mechanisms are poorly understood. In this study, we focused on the modification of viral IE proteins by the crayfish small ubiquitin-related modifier (SUMO) and investigated the role of SUMOylation during the viral life cycle. SUMO and SUMO ubiquitin-conjugating enzyme 9 (UBC9) involved in SUMOylation were identified in red swamp crayfish (Procambarus clarkii). Both SUMO and UBC9 were upregulated in crayfish challenged with white spot syndrome virus (WSSV). Replication of WSSV genes increased in crayfish injected with recombinant SUMO or UBC9, but injection of mutant SUMO or UBC9 protein had no effect. Subsequently, we analyzed the mechanism by which crayfish SUMOylation facilitates WSSV replication. Crayfish UBC9 bound to all three WSSV IE proteins tested, and one of these IE proteins (WSV051) was covalently modified by SUMO in vitro. The expression of viral ie genes was affected and that of late genes was significantly inhibited in UBC9-silenced or SUMO-silenced crayfish, and the inhibition effect was rescued by injection of recombinant SUMO or UBC9. The results of this study demonstrate that viral IE proteins can be modified by crayfish SUMOylation, prompt the expression of viral genes, and ultimately benefit WSSV replication. Understanding of the mechanisms by which viruses exploit host components will greatly improve our knowledge of the virus-host "arms race" and contribute to the development of novel methods against virulent viruses.

  19. GREAT optics

    NASA Astrophysics Data System (ADS)

    Wagner-Gentner, Armin; Graf, Urs U.; Philipp, Martin; Rabanus, David; Stutzki, Jürgen

    2004-10-01

    The German REceiver for Astronomy at Terahertz frequencies (GREAT) is a first generation PI instrument for the SOFIA telescope, developed by a collaboration between the MPIfR, KOSMA, DLR, and the MPAe. The first three institutes each contribute one heterodyne receiver channel to operate at 1.9, 2.7 and 4.7 THz, respectively. A later addition of a e.g. 1.4 THz channel is planned. The GREAT instrument is developed to carry two cryostats at once. That means that any two of the three frequencies can be observed simultaneously. Therefore, we need to be able to quickly exchange the optics benches, the local oscillator (LO) subsystems, and the cryostats containing the mixer devices. This demands a high modularity and flexibility of our receiver concept. Our aim is to avoid the need for realignment when swapping receiver channels. After an overview of the common GREAT optics, a detailed description of several parts (optics benches, calibration units, diplexer, focal plane imager) is given. Special emphasis is given to the LO optics of the KOSMA 1.9 THz channel, because its backward wave oscillator has an astigmatic output beam profile, which has to be corrected for. We developed astigmatic off-axis mirrors to compensate this astigmatism. The mirrors are manufactured in-house on a 5 axis CNC milling machine. We use this milling machine to obtain optical components with highest surface accuracy (about 5 microns) appropriate for these wavelengths. Based on the CNC machining capabilities we present our concept of integrated optics, which means to manufacture optical subsystems monolithically. The optics benches are located on three point mounts, which in conjunction with the integrated optics concept ensure the required adjustment free optics setup.

  20. Statistical Mechanics and Thermodynamics of Viral Evolution

    NASA Astrophysics Data System (ADS)

    Jones, Barbara; Kaufman, James

    Using methods drawn from physics we study the life cycle of viruses. We analyze a model of viral infection and evolution using the ``grand canonical ensemble'' and formalisms from statistical mechanics and thermodynamics. Using this approach we determine possible genetic states of a model virus and host as a function of two independent pressures-immune response and system temperature. We show the system has a real thermodynamic temperature, and discover a new phase transition between a positive temperature regime of normal replication and a negative temperature ``disordered'' phase of the virus. We distinguish this from previous observations of a phase transition that arises as a function of mutation rate. From an evolutionary biology point of view, at steady state the viruses naturally evolve to distinct quasispecies. The approach used here could be refined to apply to real biological systems, perhaps providing insight into immune escape, the emergence of novel pathogens and other results of viral evolution.

  1. Cholesterol Is Required for Endocytosis and Endosomal Escape of Adenovirus Type 2

    PubMed Central

    Imelli, Nicola; Meier, Oliver; Boucke, Karin; Hemmi, Silvio; Greber, Urs F.

    2004-01-01

    The species C adenovirus type 2 (Ad2) and Ad5 bind the coxsackievirus B Ad receptor and αv integrin coreceptors and enter epithelial cells by clathrin-mediated endocytosis. This pathway is rapid and efficient. It leads to cell activation and the cholesterol-dependent formation of macropinosomes. Macropinosomes are triggered to release their contents when incoming Ad2 escapes from endosomes. Here, we show that cholesterol extraction of epithelial cells by methyl-β-cyclodextrin (mβCD) treatment reduced Ad5-mediated luciferase expression ∼4-fold. The addition of cholesterol to normal cells increased gene expression in a dose-dependent manner up to threefold, but it did not restore gene expression in mβCD-treated cells. mβCD had no effect in the presence of excess cholesterol, indicating that the inhibition of gene expression was due specifically to cholesterol depletion. Cholesterol depletion inhibited rapid Ad2 endocytosis, endosomal escape, and nuclear targeting, consistent with the notion that clathrin-dependent endocytosis of Ad2 is cholesterol dependent. In cholesterol-reduced cells, Ad2 internalized at a low rate, suggestive of an alternative, clathrin-independent, low-capacity entry pathway. While exogenous cholesterol completely restored rapid Ad2 endocytosis, macropinocytosis, and macropinosome disruption, it did not, surprisingly, restore viral escape from endosomes. Our results indicate that macropinosome disruption and endosomal escape of Ad2 are independent events in cells depleted of and then refilled with cholesterol, suggesting that viral escape from endosomes requires lipid-controlled membrane homeostasis, trafficking, or signaling. PMID:14990728

  2. Waiting times for the appearance of cytotoxic T-lymphocyte escape mutants in chronic HIV-1 infection

    SciTech Connect

    Liu Yi . E-mail: yiliu197@u.washington.edu; Mullins, James I.; Mittler, John E.

    2006-03-30

    The failure of HIV-1 to escape at some cytotoxic T-lymphocyte (CTL) epitopes has generally been explained in terms of viral fitness costs or ineffective or attenuated CTL responses. Relatively little attention has been paid to the evolutionary time required for escape mutants to be detected. This time is significantly affected by selection, mutation rates, the presence of other advantageous mutations, and the effective population size of HIV-1 in vivo (typically estimated to be {approx}10{sup 3} in chronically infected patients, though one study has estimated it to be {approx}10{sup 5}). Here, we use a forward simulator with experimentally estimated HIV-1 parameters to show that these delays can be substantial. For an effective population size of 10{sup 3}, even highly advantageous mutants (s = 0.5) may not be detected for a couple of years in chronically infected patients, while moderately advantageous escape mutants (s = 0.1) may not be detected for up to 10 years. Even with an effective population size of 10{sup 5}, a moderately advantageous escape mutant (s = 0.1) may not be detected in the population within 2 years if it has to compete with other selectively advantageous mutants. Stochastic evolutionary forces, therefore, in addition to viral fitness costs and ineffective or attenuated CTL responses, must be taken into account when assessing the selection of CTL escape mutations.

  3. 46 CFR 28.390 - Means of escape.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Means of escape. 28.390 Section 28.390 Shipping COAST... Operate With More Than 16 Individuals on Board § 28.390 Means of escape. (a) Each space which is used by... two widely separated means of escape. At least one of the means of escape must be independent...

  4. Hydrogen Escape from early Earth and Mars

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  5. MEMO: Mars Escape and Magnetic Orbiter

    NASA Astrophysics Data System (ADS)

    Chassefiere, E.; Langlais, B.; Leblanc, F.; Sotin, C.; Barabash, S.; Dehant, V.; Dougherty, M.; Lammer, H.; Mandea, M.; Vennerstrom, S.

    There are several reasons to believe that Mars could have become an Earth like planet rather than the present dry and cold planet. In particular, many elements suggest the presence of liquid water at the Martian surface during a relatively short period at an early stage of its history. Since liquid water may have been the birthplace for life on Earth, the fate of Martian water is one of the major key and yet unanswered question to be solved. Mars Escape and Magnetic Orbiter (MEMO) is a low periapsis orbiter of Mars devoted to the measurement of present escape and the characterization of the fossil magnetic field of Mars. The use of a low periapsis altitude orbit (120-150 km) is required to detect and quantify all populations of atoms and molecules involved in escape. It is also required to measure the magnetic field of Mars with an unprecedented spatial resolution that would allow getting a more precise timing of the dynamo and its disappearance. Achieving a full characterization of atmospheric escape, and extrapolating it back to the past requires: (i) to measure escape fluxes of neutral and ion species, and characterize the dynamics and chemistry of the regions of the atmosphere where escape occurs (thermosphere, ionosphere, exosphere), as well as their responses to solar activity, and (ii) to characterize the lateral variations of the magnetic field of lithospheric origin, and by extension, the timing of the Martian dynamo. Of particular interest is the extinction of the dynamo that is thought to have enhanced the atmospheric escape processes still operating today. The proposed low-periapsis orbiter will consist of the following elements: • An "Escape Package" to characterize by both in-situ and remote measurements the thermosphere, ionosphere, exosphere and solar wind interaction regions (from one hundred to several thousand km), including thermal, suprathermal 1 and energetic particles. • A "Magnetic Field Package", to characterize the magnetization of the

  6. Compensatory escape mechanism at low Reynolds number

    PubMed Central

    Gemmell, Brad J.; Sheng, Jian; Buskey, Edward J.

    2013-01-01

    Despite high predation pressure, planktonic copepods remain one of the most abundant groups on the planet. Their escape response provides one of most effective mechanisms to maximize evolutionary fitness. Owing to their small size (100 µm) compared with their predators (>1 mm), increasing viscosity is believed to have detrimental effects on copepods’ fitness at lower temperature. Using high-speed digital holography we acquire 3D kinematics of the nauplius escape including both location and detailed appendage motion. By independently varying temperature and viscosity we demonstrate that at natural thermal extremes, contrary to conventional views, nauplii achieve equivalent escape distance while maintaining optimal velocity. Using experimental results and kinematic simulations from a resistive force theory propulsion model, we demonstrate that a shift in appendage timing creates an increase in power stroke duration relative to recovery stroke duration. This change allows the nauplius to limit losses in velocity and maintain distance during escapes at the lower bound of its natural thermal range. The shift in power stroke duration relative to recovery stroke duration is found to be regulated by the temperature dependence of swimming appendage muscle groups, not a dynamic response to viscosity change. These results show that copepod nauplii have natural adaptive mechanisms to compensate for viscosity variations with temperature but not in situations in which viscosity varies independent of temperature, such as in some phytoplankton blooms. Understanding the robustness of escapes in the wake of environmental changes such as temperature and viscosity has implications in assessing the future health of performance compensation. PMID:23487740

  7. Escape as reinforcement and escape extinction in the treatment of feeding problems.

    PubMed

    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 similar to those of previous studies, in that reinforcement alone did not result in increases in mouth clean or decreases in inappropriate behavior (e.g., Piazza, Patel, Gulotta, Sevin, & Layer, 2003). Increases in mouth clean and decreases in inappropriate behavior occurred when the therapist implemented EE independent of the presence or absence of reinforcement. Results are discussed in terms of the role of negative reinforcement in the etiology and treatment of feeding problems.

  8. Escape as reinforcement and escape extinction in the treatment of feeding problems.

    PubMed

    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 similar to those of previous studies, in that reinforcement alone did not result in increases in mouth clean or decreases in inappropriate behavior (e.g., Piazza, Patel, Gulotta, Sevin, & Layer, 2003). Increases in mouth clean and decreases in inappropriate behavior occurred when the therapist implemented EE independent of the presence or absence of reinforcement. Results are discussed in terms of the role of negative reinforcement in the etiology and treatment of feeding problems. PMID:22219525

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

    PubMed Central

    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 similar to those of previous studies, in that reinforcement alone did not result in increases in mouth clean or decreases in inappropriate behavior (e.g., Piazza, Patel, Gulotta, Sevin, & Layer, 2003). Increases in mouth clean and decreases in inappropriate behavior occurred when the therapist implemented EE independent of the presence or absence of reinforcement. Results are discussed in terms of the role of negative reinforcement in the etiology and treatment of feeding problems. PMID:22219525

  10. HIV-1 Integrase Binds the Viral RNA Genome and Is Essential during Virion Morphogenesis.

    PubMed

    Kessl, Jacques J; Kutluay, Sebla B; Townsend, Dana; Rebensburg, Stephanie; Slaughter, Alison; Larue, Ross C; Shkriabai, Nikoloz; Bakouche, Nordine; Fuchs, James R; Bieniasz, Paul D; Kvaratskhelia, Mamuka

    2016-08-25

    While an essential role of HIV-1 integrase (IN) for integration of viral cDNA into human chromosome is established, studies with IN mutants and allosteric IN inhibitors (ALLINIs) have suggested that IN can also influence viral particle maturation. However, it has remained enigmatic as to how IN contributes to virion morphogenesis. Here, we demonstrate that IN directly binds the viral RNA genome in virions. These interactions have specificity, as IN exhibits distinct preference for select viral RNA structural elements. We show that IN substitutions that selectively impair its binding to viral RNA result in eccentric, non-infectious virions without affecting nucleocapsid-RNA interactions. Likewise, ALLINIs impair IN binding to viral RNA in virions of wild-type, but not escape mutant, virus. These results reveal an unexpected biological role of IN binding to the viral RNA genome during virion morphogenesis and elucidate the mode of action of ALLINIs. PMID:27565348

  11. Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins.

    PubMed

    Boutwell, Christian L; Carlson, Jonathan M; Lin, Tien-Ho; Seese, Aaron; Power, Karen A; Peng, Jian; Tang, Yanhua; Brumme, Zabrina L; Heckerman, David; Schneidewind, Arne; Allen, Todd M

    2013-04-01

    Cytotoxic-T-lymphocyte (CTL) escape mutations undermine the durability of effective human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cell responses. The rate of CTL escape from a given response is largely governed by the net of all escape-associated viral fitness costs and benefits. The observation that CTL escape mutations can carry an associated fitness cost in terms of reduced virus replication capacity (RC) suggests a fitness cost-benefit trade-off that could delay CTL escape and thereby prolong CD8 response effectiveness. However, our understanding of this potential fitness trade-off is limited by the small number of CTL escape mutations for which a fitness cost has been quantified. Here, we quantified the fitness cost of the 29 most common HIV-1B Gag CTL escape mutations using an in vitro RC assay. The majority (20/29) of mutations reduced RC by more than the benchmark M184V antiretroviral drug resistance mutation, with impacts ranging from 8% to 69%. Notably, the reduction in RC was significantly greater for CTL escape mutations associated with protective HLA class I alleles than for those associated with nonprotective alleles. To speed the future evaluation of CTL escape costs, we also developed an in silico approach for inferring the relative impact of a mutation on RC based on its computed impact on protein thermodynamic stability. These data illustrate that the magnitude of CTL escape-associated fitness costs, and thus the barrier to CTL escape, varies widely even in the conserved Gag proteins and suggest that differential escape costs may contribute to the relative efficacy of CD8 responses. PMID:23365420

  12. Pyrolaser development for aircrew escape systems

    NASA Astrophysics Data System (ADS)

    Paul, Ben E.; Cobbett, John A.

    A Laser Ordnance Initiation System (LOIS) has been developed for use in military aircraft emergency escape/egress systems. Applying LOIS to a single-seat and a two-seat F-16 aircraft escape system has proven both cost and weight effective. In both cases, system redundancy is supplied. The large weight reduction is attributed to the elimination of certain initiators, the small size of the logic components and the low weight of the fiber-optic lines (0.037 lb/ft). The required components for a laser operated escape systems are described, with emphasis on the mechanically actuated pyrolaser, which supplies the required energy to activate the various seat devices; the optical AND gate, which provides the logic to ensure proper event sequencing; and the optical mode selector, which establishes aircrew control of the ejection sequence in multiseat aircraft only.

  13. Pair production and escape in accretion disks.

    NASA Astrophysics Data System (ADS)

    Meirelles Filho, C.; Liang, E. P.

    It is shown that, in the absence of confining mechanisms, there will be a non-negligible amount of pairs escaping from the inner region of a Comptonized soft photon two-temperature accretion disk, when pair production is not balanced by annihilation. Assuming conditions such that the photons and particles in the disk can be regarded as close to a Wien plasma (Svensson, 1984), the authors calculate the rate of pair escape from the disk for both a situation close to pair balance and a situation with the rate of escape exceeding annihilation. The pairs are assumed to be created by photon-photon processes. Within this model one can account for the 511 keV γ-ray luminosity due to pair annihilation in the ISM, as recently observed in the Einstein source.

  14. Martian magnetic anomalies and ionosphere escape rate.

    NASA Astrophysics Data System (ADS)

    Fedorov, A.; Barabash, S.; Sauvaud, J.-A.

    2012-04-01

    Looking forward to the MAVEN mission, it seems very useful to return to Mars Express data to refresh an important problem of Martian atmosphere escape: what role the crustal magnetic field may play in this process? There are several publications on this topic with completely opposite conclusions. The last hybrid simulations show that the magnetic anomalies significantly reduce the ion loss rate during solar minimum. We are trying to use a new approach to Mars Express IMA data analysis to check how it is possible.On the base of a statistical study of the ion distributions in the Martian magnetotail we show that the characteristic accelerated ions are not associated with the magnetic anomalies but only with interplanetary magnetic field clock angle. Moreover the magnetic anomalies screen and deviate the escaping flow leading to reducing of the total loss rate. Finally the observed heavy ions escaping rate is in a fantastic agreement with simulation results.

  15. Escape statistics for parameter sweeps through bifurcations.

    PubMed

    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.

  16. Thermal escape from extrasolar giant planets

    PubMed Central

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

    2014-01-01

    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. PMID:24664923

  17. Thermal escape from extrasolar giant planets.

    PubMed

    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. PMID:24664923

  18. Thermal escape from extrasolar giant planets.

    PubMed

    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.

  19. Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection.

    PubMed

    Guglietta, Silvia; Garbuglia, Anna Rosa; Pacciani, Valentina; Scottà, Cristiano; Perrone, Maria Paola; Laurenti, Luca; Spada, Enea; Mele, Alfonso; Capobianchi, Maria Rosaria; Taliani, Gloria; Folgori, Antonella; Vitelli, Alessandra; Ruggeri, Lionello; Nicosia, Alfredo; Piccolella, Enza; Del Porto, Paola

    2005-09-01

    Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8+ T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8+ T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8(+ T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi-species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8+ T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage. PMID:16114108

  20. Two Escape Mechanisms of Influenza A Virus to a Broadly Neutralizing Stalk-Binding Antibody

    PubMed Central

    Chai, Ning; Swem, Lee R.; Reichelt, Mike; Chen-Harris, Haiyin; Luis, Elizabeth; Park, Summer; Fouts, Ashley; Lupardus, Patrick; Wu, Thomas D.; Li, Olga; McBride, Jacqueline; Lawrence, Michael; Xu, Min; Tan, Man-Wah

    2016-01-01

    Broadly neutralizing antibodies targeting the stalk region of influenza A virus (IAV) hemagglutinin (HA) are effective in blocking virus infection both in vitro and in vivo. The highly conserved epitopes recognized by these antibodies are critical for the membrane fusion function of HA and therefore less likely to be permissive for virus mutational escape. Here we report three resistant viruses of the A/Perth/16/2009 strain that were selected in the presence of a broadly neutralizing stalk-binding antibody. The three resistant viruses harbor three different mutations in the HA stalk: (1) Gln387Lys; (2) Asp391Tyr; (3) Asp391Gly. The Gln387Lys mutation completely abolishes binding of the antibody to the HA stalk epitope. The other two mutations, Asp391Tyr and Asp391Gly, do not affect antibody binding at neutral pH and only slightly reduce binding at low pH. Interestingly, they enhance the fusion ability of the HA, representing a novel mechanism that allows productive membrane fusion even in the presence of antibody and hence virus escape from antibody neutralization. Therefore, these mutations illustrate two different resistance mechanisms used by IAV to escape broadly neutralizing stalk-binding antibodies. Compared to the wild type virus, the resistant viruses release fewer progeny viral particles during replication and are more sensitive to Tamiflu, suggesting reduced viral fitness. PMID:27351973

  1. Modelling the Spread of HIV Immune Escape Mutants in a Vaccinated Population

    PubMed Central

    Fryer, Helen R.; McLean, Angela R.

    2011-01-01

    Because cytotoxic T-lymphocytes (CTLs) have been shown to play a role in controlling human immunodeficiency virus (HIV) infection and because CTL-based simian immunodeficiency virus (SIV) vaccines have proved effective in non-human primates, one goal of HIV vaccine design is to elicit effective CTL responses in humans. Such a vaccine could improve viral control in patients who later become infected, thereby reducing onwards transmission and enhancing life expectancy in the absence of treatment. The ability of HIV to evolve mutations that evade CTLs and the ability of these ‘escape mutants’ to spread amongst the population poses a challenge to the development of an effective and robust vaccine. We present a mathematical model of within-host evolution and between-host transmission of CTL escape mutants amongst a population receiving a vaccine that elicits CTL responses to multiple epitopes. Within-host evolution at each epitope is represented by the outgrowth of escape mutants in hosts who restrict the epitope and their reversion in hosts who do not restrict the epitope. We use this model to investigate how the evolution and spread of escape mutants could affect the impact of a vaccine. We show that in the absence of escape, such a vaccine could markedly reduce the prevalence of both infection and disease in the population. However the impact of such a vaccine could be significantly abated by CTL escape mutants, especially if their selection in hosts who restrict the epitope is rapid and their reversion in hosts who do not restrict the epitope is slow. We also use the model to address whether a vaccine should span a broad or narrow range of CTL epitopes and target epitopes restricted by rare or common HLA types. We discuss the implications and limitations of our findings. PMID:22144883

  2. Statistical theory of asteroid escape rates.

    PubMed

    Jaffé, Charles; Ross, Shane D; Lo, Martin W; Marsden, Jerrold; Farrelly, David; Uzer, T

    2002-07-01

    Transition states in phase space are identified and shown to regulate the rate of escape of asteroids temporarily captured in circumplanetary orbits. The transition states, similar to those occurring in chemical reaction dynamics, are then used to develop a statistical semianalytical theory for the rate of escape of asteroids temporarily captured by Mars. Theory and numerical simulations are found to agree to better than 1%. These calculations suggest that further development of transition state theory in celestial mechanics, as an alternative to large-scale numerical simulations, will be a fruitful approach to mass transport calculations. PMID:12097024

  3. Statistical theory of asteroid escape rates.

    PubMed

    Jaffé, Charles; Ross, Shane D; Lo, Martin W; Marsden, Jerrold; Farrelly, David; Uzer, T

    2002-07-01

    Transition states in phase space are identified and shown to regulate the rate of escape of asteroids temporarily captured in circumplanetary orbits. The transition states, similar to those occurring in chemical reaction dynamics, are then used to develop a statistical semianalytical theory for the rate of escape of asteroids temporarily captured by Mars. Theory and numerical simulations are found to agree to better than 1%. These calculations suggest that further development of transition state theory in celestial mechanics, as an alternative to large-scale numerical simulations, will be a fruitful approach to mass transport calculations.

  4. The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection

    PubMed Central

    Hodcroft, Emma; Hadfield, Jarrod D.; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O'Shea, Siobhan; Pillay, Deenan; Leigh Brown, Andrew J.

    2014-01-01

    Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8–8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms. PMID:24789308

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

    PubMed

    Miller, Craig R; Johnson, Erin L; Burke, Aran Z; Martin, Kyle P; Miura, Tanya A; Wichman, Holly A; Brown, Celeste J; Ytreberg, F Marty

    2016-01-01

    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.

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

    PubMed

    Miller, Craig R; Johnson, Erin L; Burke, Aran Z; Martin, Kyle P; Miura, Tanya A; Wichman, Holly A; Brown, Celeste J; Ytreberg, F Marty

    2016-01-01

    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. PMID:26925318

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

    PubMed Central

    Johnson, Erin L.; Burke, Aran Z.; Martin, Kyle P.; Miura, Tanya A.; Wichman, Holly A.; Brown, Celeste J.

    2016-01-01

    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. PMID:26925318

  8. Martian Atmospheric and Ionospheric plasma Escape

    NASA Astrophysics Data System (ADS)

    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

  9. Effects of analgesic midbrain stimulation on reflex withdrawal and thermal escape in the rat.

    PubMed

    Soper, W Y

    1976-01-01

    Strong analgesia produced by mesencephalic electrical brain stimulation in rats significantly increased escape latencies in two-way escape from a floor heated by hydraulic circulation. Reflective reactions to pinching and needling were abolished or greatly diminished. Individual differences in the strengths of analgesia, as assessed by instrumental and reflex indicants, were highly correlated. Induction of analgesia was demonstrated in the absence of positive reinforcement effects produced by brain stimulation. The findings are discussed in relation to possible neural pain suppression systems with critical components situated in the midbrain.

  10. Escape from Albuquerque: An Apache Memorate.

    ERIC Educational Resources Information Center

    Greenfeld, Philip J.

    2001-01-01

    Clarence Hawkins, a White Mountain Apache, escaped from the Albuquerque Indian School around 1920. His 300-mile trip home, made with two other boys, exemplifies the reaction of many Indian youths to the American government's plans for cultural assimilation. The tale is told in the form of traditional Apache narrative. (TD)

  11. Developing the E-Scape Software System

    ERIC Educational Resources Information Center

    Derrick, Karim

    2012-01-01

    Most innovations have contextual pre-cursors that prompt new ways of thinking and in their turn help to give form to the new reality. This was the case with the e-scape software development process. The origins of the system existed in software components and ideas that we had developed through previous projects, but the ultimate direction we took…

  12. Animal escapology II: escape trajectory case studies

    PubMed Central

    Domenici, Paolo; Blagburn, Jonathan M.; Bacon, Jonathan P.

    2011-01-01

    Summary Escape trajectories (ETs; measured as the angle relative to the direction of the threat) have been studied in many taxa using a variety of methodologies and definitions. Here, we provide a review of methodological issues followed by a survey of ET studies across animal taxa, including insects, crustaceans, molluscs, lizards, fish, amphibians, birds and mammals. Variability in ETs is examined in terms of ecological significance and morpho-physiological constraints. The survey shows that certain escape strategies (single ETs and highly variable ETs within a limited angular sector) are found in most taxa reviewed here, suggesting that at least some of these ET distributions are the result of convergent evolution. High variability in ETs is found to be associated with multiple preferred trajectories in species from all taxa, and is suggested to provide unpredictability in the escape response. Random ETs are relatively rare and may be related to constraints in the manoeuvrability of the prey. Similarly, reports of the effect of refuges in the immediate environment are relatively uncommon, and mainly confined to lizards and mammals. This may be related to the fact that work on ETs carried out in laboratory settings has rarely provided shelters. Although there are a relatively large number of examples in the literature that suggest trends in the distribution of ETs, our understanding of animal escape strategies would benefit from a standardization of the analytical approach in the study of ETs, using circular statistics and related tests, in addition to the generation of large data sets. PMID:21753040

  13. Centrifugally Stimulated Exospheric Ion Escape at Mercury

    NASA Technical Reports Server (NTRS)

    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.

  14. Nociception and escape behavior in planarians

    NASA Astrophysics Data System (ADS)

    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.

  15. Viral Entry into Cells

    NASA Astrophysics Data System (ADS)

    D'Orsogna, Maria R.

    2010-09-01

    Successful viral infection of a healthy cell requires complex host-pathogen interactions. In this talk we focus on the dynamics specific to the HIV virus entering a eucaryotic cell. We model viral entry as a stochastic engagement of receptors and coreceptors on the cell surface. We also consider the transport of virus material to the cell nucleus by coupling microtubular motion to the concurrent biochemical transformations that render the viral material competent for nuclear entry. We discuss both mathematical and biological consequences of our model, such as the formulation of an effective integrodifferential boundary condition embodying a memory kernel and optimal timing in maximizing viral probabilities.

  16. Harnessing RNA interference for the treatment of viral infections.

    PubMed

    Arbuthnot, Patrick

    2010-01-01

    Exploiting the RNA interference (RNAi) pathway to inhibit viral gene expression has become an active field of research. The approach has potential for therapeutic application and several viruses are susceptible to RNAi-mediated knockdown. Differences in the characteristics of individual viruses require that viral gene silencing be tailored to specific infections. Important considerations are viral tissue tropism, acute or chronic nature of the infection and the efficiency with which antiviral sequences can be delivered to affected tissue. Both synthetic short interfering RNAs (siRNAs) and expressed RNAi activators are being developed for viral therapy. The sustained silencing of expressed antiviral sequences is useful for countering chronic viral infection. siRNAs, which may be chemically modified to improve specificity and stability, are being developed for knockdown of viruses that cause acute or chronic infections. Preventing viral escape from silencing is important and overcoming this problem using combinatorial RNAi or through silencing of host dependency factors is promising. Although improving delivery efficiency and limiting off-target effects remain obstacles, rapid progress continues to be made in the field and it is likely that the goal of achieving licensed RNAi-based viral therapies will soon be realized. PMID:20697601

  17. The age structure of selected countries in the ESCAP region.

    PubMed

    Hong, S

    1982-01-01

    The study objective was to examine the age structure of selected countries in the Economic and Social Commission for Asia and the Pacific (ESCAP) region, using available data and frequently applied indices such as the population pyramid, aged-child ratio, and median age. Based on the overall picture of the age structure thus obtained, age trends and their implication for the near future were arrived at. Countries are grouped into 4 types based on the fertility and mortality levels. Except for Japan, Hong Kong, and Singapore, the age structure in the 18 ESCAP region countries changed comparatively little over the 1950-80 period. The largest structural change occurred in Singapore, where the proportion of children under age 15 in the population declined significantly from 41-27%, while that of persons 65 years and older more than doubled. This was due primarily to the marked decline in fertility from a total fertility rate (TFR) of 6.7-1.8 during the period. Hong Kong also had a similar major transformation during the same period: the proportion of the old age population increased 2 1/2 times, from 2.5-6.3%. The age structures of the 18 ESCAP countries varied greatly by country. 10 countries of the 2 high fertility and mortality types showed a similar young age structural pattern, i.e., they have higher dependency ratios, a higher proportion of children under 15 years, a lower proportion of population 65 years and older, lower aged-child ratios, and younger median ages than the average countries in the less developed regions of the world. With minimal changes over the 1950-80 period, the gap between these countries and the average of the less developed regions widened. Unlike these 10 (mostly South Asian) countries, moderately low fertility and mortality countries (China, Korea, and Sri Lanka) are located between the world average and the less developed region in most of the indices, particularly during the last decade. Although their rate of population aging is not

  18. Testing a Simple Recipe for Estimating Thermal Hydrodynamic Escape Rates in Primitive Terrestrial Atmospheres

    NASA Astrophysics Data System (ADS)

    Friedson, A. J.; Yung, Y. L.; Chen, P.

    2014-12-01

    During the first billion years of the Sun's history, the emission of ultraviolet and X-ray radiation varied from ~100 to ~6 times greater than its present level. The absorption of this intense radiation in the upper atmospheres of the terrestrial planets is believed to have driven rapid hydrodynamic escape, either in the form of energy-limited escape or transonic blow-off. The calculation of escape rates under these circumstances, and in particular the nature of the correct condition to apply at the upper boundary, depends on whether or not the flow remains subsonic below the exobase. If the flow remains subsonic, the kinetic Jeans equations may be applied at the exobase; otherwise, the radius of the sonic point must be located and then appropriate boundary conditions applied at this radius. This seems to suggest that the full hydrodynamic escape problem needs to be solved iteratively to determine where the sonic radius falls and the type of boundary conditions that should be applied. Such an arduous undertaking is generally impractical for standard application in chemical evolution models or related studies. Fortunately, a much easier but still accurate approach to determining whether the flow remains subsonic below the exobase for a given amount of energy deposition has been provided by Johnson et al. (2013, Ap. J. Lett. 768:L4), who base their results on rigorous Discrete Simulation Monte Carlo models. Their model provides the ratio of the escape rate to the energy-limited value as a function of the total XUV heating. The XUV heating, however, is itself coupled to the escape rate through the radial structure of the upper atmosphere, which can become greatly distended for large heating rates. Here we present a simple recipe for estimating the hydrodynamic escape rate that includes the coupling between the escape rate, the radial structure, and the XUV heating while avoiding the use of demanding numerical calculations. The approach involves an iterative semi

  19. Countermeasures against viral diseases of farmed fish.

    PubMed

    Kibenge, Frederick S B; Godoy, Marcos G; Fast, Mark; Workenhe, Samuel; Kibenge, Molly J T

    2012-09-01

    Farmed fish provide an increasing fraction of the human food supply, and are of major economic importance in many countries. As in the case of terrestrial agriculture, bringing together large numbers of animals of a single species (i.e., monoculture) increases the risk of infectious disease outbreaks, including viral infections. Aquaculture, in which farmed fish are kept at high population densities in close proximity with wild fish reservoirs, is ideal for the emergence of wild-type pathogens that exist benignly in local wild fish and/or the spreading of aquatic pathogens to wild fish that enter into or come into close proximity with net cages and with fish escaping from them. This paper provides a general review for the nonspecialist of viral diseases of farmed fish and how they could be prevented or treated. It has five principal objectives: (1) to provide an update on the most important and emerging viral diseases of salmonid aquaculture; (2) to review general aspects of innate antiviral defense against virus infections in fish, including recent advances in antiviral signaling; (3) to discuss current principles and practices of vaccinating fish; (4) to review antiviral drugs that have activity against viruses of farmed fish, and current barriers to employing them in aquaculture; and (5) to discuss the growing use of "functional feeds" in salmonid aquaculture to mitigate viral diseases. In conclusion, despite the challenging aquatic environment, it is expected that well thought-out combinations of vaccination and immunostimulants and/or antiviral drugs could provide solid protection against viral diseases of farmed fish.

  20. Plasticity of Escape Responses: Prior Predator Experience Enhances Escape Performance in a Coral Reef Fish

    PubMed Central

    Ramasamy, Ryan A.; Allan, Bridie J. M.; McCormick, Mark I.

    2015-01-01

    Teleost and amphibian prey undertake fast-start escape responses during a predatory attack in an attempt to avoid being captured. Although previously viewed as a reflex reaction controlled by the autonomic nervous system, the escape responses of individuals when repeatedly startled are highly variable in their characteristics, suggesting some behavioural mediation of the response. Previous studies have shown that fishes are able to learn from past experiences, but few studies have assessed how past experience with predators affect the fast-start response. Here we determined whether prior experience with the smell or sight of a predator (the Dottyback, Pseudochromis fuscus) affected the escape response of juveniles of the Spiny Chromis (Acanthochromis polyacanthus). Results show that individuals exposed to any of the predator cues prior to being startled exhibited a stronger escape response (i.e., reduced latency, increased escape distance, mean response speed, maximum response speed and maximum acceleration) when compared with controls. This study demonstrates the plasticity of escape responses and highlights the potential for naïve reef fish to take into account both visual and olfactory threat cues simultaneously to optimise the amplitude of their kinematic responses to perceived risk. PMID:26244861

  1. Determining the Cellular Diversity of Hepatitis C Virus Quasispecies by Single-Cell Viral Sequencing

    PubMed Central

    McLauchlan, John

    2013-01-01

    Single-cell genomics is emerging as an important tool in cellular biology. We describe for the first time a system to investigate RNA virus quasispecies diversity at the cellular level utilizing hepatitis C virus (HCV) replicons. A high-fidelity nested reverse transcription (RT)-PCR assay was developed, and validation using control transcripts of known copy number indicated a detection limit of 3 copies of viral RNA/reaction. This system was used to determine the cellular diversity of subgenomic JFH-1 HCV replicons constitutively expressed in Huh7 cells. Each cell contained a unique quasispecies that was much less diverse than the quasispecies of the bulk cell population from which the single cells were derived, suggesting the occurrence of independent evolution at the cellular level. An assessment of the replicative fitness of the predominant single-cell quasispecies variants indicated a modest reduction in fitness compared to the wild type. Real-time RT-PCR methods capable of determining single-cell viral loads were developed and indicated an average of 113 copies of replicon RNA per cell, correlating with calculated RNA copy numbers in the bulk cell population. This study introduces a single-cell RNA viral-sequencing method with numerous potential applications to explore host-virus interactions during infection. HCV quasispecies diversity varied greatly between cells in vitro, suggesting different within-cell evolutionary pathways. Such divergent trajectories in vivo could have implications for the evolution and establishment of antiviral-resistant variants and host immune escape mutants. PMID:24049174

  2. HIV-HBV vaccine escape mutant infection with loss of HBV surface antibody and persistent HBV viremia on tenofovir/emtricitabine without antiviral resistance.

    PubMed

    Schirmer, P; Winters, M; Holodniy, M

    2011-11-01

    We report a case of acute hepatitis B virus genotype A vaccine escape mutant infection with loss of HBV vaccine-induced seropositivity in a HIV-1 infected patient. His HBV is unresponsive to tenofovir/emtricitabine treatment demonstrated by persistent viremia despite lacking known resistance mutations and while having an undetectable HIV-1 viral load. PMID:21840252

  3. Launch Pad Escape System Design (Human Spaceflight)

    NASA Technical Reports Server (NTRS)

    Maloney, Kelli

    2011-01-01

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

  4. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import.

    PubMed

    Götz, Veronika; Magar, Linda; Dornfeld, Dominik; Giese, Sebastian; Pohlmann, Anne; Höper, Dirk; Kong, Byung-Whi; Jans, David A; Beer, Martin; Haller, Otto; Schwemmle, Martin

    2016-01-01

    To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome the intracellular restriction factor MxA. Partial escape from MxA restriction can be achieved when the viral nucleoprotein (NP) acquires the critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three residues into the NP of an avian H5N1 virus renders it genetically unstable, resulting in viruses harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded viruses with varying degrees of attenuation in mammalian and avian cells. Additionally, most of the mutant viruses lost the capacity to escape MxA restriction, with the exception of the G16D virus. We show that MxA escape is linked to attenuation by demonstrating that the three substitutions promoting MxA escape disturbed intracellular trafficking of incoming viral ribonucleoprotein complexes (vRNPs), thereby resulting in impaired nuclear import, and that the additional acquired mutations only partially compensate for this import block. We conclude that for adaptation to the human host, AIV must not only overcome MxA restriction but also an associated block in nuclear vRNP import. This inherent difficulty may partially explain the frequent failure of AIV to become pandemic. PMID:26988202

  5. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import

    PubMed Central

    Götz, Veronika; Magar, Linda; Dornfeld, Dominik; Giese, Sebastian; Pohlmann, Anne; Höper, Dirk; Kong, Byung-Whi; Jans, David A.; Beer, Martin; Haller, Otto; Schwemmle, Martin

    2016-01-01

    To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome the intracellular restriction factor MxA. Partial escape from MxA restriction can be achieved when the viral nucleoprotein (NP) acquires the critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three residues into the NP of an avian H5N1 virus renders it genetically unstable, resulting in viruses harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded viruses with varying degrees of attenuation in mammalian and avian cells. Additionally, most of the mutant viruses lost the capacity to escape MxA restriction, with the exception of the G16D virus. We show that MxA escape is linked to attenuation by demonstrating that the three substitutions promoting MxA escape disturbed intracellular trafficking of incoming viral ribonucleoprotein complexes (vRNPs), thereby resulting in impaired nuclear import, and that the additional acquired mutations only partially compensate for this import block. We conclude that for adaptation to the human host, AIV must not only overcome MxA restriction but also an associated block in nuclear vRNP import. This inherent difficulty may partially explain the frequent failure of AIV to become pandemic. PMID:26988202

  6. 33 CFR 143.101 - Means of escape.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Officer in Charge, Marine Inspection, one or more “secondary means of escape.” (d) Unmanned OCS facilities... board, unmanned facilities shall also be provided with one or more “secondary means of escape,” but...

  7. 33 CFR 143.101 - Means of escape.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Officer in Charge, Marine Inspection, one or more “secondary means of escape.” (d) Unmanned OCS facilities... board, unmanned facilities shall also be provided with one or more “secondary means of escape,” but...

  8. 33 CFR 143.101 - Means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Officer in Charge, Marine Inspection, one or more “secondary means of escape.” (d) Unmanned OCS facilities... board, unmanned facilities shall also be provided with one or more “secondary means of escape,” but...

  9. 23. VIEW OF ESCAPE TRAINING TANK, LOOKING NORTHWEST, SHOWING TWOLOCK ...

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

    23. VIEW OF ESCAPE TRAINING TANK, LOOKING NORTHWEST, SHOWING TWO-LOCK RECOMPRESSION CHAMBER IN PASSAGEWAY FROM ELEVATOR TO CUPOLA - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  10. 17. VIEW OF ESCAPE TRAINING TANK, SHOWING ENCLOSED PASSAGEWAY FROM ...

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

    17. VIEW OF ESCAPE TRAINING TANK, SHOWING ENCLOSED PASSAGEWAY FROM ELEVATOR TO 18-FOOT LOCK, LOOKING EAST - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  11. 21. VIEW OF ESCAPE TRAINING TANK, SHOWING INTERIOR OF CUPOLA ...

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

    21. VIEW OF ESCAPE TRAINING TANK, SHOWING INTERIOR OF CUPOLA AND TOP OF THE TANK, LOOKING NORTHEAST - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  12. 15. VIEW OF ESCAPE TRAINING TANK, LOOKING EAST ACROSS MEZZANINE, ...

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

    15. VIEW OF ESCAPE TRAINING TANK, LOOKING EAST ACROSS MEZZANINE, SHOWING ENTRANCE TO SUBMARINE SECTION AT 110-FOOT LEVEL - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  13. 34. VIEW OF SUBMARINE ESCAPE TRAINING TANK PRIOR TO ADDITION ...

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

    34. VIEW OF SUBMARINE ESCAPE TRAINING TANK PRIOR TO ADDITION OF BLISTERS IN 1959, LOOKING SOUTHEAST - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  14. 18. VIEW OF ESCAPE TRAINING TANK, SHOWING ENCLOSED PASSAGEWAY FROM ...

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

    18. VIEW OF ESCAPE TRAINING TANK, SHOWING ENCLOSED PASSAGEWAY FROM 50-FOOT LOCK TO ELEVATOR, LOOKING WEST - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  15. 14. DETAIL VIEW OF ESCAPE TRAINING TANK, SHOWING HOLDDOWN RODS, ...

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

    14. DETAIL VIEW OF ESCAPE TRAINING TANK, SHOWING HOLD-DOWN RODS, LOOKING SOUTH - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  16. 46 CFR 169.313 - Means of escape.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... onboard. At least one means of escape must be independent of watertight doors and lead directly to the... escape is acceptable provided that— (1) There is no source of fire in the space, such as a galley...

  17. 46 CFR 169.313 - Means of escape.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... onboard. At least one means of escape must be independent of watertight doors and lead directly to the... escape is acceptable provided that— (1) There is no source of fire in the space, such as a galley...

  18. Exosomes in Viral Disease.

    PubMed

    Anderson, Monique R; Kashanchi, Fatah; Jacobson, Steven

    2016-07-01

    Viruses have evolved many mechanisms by which to evade and subvert the immune system to ensure survival and persistence. However, for each method undertaken by the immune system for pathogen removal, there is a counteracting mechanism utilized by pathogens. The new and emerging role of microvesicles in immune intercellular communication and function is no different. Viruses across many different families have evolved to insert viral components in exosomes, a subtype of microvesicle, with many varying downstream effects. When assessed cumulatively, viral antigens in exosomes increase persistence through cloaking viral genomes, decoying the immune system, and even by increasing viral infection in uninfected cells. Exosomes therefore represent a source of viral antigen that can be used as a biomarker for disease and targeted for therapy in the control and eradication of these disorders. With the rise in the persistence of new and reemerging viruses like Ebola and Zika, exploring the role of exosomes become more important than ever. PMID:27324390

  19. Viral Disease Networks?

    NASA Astrophysics Data System (ADS)

    Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

    2010-03-01

    Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

  20. HIV suppression by host restriction factors and viral immune evasion.

    PubMed

    Jia, Xiaofei; Zhao, Qi; Xiong, Yong

    2015-04-01

    Antiviral restriction factors are an integral part of the host innate immune system that protects cells from viral pathogens, such as human immunodeficiency virus (HIV). Studies of the interactions between restriction factors and HIV have greatly advanced our understanding of both the viral life cycle and basic cell biology, as well as provided new opportunities for therapeutic intervention of viral infection. Here we review the recent developments towards establishing the structural and biochemical bases of HIV inhibition by, and viral countermeasures of, the restriction factors TRIM5, MxB, APOBEC3, SAMHD1, and BST2/tetherin.

  1. Observations of Ionospheric Escape on Venus' Nightside

    NASA Technical Reports Server (NTRS)

    Mihalov, J. D.; Russell, C. T.; Kasprzak, W. T.; Knudsen, W. C.

    1995-01-01

    A population of low-energy (0-250 V E/q) ions with tailward directed velocity vectors and energies above that for escape from Venus is evident in nightside data from the Ames plasma analyzer on the Pioneer Venus Orbiter spacecraft. Good correlations with solar wind parameters were not obtained for the magnitudes of these ion fluxes, but tendencies for occurrence at times of tailward oriented magnetic fields and for alignment of the ion flows with the magnetic field were found. These tendencies seemed to be enhanced for higher-energy ions. In a few cases where comparisons were made, the ion fluxes were consistent with simultaneous O(+) measurements by the neutral mass spectrometer experiment on the spacecraft. The mean flux observed of the escaping nightside ions, averaged over an approximately 10-week-long spacecraft nightside season, was less than 2 x 10(exp 6) cm(exp -2) s(exp -1).

  2. Observations of Ionospheric Escape on Venus' Nightside

    NASA Technical Reports Server (NTRS)

    Mihalov, J. D.; Russell, C. T.; Kasprzak, W. T.; Knudsen, W. C.

    1995-01-01

    A population of low-energy (0-250 V E/q) ions with tailward directed velocity vectors and energies above that for escape from Venus is evident in nightside data from the Ames plasma analyzer on the Pioneer Venus Orbiter spacecraft. Good correlations with solar wind parameters were not obtained for the magnitudes of these ion fluxes, but tendencies for occurrence at times of tailward oriented magnetic fields and for alignment of the ion flows with the magnetic field were found. These tendencies seemed to be enhanced for higher-energy ions. In a few cases where comparisons were made, the ion fluxes were consistent with simultaneous O(+) measurements by the neutral mass spectrometer experiment on the spacecraft. The mean flux observed of the escaping nightside ions, averaged over an approximately 10-week-long spacecraft nightside season, was less than 2 x 10(exp 6)/sq cm/s.

  3. Lithium clearance in mineralocorticoid escape in humans

    SciTech Connect

    Boer, W.H.; Koomans, H.A.; Mees, E.J.D.

    1987-03-01

    Lithium clearance (C/sub Li/) has been advanced as an indicator of Na delivery from the proximal tubules. The authors studied C/sub Li/ in eight healthy males before and after mineralocorticoid escape, a maneuver that may induce suppression of fractional proximal Na reabsorption (FPR/sub Na/). FPR/sub Na/ was also estimated from changes in maximal free water clearance (C/sub H/sub 2/O/). Plasma volume was measured as the /sup 131/I-labeled albumin distribution space. Extracellular fluid volume was estimated as the /sup 82/Br vector distribution volume. According to the latter method, FPR/sub Na/ dropped whereas inulin clearance rose. The changes in C/sub Li/ were surprisingly large. If lithium is a valid marker of Na handling in the proximal tubule in humans, this change would imply a fall in FPR/sub Na/, suggesting a much larger shift in tubular Na reabsorption in escape than hitherto suspected. In addition, it would suggest that the inevitable back diffusion of a part of the solute-free water in the distal nephron, and thus overestimation of FPR/sub Na/ by the C/sub H/sub 2/O/ method, increases importantly during escape. Alternately, lithium may not be a good marker of proximal tubular Na handling. For instance, both lithium reabsorption and escape may take place beyond the proximal tubule, or lithium may be excreted in the distal nephron in certain conditions. Present methods do not permit further analysis of these options in the human model.

  4. Endosomal escape: a bottleneck in intracellular delivery.

    PubMed

    Shete, Harshad K; Prabhu, Rashmi H; Patravale, Vandana B

    2014-01-01

    With advances in therapeutic science, apart from drugs, newer bioactive moieties like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly being introduced for the betterment of therapeutic efficacy. These moieties have intracellular components of the cells like cytoplasm and nucleus as one of their pharmacological sites for exhibiting therapeutic activity. Despite their promising efficacy, their intracellular bioavailability has been critically hampered leading to failure in the treatment of numerous diseases and disorders. The endosomal uptake pathway is known to be a rate-limiting barrier for such systems. Bioactive molecules get trapped in the endosomal vesicles and degraded in the lysosomal compartment, necessitating the need for effective strategies that facilitate the endosomal escape and enhance the cytosolic bioavailability of bioactives. Microbes like viruses and bacteria have developed their innate mechanistic tactics to translocate their genome and toxins by efficiently penetrating the host cell membrane. Understanding this mechanism and exploring it further for intracellular delivery has opened new avenues to surmount the endosomal barrier. These strategies include membrane fusion, pore formation and proton sponge effects. On the other hand, progress in designing a novel smart polymeric carrier system that triggers endosomal escape by undergoing modulations in the intracellular milieu has further led to an improvement in intracellular delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic cationic lipids and photo-induced physical disruption. Each of the aforementioned strategies has its own unique mechanism to escape the endosome. This review recapitulates the numerous strategies designed to surmount the bottleneck of endosomal escape and thereby achieve successful intracellular uptake of bioactives. PMID:24730275

  5. Neuroanatomy goes viral!

    PubMed

    Nassi, Jonathan J; Cepko, Constance L; Born, Richard T; Beier, Kevin T

    2015-01-01

    The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and extending

  6. Neuroanatomy goes viral!

    PubMed Central

    Nassi, Jonathan J.; Cepko, Constance L.; Born, Richard T.; Beier, Kevin T.

    2015-01-01

    The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist’s toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and

  7. Pseudorabies virus can escape from CRISPR-Cas9-mediated inhibition.

    PubMed

    Peng, Zhiyuan; Ouyang, Ting; Pang, Daxin; Ma, Teng; Chen, Xinrong; Guo, Ning; Chen, Fuwang; Yuan, Lin; Ouyang, Hongsheng; Ren, Linzhu

    2016-09-01

    The CRISPR-Cas9 system is a newly developed genome-engineering tool used to inhibit virus infection by targeting the conserved regions of the viral genomic DNA. In the present study, we constructed a cell line stably expressing Cas9 endonuclease and sgRNA targeting the conserved UL30 gene of pseudorabies virus (PRV). During the PRV infection, the CRISPR-Cas9 system was efficient in cleaving the UL30 gene in each passage. However, deletions and insertions occurred at low passages, while substitutions were frequently observed at high passages. Furthermore, copy numbers and virus titers of PRV were significantly increased in a passage-dependent manner, indicating that viral genomic replication and assembly were more effective at the high passages than at low passages. These results demonstrated that PRV could escape from CRISPR-Cas9-mediated inhibition. Therefore, whether the CRISPR-Cas9 system is suitable for antiviral application should be considered and carefully verified.

  8. Scrunching: a novel escape gait in planarians

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  9. Scrunching: a novel escape gait in planarians.

    PubMed

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

    2015-09-10

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

  10. Scrunching: a novel escape gait in planarians.

    PubMed

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

    2015-10-01

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

  11. Xenon Fractionation and Archean Hydrogen Escape

    NASA Technical Reports Server (NTRS)

    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.

  12. Cold ion escape from the Martian ionosphere

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  13. 30 CFR 75.382 - Mechanical escape facilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Mechanical escape facilities. 75.382 Section 75... HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Ventilation § 75.382 Mechanical escape facilities. (a) Mechanical escape facilities shall be provided with overspeed, overwind, and automatic...

  14. 30 CFR 75.382 - Mechanical escape facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical escape facilities. 75.382 Section 75... HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Ventilation § 75.382 Mechanical escape facilities. (a) Mechanical escape facilities shall be provided with overspeed, overwind, and automatic...

  15. 30 CFR 75.382 - Mechanical escape facilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mechanical escape facilities. 75.382 Section 75... HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Ventilation § 75.382 Mechanical escape facilities. (a) Mechanical escape facilities shall be provided with overspeed, overwind, and automatic...

  16. 30 CFR 75.382 - Mechanical escape facilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Mechanical escape facilities. 75.382 Section 75... HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Ventilation § 75.382 Mechanical escape facilities. (a) Mechanical escape facilities shall be provided with overspeed, overwind, and automatic...

  17. 30 CFR 75.382 - Mechanical escape facilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Mechanical escape facilities. 75.382 Section 75... HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Ventilation § 75.382 Mechanical escape facilities. (a) Mechanical escape facilities shall be provided with overspeed, overwind, and automatic...

  18. Immune regulation and evasion of Mammalian host cell immunity during viral infection.

    PubMed

    Pratheek, B M; Saha, Soham; Maiti, Prasanta K; Chattopadhyay, Soma; Chattopadhyay, Subhasis

    2013-06-01

    The mammalian host immune system has wide array of defence mechanisms against viral infections. Depending on host immunity and the extent of viral persistence, either the host immune cells might clear/restrict the viral load and disease progression or the virus might evade host immunity by down regulating host immune effector response(s). Viral antigen processing and presentation in the host cells through major histocompatibility complex (MHC) elicit subsequent anti-viral effector T cell response(s). However, modulation of such response(s) might generate one of the important viral immune evasion strategies. Viral peptides are mostly generated by proteolytic cleavage in the cytosol of the infected host cells. CD8(+) T lymphocytes play critical role in the detection of viral infection by recognizing these peptides displayed at the plasma membrane by MHC-I molecules. The present review summarises the current knowledge on the regulation of mammalian host innate and adaptive immune components, which are operative in defence mechanisms against viral infections and the variety of strategies that viruses have evolved to escape host cell immunity. The understanding of viral immune evasion strategies is important for designing anti-viral immunotherapies.

  19. Engineering targeted viral vectors for gene therapy.

    PubMed

    Waehler, Reinhard; Russell, Stephen J; Curiel, David T

    2007-08-01

    To achieve therapeutic success, transfer vehicles for gene therapy must be capable of transducing target cells while avoiding impact on non-target cells. Despite the high transduction efficiency of viral vectors, their tropism frequently does not match the therapeutic need. In the past, this lack of appropriate targeting allowed only partial exploitation of the great potential of gene therapy. Substantial progress in modifying viral vectors using diverse techniques now allows targeting to many cell types in vitro. Although important challenges remain for in vivo applications, the first clinical trials with targeted vectors have already begun to take place.

  20. Increased Antibody Affinity Confers Broad In Vitro Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus

    PubMed Central

    Rani, Mridula; Bolles, Meagan; Donaldson, Eric F.; Van Blarcom, Thomas; Baric, Ralph; Iverson, Brent

    2012-01-01

    Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (KD) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection. PMID:22696652

  1. Viruses and viral proteins

    PubMed Central

    Verdaguer, Nuria; Ferrero, Diego; Murthy, Mathur R. N.

    2014-01-01

    For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes. PMID:25485129

  2. Viral evasion of intracellular DNA and RNA sensing.

    PubMed

    Chan, Ying Kai; Gack, Michaela U

    2016-06-01

    The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern recognition receptors (PRRs) are key components of antiviral immunity that detect conserved molecular features of viral pathogens and initiate signalling that results in the expression of antiviral genes. In this Review, we discuss the strategies that viruses use to escape immune surveillance by key intracellular sensors of viral RNA or DNA, with a focus on RIG-I-like receptors (RLRs), cyclic GMP-AMP synthase (cGAS) and interferon-γ (IFNγ)-inducible protein 16 (IFI16). Such viral strategies include the sequestration or modification of viral nucleic acids, interference with specific post-translational modifications of PRRs or their adaptor proteins, the degradation or cleavage of PRRs or their adaptors, and the sequestration or relocalization of PRRs. An understanding of viral immune-evasion mechanisms at the molecular level may guide the development of vaccines and antivirals. PMID:27174148

  3. Viral evasion of intracellular DNA and RNA sensing.

    PubMed

    Chan, Ying Kai; Gack, Michaela U

    2016-06-01

    The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern recognition receptors (PRRs) are key components of antiviral immunity that detect conserved molecular features of viral pathogens and initiate signalling that results in the expression of antiviral genes. In this Review, we discuss the strategies that viruses use to escape immune surveillance by key intracellular sensors of viral RNA or DNA, with a focus on RIG-I-like receptors (RLRs), cyclic GMP-AMP synthase (cGAS) and interferon-γ (IFNγ)-inducible protein 16 (IFI16). Such viral strategies include the sequestration or modification of viral nucleic acids, interference with specific post-translational modifications of PRRs or their adaptor proteins, the degradation or cleavage of PRRs or their adaptors, and the sequestration or relocalization of PRRs. An understanding of viral immune-evasion mechanisms at the molecular level may guide the development of vaccines and antivirals.

  4. Risks incurred by hydrogen escaping from containers and conduits

    SciTech Connect

    Swain, M.R.; Grilliot, E.S.; Swain, M.N.

    1998-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Jin, S.

    2014-11-01

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

  6. Viral infections during pregnancy.

    PubMed

    Silasi, Michelle; Cardenas, Ingrid; Kwon, Ja-Young; Racicot, Karen; Aldo, Paula; Mor, Gil

    2015-03-01

    Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be 'immunosuppressed', the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy and offer potential mechanisms for the associated adverse pregnancy outcomes. PMID:25582523

  7. Viral Hemorrhagic Fevers

    MedlinePlus

    ... Related Links About VSPB (Viral Special Pathogens Branch) File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  8. VIRAL INFECTIONS DURING PREGNANCY

    PubMed Central

    Silasi, Michelle; Cardenas, Ingrid; Racicot, Karen; Kwon, Ja-Young; Aldo, Paula; Mor, Gil

    2015-01-01

    Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be “immunosuppressed”, the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy, and offer potential mechanisms for the associated adverse pregnancy outcomes. PMID:25582523

  9. HIV and Viral Hepatitis

    MedlinePlus

    ... prevalent among blacks as among whites. Viral Hepatitis Transmission People can be infected with the three most ... risk for HAV. • • New data suggest that sexual transmission of HCV among MSM with HIV occurs more ...

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

    PubMed

    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.

  11. Viral miRNAs.

    PubMed

    Plaisance-Bonstaff, Karlie; Renne, Rolf

    2011-01-01

    Since 2004, more than 200 microRNAs (miRNAs) have been discovered in double-stranded DNA viruses, mainly herpesviruses and polyomaviruses (Nucleic Acids Res 32:D109-D111, 2004). miRNAs are short 22  ±  3 nt RNA molecules that posttranscriptionally regulate gene expression by binding to 3'-untranslated regions (3'UTR) of target mRNAs, thereby inducing translational silencing and/or transcript degradation (Nature 431:350-355, 2004; Cell 116:281-297, 2004). Since miRNAs require only limited complementarity for binding, miRNA targets are difficult to determine (Mol Cell 27:91-105, 2007). To date, targets have only been experimentally verified for relatively few viral miRNAs, which either target viral or host cellular gene expression: For example, SV40 and related polyomaviruses encode miRNAs which target viral large T antigen expression (Nature 435:682-686, 2005; J Virol 79:13094-13104, 2005; Virology 383:183-187, 2009; J Virol 82:9823-9828, 2008) and miRNAs of α-, β-, and γ-herpesviruses have been implicated in regulating the transition from latent to lytic gene expression, a key step in the herpesvirus life cycle. Viral miRNAs have also been shown to target various host cellular genes. Although this field is just beginning to unravel the multiple roles of viral miRNA in biology and pathogenesis, the current data strongly suggest that virally encoded miRNAs are able to regulate fundamental biological processes such as immune recognition, promotion of cell survival, angiogenesis, proliferation, and cell differentiation. This chapter aims to summarize our current knowledge of viral miRNAs, their targets and function, and the challenges lying ahead to decipher their role in viral biology, pathogenesis, and for γ-herepsvirus-encoded miRNAs, potentially tumorigenesis. PMID:21431678

  12. Nuclear actin and lamins in viral infections.

    PubMed

    Cibulka, Jakub; Fraiberk, Martin; Forstova, Jitka

    2012-03-01

    Lamins are the best characterized cytoskeletal components of the cell nucleus that help to maintain the nuclear shape and participate in diverse nuclear processes including replication or transcription. Nuclear actin is now widely accepted to be another cytoskeletal protein present in the nucleus that fulfills important functions in the gene expression. Some viruses replicating in the nucleus evolved the ability to interact with and probably utilize nuclear actin for their replication, e.g., for the assembly and transport of capsids or mRNA export. On the other hand, lamins play a role in the propagation of other viruses since nuclear lamina may represent a barrier for virions entering or escaping the nucleus. This review will summarize the current knowledge about the roles of nuclear actin and lamins in viral infections.

  13. Relationship of scores on the Escapism Scale of the MMPI to escape from minimum security federal custody.

    PubMed

    White, R B

    1979-04-01

    Investigated the ability of the Escapism (Ec) scale of the MMPI to differentiate between escape and non-escape minimum security federal prisoners. At the .05 level there was no difference between the scores of the two groups on the Ec scale or on comparisons of other correctional data, age, and ethnic composition. It appears that the Ec scale alone or in combination with other data will be a poor predictor of escape. Also, the rate of escape was so low as to make accurate prediction from any criteria extremely unlikely.

  14. NCBI viral genomes resource.

    PubMed

    Brister, J Rodney; Ako-Adjei, Danso; Bao, Yiming; Blinkova, Olga

    2015-01-01

    Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets.

  15. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  16. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants.

  17. Belt fires and mine escape problems

    SciTech Connect

    Kovac, J.G.; Lazzara, C.P.; Kravitz, J.H.

    1996-12-31

    A conveyor belt fire in an underground coal mine is a serious threat to life and property. About 30% of the reportable underground coal mine fires from 1988 through 1992 occurred in belt entries. In one instance, a fire started in the drive area of a belt line, spread rapidly, and resulted in seating of the entire mine. Large-scale studies conducted by the U.S. Bureau of Mines in an aboveground fire gallery at Lake Lynn Laboratory clearly show the hazards of conveyor belt fires. Mine conveyor belt formulations which passed the current Federal acceptance test for fire-resistant betting were completely consumed by propagating fires or propagated flame, with flame spread rates ranging from 0.3 to 9 m/min. High downstream temperatures and large quantities of smoke and toxic gases, such as carbon monoxide, were generated as the belting burned. The smoke and gases can be spread by the mine`s ventilation system and can create significant problems for miners in the process of evacuation, such as reduction in visibility and incapacitation. In the aftermath of a belt fire, the atmosphere inside of the mine can become smoke filled or unbreathable, forcing miners to evacuate while wearing Self-Contained Self-Rescuers (SCSR`s), Sometimes there is confusion about how to regard the rated duration of an MSHA/NIOSH-approved 60-min. SCSR, especially when an SCSR is used in a way which takes it outside of the test conditions under which it was approved. As examples, for a mine escape that takes a miner from the deepest point of penetration in the mine to the surface: How long will a 60-min. SCSR actually last? and How many SCSR`s will a miner need? To answer these kinds of questions, in-mine data being gathered on escape times, distance and heart rates using miners escaping on foot and under oxygen. A model will be developed and validated which predicts how much oxygen is actually needed for a mine escape, and compares oxygen consumption bare faced versus wearing an SCSR.

  18. Suicide as escape from psychotic panic.

    PubMed

    Goldblatt, Mark J; Ronningstam, Elsa; Schechter, Mark; Herbstman, Benjamin; Maltsberger, John T

    2016-01-01

    Suicides of patients in states of acute persecutory panic may be provoked by a subjective experience of helpless terror threatening imminent annihilation or dismemberment. These patients are literally scared to death and try to run away. They imagine suicide is survivable and desperately attempt to escape from imaginary enemies. These states of terror occur in a wide range of psychotic illnesses and are often associated with command hallucinations and delusions. In this article, the authors consider the subjective experience of persecutory panic and the suicide response as an attempt to flee from danger. PMID:27294586

  19. Escape Artists of the X Chromosome.

    PubMed

    Balaton, Bradley P; Brown, Carolyn J

    2016-06-01

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

  20. [Clinical aspects and diagnosis of viral hepatitis].

    PubMed

    Vince, Adriana

    2003-01-01

    public health problem worldwide. In classical infectology, four clinical stages of the disease have been described: incubation or preclinical stage characterized by intensive virus replication; prodromal or preicteric stage with pronounced general symptoms of infection; icteric stage; and stage of recovery. The stages may show great interindividual variation in length and severity. The development of molecular technologies over the last decade has greatly contributed to better understanding of the pathogenesis of viral hepatitides and allowed for appropriate monitoring of the effect of antiviral therapy. However, major disadvantage of these tests is their high cost. The basic clinical characteristics of and diagnostic options for particular types of viral hepatitis are described, with special reference to the latest important concepts on the disease pathogenesis. PMID:14582462

  1. Bacterial coinfections in children with viral wheezing.

    PubMed

    Lehtinen, P; Jartti, T; Virkki, R; Vuorinen, T; Leinonen, M; Peltola, V; Ruohola, A; Ruuskanen, O

    2006-07-01

    Bacterial coinfections occur in respiratory viral infections, but the attack rates and the clinical profile are not clear. The aim of this study was to determine bacterial coinfections in children hospitalized for acute expiratory wheezing with defined viral etiology. A total of 220 children aged 3 months to 16 years were investigated. The viral etiology of wheezing was confirmed by viral culture, antigen detection, serologic investigation, and/or PCR. Specific antibodies to common respiratory bacteria were measured from acute and convalescent serum samples. All children were examined clinically for acute otitis media, and subgroups of children were examined radiologically for sinusitis and pneumonia. Rhinovirus (32%), respiratory syncytial virus (31%), and enteroviruses (31%) were the most common causative viruses. Serologic evidence of bacterial coinfection was found in 18% of the children. Streptococcus pneumoniae (8%) and Mycoplasma pneumoniae (5%) were the most common causative bacteria. Acute otitis media was diagnosed in 44% of the children. Chest radiographs showed alveolar infiltrates in 10%, and paranasal radiographs and clinical signs showed sinusitis in 17% of the older children studied. Leukocyte counts and serum C-reactive protein levels were low in a great majority of patients. Viral lower respiratory tract infection in children is often associated with bacterial-type upper respiratory tract infections. However, coexisting bacterial lower respiratory tract infections that induce systemic inflammatory response are seldom detected.

  2. Emerging viral diseases in kidney transplant recipients.

    PubMed

    Moal, Valérie; Zandotti, Christine; Colson, Philippe

    2013-01-01

    Viruses are the most important cause of infections and a major source of mortality in Kidney Transplant Recipients (KTRs). These patients may acquire viral infections through exogenous routes including community exposure, donor organs, and blood products or by endogenous reactivation of latent viruses. Beside major opportunistic infections due to CMV and EBV and viral hepatitis B and C, several viral diseases have recently emerged in KTRs. New medical practices or technologies, implementation of new diagnostic tools, and improved medical information have contributed to the emergence of these viral diseases in this special population. The purpose of this review is to summarize the current knowledge on emerging viral diseases and newly discovered viruses in KTRs over the last two decades. We identified viruses in the field of KT that had shown the greatest increase in numbers of citations in the NCBI PubMed database. BKV was the most cited in the literature and linked to an emerging disease that represents a great clinical concern in KTRs. HHV-8, PVB19, WNV, JCV, H1N1 influenza virus A, HEV, and GB virus were the main other emerging viruses. Excluding HHV8, newly discovered viruses have been infrequently linked to clinical diseases in KTRs. Nonetheless, pathogenicity can emerge long after the discovery of the causative agent, as has been the case for BKV. Overall, antiviral treatments are very limited, and reducing immunosuppressive therapy remains the cornerstone of management. PMID:23132728

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

    PubMed

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

    2016-06-01

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

  4. F111 Crew Escape Module pilot parachute

    SciTech Connect

    Tadios, E.L.

    1991-01-01

    A successfully deployment of a parachute system highly depends on the efficiency of the deployment device and/or method. There are several existing methods and devices that may be considered for a deployment system. For the F111 Crew Escape Module (CEM), the recovery parachute system deployment is initiated by the firing of a catapult that ejects the complete system from the CEM. At first motion of the pack, a drogue gun is fired, which deploys the pilot parachute system. The pilot parachute system then deploys the main parachute system, which consists of a cluster of three 49-ft diameter parachutes. The pilot parachute system which extracts the F111 Crew Escape Module recovery parachute system must provide reasonable bag strip velocities throughout the flight envelope (10 psf to 300 psf). The pilot parachute system must, therefore, have sufficient drag area at the lower dynamic pressures and a reduced drag area at the high end of the flight envelope. The final design that was developed was a dual parachute system which consists of a 5-ft diameter guide surface parachute tethered inside a 10-ft diameter flat circular parachute. The high drag area is sustained at the low dynamic pressures by keeping both parachutes intact. The drag area is reduced at the higher extreme by allowing the 10-ft parachute attachment to fail. The discussions to follow describe in detail how the system was developed. 4 refs., 10 figs., 2 tabs.

  5. Orbital Effects on Mercury's Escaping Sodium Exosphere

    NASA Technical Reports Server (NTRS)

    Schmidt, Carl A.; Wilson, Jody K.; Baumgardner, Jeffrey; Mendillo, Michael

    2009-01-01

    We present results from coronagraphic imaging of Mercury's sodium tail over a 7 deg field of view. Several sets of observations made at the McDonald Observatory since May 2007 show a tail of neutral sodium atoms stretching more than 1000 Mercury radii (R(sub m)) in length, or a full degree of sky. However, no tail was observed extending beyond 120 R(sub m) during the January 2008 MESSENGER Fly-by period, or during a similar orbital phase of Mercury in July 2008. Large changes in Mercury's heliocentric radial velocity cause Doppler shifts about the Fraunhofer absorption features; the resultant change in solar flux and radiation pressure is the primary cause of the observed variation in tail brightness. Smaller fluctuations in brightness may exist due to changing source rates at the surface, but we have no explicit evidence for such changes in this data set. The effects of radiation pressure on Mercury's escaping atmosphere are investigated using seven observations spanning different orbital phases. Total escape rates of atmospheric sodium are estimated to be between 5 and 13 x 10(exp 23) atoms/s and show a correlation to radiation pressure. Candidate sources of Mercury's sodium exosphere include desorption by UV sunlight, thermal desorption, solar wind channeled along Mercury's magnetic field lines, and micro-meteor impacts. Wide-angle observations of the full extent of Mercury's sodium tail offer opportunities to enhance our understanding of the time histories of these source rates.

  6. The escape model for Galactic cosmic rays

    NASA Astrophysics Data System (ADS)

    Giacinti, G.; Kachelrieß, M.; Semikoz, D. V.

    2015-08-01

    The escape model explains the cosmic ray (CR) knee by energy-dependent CR leakage from the Milky Way, with an excellent fit to all existing data. We test this model calculating the trajectories of individual CRs in the Galactic magnetic field. We find that the CR escape time τesc(E) exhibits a knee-like structure around E/Z = few × 1015 eV for small coherence lengths and strengths of the turbulent magnetic field. The resulting intensities for different groups of nuclei are consistent with the ones determined by KASCADE and KASCADE-Grande, using simple power-laws as injection spectra. The transition from Galactic to extragalactic CRs happens in this model at low energies and is terminated below ≈ 3 × 1018 eV. The intermediate energy region up to the ankle is populated by CRs accelerated in starburst galaxies. This model provides a good fit to ln(A) data, while the estimated CR dipole anisotropy is close to, or below, upper limits in the energy range 1017 - 1018 eV. The phase of the dipole is expected to change between 1 × 1017 and 3 × 1018 eV.

  7. Escape dynamics of many hard disks.

    PubMed

    Taniguchi, Tooru; Murata, Hiroki; Sawada, Shin-Ichi

    2014-11-01

    Many-particle effects in escapes of hard disks from a square box via a hole are discussed in a viewpoint of dynamical systems. Starting from N disks in the box at the initial time, we calculate the probability P_{n}(t) for at least n disks to remain inside the box at time t for n=1,2,...,N. At early times, the probabilities P_{n}(t),n=2,3,...,N-1, are described by superpositions of exponential decay functions. On the other hand, after a long time the probability P_{n}(t) shows a power-law decay ∼t^{-2n} for n≠1, in contrast to the fact that it decays with a different power law ∼t^{-n} for cases without any disk-disk collision. Chaotic or nonchaotic properties of the escape systems are discussed by the dynamics of a finite-time largest Lyapunov exponent, whose decay properties are related with those of the probability P_{n}(t). PMID:25493874

  8. Escape from X Inactivation Varies in Mouse Tissues

    PubMed Central

    Yang, Fan; Shendure, Jay; Noble, William S.; Disteche, Christine M.; Deng, Xinxian

    2015-01-01

    X chromosome inactivation (XCI) silences most genes on one X chromosome in female mammals, but some genes escape XCI. To identify escape genes in vivo and to explore molecular mechanisms that regulate this process we analyzed the allele-specific expression and chromatin structure of X-linked genes in mouse tissues and cells with skewed XCI and distinguishable alleles based on single nucleotide polymorphisms. Using a binomial model to assess allelic expression, we demonstrate a continuum between complete silencing and expression from the inactive X (Xi). The validity of the RNA-seq approach was verified using RT-PCR with species-specific primers or Sanger sequencing. Both common escape genes and genes with significant differences in XCI status between tissues were identified. Such genes may be candidates for tissue-specific sex differences. Overall, few genes (3–7%) escape XCI in any of the mouse tissues examined, suggesting stringent silencing and escape controls. In contrast, an in vitro system represented by the embryonic-kidney-derived Patski cell line showed a higher density of escape genes (21%), representing both kidney-specific escape genes and cell-line specific escape genes. Allele-specific RNA polymerase II occupancy and DNase I hypersensitivity at the promoter of genes on the Xi correlated well with levels of escape, consistent with an open chromatin structure at escape genes. Allele-specific CTCF binding on the Xi clustered at escape genes and was denser in brain compared to the Patski cell line, possibly contributing to a more compartmentalized structure of the Xi and fewer escape genes in brain compared to the cell line where larger domains of escape were observed. PMID:25785854

  9. Mathematical models of immune effector responses to viral infections: Virus control versus the development of pathology

    NASA Astrophysics Data System (ADS)

    Wodarz, Dominik

    2005-12-01

    This article reviews mathematical models which have investigated the importance of lytic and non-lytic immune responses for the control of viral infections. Lytic immune responses fight the virus by killing infected cells, while non-lytic immune responses fight the virus by inhibiting viral replication while leaving the infected cell alive. The models suggest which types or combinations of immune responses are required to resolve infections which vary in their characteristics, such as the rate of viral replication and the rate of virus-induced target cell death. This framework is then applied to persistent infections and viral evolution. It is investigated how viral evolution and antigenic escape can influence the relative balance of lytic and non-lytic responses over time, and how this might correlate with the transition from an asymptomatic infection to pathology. This is discussed in the specific context of hepatitis C virus infection.

  10. Coping with Viral Diversity in HIV Vaccine Design

    PubMed Central

    Nickle, David C; Rolland, Morgane; Jensen, Mark A; Pond, Sergei L. Kosakovsky; Deng, Wenjie; Seligman, Mark; Heckerman, David; Mullins, James I; Jojic, Nebojsa

    2007-01-01

    The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus. PMID:17465674

  11. Coping with viral diversity in HIV vaccine design.

    PubMed

    Nickle, David C; Rolland, Morgane; Jensen, Mark A; Pond, Sergei L Kosakovsky; Deng, Wenjie; Seligman, Mark; Heckerman, David; Mullins, James I; Jojic, Nebojsa

    2007-04-27

    The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT(+) antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus.

  12. Characterization of epitopes on the rabies virus glycoprotein by selection and analysis of escape mutants.

    PubMed

    Fallahi, Firouzeh; Wandeler, Alexander I; Nadin-Davis, Susan A

    2016-07-15

    The glycoprotein (G) is the only surface protein of the lyssavirus particle and the only viral product known to be capable of eliciting the production of neutralizing antibodies. In this study, the isolation of escape mutants resistant to monoclonal antibody (Mab) neutralization was attempted by a selection strategy employing four distinct rabies virus strains: the extensively passaged Evelyn Rokitnicki Abelseth (ERA) strain and three field isolates representing two bat-associated variants and the Western Canada skunk variant (WSKV). No escape mutants were generated from either of the bat-associated viral variants but two neutralization mutants were derived from the WSKV isolate. Seven independent ERA mutants were recovered using Mabs directed against antigenic sites I (four mutants) and IIIa (three mutants) of the glycoprotein. The cross-neutralization patterns of these viral mutants were used to determine the precise location and nature of the G protein epitopes recognized by these Mabs. Nucleotide sequencing of the G gene indicated that those mutants derived using Mabs directed to antigenic site (AS) III all contained amino acid substitutions in this site. However, of the four mutants selected with AS I Mabs, two bore mutations within AS I as expected while the remaining two carried mutations in AS II. WSKV mutants exhibited mutations at the sites appropriate for the Mabs used in their selection. All ERA mutant preparations were more cytopathogenic than the parental virus when propagated in cell culture; when in vivo pathogenicity in mice was examined, three of these mutants exhibited reduced pathogenicity while the remaining four mutants exhibited comparable pathogenic properties to those of the parent virus. PMID:27132040

  13. Some Possible Cases of Escape Mimicry in Neotropical Butterflies.

    PubMed

    Pinheiro, C E G; Freitas, A V L

    2014-10-01

    The possibility that escape or evasive mimicry evolved in butterflies and other prey insects in a similar fashion to classical Batesian and Müllerian mimicry has long been advanced in the literature. However, there is a general disagreement among lepidopterists and evolutionary biologists on whether or not escape mimicry exists, as well as in which mimicry rings this form of mimicry has evolved. Here, we review some purported cases of escape mimicry in Neotropical butterflies and suggest new mimicry rings involving several species of Archaeoprepona, Prepona, and Doxocopa (the "bright blue bands" ring) and species of Colobura and Hypna (the "creamy bands" ring) where the palatability of butterflies, their ability to escape predator attacks, geographic distribution, relative abundance, and co-occurrence in the same habitats strongly suggest that escape mimicry is involved. In addition, we also indicate other butterfly taxa whose similarities of coloration patterns could be due to escape mimicry and would constitute important case studies for future investigation.

  14. Nosocomial viral respiratory infections.

    PubMed

    Graman, P S; Hall, C B

    1989-12-01

    Nosocomial infections with respiratory tract viruses, particularly influenza and respiratory syncytial viruses, account for the majority of serious nosocomial viral disease. Chronically ill, immunocompromised, elderly, and very young hosts are especially vulnerable to potentially life-threatening involvement of the lower respiratory tract. Effective preventive strategies are based upon early accurate viral diagnosis and an appreciation of the epidemiology and mechanisms of transmission for each viral agent. Influenza viruses spread via airborne dispersion of small particle aerosols, resulting in explosive outbreaks; control measures emphasize immunization and chemoprophylaxis of susceptible patients and personnel, and isolation of those already infected. Transmission of respiratory syncytial virus, in contrast, seems to require closer contact, with virus passed on hands, fomites, or in large droplets inoculated into the eyes and nose at close range. Strategies for control of nosocomial respiratory syncytial virus are designed to interrupt hand carriage and inoculation of virus onto mucous membranes.

  15. Viral hepatitis: Indian scenario.

    PubMed

    Satsangi, Sandeep; Chawla, Yogesh K

    2016-07-01

    Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India. PMID:27546957

  16. Modeling Viral Capsid Assembly

    PubMed Central

    2014-01-01

    I present a review of the theoretical and computational methodologies that have been used to model the assembly of viral capsids. I discuss the capabilities and limitations of approaches ranging from equilibrium continuum theories to molecular dynamics simulations, and I give an overview of some of the important conclusions about virus assembly that have resulted from these modeling efforts. Topics include the assembly of empty viral shells, assembly around single-stranded nucleic acids to form viral particles, and assembly around synthetic polymers or charged nanoparticles for nanotechnology or biomedical applications. I present some examples in which modeling efforts have promoted experimental breakthroughs, as well as directions in which the connection between modeling and experiment can be strengthened. PMID:25663722

  17. Optimal viral strategies for bypassing RNA silencing

    PubMed Central

    Rodrigo, Guillermo; Carrera, Javier; Jaramillo, Alfonso; Elena, Santiago F.

    2011-01-01

    The RNA silencing pathway constitutes a defence mechanism highly conserved in eukaryotes, especially in plants, where the underlying working principle relies on the repressive action triggered by the intracellular presence of double-stranded RNAs. This immune system performs a post-transcriptional suppression of aberrant mRNAs or viral RNAs by small interfering RNAs (siRNAs) that are directed towards their target in a sequence-specific manner. However, viruses have evolved strategies to escape from silencing surveillance while promoting their own replication. Several viruses encode suppressor proteins that interact with different elements of the RNA silencing pathway and block it. The different suppressors are not phylogenetically nor structurally related and also differ in their mechanism of action. Here, we adopt a model-driven forward-engineering approach to understand the evolution of suppressor proteins and, in particular, why viral suppressors preferentially target some components of the silencing pathway. We analysed three strategies characterized by different design principles: replication in the absence of a suppressor, suppressors targeting the first protein component of the pathway and suppressors targeting the siRNAs. Our results shed light on the question of whether a virus must opt for devoting more time into transcription or into translation and on which would be the optimal step of the silencing pathway to be targeted by suppressors. In addition, we discussed the evolutionary implications of such designing principles. PMID:20573628

  18. Statistical Mechanics and Thermodynamics of Viral Evolution

    PubMed Central

    Jones, Barbara A.; Lessler, Justin; Bianco, Simone; Kaufman, James H.

    2015-01-01

    This paper uses methods drawn from physics to study the life cycle of viruses. The paper analyzes a model of viral infection and evolution using the "grand canonical ensemble" and formalisms from statistical mechanics and thermodynamics. Using this approach we enumerate all possible genetic states of a model virus and host as a function of two independent pressures–immune response and system temperature. We prove the system has a real thermodynamic temperature, and discover a new phase transition between a positive temperature regime of normal replication and a negative temperature “disordered” phase of the virus. We distinguish this from previous observations of a phase transition that arises as a function of mutation rate. From an evolutionary biology point of view, at steady state the viruses naturally evolve to distinct quasispecies. This paper also reveals a universal relationship that relates the order parameter (as a measure of mutational robustness) to evolvability in agreement with recent experimental and theoretical work. Given that real viruses have finite length RNA segments that encode proteins which determine virus fitness, the approach used here could be refined to apply to real biological systems, perhaps providing insight into immune escape, the emergence of novel pathogens and other results of viral evolution. PMID:26422205

  19. Viral vaccines: selected topics.

    PubMed

    Kańtoch, M

    1996-01-01

    Significant role of viruses in pathology, their dominating position in etiology of infectious diseases point at the special position of active prophylactic procedures based on vaccination. The real role and value of viral vaccines of classic and modern generations, the limitation of immune potency in suppression of defence mechanisms, some problems of immunization against virus vertical transmission are presented in the paper. The reader may find tables which cumulate selected but significant patterns of viral vaccines and vaccinations, and selected papers devoted to topics discussed. PMID:9017153

  20. Viral meningitis and encephalitis.

    PubMed

    Tuppeny, Misti

    2013-09-01

    Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date.

  1. Viral infections in pigeons.

    PubMed

    Marlier, D; Vindevogel, H

    2006-07-01

    This review provides a current update on the major viral diseases of the domestic pigeon (Columba livia domestica), based on scientific reports and clinical experience. Paramyxovirus 1, adenovirus, rotavirus, herpesvirus 1, poxvirus and circovirus infections are described according to common clinical signs and target tissues. Since pigeons are sometimes treated as if they were poultry, the review also summarises the common viral infections of poultry for which pigeons are considered resistant. It is hoped that the review will provide a useful reference for veterinarians and others and offer advice on the diagnosis, treatment and prevention of the major infectious diseases of pigeons.

  2. Failure of Viral Shells

    NASA Astrophysics Data System (ADS)

    Klug, William S.; Bruinsma, Robijn F.; Michel, Jean-Philippe; Knobler, Charles M.; Ivanovska, Irena L.; Schmidt, Christoph F.; Wuite, Gijs J. L.

    2006-12-01

    We report a combined theoretical and experimental study of the structural failure of viral shells under mechanical stress. We find that discontinuities in the force-indentation curve associated with failure should appear when the so-called Föppl von Kármán (FvK) number exceeds a critical value. A nanoindentation study of a viral shell subject to a soft-mode instability, where the stiffness of the shell decreases with increasing pH, confirms the predicted onset of failure as a function of the FvK number.

  3. Dengue viral infection.

    PubMed

    Sarin, Y K; Singh, S; Singh, T

    1998-02-01

    Dengue viral infection produces a spectrum of disease. For example, mild dengue disease is characterized by biphasic fever, myalgia, arthralgia, leukopenia, and lymphadenopathy, while dengue hemorrhagic fever is an often fatal disease characterized by hemorrhages and shock syndrome. The disease, especially in its severe form, is seen more often among children than among adults. With focus upon India, dengue's etiology, epidemiology, pathology, pathogenesis of dengue hemorrhagic fever, clinical manifestations of both the mild and severe forms of dengue viral infection, diagnosis, differential diagnosis, treatment, prevention, and prognosis are discussed.

  4. Emerging viral infections.

    PubMed

    Bale, James F

    2012-09-01

    Unique disorders appear episodically in human populations and cause life-threatening systemic or neurological disease. Historical examples of such disorders include von Economo encephalitis, a disorder of presumed viral etiology; acquired immune deficiency syndrome, caused by the human immunodeficiency virus; and severe acute respiratory syndrome, caused by a member of the coronavirus family. This article describes the factors that contribute to the emergence of infectious diseases and focuses on selected recent examples of emerging viral infections that can affect the nervous system of infants, children, and adolescents.

  5. Viral apoptotic mimicry.

    PubMed

    Amara, Ali; Mercer, Jason

    2015-08-01

    As opportunistic pathogens, viruses have evolved many elegant strategies to manipulate host cells for infectious entry and replication. Viral apoptotic mimicry, defined by the exposure of phosphatidylserine - a marker for apoptosis - on the pathogen surface, is emerging as a common theme used by enveloped viruses to promote infection. Focusing on the four best described examples (vaccinia virus, dengue virus, Ebola virus and pseudotyped lentivirus), we summarize our current understanding of apoptotic mimicry as a mechanism for virus entry, binding and immune evasion. We also describe recent examples of non-enveloped viruses that use this mimicry strategy, and discuss future directions and how viral apoptotic mimicry could be targeted therapeutically.

  6. Submarine escape trials 1999-2001--provision of medical support.

    PubMed

    Benton, Peter

    2002-01-01

    Since the early 1960s all Royal Navy submarines have been fitted with an escape system comprising a single escape tower (SET) and submarine escape immersion suit (SEIS). This system enables escape from a submarine at a depth of 180 metres (1.9 MPa) provided that the submarine compartment is at a pressure of no greater than 1 bar (0.1 MPa). Due to a variety of causes which may include flooding and leakage of high pressure air systems it is the highly probable that the submarine compartment will be at a pressure in excess of 1 bar (0.1 MPa) at the time of the escape. To investigate and determine what constitutes a 'safe' maximum escape depth from any given compartment pressure (the safe to escape curve), a purpose built chamber complex, the Submarine Escape Simulator (SES) has been constructed at the QinetiQ, formerly the Defence Evaluation and Research Agency (DERA), Alverstoke site. Unlike escapes from a submarine where once released from the submarine the escapee's ascent can not be halted, within the SES it is possible to halt the ascent phase. This article describes the systems and procedures developed to enable medical support to be provided rapidly to a subject at any stage of the compression decompression profile. The article also provides details of the results to date that have been obtained from this work. PMID:12838773

  7. Wind and Rotation Enhanced Escape from the Early Terrestrial Atmospheres

    NASA Technical Reports Server (NTRS)

    Hartle, Richard E.; Einaudi, Franco (Technical Monitor)

    2001-01-01

    The earliest atmospheres of the terrestrial planets are thought to have been hotter, have stronger winds and rotate faster than atmospheres of today. Since these primitive atmospheres were weakly bound, they evolved rapidly because atmospheric escape was very strong, often referred to as "blowoff." Such escape has been treated as hydrodynamic, transonic flow; similar to solar wind flow dynamics. However, in many cases, although the outward flow is hydrodynamic at low altitudes, it becomes collisionless at higher altitudes, before sonic speeds are ever attained. Recent models dealing with the transition from fluid to kinetic flow have applied the Jeans escape flux at the exobase. This approach leads to escape rates that are too low, because thermospheric winds and planetary rotation are known to increase the escape flux above the corresponding Jeans flux. In particular, for a given density and temperature at the exobase, the escape flux increases as the wind speed and/or the rotation rate increase. Also, for a given wind speed and rotation rate, the escape flux enhancement over the Jeans flux increases as the mass of an escaping constituent increases, an important factor in isotope fractionation, especially the enrichment of deuterium on Mars. Accounting for a range of possible temperatures, thermospheric wind speeds and planetary rotation rates in the primitive atmospheres of the terrestrial planets, estimates are made of light constituent escape flux increases over the corresponding Jeans fluxes.

  8. Critical escape velocity for a charged particle in Ernst spacetime

    NASA Astrophysics Data System (ADS)

    Huang, Qihong; Chen, Juhua; Wang, Yongjiu

    2015-05-01

    Motion of a charged particle in Ernst spacetime is discussed. We study the conditions that a charged particle, originally revolving around this black hole in the innermost stable circular orbit (ISCO), will escape to infinity after being kicked by another particle or photon. The motion of the kicked particle is chaotic. The critical escape energy and velocity of the charged particle are obtained in the present paper. Comparing to the Schwarzschild case, the kicked charged particle without the radial velocity needs more energy to escape in Ernst case for l > 0 and less energy to escape for l < 0.

  9. Escape of black holes from the brane.

    PubMed

    Flachi, Antonino; Tanaka, Takahiro

    2005-10-14

    TeV-scale gravity theories allow the possibility of producing small black holes at energies that soon will be explored at the CERN LHC or at the Auger observatory. One of the expected signatures is the detection of Hawking radiation that might eventually terminate if the black hole, once perturbed, leaves the brane. Here, we study how the "black hole plus brane" system evolves once the black hole is given an initial velocity that mimics, for instance, the recoil due to the emission of a graviton. The results of our dynamical analysis show that the brane bends around the black hole, suggesting that the black hole eventually escapes into the extra dimensions once two portions of the brane come in contact and reconnect. This gives a dynamical mechanism for the creation of baby branes.

  10. The humanitarians' tragedy: escapable and inescapable cruelties.

    PubMed

    de Waal, Alex

    2010-04-01

    Paradoxically, elements of cruelty are intrinsic to the humanitarian enterprise.(1) This paper focuses on some of these. Escapable cruelties arise from technical failings, but the gradual professionalisation of the field and improvements in relief technologies mean that they have been significantly reduced in comparison to earlier eras. Other cruelties arise from clashes among rights, and the tensions inherent in trying to promote humanity amid the horrors of war. These are inescapable and constitute the 'humanitarians' tragedy'. Among them is the individual cruelty of failing to do good at the margin: a clash between the individual's impulses and ideals and the constraints of operating in constrained circumstances. This is a version of triage. In addition, there is the cruelty of compromising dearly-held principles when faced with other competing or overriding demands. There is also the cruelty whereby humanitarians feed victims' dreams that there is an alternative reality, which in fact cannot be attained.

  11. Metamodulation of the crayfish escape circuit.

    PubMed

    Edwards, Donald H; Yeh, Shih-Rung; Musolf, Barbara E; Antonsen, Brian L; Krasne, Franklin B

    2002-01-01

    Neuromodulation provides a means of changing the excitability of neurons or the effect of synapses, and so extends the performance range of neural circuits. Metamodulation occurs when the neuromodulatory effect is itself modulated, often in response to a change in the behavioral state of the animal. The well-studied neural circuit that mediates escape in the crayfish is modulated by serotonin, and this modulation is subject to two forms of metamodulation. First, the serotonergic modulation of the Lateral Giant (LG) command neuron for escape depends on the pattern of exposure of the cell to serotonin. High and low concentrations, and rapid and slow exposures each produce opposite modulatory effects on sensory-evoked EPSPs in LG. In addition, brief exposures produce transient modulatory effects, whereas longer exposures produce long-term facilitation. These different patterns of exposure may result from serotonin neurotransmission, paracrine transmission, and hormonal release, all of which occur in the vicinity of LG. The second form of metamodulation enables serotonergic modulation to track slow changes in the social status of the crayfish. Slowly applied serotonin facilitates LG's response in socially isolated crayfish and in new dominant and subordinate animals. Facilitation is retained in the dominant animal during two weeks of continuous pairing of the animals, but facilitation gradually changes to inhibition in the subordinate crayfish. These and related changes in serotonin modulation appear to result from changes in the population of serotonin receptors that mediate the modulatory effects in LG. Whereas the exposure-dependent metamodulation enables rapid changes in serotonergic modulation of LG to occur, the status-dependent metamodulation enables serotonergic modulation of LG to track the slow maturation of social relationships. PMID:12563168

  12. BIOMARKERS OF VIRAL EXPOSURE

    EPA Science Inventory

    Viral and protozoan pathogens associated with raw sludge can cause encephalitis, gastroenteritis, hepatitis, myocarditis, and a number of other diseases. Raw sludge that has been treated to reduce these pathogens can be used for land application according to the regulations spec...

  13. Viral Space Situational Awareness

    NASA Astrophysics Data System (ADS)

    Gleckler, A.; Butterfield, M. C.

    2012-09-01

    Viral SSA takes advantage of the amateur astronomy community to provide an extremely low-cost and geographically-diverse network of optical SSA sites. In the spirit of programs such as DARPA's Grand Challenge and the National Weather Service's program of providing amateur meteorologists with weather stations linked to a central professional meteorological facility, we form a cooperative bond with a willing community of technically-minded individuals. We term this program "viral" because we will qualify an initial set of astronomers for SSA operation and then use word of mouth in the astronomy community, as well as an outreach program, to pull in new observers. The use of modern remote controlled telescopes allows the incorporation of certified amateur, university, and commercial telescope systems. The availability of the local Viral SSA member for troubleshooting eliminates most significant costs of operating a large network. In this talk, we discuss the key concepts of Viral SSA and the route to a network of 100+ sites in a three year or less timeframe.

  14. Leafhopper viral pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four newly discovered viral pathogens in leafhopper vectors of Pierce’s disease of grapes, have been shown to replicate in sharpshooter leafhoppers; the glassy-winged sharpshooter, GWSS, Homalodisca vitripennis, and Oncometopia nigricans (Hemiptera: Cicadellidae). The viruses were classified as memb...

  15. Energy Release, Acceleration, and Escape of Solar Energetic Ions

    NASA Astrophysics Data System (ADS)

    de Nolfo, G. A.; Ireland, J.; Ryan, J. M.; Young, C. A.

    2013-12-01

    Solar flares are prodigious producers of energetic particles, and thus a rich laboratory for studying particle acceleration. The acceleration occurs through the release of magnetic energy, a significant fraction of which can go into the acceleration of particles. Coronal mass ejections (CMEs) certainly produce shocks that both accelerate particles and provide a mechanism for escape into the interplanetary medium (IP). What is less well understood is whether accelerated particles produced from the flare reconnection process escape, and if so, how these same particles are related to solar energetic particles (SEPs) detected in-situ. Energetic electron SEPs have been shown to be correlated with Type III radio bursts, hard X-ray emission, and EUV jets, making a very strong case for the connection between acceleration at the flare and escape along open magnetic field lines. Because there has not been a clear signature of ion escape, as is the case with the Type III radio emission for electrons, sorting out the avenues of escape for accelerated flare ions and the possible origin of the impulsive SEPs continues to be a major challenge. The key to building a clear picture of particle escape relies on the ability to map signatures of escape such as EUV jets at the Sun and to follow the progression of these escape signatures as they evolve in time. Furthermore, nuclear γ-ray emissions provide critical context relating ion acceleration to that of escape. With the advent observations from Fermi as well as RHESSI and the Solar Dynamics Observatory (SDO), the challenge of ion escape from the Sun can now be addressed. We present a preliminary study of the relationship of EUV jets with nuclear γ-ray emission and Type III radio observations and discuss the implications for possible magnetic topologies that allow for ion escape from deep inside the corona to the interplanetary medium.

  16. Escape behaviour in the stomatopod crustacean Squilla mantis, and the evolution of the caridoid escape reaction.

    PubMed

    Heitler, W J; Fraser, K; Ferrero, E A

    2000-01-01

    The mantis shrimp Squilla mantis shows a graded series of avoidance/escape responses to visual and mechanical (vibration and touch) rostral stimuli. A low-threshold response is mediated by the simultaneous protraction of the thoracic walking legs and abdominal swimmerets and telson, producing a backwards 'lurch' or jump that can displace the animal by up to one-third of its body length, but leaves it facing in the same direction. A stronger response starts with similar limb protraction, but is followed by partial abdominal flexion. The maximal response also consists of limb protraction followed by abdominal flexion, but in this case the abdominal flexion is sufficiently vigorous to pull the animal into a tight vertical loop, which leaves it inverted and facing away from the stimulus. The animal then swims forward (away from the stimulus) and rights itself by executing a half-roll. A bilaterally paired, large-diameter, rapidly conducting axon in the dorsal region of the ventral nerve excites swimmeret protractor motoneurons in several ganglia and is likely to be the driver neuron for the limb-protraction response. The same neuron also excites unidentified abdominal trunk motoneurons, but less reliably. The escape response is a key feature of the malacostracan caridoid facies, and we provide the first detailed description of this response in a group that diverged early in malacostracan evolution. We show that the components of the escape response contrast strongly with those of the full caridoid reaction, and we provide physiological and behavioural evidence for the biological plausibility of a limb-before-tail thesis for the evolution of the escape response. PMID:10607528

  17. 46 CFR 177.500 - Means of escape.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... this section, each space accessible to passengers or used by the crew on a regular basis, must have at... escape must be widely separated and, if possible, at opposite ends or sides of the space to minimize the... windows. (d) The number and dimensions of the means of escape from each space must be sufficient for...

  18. 46 CFR 116.500 - Means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... this section, each space accessible to passengers or used by the crew on a regular basis, must have at... escape must be widely separated and, if possible, at opposite ends or sides of the space to minimize the... windows. (d) The number and dimensions of the means of escape from each space must be sufficient for...

  19. 46 CFR 177.500 - Means of escape.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... this section, each space accessible to passengers or used by the crew on a regular basis, must have at... escape must be widely separated and, if possible, at opposite ends or sides of the space to minimize the... windows. (d) The number and dimensions of the means of escape from each space must be sufficient for...

  20. 46 CFR 177.500 - Means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the ladder. Rungs must be: (1) At least 405 millimeters (16 inches) in width; and (2) Not more than... millimeters (4.5 inches) clearance above each rung. (l) When a deck scuttle serves as a means of escape, it... designed to be kicked or pushed out; and (3) Is suitably marked. (o) Only one means of escape is...

  1. 33 CFR 143.101 - Means of escape.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Means of escape. 143.101 Section 143.101 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES DESIGN AND EQUIPMENT OCS Facilities § 143.101 Means of escape. (a) “Primary...

  2. 46 CFR 177.500 - Means of escape.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the ladder. Rungs must be: (1) At least 405 millimeters (16 inches) in width; and (2) Not more than... millimeters (4.5 inches) clearance above each rung. (l) When a deck scuttle serves as a means of escape, it... designed to be kicked or pushed out; and (3) Is suitably marked. (o) Only one means of escape is...

  3. 46 CFR 127.240 - Means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Means of escape. 127.240 Section 127.240 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS CONSTRUCTION AND ARRANGEMENTS...) and (m) of this section, there must be at least two means of escape, exclusive of windows...

  4. 46 CFR 127.240 - Means of escape.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Means of escape. 127.240 Section 127.240 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS CONSTRUCTION AND ARRANGEMENTS Particular Construction and Arrangements § 127.240 Means of escape. (a) Except as provided by paragraphs (l) and (m) of this section, there...

  5. 46 CFR 169.313 - Means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Means of escape. 169.313 Section 169.313 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Construction and Arrangement Hull Structure § 169.313 Means of escape. (a) Except as provided by paragraph (f)...

  6. 46 CFR 169.313 - Means of escape.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Means of escape. 169.313 Section 169.313 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Construction and Arrangement Hull Structure § 169.313 Means of escape. (a) Except as provided by paragraph (f)...

  7. 29. VIEW OF SUBMARINE ESCAPE TRAINING TANK DURING CONSTRUCTION AT ...

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

    29. VIEW OF SUBMARINE ESCAPE TRAINING TANK DURING CONSTRUCTION AT POINT JUST ABOVE THE SUBMARINE SECTION AT THE 110-FOOT LEVEL 1929-1930 - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  8. 35. INTERIOR VIEW OF EQUIPMENT HOUSE, SUBMARINE ESCAPE TRAINING TANK, ...

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

    35. INTERIOR VIEW OF EQUIPMENT HOUSE, SUBMARINE ESCAPE TRAINING TANK, PRIOR TO ENLARGEMENT OF ROOM AND INSTALLATION OF TRIPLE-LOCK RECOMPRESSION CHAMBER IN 1957 - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  9. 22. VIEW OF ESCAPE TRAINING TANK, LOOKING WEST FROM EAST ...

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

    22. VIEW OF ESCAPE TRAINING TANK, LOOKING WEST FROM EAST SIDE OF CUPOLA TOWARD ELEVATOR. TWO-LOCK RECOMPRESSION CHAMBER AT REAR - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  10. 31. VIEW OF SUBMARINE ESCAPE TRAINING TANK DURING CONSTRUCTION OF ...

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

    31. VIEW OF SUBMARINE ESCAPE TRAINING TANK DURING CONSTRUCTION OF THE ELEVATOR AND PASSAGEWAYS TO THE 18- AND 50-FOOT LOCKS AND CUPOLA 1932 - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  11. 36. VIEW OF CUPOLA, SUBMARINE ESCAPE TRAINING TANK, SHOWING ROVING ...

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

    36. VIEW OF CUPOLA, SUBMARINE ESCAPE TRAINING TANK, SHOWING ROVING RESCUE BELL SUSPENDED ABOVE TANK, WITH TWO-LOCK RECOMPRESSION CHAMBER AT REAR, LOOKING WEST. Photo taken after installation of recompression chamber in 1956. - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  12. Green Pea Galaxies Reveal Secrets of Lyα Escape

    NASA Astrophysics Data System (ADS)

    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.

  13. 7. VIEW OF ESCAPE TRAINING TANK, LOOKING UP SOUTH SIDE ...

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

    7. VIEW OF ESCAPE TRAINING TANK, LOOKING UP SOUTH SIDE FROM 50-FOOT PASSAGEWAY, SHOWING 25-FOOT BLISTER AT LEFT, 18-FOOT PASSAGEWAY AND PLATFORM AT RIGHT - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  14. The Origins and Underpinning Principles of E-Scape

    ERIC Educational Resources Information Center

    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…

  15. Fire Won't Wait--Plan Your Escape!

    ERIC Educational Resources Information Center

    PTA Today, 1991

    1991-01-01

    Discusses the importance of home fire escape drills, detailing fire safety plans. Early detection and warning (smoke detectors) coupled with well-rehearsed escape plans help prevent serious injury. Children need to be taught about fire safety beginning at a very early age. (SM)

  16. How many ions have escaped the Martian atmosphere?

    NASA Astrophysics Data System (ADS)

    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.

  17. History and Global Burden of Viral Hepatitis.

    PubMed

    Blum, Hubert E

    2016-01-01

    Between 1963 and 1989, 5 hepatotropic viruses have been discovered that are the major causes of viral hepatitides worldwide: hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus and hepatitis E virus. Their epidemiology and pathogenesis have been studied in great detail. Furthermore, the structure and genetic organization of their DNA or RNA genome including the viral life cycle have been elucidated and have been successfully translated into important clinical applications, such as the specific diagnosis, therapy and prevention of the associated liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC). The prevalence of acute and chronic viral hepatitis A-E shows distinct geographic differences. The global burden of disease (prevalence, incidence, death, disability-adjusted life years) has been analyzed in seminal studies that show that the worldwide prevalence of hepatitis A-E has significantly decreased between 1990 and 2013. During the same time, the incidence of HBV-related liver cirrhosis and HCC, respectively, also decreased or increased slightly, the incidence of the HCV-related liver cirrhosis remained stable and the incidence of HCV-related HCC showed a major increase. During the coming years, we expect to improve our ability to prevent and effectively treat viral hepatitis A-E, resulting in the control of these global infections and the elimination of their associated morbidities and mortalities. PMID:27170381

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Hydrodynamics of the escape response in bluegill sunfish, Lepomis macrochirus

    PubMed Central

    Tytell, Eric D.; Lauder, George V.

    2009-01-01

    SUMMARY Escape responses of fishes are one of the best characterized vertebrate behaviors, with extensive previous research on both the neural control and biomechanics of startle response performance. However, very little is known about the hydrodynamics of escape responses, despite the fact that understanding fluid flow patterns during the escape is critical for evaluating how body movement transfers power to the fluid, for defining the time course of power generation, and for characterizing the wake signature left by escaping fishes, which may provide information to predators. In this paper we present an experimental hydrodynamic analysis of the C-start escape response in bluegill sunfish (Lepomis macrochirus). We used time-resolved digital particle image velocimetry at 1000 fps to image flow patterns during the escape response. We analyzed flow patterns generated by the body separately from those generated by the dorsal and anal fins, to assess the contribution of these median fins to escape momentum. Each escape response produced three distinct jets of fluid. Summing the components of fluid momentum in the jets provided an estimate of fish momentum that did not differ significantly from momentum measured from the escaping fish body. In contrast to conclusions drawn from previous kinematic analyses and theoretical models, the caudal fin generated momentum that opposes the escape during stage one, while the body bending during stage one contributed substantial propulsive momentum. Additionally, the dorsal and anal fins each contributed substantial momentum. The results underscore the importance of the dorsal and anal fins as propulsors and suggest that the size and placement of these fins may be a key determinant of fast start performance. PMID:18931309

  20. Ion Escape from the Ionosphere of Titan

    NASA Technical Reports Server (NTRS)

    Hartle, R.; Sittler, E.; Lipatov, A.

    2008-01-01

    Ions have been observed to flow away from Titan along its induced magnetic tail by the Plasma Science Instrument (PLS) on Voyager 1 and the Cassini Plasma Spectrometer (CAPS) on Cassini. In both cases, the ions have been inferred to be of ionospheric origin. Recent plasma measurements made at another unmagnetized body, Venus, have also observed similar flow in its magnetic tail. Much earlier, the possibility of such flow was inferred when ionospheric measurements made from the Pioneer Venus Orbiter (PVO) were used to derive upward flow and acceleration of H(+), D(+) and O(+) within the nightside ionosphere of Venus. The measurements revealed that the polarization electric field in the ionosphere produced the principal upward force on these light ions. The resulting vertical flow of H(+) and D(+) was found to be the dominant escape mechanism of hydrogen and deuterium, corresponding to loss rates consistent with large oceans in early Venus. Other electrodynamic forces were unimportant because the plasma beta in the nightside ionosphere of Venus is much greater than one. Although the plasma beta is also greater than one on Titan, ion acceleration is expected to be more complex, especially because the subsolar point and the subflow points can be 180 degrees apart. Following what we learned at Venus, upward acceleration of light ions by the polarization electric field opposing gravity in the ionosphere of Titan will be described. Additional electrodynamic forces resulting from the interaction of Saturn's magnetosphere with Titan's ionosphere will be examined using a recent hybrid model.

  1. WANDERING STARS: AN ORIGIN OF ESCAPED POPULATIONS

    SciTech Connect

    Teyssier, Maureen; Johnston, Kathryn V.; Shara, Michael M.

    2009-12-10

    We demonstrate that stars beyond the virial radii of galaxies may be generated by the gravitational impulse received by a satellite as it passes through the pericenter of its orbit around its parent. These stars may become energetically unbound (escaped stars), or may travel to further than a few virial radii for longer than a few Gyr, but still remain energetically bound to the system (wandering stars). Larger satellites (10%-100% the mass of the parent), and satellites on more radial orbits are responsible for the majority of this ejected population. Wandering stars could be observable on Mpc scales via classical novae, and on 100 Mpc scales via Type Ia supernova. The existence of such stars would imply a corresponding population of barely bound, old, high-velocity stars orbiting the Milky Way, generated by the same physical mechanism during the Galaxy's formation epoch. Sizes and properties of these combined populations should place some constraints on the orbits and masses of the progenitor objects from which they came, providing insight into the merging histories of galaxies in general and the Milky Way in particular.

  2. Immune Escape Strategies of Malaria Parasites

    PubMed Central

    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

  3. Nonthermal atmospheric escape from Mars and Titan

    NASA Astrophysics Data System (ADS)

    Lammer, H.; Bauer, S. J.

    1991-02-01

    Energy flux spectra and particle concentrations of the hot O and N coronae from Mars and Titan, respectively, resulting primarily from dissociative recombination of molecular ions, have been calculated by means of a Monte Carlo method. The calculated energy flux spectra lead to an escape flux phi(esc) about 6 x 10 to the 6th/sq cm per sec for Mars and phi(esc) about 2 x 10 to 6th/sq cm per sec for Titan, corresponding to a mass loss of about 0.14 kg/s for Mars and about 0.3 kg/s for Titan. (The contribution of electron impact ionization on N2 amounts to only about 25 percent of Titan's mass loss). Mass loss via solar and magnetospheric wind is also estimated using newly calculated mass loading limits. The mass loss via ion pickup from the extended hot atom corona for Mars amounts to about 0.25 kg/s (O/+/) and for Titan to about 50 g/s (N2/+/or H2CN/+/). Thus, the total mass loss rate from Mars and Titan is about the same (i.e., 0.4 kg/s).

  4. Escaping the resource curse in China.

    PubMed

    Cao, Shixiong; Li, Shurong; Ma, Hua; Sun, Yutong

    2015-02-01

    Many societies face an income gap between rich regions with access to advanced technology and regions that are rich in natural resources but poorer in technology. This "resource curse" can lead to a Kuznets trap, in which economic inequalities between the rich and the poor increase during the process of socioeconomic development. This can also lead to depletion of natural resources, environmental degradation, social instability, and declining socioeconomic development. These problems will jeopardize China's achievements if the current path continues to be pursued without intervention by the government to solve the problems. To mitigate the socioeconomic development gap between western and eastern China, the government implemented its Western Development Program in 2000. However, recent data suggest that this program has instead worsened the resource curse. Because each region has its own unique strengths and weaknesses, China must escape the resource curse by accounting for this difference; in western China, this can be done by improving education, promoting high-tech industry, adjusting its economic strategy to balance regional development, and seeking more sustainable approaches to socioeconomic development.

  5. Candida albicans escapes from mouse neutrophils.

    PubMed

    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.

  6. Viral Membrane Scission

    PubMed Central

    Rossman, Jeremy S.; Lamb, Robert A.

    2014-01-01

    Virus budding is a complex, multistep process in which viral proteins make specific alterations in membrane curvature. Many different viral proteins can deform the membrane and form a budding virion, but very few can mediate membrane scission to complete the budding process. As a result, enveloped viruses have developed numerous ways of facilitating membrane scission, including hijacking host cellular scission machinery and expressing their own scission proteins. These proteins mediate scission in very different ways, though the biophysical mechanics underlying their actions may be similar. In this review, we explore the mechanisms of membrane scission and the ways in which enveloped viruses use these systems to mediate the release of budding virions. PMID:24099087

  7. Viral membrane fusion.

    PubMed

    Harrison, Stephen C

    2015-05-01

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a "fusion loop" or "fusion peptide") engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics.

  8. Viral membrane fusion

    SciTech Connect

    Harrison, Stephen C.

    2015-05-15

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  9. Dications and thermal ions in planetary atmospheric escape

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  10. Evolution of viral life-cycle in response to cytotoxic T lymphocyte-mediated immunity.

    PubMed

    Louzoun, Yoram; Ganusov, Vitaly V

    2012-10-01

    Viruses in mammals are constantly faced with the problem of elimination by the host immunity. Cytotoxic T lymphocyte (CTL) responses are thought to play a major role in the control and clearance of several viral infections in mice and humans. It is therefore expected that over evolutionary time, viruses would be forced to evolve to avoid recognition by CTLs. Indeed, a number of studies have documented the accumulation of viral variants with escape mutations. These mutations allow viruses to hide from CTL responses common in the host population. CTLs recognize viruses by short protein sequences, named epitopes, derived from viral proteins. The efficiency of viral recognition by epitope-specific CTL responses depends on the expression pattern of the proteins carrying these epitopes, and the total amount of that protein (and thus epitopes) in the cell. When a virus replicates in a cell, some viral genes are expressed early in the life cycle of the virus, while other proteins are expressed late. For example, HIV infected cells first express Rev and Tat proteins, and the Gag proteins are expressed late. Here we propose a dynamical model of the viral life cycle to study how expression level of early vs. late genes may affect viral dynamics within the host and virus transmission over the course of infection. We find that for acute and chronic viral infections lower expression of early genes than that of the late genes is expected to give selective advantage and higher transmission to viruses.

  11. Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes

    NASA Astrophysics Data System (ADS)

    Shekhar, Karthik; Ruberman, Claire F.; Ferguson, Andrew L.; Barton, John P.; Kardar, Mehran; Chakraborty, Arup K.

    2013-12-01

    Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.

  12. Optimizing Viral Discovery in Bats

    PubMed Central

    Young, Cristin C. W.; Olival, Kevin J.

    2016-01-01

    Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007–2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches. PMID:26867024

  13. Optimizing Viral Discovery in Bats.

    PubMed

    Young, Cristin C W; Olival, Kevin J

    2016-01-01

    Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007-2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches. PMID:26867024

  14. Evolutionary escape on complex genotype-phenotype networks.

    PubMed

    Ibáñez-Marcelo, Esther; Alarcón, Tomás

    2016-04-01

    We study the problem of evolutionary escape that is the process whereby a population under sudden changes in the selective pressures acting upon it try to evade extinction by evolving from previously well-adapted phenotypes to those that are favoured by the new selective pressure. We perform a comparative analysis between results obtained by modelling genotype space as a regular hypercube (H-graphs), which is the scenario considered in previous work on the subject, to those corresponding to a complex genotype-phenotype network (B-graphs). In order to analyse the properties of the escape process on both these graphs, we apply a general theory based on multi-type branching processes to compute the evolutionary dynamics and probability of escape. We show that the distribution of distances between phenotypes in B-graphs exhibits a much larger degree of heterogeneity than in H-graphs. This property, one of the main structural differences between both types of graphs, causes heterogeneous behaviour in all results associated to the escape problem. We further show that, due to the heterogeneity characterising escape on B-graphs, escape probability can be underestimated by assuming a regular hypercube genotype network, even if we compare phenotypes at the same distance in H-graphs. Similarly, it appears that the complex structure of B-graphs slows down the rate of escape.

  15. Efficiently estimating salmon escapement uncertainty using systematically sampled data

    USGS Publications Warehouse

    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.

  16. [The great virus comeback].

    PubMed

    Forterre, Patrick

    2013-01-01

    Viruses have been considered for a long time as by-products of biological evolution. This view is changing now as a result of several recent discoveries. Viral ecologists have shown that viral particles are the most abundant biological entities on our planet, whereas metagenomic analyses have revealed an unexpected abundance and diversity of viral genes in the biosphere. Comparative genomics have highlighted the uniqueness of viral sequences, in contradiction with the traditional view of viruses as pickpockets of cellular genes. On the contrary, cellular genomes, especially eukaryotic ones, turned out to be full of genes derived from viruses or related elements (plasmids, transposons, retroelements and so on). The discovery of unusual viruses infecting archaea has shown that the viral world is much more diverse than previously thought, ruining the traditional dichotomy between bacteriophages and viruses. Finally, the discovery of giant viruses has blurred the traditional image of viruses as small entities. Furthermore, essential clues on virus history have been obtained in the last ten years. In particular, structural analyses of capsid proteins have uncovered deeply rooted homologies between viruses infecting different cellular domains, suggesting that viruses originated before the last universal common ancestor (LUCA). These studies have shown that several lineages of viruses originated independently, i.e., viruses are polyphyletic. From the time of LUCA, viruses have coevolved with their hosts, and viral lineages can be viewed as lianas wrapping around the trunk, branches and leaves of the tree of life. Although viruses are very diverse, with genomes encoding from one to more than one thousand proteins, they can all be simply defined as organisms producing virions. Virions themselves can be defined as infectious particles made of at least one protein associated with the viral nucleic acid, endowed with the capability to protect the viral genome and ensure its

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. 46 CFR 108.155 - Restrictions on means of escape utilized.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... means of escape utilized. A required means of escape may not be a vertical ladder or deck scuttle, except that one of the means of escape may be a vertical ladder or deck scuttle if a stairway would...

  20. 16. INTERIOR VIEW OF SUBMARINE SECTION AT 110FOOT LEVEL, ESCAPE ...

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

    16. INTERIOR VIEW OF SUBMARINE SECTION AT 110-FOOT LEVEL, ESCAPE TRAINING TANK, SHOWING LADDER TO ESCAPE TANK, LOOKING SOUTH - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  1. Great Lakes: Chemical Monitoring

    ERIC Educational Resources Information Center

    Delfino, Joseph J.

    1976-01-01

    The Tenth Great Lakes Regional Meeting of the American Chemical Society met to assess current Chemical Research activity in the Great Lakes Basin, and addressed to the various aspects of the theme, Chemistry of the Great Lakes. Research areas reviewed included watershed studies, atmospheric and aquatic studies, and sediment studies. (BT)

  2. Detection of viral hemorrhagic septicemia virus

    USGS Publications Warehouse

    Winton, James; Kurath, Gael; Batts, William

    2007-01-01

    Viral hemorrhagic septicemia virus (VHSV) is considered to be one of the most important viral pathogens of finfish and is listed as reportable by many nations and international organizations (Office International des Epizooties 2006). Prior to 1988, VHSV was thought to be limited to Europe (Wolf 1988; Smail 1999). Subsequently, it was shown that the virus is endemic among many marine and anadromous fish species in both the Pacific and Atlantic Oceans (Meyers and Winton 1995; Skall et al. 2005). Genetic analysis reveals that isolates of VHSV can be divided into four genotypes that generally correlate with geographic location with the North American isolates generally falling into VHSV Genotype IV (Snow et al. 2004). In 2005-2006, reports from the Great Lakes region indicated that wild fish had experienced disease or, in some cases, very large die-offs from VHSV (Elsayed et al. 2006, Lumsden et al. 2007). The new strain from the Great Lakes, now identified as VHSV Genotype IVb, appears most closely related to isolates of VHSV from mortalities that occurred during 2000-2004 in rivers and near-shore areas of New Brunswick and Nova Scotia, Canada (Gagne et al. 2007). The type IVb isolate found in the Great Lakes region is the only strain outside of Europe that has been associated with significant mortality in freshwater species.

  3. Broadening our expectations for viral safety risk mitigation.

    PubMed

    Kljavin, Ivar J

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) The production of biotechnology products using mammalian cell lines offers an inherent risk of viral contamination because of the scale of the process and the complexity of the materials employed. The testing of production cell lines, raw materials, and test execution at appropriate stages of production all combined with viral inactivation or removal strategies ensures that an infectious agent is absent from the purified final product. Perhaps because of these efforts, biotechnology products have not been linked to a negative clinical consequence. However, manufacturing viral contaminations still do occur and may have a great potential negative impact to our patients by disrupting the drug product supply chain. In this paper, additional end-to-end complementary viral safety program considerations are suggested beyond the traditional viral testing and inactivation/removal strategies. These additional points of consideration should be thought of as augmenting the above approaches to further provide a reasonable measure of mitigating the risk of viral contaminations within the biopharmaceutical manufacturing facility. The scope of this paper is on biologics produced in mammalian cells with an emphasis on viral contaminations involving Chinese hamster ovary cell production, although for the examples given as lessons learned with previous industry contaminations, vaccine production issues have been included as a general reference.

  4. Combating emerging viral threats

    PubMed Central

    Bekerman, Elena; Einav, Shirit

    2015-01-01

    Synopsis Most approved antiviral therapeutics selectively inhibit proteins encoded by a single virus, thereby providing a “one drug-one bug” solution. As a result of this narrow spectrum of coverage and the high cost of drug development, therapies are currently approved for fewer than ten viruses out of the hundreds known to cause human disease. This perspective summarizes progress and challenges in the development of broad-spectrum antiviral therapies. These strategies include targeting enzymatic functions shared by multiple viruses and host cell machinery by newly discovered compounds or by repurposing approved drugs. These approaches offer new practical means for developing therapeutics against existing and emerging viral threats. PMID:25883340

  5. Viral complement regulatory proteins.

    PubMed

    Rosengard, A M; Ahearn, J M

    1999-05-01

    The inactivation of complement provides cells and tissues critical protection from complement-mediated attack and decreases the associated recruitment of other inflammatory mediators. In an attempt to evade the host immune response, viruses have evolved two mechanisms to acquire complement regulatory proteins. They can directly seize the host cell complement regulators onto their outer envelope and/or they can produce their own proteins which are either secreted into the neighboring intercellular space or expressed as membrane-bound proteins on the infected host cell. The following review will concentrate on the viral homologues of the mammalian complement regulatory proteins, specifically those containing complement control protein (CCP) repeats. PMID:10408371

  6. [Viral exanthematic childhood diseases].

    PubMed

    Allwinn, R; Doerr, H W

    1997-01-01

    Exanthem is defined as multiple, inflammatory skin alteration with a hematogenic, lymphogenic or neurogenic origin. Typically, so called exanthematic children's diseases are measles, mumps, rubella, varicella, erythema infectiosum (fifth disease) and in the past small pox. The pathogenesis of the viral-caused diseases primarily occurs in the vascular connective tissue. The cytopathogenetic effects result in inflammatory tissue reactions with activation of defence mechanism and producing of immune complexes. First symptoms are hyperemia, edema and inflammatory infiltrates with itchy swellings. Virological laboratory diagnosis are necessary especially for the progress of atypical infectious diseases, for persons with immunological or chronical illness and under chemotherapeutical or immunosuppressival treatment.

  7. Viral surveillance and discovery

    PubMed Central

    Lipkin, Walter Ian; Firth, Cadhla

    2014-01-01

    The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health. PMID:23602435

  8. Equine viral arteritis.

    PubMed

    Balasuriya, Udeni B R

    2014-12-01

    Equine arteritis virus (EAV), the causative agent of equine viral arteritis (EVA), is a respiratory and reproductive disease that occurs throughout the world. EAV infection is highly species-specific and exclusively limited to members of the family Equidae, which includes horses, donkeys, mules, and zebras. EVA is an economically important disease and outbreaks could cause significant losses to the equine industry. The primary objective of this article is to summarize current understanding of EVA, specifically the disease, pathogenesis, epidemiology, host immune response, vaccination and treatment strategies, prevention and control measures, and future directions.

  9. Low LET radiolysis escape yields for reducing radicals and H2 in pressurized high temperature water

    NASA Astrophysics Data System (ADS)

    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.

  10. 42. Launch Area, Underground Missile Storage Structure, detail of escape ...

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

    42. Launch Area, Underground Missile Storage Structure, detail of escape hatch, elevator and air vent VIEW SOUTH - NIKE Missile Battery PR-79, Launch Area, East Windsor Road south of State Route 101, Foster, Providence County, RI

  11. 40. Launch Area, Underground Missile Storage Structure, detail of escape ...

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

    40. Launch Area, Underground Missile Storage Structure, detail of escape hatch and decontamination shower VIEW WEST - NIKE Missile Battery PR-79, Launch Area, East Windsor Road south of State Route 101, Foster, Providence County, RI

  12. Is tube-escape learning by protozoa associative learning?

    PubMed

    Hinkle, D J; Wood, D C

    1994-02-01

    The ciliate protozoa, Stentor and Paramecium, have been reported to escape from the bottom end of narrow capillary tubes into a larger volume of medium with increasing rapidity over the course of trials. This change in behavior has been considered an apparent example of associative learning. This decrease in escape time is not due to a change in the protozoa's environment, their swimming speed, frequency of ciliary reversals, or the proportion of time spent forward or backward swimming. Instead, most of the decrease results from a decrease in the proportion of time spent in upward swimming. However, a similar decrease in upward swimming occurs when the task is altered to require escape from the upper end of the capillary tubes. Because the protozoa exhibit the same change in behavior regardless of the reinforcing stimulus, tube-escape learning is not associative learning. PMID:8192854

  13. 10. VIEW OF SILO DOORS, AIR VENTS, AND ESCAPE HATCH, ...

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

    10. VIEW OF SILO DOORS, AIR VENTS, AND ESCAPE HATCH, LOOKING EAST. WHITE STRUCTURES BELONG TO CURRENT OCCUPANTS Everett Weinreb, photographer, April 1988 - Los Pinetos Nike Missile Site, Santa Clara Road, Los Angeles National Forest, Sylmar, Los Angeles County, CA

  14. 14. View inside Building 802, the "Escape Hatch" at the ...

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

    14. View inside Building 802, the "Escape Hatch" at the rear of the "Sleeping Quarters", facing south. - Naval Air Station Fallon, 100-man Fallout Shelter, 800 Complex, off Carson Road near intersection of Pasture & Berney Roads, Fallon, Churchill County, NV

  15. 39. VIEW OF HORSE AND ESCAPE STEPS ON ARIZONA CANAL, ...

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

    39. VIEW OF HORSE AND ESCAPE STEPS ON ARIZONA CANAL, LOOKING NORTH ON THE SALT RIVER INDIAN RESERVATION Photographer: James Eastwood, June 1990 - Arizona Canal, North of Salt River, Phoenix, Maricopa County, AZ

  16. 46 CFR 169.313 - Means of escape.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... escape is acceptable provided that— (1) There is no source of fire in the space, such as a galley stove... vessel or those on board. (g) Dead end corridors or the equivalent, more than 40 feet in length...

  17. Prey escaping wolves, Canis lupus, despite close proximity

    USGS Publications Warehouse

    Nelson, M.E.; Mech, L.D.

    1993-01-01

    We describe attacks by wolf (Canis lupus) packs in Minnesota on a white-tailed deer (Odocoileus virginianus) and a moose (Alces alces) in which wolves were within contact distance of the prey but in which the prey escaped.

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

    ERIC Educational Resources Information Center

    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 applied…

  19. Dissociated neural effects of cortisol depending on threat escapability.

    PubMed

    Montoya, Estrella R; van Honk, Jack; Bos, Peter A; Terburg, David

    2015-11-01

    Evolution has provided us with a highly flexible neuroendocrine threat system which, depending on threat imminence, switches between active escape and passive freezing. Cortisol, the "stress-hormone", is thought to play an important role in both fear behaviors, but the exact mechanisms are not understood. Using pharmacological functional magnetic resonance imaging we investigated how cortisol modulates the brain's fear systems when humans are under virtual-predator attack. We show dissociated neural effects of cortisol depending on whether escape from threat is possible. During inescapable threat cortisol reduces fear-related midbrain activity, whereas in anticipation of active escape cortisol boosts activity in the frontal salience network (insula and anterior cingulate cortex), which is involved in autonomic control, visceral perception and motivated action. Our findings suggest that cortisol adjusts the human neural threat system from passive fear to active escape, which illuminates the hormone's crucial role in the adaptive flexibility of fear behaviors.

  20. Escaping the trap of allergic rhinitis.

    PubMed

    Rossi, Oliviero; Massaro, Ilaria; Caminati, Marco; Quecchia, Cristina; Fassio, Filippo; Heffler, Enrico; Canonica, Giorgio Walter

    2015-01-01

    allergic rhinitis or non-allergic rhinitis, with statistical significance noted from the first day of treatment, with treatment difference maintained for a full year. Taken together, these data suggest that MP29-02 may improve the lives of many of our patients, enabling them to finally escape the allergic rhinitis trap. PMID:26244040

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

    NASA Astrophysics Data System (ADS)

    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

  2. Atlas of Great Comets

    NASA Astrophysics Data System (ADS)

    Stoyan, Ronald; Dunlop, Storm

    2015-01-01

    Foreword; Using this book; Part I. Introduction: Cometary beliefs and fears; Comets in art; Comets in literature and poetry; Comets in science; Cometary science today; Great comets in antiquity; Great comets of the Middle Ages; Part II. The 30 Greatest Comets of Modern Times: The Great Comet of 1471; Comet Halley 1531; The Great Comet of 1556; The Great Comet of 1577; Comet Halley, 1607; The Great Comet of 1618; The Great Comet of 1664; Comet Kirch, 1680; Comet Halley, 1682; The Great Comet of 1744; Comet Halley, 1759; Comet Messier, 1769; Comet Flaugergues, 1811; Comet Halley, 1835; The Great March Comet of 1843; Comet Donati, 1858; Comet Tebbutt, 1861; The Great September Comet of 1882; The Great January Comet of 1910; Comet Halley, 1910; Comet Arend-Roland, 1956; Comet Ikeya-Seki, 1965; Comet Bennett, 1970; Comet Kohoutek, 1973-4; Comet West, 1976; Comet Halley, 1986; Comet Shoemaker-Levy 9, 1994; Comet Hyakutake, 1996; Comet Hale-Bopp, 1997; Comet McNaught, 2007; Part III. Appendices; Table of comet data; Glossary; References; Photo credits; Index.

  3. Quantifying Distributions of the Lyman Continuum Escape Fraction

    NASA Astrophysics Data System (ADS)

    Cen, Renyue; Kimm, Taysun

    2015-03-01

    Simulations have indicated that most of the escaped Lyman continuum (LyC) 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 LyC 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 the true escape fraction of the galaxy averaged over its full sky. Here we study how LyC 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 (< {{f}esc,1D}> ) averaged over mock observational samples, as a function of the sample size, compared to the true mean (if an infinite sample size is used). We find that, when the sample size is small, the apparent mean skews to the low end. For example, for a true mean of 6.7%, an observational sample of (2,10,50) galaxies at z = 4 would have have a 2.5% probability of obtaining the sample mean lower than ≤ft< {{f}esc,1D} \\right> = (0.007%, 1.8%, 4.1%) and a 2.5% probability of obtaining the sample mean greater than (43%, 18%, 11%). Our simulations suggest that at least ∼100 galaxies should be stacked in order to constrain the true escape fraction within 20% uncertainty.

  4. Ion escape from Venus using statistical distribution functions

    NASA Astrophysics Data System (ADS)

    Nordstrom, T.; Stenberg, G.; Nilsson, H.; Barabash, S.; Futaana, Y.

    2012-04-01

    We use more than three years of data from the ASPERA-4 instrument onboard Venus Express to compile statistical distribution functions of ion flux in and around induced magnetosphere of Venus. We present samples of statistical distribution functions, as well average flux patterns in the near Venus space based on the statistical distribution functions. The statistical distribution functions allows for a compensation of biased sampling regarding both position and angular coverage of the instrument. Protons and heavy ions (mass/charge > 16) are the major ion species escaping from Venus. The escape is due to acceleration of planetary ions by energy transfer from the solar wind. The ion escape appears to exclusively take place in the induced magnetotail region and no heavy ions are present in the magnetosheath. Protons of solar wind origin are travelling around the planet and penetrating the tail, resulting in a mix of planetary and solar wind protons inside the induced magnetosphere boundary. The escape rates of ions inside the tail agree with results from recent published studies, where other analysis methods have been used. We also compare our results for Venus with a recent study of ion escape from Mars, where the same analysis method has been applied to data from the ASPERA-3 instrument on Mars Express. Both Mars and Venus are unmagnetized planets and are expected to interact similarly with the solar wind. On Mars the heavy ions are seen escaping in both the magnetosheath and tail regions as opposed to Venus where escape only takes place inside the tail. A possible explanation is that the magnetosphere of Mars is smaller compared to the ion gyroradius, making it easier for the ions to pass through the induced magnetosphere boundary. On both planets the escape rates of heavy ions in the tail are constant with increasing tail distance, verifying that the ions are leaving the planet in this region.

  5. Human viral gastroenteritis.

    PubMed Central

    Christensen, M L

    1989-01-01

    During the last 15 years, several different groups of fastidious viruses that are responsible for a large proportion of acute viral gastroenteritis cases have been discovered by the electron microscopic examination of stool specimens. This disease is one of the most prevalent and serious clinical syndromes seen around the world, especially in children. Rotaviruses, in the family Reoviridae, and fastidious fecal adenoviruses account for much of the viral gastroenteritis in infants and young children, whereas the small caliciviruses and unclassified astroviruses, and possibly enteric coronaviruses, are responsible for significantly fewer cases overall. In addition to electron microscopy, enzyme immunoassays and other rapid antigen detection systems have been developed to detect rotaviruses and fastidious fecal adenoviruses in the stool specimens of both nonhospitalized patients and those hospitalized for dehydration and electrolyte imbalance. Experimental rotavirus vaccines have also been developed, due to the prevalence and seriousness of rotavirus infection. The small, unclassified Norwalk virus and morphologically similar viruses are responsible for large and small outbreaks of acute gastroenteritis in older children, adolescents, and adults. Hospitalization of older patients infected with these viruses is usually not required, and their laboratory diagnoses have been limited primarily to research laboratories. Images PMID:2644024

  6. [Emergent viral infections].

    PubMed

    Galama, J M

    2001-03-31

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic infections such as dengue and hepatitis E, but also of hepatitis A, which is no longer endemic. Apart from import diseases new viruses have appeared (Nipah-virus and transfusion-transmitted virus). Existing viruses may suddenly cause more severe diseases, e.g. infection by enterovirus 71. The distribution area of a virus may change, e.g. in case of West Nile virus, an Egyptian encephalitis virus that appears to have established itself in the USA. Furthermore, there is no such thing as a completely new virus; it is always an existing virus that has adapted itself to another host or that was already present in humans but has only recently been discovered. A number of factors facilitate the emergence of new infectious diseases. These include intensive animal husbandry and the transport of animals. The unexpected appearance of West Nile virus in the western hemisphere was possibly due to animal transportation.

  7. Initiation and spread of escape waves within animal groups

    PubMed Central

    Herbert-Read, James E.; Buhl, Jerome; Hu, Feng; Ward, Ashley J. W.; Sumpter, David J. T.

    2015-01-01

    The exceptional reactivity of animal collectives to predatory attacks is thought to be owing to rapid, but local, transfer of information between group members. These groups turn together in unison and produce escape waves. However, it is not clear how escape waves are created from local interactions, nor is it understood how these patterns are shaped by natural selection. By startling schools of fish with a simulated attack in an experimental arena, we demonstrate that changes in the direction and speed by a small percentage of individuals that detect the danger initiate an escape wave. This escape wave consists of a densely packed band of individuals that causes other school members to change direction. In the majority of cases, this wave passes through the entire group. We use a simulation model to demonstrate that this mechanism can, through local interactions alone, produce arbitrarily large escape waves. In the model, when we set the group density to that seen in real fish schools, we find that the risk to the members at the edge of the group is roughly equal to the risk of those within the group. Our experiments and modelling results provide a plausible explanation for how escape waves propagate in nature without centralized control. PMID:26064630

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

    NASA Astrophysics Data System (ADS)

    Gemmell, Brad; Sheng, Jian; Buskey, Ed

    2010-11-01

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

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

    PubMed

    Holden, Matthew H; Conrad, Jon M

    2015-11-01

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

  10. Pseudorabies virus can escape from CRISPR-Cas9-mediated inhibition.

    PubMed

    Peng, Zhiyuan; Ouyang, Ting; Pang, Daxin; Ma, Teng; Chen, Xinrong; Guo, Ning; Chen, Fuwang; Yuan, Lin; Ouyang, Hongsheng; Ren, Linzhu

    2016-09-01

    The CRISPR-Cas9 system is a newly developed genome-engineering tool used to inhibit virus infection by targeting the conserved regions of the viral genomic DNA. In the present study, we constructed a cell line stably expressing Cas9 endonuclease and sgRNA targeting the conserved UL30 gene of pseudorabies virus (PRV). During the PRV infection, the CRISPR-Cas9 system was efficient in cleaving the UL30 gene in each passage. However, deletions and insertions occurred at low passages, while substitutions were frequently observed at high passages. Furthermore, copy numbers and virus titers of PRV were significantly increased in a passage-dependent manner, indicating that viral genomic replication and assembly were more effective at the high passages than at low passages. These results demonstrated that PRV could escape from CRISPR-Cas9-mediated inhibition. Therefore, whether the CRISPR-Cas9 system is suitable for antiviral application should be considered and carefully verified. PMID:27507009

  11. Viral noncoding RNAs: more surprises

    PubMed Central

    Tycowski, Kazimierz T.; Guo, Yang Eric; Lee, Nara; Moss, Walter N.; Vallery, Tenaya K.; Xie, Mingyi

    2015-01-01

    Eukaryotic cells produce several classes of long and small noncoding RNA (ncRNA). Many DNA and RNA viruses synthesize their own ncRNAs. Like their host counterparts, viral ncRNAs associate with proteins that are essential for their stability, function, or both. Diverse biological roles—including the regulation of viral replication, viral persistence, host immune evasion, and cellular transformation—have been ascribed to viral ncRNAs. In this review, we focus on the multitude of functions played by ncRNAs produced by animal viruses. We also discuss their biogenesis and mechanisms of action. PMID:25792595

  12. Trade-offs between performance and variability in the escape responses of bluegill sunfish (Lepomis macrochirus)

    PubMed Central

    Hitchcock, Amanda C.; Chen, Tiffany; Connolly, Erin; Darakananda, Karin; Jeong, Janet; Quist, Arbor; Robbins, Allison; Ellerby, David J.

    2015-01-01

    Successful predator evasion is essential to the fitness of many animals. Variation in escape behaviour may be adaptive as it reduces predictability, enhancing escape success. High escape velocities and accelerations also increase escape success, but biomechanical factors likely constrain the behavioural range over which performance can be maximized. There may therefore be a trade-off between variation and performance during escape responses. We have used bluegill sunfish (Lepomis macrochirus) escape responses to examine this potential trade-off, determining the full repertoire of escape behaviour for individual bluegill sunfish and linking this to performance as indicated by escape velocity and acceleration. Fish escapes involve an initial C-bend of the body axis, followed by variable steering movements. These generate thrust and establish the escape direction. Directional changes during the initial C-bend were less variable than the final escape angle, and the most frequent directions were associated with high escape velocity. Significant inter-individual differences in escape angles magnified the overall variation, maintaining unpredictability from a predator perspective. Steering in the latter stages of the escape to establish the final escape trajectory also affected performance, with turns away from the stimulus associated with reduced velocity. This suggests that modulation of escape behaviour by steering may also have an associated performance cost. This has important implications for understanding the scope and control of intra- and inter-individual variation in escape behaviour and the associated costs and benefits. PMID:25910940

  13. Acute-Phase CD8 T Cell Responses That Select for Escape Variants Are Needed to Control Live Attenuated Simian Immunodeficiency Virus

    PubMed Central

    Harris, Max; Burns, Charles M.; Becker, Ericka A.; Braasch, Andrew T.; Gostick, Emma; Johnson, Randall C.; Broman, Karl W.; Price, David A.; Friedrich, Thomas C.

    2013-01-01

    The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select for sequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escape variants are unable to control viral replication in vivo as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239Δnef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KOΔnef. Viremia was significantly higher in M3 homozygous MCMs infected with m3KOΔnef than in either MHC-mismatched MCMs infected with m3KOΔnef or MCMs infected with SIVmac239Δnef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during early m3KOΔnef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These results provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase of infection are needed to establish viral control in vivo. PMID:23785211

  14. [Update chronic viral hepatitis].

    PubMed

    Ziegenhagen, D J

    2016-03-01

    More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade. PMID:27111951

  15. Dengue viral infections

    PubMed Central

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections. PMID:15466994

  16. Viral quasispecies evolution.

    PubMed

    Domingo, Esteban; Sheldon, Julie; Perales, Celia

    2012-06-01

    Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory.

  17. Viral Quasispecies Evolution

    PubMed Central

    Sheldon, Julie; Perales, Celia

    2012-01-01

    Summary: Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory. PMID:22688811

  18. Dengue viral infections.

    PubMed

    Malavige, G N; Fernando, S; Fernando, D J; Seneviratne, S L

    2004-10-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections.

  19. [Viral hemorrhagic fever].

    PubMed

    Kager, P A

    1998-02-28

    Viral haemorrhagic fevers, such as Lassa fever and yellow fever, cause tens of thousands of deaths annually outside the Netherlands. The viruses are mostly transmitted by mosquitoes, ticks or via excreta of rodents. Important to travellers are yellow fever, dengue and Lassa and Ebola fever. For yellow fever there is an efficacious vaccine. Dengue is frequently observed in travellers; prevention consists in avoiding mosquito bites, the treatment is symptomatic. Lassa and Ebola fever are extremely rare among travellers; a management protocol can be obtained from the Netherlands Ministry of Health, Welfare and Sports. Diagnostics of a patient from the tropics with fever and haemorrhagic diathesis should be aimed at treatable disorders such as malaria, typhoid fever, rickettsiosis or bacterial sepsis, because the probability of such a disease is much higher than that of Lassa or Ebola fever.

  20. Green Pea Galaxies Reveal Secrets of Lyα Escape

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

    In star-forming galaxies, a lot of Lyα photons were generated in HII regions surrounding massive stars. The escape of Lyα photons from galaxies is a key issue in studying high redshift galaxies and probing cosmic reionization with Lyα. To understand Lyα escape, it is valuable to study high quality Lyα profiles in Lyα emitters. However, such studies are rare due to the faintness of high-z Lyα emitters and the lack of local analogs with high Lyα equivalent width. Here we show that "Green Pea" galaxies are the best local analogs of high-z Lyα emitters and their high quality Lyα profiles demonstrate low HI column density is the key to Lyα escape. The Lyα escape fraction shows correlations with the ratio of Lyα blue peak velocity to Hα line width, the normalized flux density at valley of Lyα profile, and a few other features of Lyα profiles. We compared the Lyα profiles with outflowing HI shell radiative transfer model and found that the best-fit HI column density is anti-correlated with the Lyα escape fraction. We also found an anti-correlation between Lyα escape fraction and galactic metallicity. Our results support that LAEs with high Lyα escape fraction have low metallicity, low HI column density, and mild HI gas outflow.

  1. Viral Replication Protein Inhibits Cellular Cofilin Actin Depolymerization Factor to Regulate the Actin Network and Promote Viral Replicase Assembly

    PubMed Central

    Kovalev, Nikolay; de Castro Martín, Isabel Fernández; Barajas, Daniel; Risco, Cristina; Nagy, Peter D.

    2016-01-01

    RNA viruses exploit host cells by co-opting host factors and lipids and escaping host antiviral responses. Previous genome-wide screens with Tomato bushy stunt virus (TBSV) in the model host yeast have identified 18 cellular genes that are part of the actin network. In this paper, we show that the p33 viral replication factor interacts with the cellular cofilin (Cof1p), which is an actin depolymerization factor. Using temperature-sensitive (ts) Cof1p or actin (Act1p) mutants at a semi-permissive temperature, we find an increased level of TBSV RNA accumulation in yeast cells and elevated in vitro activity of the tombusvirus replicase. We show that the large p33 containing replication organelle-like structures are located in the close vicinity of actin patches in yeast cells or around actin cable hubs in infected plant cells. Therefore, the actin filaments could be involved in VRC assembly and the formation of large viral replication compartments containing many individual VRCs. Moreover, we show that the actin network affects the recruitment of viral and cellular components, including oxysterol binding proteins and VAP proteins to form membrane contact sites for efficient transfer of sterols to the sites of replication. Altogether, the emerging picture is that TBSV, via direct interaction between the p33 replication protein and Cof1p, controls cofilin activities to obstruct the dynamic actin network that leads to efficient subversion of cellular factors for pro-viral functions. In summary, the discovery that TBSV interacts with cellular cofilin and blocks the severing of existing filaments and the formation of new actin filaments in infected cells opens a new window to unravel the way by which viruses could subvert/co-opt cellular proteins and lipids. By regulating the functions of cofilin and the actin network, which are central nodes in cellular pathways, viruses could gain supremacy in subversion of cellular factors for pro-viral functions. PMID:26863541

  2. The Next Great Generation?

    ERIC Educational Resources Information Center

    Brownstein, Andrew

    2000-01-01

    Discusses ideas from a new book, "Millennials Rising: The Next Great Generation," (by Neil Howe and William Strauss) suggesting that youth culture is on the cusp of a radical shift with the generation beginning with this year's college freshmen who are typically team oriented, optimistic, and poised for greatness on a global scale. Includes a…

  3. Great Lakes Literacy Principles

    NASA Astrophysics Data System (ADS)

    Fortner, Rosanne W.; Manzo, Lyndsey

    2011-03-01

    Lakes Superior, Huron, Michigan, Ontario, and Erie together form North America's Great Lakes, a region that contains 20% of the world's fresh surface water and is home to roughly one quarter of the U.S. population (Figure 1). Supporting a $4 billion sport fishing industry, plus $16 billion annually in boating, 1.5 million U.S. jobs, and $62 billion in annual wages directly, the Great Lakes form the backbone of a regional economy that is vital to the United States as a whole (see http://www.miseagrant.umich.edu/downloads/economy/11-708-Great-Lakes-Jobs.pdf). Yet the grandeur and importance of this freshwater resource are little understood, not only by people in the rest of the country but also by many in the region itself. To help address this lack of knowledge, the Centers for Ocean Sciences Education Excellence (COSEE) Great Lakes, supported by the U.S. National Science Foundation and the National Oceanic and Atmospheric Administration, developed literacy principles for the Great Lakes to serve as a guide for education of students and the public. These “Great Lakes Literacy Principles” represent an understanding of the Great Lakes' influences on society and society's influences on the Great Lakes.

  4. Great Lakes Teacher's Guide.

    ERIC Educational Resources Information Center

    Reid, Ron

    The Great Lakes are one of the world's greatest reservoirs of fresh water, the foundation of Ontario's economic development, a primary force in ecological systems, and a base for pleasure and recreation. They are also a magnificent resource for the teachers of Ontario. Study of the Great Lakes can bring to life the factors that shape the ecology…

  5. Viral reproductive strategies: How can lytic viruses be evolutionarily competitive?

    PubMed

    Komarova, Natalia L

    2007-12-21

    Viral release strategies can be roughly classified as lytic (the ones that accumulate inside the host cell and exit in a burst, killing the cell), and budding (the ones that are produced and released from the host cell gradually). Here we study the evolutionary competition between the two strategies. If all the parameters, such as the rate of viral production, cell life-span and the neutralizing capacity of the antibodies, were the same for lytic and budding viruses, the budding life-strategy would have a large evolutionary advantage. The question arises what makes lytic viruses evolutionarily competitive. We propose that it is the different removal capacity of the antibodies against budding and lytic virions. The latter exit the cell in a large burst such that the antibodies are "flooded" and a larger proportion of virions can escape the immune system and spread to new cells. We create two spatial models of virus-antibody interaction and show that for realistic parameter values, the effect of antibody flooding can indeed take place. We also argue that the lytic life cycle, including a relatively large burst-size, has evolved to promote survival in the face of antibody attack. According to the calculations, in the absence of efficient antibodies, the optimal burst size of lytic viruses would be only a few virus particles, as opposed to the observed 10(2)-10(5) viral particles. Similarly, there is an evolutionary pressure to extend the life-span as a response to antibody action.

  6. 42 CFR 84.300 - Closed-circuit escape respirator; description.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Closed-circuit escape respirator; description. 84... Closed-Circuit Escape Respirators § 84.300 Closed-circuit escape respirator; description. The closed-circuit escape respirator (CCER), technically a subset of self-contained breathing apparatus (SCBAs)...

  7. 42 CFR 84.300 - Closed-circuit escape respirator; description.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Closed-circuit escape respirator; description. 84... Closed-Circuit Escape Respirators § 84.300 Closed-circuit escape respirator; description. The closed-circuit escape respirator (CCER), technically a subset of self-contained breathing apparatus (SCBAs)...

  8. MAVEN Measurements of the Ion Escape Rate from Mars

    NASA Astrophysics Data System (ADS)

    Brain, Dave; Dong, Yaxue; Fortier, Kier; Fang, Xiaohua; McFadden, James; Halekas, Jasper; Connerney, Jack; Eparvier, Frank; Dong, Chuanfei; Bougher, Stephen; Ma, Yingjuan; Modolo, Ronan; Lillis, Rob; Luhmann, Janet; Curry, Shannon; Seki, Kanako; Jakosky, Bruce

    2015-04-01

    The loss of atmospheric particles (neutral atoms, neutral molecules, ions) to space is thought to have played a role in the evolution of Martian climate over the past ~4 billion years. Due to the lack of a global magnetic field on Mars, the solar wind has direct access to the upper layers of the Martian atmosphere, and can drive non-thermal escape of charged particles (ions) from the atmosphere. Two spacecraft (Phobos 2 and Mars Express) have previously measured escaping ions at Mars. The recently arrived MAVEN spacecraft is equipped with instruments to measure escaping ions with high time cadence and high energy and mass resolution, as well as instruments to provide contextual information about what controls the variation in escape rates. We report on the total escape rate of heavy planetary ions from the Martian atmosphere measured by MAVEN. Heavy ions are identified in data from the SupraThermal And Thermal Ion Composition (STATIC) instrument. Rudimentary estimates of ion escape rate are obtained by summing the measured ion fluxes over a surface downstream from Mars with respect to the solar wind flow. This estimate can then be refined to account for the limited field of view of the instrument (investigation of measured particle distributions) and the limited spatial coverage of the spacecraft orbit trajectory. Variability in measured escape rates can also be grouped according to upstream conditions and the orientation of Mars (and its crustal magnetic fields) with respect to the solar wind. Important upstream drivers include the solar Extreme Ultraviolet (EUV) flux, solar wind pressure, and the interplanetary magnetic field strength and direction. These drivers are measured directly by MAVEN's EUV, SWIA, and MAG instruments. We will provide an initial estimate of ion escape rates based on the first several months of MAVEN data. We will then report on progress to refine these estimates to correct for instrument field of view and spacecraft coverage effects, as

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  10. Ion Energization and Escape on Mars and Venus

    NASA Astrophysics Data System (ADS)

    Dubinin, E.; Fraenz, M.; Fedorov, A.; Lundin, R.; Edberg, N.; Duru, F.; Vaisberg, O.

    2011-12-01

    Mars and Venus do not have a global magnetic field and as a result solar wind interacts directly with their ionospheres and upper atmospheres. Neutral atoms ionized by solar UV, charge exchange and electron impact, are extracted and scavenged by solar wind providing a significant loss of planetary volatiles. There are different channels and routes through which the ionized planetary matter escapes from the planets. Processes of ion energization driven by direct solar wind forcing and their escape are intimately related. Forces responsible for ion energization in different channels are different and, correspondingly, the effectiveness of escape is also different. Classification of the energization processes and escape channels on Mars and Venus and also their variability with solar wind parameters is the main topic of our review. We will distinguish between classical pickup and `mass-loaded' pickup processes, energization in boundary layer and plasma sheet, polar winds on unmagnetized planets with magnetized ionospheres and enhanced escape flows from localized auroral regions in the regions filled by strong crustal magnetic fields.

  11. Ion Energization and Escape on Mars and Venus

    NASA Astrophysics Data System (ADS)

    Dubinin, E.; Fraenz, M.; Fedorov, A.; Lundin, R.; Edberg, N.; Duru, F.; Vaisberg, O.

    Mars and Venus do not have a global magnetic field and as a result solar wind interacts directly with their ionospheres and upper atmospheres. Neutral atoms ionized by solar UV, charge exchange and electron impact, are extracted and scavenged by solar wind providing a significant loss of planetary volatiles. There are different channels and routes through which the ionized planetary matter escapes from the planets. Processes of ion energization driven by direct solar wind forcing and their escape are intimately related. Forces responsible for ion energization in different channels are different and, correspondingly, the effectiveness of escape is also different. Classification of the energization processes and escape channels on Mars and Venus and also their variability with solar wind parameters is the main topic of our review. We will distinguish between classical pickup and `mass-loaded' pickup processes, energization in boundary layer and plasma sheet, polar winds on unmagnetized planets with magnetized ionospheres and enhanced escape flows from localized auroral regions in the regions filled by strong crustal magnetic fields.

  12. THE ESCAPE FRACTION OF IONIZING RADIATION FROM GALAXIES

    SciTech Connect

    Benson, Andrew; Venkatesan, Aparna; Shull, J. Michael E-mail: avenkatesan@usfca.edu

    2013-06-10

    The escape of ionizing radiation from galaxies plays a critical role in the evolution of gas in galaxies, and the heating and ionization history of the intergalactic medium. We present semi-analytic calculations of the escape fraction of ionizing radiation for both hydrogen and helium from galaxies ranging from primordial systems to disk-type galaxies that are not heavily dust-obscured. We consider variations in the galaxy density profile, source type, location, and spectrum, and gas overdensity/distribution factors. For sufficiently hard first-light sources, the helium ionization fronts closely track or advance beyond that of hydrogen. Key new results in this work include calculations of the escape fractions for He I and He II ionizing radiation, and the impact of partial ionization from X-rays from early active galactic nuclei or stellar clusters on the escape fractions from galaxy halos. When factoring in frequency-dependent effects, we find that X-rays play an important role in boosting the escape fractions for both hydrogen and helium, but especially for He II. We briefly discuss the implications of these results for recent observations of the He II reionization epoch at low redshifts, as well as the UV data and emission-line signatures from early galaxies anticipated from future satellite missions.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2016-07-15

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

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

    PubMed

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

    2016-07-15

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

  16. Loss of water from Venus. I - Hydrodynamic escape of hydrogen

    NASA Technical Reports Server (NTRS)

    Kasting, J. F.; Pollack, J. B.

    1983-01-01

    A one-dimensional photochemical-dynamic model is used to study hydrodynamic loss of hydrogen from a primitive, water-rich atmosphere on Venus. The escape flux is calculated as a function of the H2O mixing ratio at the atmospheric cold trap. The cold trap mixing ratio is then related in an approximate fashion to the H2O concentration in the lower atmosphere. Hydrodynamic escape should have been the dominant loss process for hydroogen when the H2O mass mixing ratio in the lower atmosphere exceeded approximately 0.1. The escape rate would have depended upon the magnitude of the solar ultraviolet flux and the atmospheric EUV heating efficiency and, to a lesser extent, on the O2 content of the atmosphere. The time required for Venus to have lost the bulk of a terrestrial ocean of water is on the order of a billion years. Deuterium would have been swept away along with hydrogen if the escape rate was high enough, but some D/H enrichment should have occurred as the escape rate slowed down.

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

    NASA Astrophysics Data System (ADS)

    Bui, Phuong Thuy; Hoang, Trinh Xuan

    2016-03-01

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

  18. Immunosuppressive cells in tumor immune escape and metastasis.

    PubMed

    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.

  19. Escape Rates in a Stochastic Environment with Multiple Scales

    NASA Astrophysics Data System (ADS)

    Forgoston, Eric; Schwartz, Ira B.

    2009-01-01

    We consider a stochastic environment with two time scales and outline a general theory that compares two methods to reduce the dimension of the original system. The first method involves the computation of the underlying deterministic center manifold followed by a naive replacement of the stochastic term. The second method allows one to more accurately describe the stochastic effects and involves the derivation of a normal form coordinate transform that is used to find the stochastic center manifold. The results of both methods are used along with the path integral formalism of large fluctuation theory to predict the escape rate from one basin of attraction to another. The general theory is applied to the example of a surface flow described by a generic, singularly perturbed, damped, nonlinear oscillator with additive, Gaussian noise. We show how both nonlinear reduction methods compare in escape rate scaling. Additionally, the center manifolds are shown to predict high prehistory probability regions of escape. The theoretical results are confirmed using numerical computation of the mean escape time and escape prehistory, and we briefly discuss the extension of the theory to stochastic control.

  20. Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

    SciTech Connect

    Liu, Donglai; Zuo, Tao; Hora, Bhavna; Song, Hongshuo; Kong, Wei; Yu, Xianghui; Goonetilleke, Nilu; Bhattacharya, Tanmoy; Perelson, Alan S.; Haynes, Barton F.; McMichael, Andrew J.; Gao, Feng

    2014-01-01

    Background: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. Results: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. Conclusions: Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.

  1. Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

    DOE PAGES

    Liu, Donglai; Zuo, Tao; Hora, Bhavna; Song, Hongshuo; Kong, Wei; Yu, Xianghui; Goonetilleke, Nilu; Bhattacharya, Tanmoy; Perelson, Alan S.; Haynes, Barton F.; et al

    2014-01-01

    Background: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. Results: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, themore » fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. Conclusions: Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.« less

  2. Experimental rabies in a great horned owl.

    PubMed

    Jorgenson, R D; Gough, P M; Graham, D L

    1976-07-01

    A great horned owl (Bubo virginianus) was fed the carcass of an experimentally infected rabid skunk. The bird developed antibody titer to rabies, detected by passive haemagglutination, 27 days after oral inoculation by ingestion. The owl suppressed the infection until corticosteroid administration, after which a maximum antibody titer was attained. Evidence of active rabies viral infection was seen by fluorescent antibody staining of oral swabs, corneal impression smears and histologic tissue smears, by suckling mouse inoculation of oral swab washings, and by transmission electron microcopy. No clinical signs of rabies virus infection were observed. PMID:16498892

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  4. Viral Hepatitis: A through E and Beyond

    MedlinePlus

    Viral Hepatitis: A through E and Beyond NATIONAL INSTITUTES OF HEALTH U.S. Department of Health and Human Services National Digestive Diseases Information Clearinghouse What is viral hepatitis? Viral hepatitis is inflammation of the liver caused ...

  5. Coexisting chaotic and periodic dynamics in clock escapements.

    PubMed

    Moon, Francis C; Stiefel, Preston D

    2006-09-15

    This paper addresses the nature of noise in machines. As a concrete example, we examine the dynamics of clock escapements from experimental, historical and analytical points of view. Experiments on two escapement mechanisms from the Reuleaux kinematic collection at Cornell University are used to illustrate chaotic-like noise in clocks. These vibrations coexist with the periodic dynamics of the balance wheel or pendulum. A mathematical model is presented that shows how self-generated chaos in clocks can break the dry friction in the gear train. This model is shown to exhibit a strange attractor in the structural vibration of the clock. The internal feedback between the oscillator and the escapement structure is similar to anti-control of chaos models.

  6. Behavior of Ants Escaping from a Single-Exit Room

    PubMed Central

    Wang, Shujie; Lv, Wei; Song, Weiguo

    2015-01-01

    To study the rules of ant behavior and group-formation phenomena, we examined the behaviors of Camponotus japonicus, a species of large ant, in a range of situations. For these experiments, ants were placed inside a rectangular chamber with a single exit that also contained a filter paper soaked in citronella oil, a powerful repellent. The ants formed several groups as they moved toward the exit to escape. We measured the time intervals between individual escapes in six versions of the experiment, each containing an exit of a different width, to quantify the movement of the groups. As the ants exited the chamber, the time intervals between individual escapes changed and the frequency distribution of the time intervals exhibited exponential decay. We also investigated the relationship between the number of ants in a group and the group flow rate. PMID:26125191

  7. Neural Circuits Underlying Visually Evoked Escapes in Larval Zebrafish.

    PubMed

    Dunn, Timothy W; Gebhardt, Christoph; Naumann, Eva A; Riegler, Clemens; Ahrens, Misha B; Engert, Florian; Del Bene, Filippo

    2016-02-01

    Escape behaviors deliver organisms away from imminent catastrophe. Here, we characterize behavioral responses of freely swimming larval zebrafish to looming visual stimuli simulating predators. We report that the visual system alone can recruit lateralized, rapid escape motor programs, similar to those elicited by mechanosensory modalities. Two-photon calcium imaging of retino-recipient midbrain regions isolated the optic tectum as an important center processing looming stimuli, with ensemble activity encoding the critical image size determining escape latency. Furthermore, we describe activity in retinal ganglion cell terminals and superficial inhibitory interneurons in the tectum during looming and propose a model for how temporal dynamics in tectal periventricular neurons might arise from computations between these two fundamental constituents. Finally, laser ablations of hindbrain circuitry confirmed that visual and mechanosensory modalities share the same premotor output network. We establish a circuit for the processing of aversive stimuli in the context of an innate visual behavior. PMID:26804997

  8. Behavior of Ants Escaping from a Single-Exit Room.

    PubMed

    Wang, Shujie; Lv, Wei; Song, Weiguo

    2015-01-01

    To study the rules of ant behavior and group-formation phenomena, we examined the behaviors of Camponotus japonicus, a species of large ant, in a range of situations. For these experiments, ants were placed inside a rectangular chamber with a single exit that also contained a filter paper soaked in citronella oil, a powerful repellent. The ants formed several groups as they moved toward the exit to escape. We measured the time intervals between individual escapes in six versions of the experiment, each containing an exit of a different width, to quantify the movement of the groups. As the ants exited the chamber, the time intervals between individual escapes changed and the frequency distribution of the time intervals exhibited exponential decay. We also investigated the relationship between the number of ants in a group and the group flow rate.

  9. Kramers escape of a self-propelled particle

    NASA Astrophysics Data System (ADS)

    Geiseler, Alexander; Hänggi, Peter; Schmid, Gerhard

    2016-08-01

    We investigate the escape rate of an overdamped, self-propelled spherical Brownian particle on a surface from a metastable potential well. Within a modeling in terms of a 1D constant speed of the particle's active dynamics we consider the associated rate using both numerical and analytical approaches. Regarding the properties of the stationary state in the potential well, two major timescales exist, each governing the translational and the rotational dynamics of the particle, respectively. The particle radius is identified to present the essential quantity in charge of regulating the ratio between those timescales. For very small and very large particle radii, approximate analytic expressions for the particle's escape rate can be derived, which, within their respective range of validity, compare favorably with the precise escape numerics of the underlying full two-dimensional Fokker-Planck description.

  10. Unravelling viral camouflage: approaches to the study and characterization of conformational epitopes.

    PubMed

    Augustin, T; Cehlar, O; Skrabana, R; Majerova, P; Hanes, J

    2015-06-01

    Antibodies are broadly used in clinical and basic research. Many of monoclonal antibodies are successfully adopted for therapeutic and diagnostic targeting of viral pathogens. Efficacy of antiviral neutralizing or protective antibodies depends on their ability to recognize epitopes interfering with viral infection. However, viruses are able to incessantly change their antigenic determinants to escape surveillance of humoral immune system and therefore the successful antiviral therapies require continuous development. Characterization of interactions of antibodies with prevalently conformational viral epitopes is important for understanding antibody mode of action and can help to identify conserved regions that may be exploited in designing new vaccines and virus neutralizing antibodies. In this article, we are reviewing techniques in use for characterization of conformational epitopes of monoclonal antibodies with focus on viruses.

  11. Unravelling viral camouflage: approaches to the study and characterization of conformational epitopes.

    PubMed

    Augustin, T; Cehlar, O; Skrabana, R; Majerova, P; Hanes, J

    2015-06-01

    Antibodies are broadly used in clinical and basic research. Many of monoclonal antibodies are successfully adopted for therapeutic and diagnostic targeting of viral pathogens. Efficacy of antiviral neutralizing or protective antibodies depends on their ability to recognize epitopes interfering with viral infection. However, viruses are able to incessantly change their antigenic determinants to escape surveillance of humoral immune system and therefore the successful antiviral therapies require continuous development. Characterization of interactions of antibodies with prevalently conformational viral epitopes is important for understanding antibody mode of action and can help to identify conserved regions that may be exploited in designing new vaccines and virus neutralizing antibodies. In this article, we are reviewing techniques in use for characterization of conformational epitopes of monoclonal antibodies with focus on viruses. PMID:26104327

  12. Immunization Against Viral Diseases

    PubMed Central

    Wehrle, Paul F.

    1965-01-01

    Means are now at hand, if properly employed, to virtually eliminate clinical poliomyelitis and measles from this country. If such control is to be accomplished, more effective means are required to reach virtually all of the four million infants born each year in this country. Influenza can be suppressed, and improvements in influenza vaccine have been achieved in recent years. It seems likely at this time that at least several of the more important viral diseases can be controlled by utilizing antigens based on the biologic characteristics of the agent, and directed toward the reservoir of infection and the conditions favoring transmission of the infection. The theoretical problem of the effects in man of viruses that are oncogenic in rodents and are derived from various tissue culture systems deserves serious attention. However, this consideration, that of antigenic potency, and other problems reviewed should not be allowed to subvert efforts to solve the real problems that face us, the disability and death resulting from these common infections. PMID:14347979

  13. DENGUE VIRAL INFECTIONS

    PubMed Central

    Gurugama, Padmalal; Garg, Pankaj; Perera, Jennifer; Wijewickrama, Ananda; Seneviratne, Suranjith L

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections. PMID:20418983

  14. Dengue viral infections.

    PubMed

    Gurugama, Padmalal; Garg, Pankaj; Perera, Jennifer; Wijewickrama, Ananda; Seneviratne, Suranjith L

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  15. Fractionation of the Early Terrestrial Atmospheres: Dynamical Escape

    NASA Technical Reports Server (NTRS)

    Hartle, Richard E.

    2002-01-01

    Hydrodynamic escape may have played a significant role in the early fractionation of the atmospheres of the terrestrial planets. This possibility has been demonstrated in the last two decades by numerous models that show radial, transonic flow of hydrogen can occur in the presence of sufficient solar EUV Hydrodynamic escape may have played a significant role in the early fractionation of the atmospheres of the terrestrial planets. This possibility has been demonstrated in the last two decades by numerous models that show radial, transonic flow of hydrogen can occur in the presence of sufficient solar EUV flux, thought to exist in the first 500 My. The models show that the larger the solar flux the greater the mass of the fractionating species, which are accelerated to escape speeds by the hydrogen wind through drag processes. As the atmospheres evolve and the solar EUV flux wanes, the maximum mass of flowing gas constituents decreases until all gases become static. We show that fractionation can continue beyond this point when non-radial flow and dynamically enhanced Jeans escape are considered. For example, the early terrestrial atmospheres are thought to have had large hydrogen contents, resulting in exobase altitudes of a planetary radius or more. In this case, rotational speeds at the exobases of Earth and Mars would be large enough so that light constituents would "spin" off and fractionate, especially at equatorial latitudes. Also, in the presence of transonic flow of hydrogen only, non-radial expansion throws heavier gases to high altitudes in the exosphere, accompanied by strong bulk speeds at the exobase, which results in enhanced thermal escape fluxes and fractionation. flux, thought to exist in the first 500 My. The models show that the larger the solar flux the greater the mass of the fractionating species, which are accelerated to escape speeds by the hydrogen wind through drag processes. As the atmospheres evolve and the solar EUV flux wanes, the

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Measuring the escaping beam ions from a tokamak plasma

    SciTech Connect

    Buchenauer, D.; Heidbrink, W.W.; Roquemore, L.; McGuire, K.

    1987-12-01

    A new technique using a silicon surface barrier (SSB) diode has been developed for measuring the escaping fast ion flux from a tokamak plasma. Calibration of the detector with an ion beam showed that at a fixed energy the diode's output current varied linearly with the incident deuteron flux. The diode was mounted inside the PDX vacuum vessel with collimating apertures designed to admit the spiraling orbits of 50-keV deuterons expelled from the plasma by MHD instabilities. Results from PDX indicated that relative measurements of the escaping fast ion flux due to several plasma instabilities could be made.

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

    PubMed

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

    2015-01-01

    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. PMID:26123532

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

    PubMed Central

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

    2015-01-01

    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. PMID:26123532

  20. Viral BLIP dynamics during HAART.

    SciTech Connect

    Markowitz, M.; Louie, M.; Hurley, A.; Ho, David D.; Perelson, Alan S.,; Di Mascio, M.

    2001-01-01

    Intermittent episodes of low-level viremia (blips) are often observed in well-suppressed, HAART-treated patients. It has been reported that viral blips do not correlate with the emergence of new HAART-related mutations; however, increased frequency of blips correlates with slower decay of latently infected cells. Since blips are transient and unpredictable, detailed knowledge about them is difficult to obtain. We present an analysis of the dynamics of viral blips from viral load (VL) measurements on 123 patients for a period of 809k480d (21-1817d) and sampled every 31{+-}12d for a total of 26{+-}15 samples per patient.

  1. Anti-influenza viral effects of novel nuclear export inhibitors from Valerianae Radix and Alpinia galanga.

    PubMed

    Watanabe, K; Takatsuki, H; Sonoda, M; Tamura, S; Murakami, N; Kobayashi, N

    2011-02-01

    Many pathogenic viruses, such as the influenza virus and the Human Immunodeficiency Virus (HIV)-1, are a threat to humans, thus leading to thousands of deaths annually. The development of antiviral drugs is urgent, and it is an essential strategy for the suppression of these infectious diseases. However, regardless of the rapid emergence of many infectious diseases, the development of novel antiviral drugs has been slow, except for the case of the AIDS. In addition, several viruses can easily mutate and escape the inhibitory activity of anti-viral drugs. It was already well-established that HIV escapes from anti-viral drug effects because of the lack of proofreading activity in its reverse transcriptase. It is known that the influenza virus, which is resistant to Tamiflu, is already spread all over the world. Viruses utilize the host cell environment and cellular factors to propagate. Therefore, the development of novel drugs which inhibit viral protein-host protein interactions or cellular functions appear to be good candidates. The influenza virus is unique in replicating in host nuclei, and we therefore focused on the nuclear export processes for the development of anti-influenza viral drugs. We previously reported that leptomycin B (LMB), which inhibited the nuclear export processes via the nuclear export signal (NES) inhibited the nuclear export of influenza viral RNP (vRNP), and resulted in the inhibition of influenza viral propagation. We herein examined novel CRM1 inhibitors, valtrate from Valerianae Radix, and 1'-acetoxychavicol acetate (ACA) from Alpinia galanga as potent inhibitors for the influenza virus replication.

  2. Influenza A Viral Replication Is Blocked by Inhibition of the Inositol-requiring Enzyme 1 (IRE1) Stress Pathway*

    PubMed Central

    Hassan, Ihab H.; Zhang, Michael S.; Powers, Linda S.; Shao, Jian Q.; Baltrusaitis, Jonas; Rutkowski, D. Thomas; Legge, Kevin; Monick, Martha M.

    2012-01-01

    Known therapies for influenza A virus infection are complicated by the frequent emergence of resistance. A therapeutic strategy that may escape viral resistance is targeting host cellular mechanisms involved in viral replication and pathogenesis. The endoplasmic reticulum (ER) stress response, also known as the unfolded protein response (UPR), is a primitive, evolutionary conserved molecular signaling cascade that has been implicated in multiple biological phenomena including innate immunity and the pathogenesis of certain viral infections. We investigated the effect of influenza A viral infection on ER stress pathways in lung epithelial cells. Influenza A virus induced ER stress in a pathway-specific manner. We showed that the virus activates the IRE1 pathway with little or no concomitant activation of the PERK and the ATF6 pathways. When we examined the effects of modulating the ER stress response on the virus, we found that the molecular chaperone tauroursodeoxycholic acid (TUDCA) significantly inhibits influenza A viral replication. In addition, a specific inhibitor of the IRE1 pathway also blocked viral replication. Our findings constitute the first evidence that ER stress plays a role in the pathogenesis of influenza A viral infection. Decreasing viral replication by modulating the host ER stress response is a novel strategy that has important therapeutic implications. PMID:22194594

  3. Polycistronic viral vectors.

    PubMed

    de Felipe, P

    2002-09-01

    Traditionally, vectors for gene transfer/therapy experiments were mono- or bicistronic. In the latter case, vectors express the gene of interest coupled with a marker gene. An increasing demand for more complex polycistronic vectors has arisen in recent years to obtain complex gene transfer/therapy effects. In particular, this demand is stimulated by the hope of a more powerful effect from combined gene therapy than from single gene therapy in a process whose parallels lie in the multi-drug combined therapies for cancer or AIDS. In the 1980's we had only splicing signals and internal promoters to construct such vectors: now a new set of biotechnological tools enables us to design new and more reliable bicistronic and polycistronic vectors. This article focuses on the description and comparison of the strategies for co-expression of two genes in bicistronic vectors, from the oldest to the more recently described: internal promoters, splicing, reinitiation, IRES, self-processing peptides (e.g. foot-and-mouth disease virus 2A), proteolytic cleavable sites (e.g. fusagen) and fusion of genes. I propose a classification of these strategies based upon either the use of multiple transcripts (with transcriptional mechanisms), or single transcripts (using translational/post-translational mechanisms). I also examine the different attempts to utilize these strategies in the construction of polycistronic vectors and the main problems encountered. Several potential uses of these polycistronic vectors, both in basic research and in therapy-focused applications, are discussed. The importance of the study of viral gene expression strategies and the need to transfer this knowledge to vector design is highlighted.

  4. Hyposoter didymator uses a combination of passive and active strategies to escape from the Spodoptera frugiperda cellular immune response.

    PubMed

    Dorémus, Tristan; Jouan, Véronique; Urbach, Serge; Cousserans, François; Wincker, Patrick; Ravallec, Marc; Wajnberg, Eric; Volkoff, Anne-Nathalie

    2013-04-01

    An endoparasitic life style is widespread among Hymenoptera, and various different strategies allowing parasitoids to escape from the host encapsulation response have been reported. Species carrying polydnaviruses (PDVs), such as the ichneumonid Hyposoter didymator, generally rely on the viral symbionts to evade host immune responses. In this work, we show that H. didymator eggs can evade encapsulation by the host in the absence of calyx fluid (containing the viral particles), whereas protection of the larvae requires the presence of calyx fluid. This evasion by the eggs depends on proteins associated with the exochorion. This type of local passive strategy has been described for a few species carrying PDVs. Immune evasion by braconid eggs appears to be related to PDVs or proteins synthesized in the oviducts being associated with the egg. We report that in H. didymator, by contrast, proteins already present in the ovarian follicles are responsible for the eggs avoiding encapsulation. Mass spectrometry analysis of the egg surface proteins revealed the presence of host immune-related proteins, including one with similarities with apolipophorin-III, and also the presence of three viral proteins encoded by IVSPERs (Ichnovirus Structural Protein Encoding Regions). PMID:23458339

  5. Understanding HIV-1 viral load.

    PubMed

    Paxton, W B

    1995-01-01

    HIV viral markers, such as p24 antigen and viral RNA, measure how much virus is present. Studies are showing a relationship between RNA levels and clinical outcomes, which can help doctors evaluate the efficacy of drug therapy. Eventually, it is believed, RNA will replace T-cell counts as the marker of choice. The challenge is to interpret what the results of a viral load test mean for a specific patient. Currently, the two main viral load tests commercially available do not have a one-to-one linear relationship, so tests should not be switched. Doctors are advised not to over-interpret minor changes because of the ten to thirty percent variation in individual test results. These tests are not FDA-approved but are available at commercial reference labs. PMID:11362660

  6. Aseptic meningitis and viral myelitis.

    PubMed

    Irani, David N

    2008-08-01

    Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.

  7. Statistical Mechanics of Viral Entry

    NASA Astrophysics Data System (ADS)

    Zhang, Yaojun; Dudko, Olga K.

    2015-01-01

    Viruses that have lipid-membrane envelopes infect cells by fusing with the cell membrane to release viral genes. Membrane fusion is known to be hindered by high kinetic barriers associated with drastic structural rearrangements—yet viral infection, which occurs by fusion, proceeds on remarkably short time scales. Here, we present a quantitative framework that captures the principles behind the invasion strategy shared by all enveloped viruses. The key to this strategy—ligand-triggered conformational changes in the viral proteins that pull the membranes together—is treated as a set of concurrent, bias field-induced activated rate processes. The framework results in analytical solutions for experimentally measurable characteristics of virus-cell fusion and enables us to express the efficiency of the viral strategy in quantitative terms. The predictive value of the theory is validated through simulations and illustrated through recent experimental data on influenza virus infection.

  8. A bright future for bioluminescent imaging in viral research

    PubMed Central

    Coleman, Stewart M; McGregor, Alistair

    2015-01-01

    Summary Bioluminescence imaging (BLI) has emerged as a powerful tool in the study of animal models of viral disease. BLI enables real-time in vivo study of viral infection, host immune response and the efficacy of intervention strategies. Substrate dependent light emitting luciferase enzyme when incorporated into a virus as a reporter gene enables detection of bioluminescence from infected cells using sensitive charge-coupled device (CCD) camera systems. Advantages of BLI include low background, real-time tracking of infection in the same animal and reduction in the requirement for larger animal numbers. Transgenic luciferase-tagged mice enable the use of pre-existing nontagged viruses in BLI studies. Continued development in luciferase reporter genes, substrates, transgenic animals and imaging systems will greatly enhance future BLI strategies in viral research. PMID:26413138

  9. High frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection.

    PubMed

    Gounder, Kamini; Padayachi, Nagavelli; Mann, Jaclyn K; Radebe, Mopo; Mokgoro, Mammekwa; van der Stok, Mary; Mkhize, Lungile; Mncube, Zenele; Jaggernath, Manjeetha; Reddy, Tarylee; Walker, Bruce D; Ndung'u, Thumbi

    2015-01-01

    In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses. PMID:25781986

  10. High Frequency of Transmitted HIV-1 Gag HLA Class I-Driven Immune Escape Variants but Minimal Immune Selection over the First Year of Clade C Infection

    PubMed Central

    Gounder, Kamini; Padayachi, Nagavelli; Mann, Jaclyn K.; Radebe, Mopo; Mokgoro, Mammekwa; van der Stok, Mary; Mkhize, Lungile; Mncube, Zenele; Jaggernath, Manjeetha; Reddy, Tarylee; Walker, Bruce D.; Ndung’u, Thumbi

    2015-01-01

    In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses. PMID:25781986

  11. Viral Control of Mitochondrial Apoptosis

    PubMed Central

    Morselli, Eugenia; Touat, Zahia; Kroemer, Guido

    2008-01-01

    Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus. PMID:18516228

  12. Viral RNAs Are Unusually Compact

    PubMed Central

    Gopal, Ajaykumar; Egecioglu, Defne E.; Yoffe, Aron M.; Ben-Shaul, Avinoam; Rao, Ayala L. N.; Knobler, Charles M.; Gelbart, William M.

    2014-01-01

    A majority of viruses are composed of long single-stranded genomic RNA molecules encapsulated by protein shells with diameters of just a few tens of nanometers. We examine the extent to which these viral RNAs have evolved to be physically compact molecules to facilitate encapsulation. Measurements of equal-length viral, non-viral, coding and non-coding RNAs show viral RNAs to have among the smallest sizes in solution, i.e., the highest gel-electrophoretic mobilities and the smallest hydrodynamic radii. Using graph-theoretical analyses we demonstrate that their sizes correlate with the compactness of branching patterns in predicted secondary structure ensembles. The density of branching is determined by the number and relative positions of 3-helix junctions, and is highly sensitive to the presence of rare higher-order junctions with 4 or more helices. Compact branching arises from a preponderance of base pairing between nucleotides close to each other in the primary sequence. The density of branching represents a degree of freedom optimized by viral RNA genomes in response to the evolutionary pressure to be packaged reliably. Several families of viruses are analyzed to delineate the effects of capsid geometry, size and charge stabilization on the selective pressure for RNA compactness. Compact branching has important implications for RNA folding and viral assembly. PMID:25188030

  13. 30 CFR 77.1101 - Escape and evacuation; plan.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....1101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Fire Protection § 77.1101 Escape and evacuation; plan. (a) Before September 30, 1971, each operator...

  14. 30 CFR 77.1101 - Escape and evacuation; plan.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....1101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Fire Protection § 77.1101 Escape and evacuation; plan. (a) Before September 30, 1971, each operator...

  15. 30 CFR 77.1101 - Escape and evacuation; plan.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....1101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Fire Protection § 77.1101 Escape and evacuation; plan. (a) Before September 30, 1971, each operator...

  16. 30 CFR 77.1101 - Escape and evacuation; plan.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....1101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Fire Protection § 77.1101 Escape and evacuation; plan. (a) Before September 30, 1971, each operator...

  17. 30 CFR 77.1101 - Escape and evacuation; plan.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....1101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Fire Protection § 77.1101 Escape and evacuation; plan. (a) Before September 30, 1971, each operator...

  18. Brain size as a driver of avian escape strategy

    PubMed Central

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

    2015-01-01

    After detecting an approaching predator, animals make a decision when to flee. Prey will initiate flight soon after detecting a predator so as to minimize attentional costs related to on-going monitoring of the whereabouts of the predator. Such costs may compete with foraging and other maintenance activities and hence be larger than the costs of immediate flight. The drivers of interspecific variation in escape strategy are poorly known. Here we investigated the morphological, life history 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. PMID:26139474

  19. Magnetic buoyancy and the escape of magnetic fields from stars

    NASA Astrophysics Data System (ADS)

    Parker, E. N.

    1984-06-01

    Magnetic buoyancy causes the azimuthal magnetic fields of stars to rise rapidly to the surface, from where they are generally assumed to escape freely into space. However, a closer look at the problem reveals the simple fact that disengagement of the field from the gas, and escape into space, require a convoluted field configuration, producing neutral point reconnection of the flux in the tenuous gas above the surface of the star. Only that flux which reconnects can escape. Recent observations of the magnetic fields emerging through the surface of the Sun show that even at sunspot maximum the gaps in longitude between bipolar magnetic regions are so wide as to limit severely the reconnection between regions. We suggest from the observations that no more than perhaps 3% of the flux that is observed to emerge through the surface is able to reconnect and escape. Hence the surface of the Sun approximates to an impenetrable barrier rather than an open surface, with quantitative consequences for theoretical dynamo models. Recent observations of the retraction of bipolar fields at the end of their appearance at the surface suggest active dynamical control by the convection beneath the surface.

  20. 46 CFR 116.500 - Means of escape.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... escape must not be less than 810 millimeters (32 inches) in width, however, doors or passageways used solely by crew members must have a clear opening not less than 710 millimeters (28 inches). The sum of... millimeters (0.333 inches) multiplied by the number of passengers for which the space is designed. (g) A...

  1. 46 CFR 116.500 - Means of escape.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... escape must not be less than 810 millimeters (32 inches) in width, however, doors or passageways used solely by crew members must have a clear opening not less than 710 millimeters (28 inches). The sum of... millimeters (0.333 inches) multiplied by the number of passengers for which the space is designed. (g) A...

  2. Neutral atmospheric escape at Venus and Mars (Invited)

    NASA Astrophysics Data System (ADS)

    Leblanc, F.

    2013-12-01

    Neutral escape is referring to neutral particles leaving a planetary object and never reimpacting it. Such particles can ultimately get ionized or simply reach the Hill sphere. The Jeans and/or hydrodynamic fluxes represent the thermal component of the neutral escape, that is, that portion of the velocity distribution at the external boundary of that object that can evaporate with enough energy to definitively escape. A second component is also usually introduced to describe the products of several energetic mechanisms that could lead also to planetary erosion. This second component, called supra-thermal, is particularly important at Mars since it is thought to be one of the possible driver of Mars' atmospheric erosion during the last 4 Gyr. Because Venus and Mars are so similar in terms of interaction with the solar wind, there are many reasons to believe that these energetic mechanisms occur at both planets. In this presentation, I will present what is understood on the possible past and present channels of neutral escape at both Mars and Venus. The respective importance of the thermal and supra-thermal components along Mars and Venus histories, the main signatures of these components in the present atmosphere and what should be learned from the forthcoming space missions will be discussed.

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

    ERIC Educational Resources Information Center

    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)

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

    PubMed

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

    2015-02-22

    Animal-vehicle collisions cause high levels of vertebrate mortality worldwide, and what goes wrong when animals fail to escape and ultimately collide with vehicles is not well understood. We investigated alert and escape behaviours of captive brown-headed cowbirds (Molothrus ater) in response to virtual vehicle approaches of different sizes and at speeds ranging from 60 to 360 km h(-1). Alert and flight initiation distances remained similar across vehicle speeds, and accordingly, alert and flight initiation times decreased at higher vehicle speeds. Thus, avoidance behaviours in cowbirds appeared to be based on distance rather than time available for escape, particularly at 60-150 km h(-1); however, at higher speeds (more than or equal to 180 km h(-1)) no trend in response behaviour was discernible. As vehicle speed increased, cowbirds did not have enough time to assess the approaching vehicle, and cowbirds generally did not initiate flight with enough time to avoid collision when vehicle speed exceeded 120 km h(-1). Although potentially effective for evading predators, the decision-making process used by cowbirds in our study appears maladaptive in the context of avoiding fast-moving vehicles. Our methodological approach and findings provide a framework to assess how novel management strategies could affect escape rules, and the sensory and cognitive abilities animals use to avoid vehicle collisions.

  5. 46 CFR 28.390 - Means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Means of escape. 28.390 Section 28.390 Shipping COAST... emergency exits, passageways, stairways, ladders, deck scuttles, and windows. (b) At least one of the means... suitable for use in emergency conditions and must be of rigid construction. (f) A window or windshield...

  6. 6. UNDERGROUND FIRING CONTROL ROOM, INTERIOR. Looking southeast to escape ...

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

    6. UNDERGROUND FIRING CONTROL ROOM, INTERIOR. Looking southeast to escape tunnel. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Firing Control Building, Test Area 1-100, northeast end of Test Area 1-100 Road, Boron, Kern County, CA

  7. The magnetic anomalies significantrly reduce the Martian ionospheric escape rate

    NASA Astrophysics Data System (ADS)

    Fedorov, A.; Barabash, S.; Sauvaud, J.-A.

    2012-09-01

    Looking forward to the MAVEN mission, it seems very useful to return to Mars Express data to refresh an important problem of Martian atmosphere escape: what role the crustal magnetic field may play in this process? There are several publications on this topic with completely opposite conclusions. The last hybrid simulations show that the magnetic anomalies significantly reduce the ion loss rate during solar minimum. We are trying to use a new approach to Mars Express IMA data analysis to check how it is possible. On the base of a statistical study of the ion distributions in the Martian magnetotail we show that the characteristic accelerated ions are not associated with the magnetic anomalies but only with interplanetary magnetic field clock angle. Moreover the magnetic anomalies screen and deviate the escaping flow leading to reducing of the total loss rate. We have calculated a "quasiexperimental" escaping rate in an assumption of the total absence of the magnetic anomalies. We are comparing this value with a real measured escape rate.

  8. 46 CFR 127.240 - Means of escape.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... portholes, from each of the following spaces: (1) Each space accessible to offshore workers. (2) Crew accommodations and each space where the crew may normally be employed. (b) At least one of the two means of... sides of the space, to minimize the possibility that one incident will block both escapes. (d) Except...

  9. 46 CFR 127.240 - Means of escape.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... portholes, from each of the following spaces: (1) Each space accessible to offshore workers. (2) Crew accommodations and each space where the crew may normally be employed. (b) At least one of the two means of... sides of the space, to minimize the possibility that one incident will block both escapes. (d) Except...

  10. 46 CFR 127.240 - Means of escape.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... portholes, from each of the following spaces: (1) Each space accessible to offshore workers. (2) Crew accommodations and each space where the crew may normally be employed. (b) At least one of the two means of... sides of the space, to minimize the possibility that one incident will block both escapes. (d) Except...

  11. 46 CFR 108.445 - Alarm and means of escape.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Alarm and means of escape. 108.445 Section 108.445 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Fire Extinguishing Systems Fixed Carbon Dioxide Fire Extinguishing Systems §...

  12. 46 CFR 108.445 - Alarm and means of escape.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Alarm and means of escape. 108.445 Section 108.445 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Fire Extinguishing Systems Fixed Carbon Dioxide Fire Extinguishing Systems §...

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

    PubMed Central

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

    1969-01-01

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

  14. 2. WEST REAR, WITH PORTHOLE ESCAPE HATCH ABOVE ENTRY DOOR. ...

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

    2. WEST REAR, WITH PORTHOLE ESCAPE HATCH ABOVE ENTRY DOOR. - Edwards Air Force Base, South Base Sled Track, Firing & Control Blockhouse for 10,000-foot Track, South of Sled Track at midpoint of 20,000-foot track, Lancaster, Los Angeles County, CA

  15. Social Escape Behaviors in Children with Fragile X Syndrome

    ERIC Educational Resources Information Center

    Hall, Scott; DeBernardis, Marie; Reiss, Allan

    2006-01-01

    Social escape behavior is a common behavioral feature of individuals with fragile X syndrome (fraX). In this observational study, we examined the effect of antecedent social and performance demands on problem behaviors in four conditions: face-to-face interview, silent reading, oral reading and a singing task. Results showed that problem behaviors…

  16. Spatial and Nonspatial Escape Strategies in the Barnes Maze

    ERIC Educational Resources Information Center

    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. Escaping Embarrassment: Face-Work in the Rap Cipher

    ERIC Educational Resources Information Center

    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,…

  18. 46 CFR 108.445 - Alarm and means of escape.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Alarm and means of escape. (a) Each CO2 system that has a supply of more than 136 kilograms (300 pounds) of CO2, except a system that protects a tank, must have an alarm that sounds for at least 20 seconds before the CO2 is released into the space. (b) Each audible alarm for a CO2 system must have the...

  19. 46 CFR 108.445 - Alarm and means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Alarm and means of escape. (a) Each CO2 system that has a supply of more than 136 kilograms (300 pounds) of CO2, except a system that protects a tank, must have an alarm that sounds for at least 20 seconds before the CO2 is released into the space. (b) Each audible alarm for a CO2 system must have the...

  20. 46 CFR 108.445 - Alarm and means of escape.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Alarm and means of escape. (a) Each CO2 system that has a supply of more than 136 kilograms (300 pounds) of CO2, except a system that protects a tank, must have an alarm that sounds for at least 20 seconds before the CO2 is released into the space. (b) Each audible alarm for a CO2 system must have the...

  1. Evolving Project E-Scape for National Assessment

    ERIC Educational Resources Information Center

    Kimbell, Richard

    2012-01-01

    In the opening paper in this Special Edition I outlined the major issues that led to the establishment of "project e-scape". The project was intended to develop systems and approaches that enabled learners to build real-time web-based portfolios of their performance (initially) in design & technology and additionally to build systems and…

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

    PubMed Central

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

    2015-01-01

    Animal–vehicle collisions cause high levels of vertebrate mortality worldwide, and what goes wrong when animals fail to escape and ultimately collide with vehicles is not well understood. We investigated alert and escape behaviours of captive brown-headed cowbirds (Molothrus ater) in response to virtual vehicle approaches of different sizes and at speeds ranging from 60 to 360 km h−1. Alert and flight initiation distances remained similar across vehicle speeds, and accordingly, alert and flight initiation times decreased at higher vehicle speeds. Thus, avoidance behaviours in cowbirds appeared to be based on distance rather than time available for escape, particularly at 60–150 km h−1; however, at higher speeds (more than or equal to 180 km h−1) no trend in response behaviour was discernible. As vehicle speed increased, cowbirds did not have enough time to assess the approaching vehicle, and cowbirds generally did not initiate flight with enough time to avoid collision when vehicle speed exceeded 120 km h−1. Although potentially effective for evading predators, the decision-making process used by cowbirds in our study appears maladaptive in the context of avoiding fast-moving vehicles. Our methodological approach and findings provide a framework to assess how novel management strategies could affect escape rules, and the sensory and cognitive abilities animals use to avoid vehicle collisions. PMID:25567648

  3. 46 CFR 167.20-10 - Means of escape.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Means of escape. 167.20-10 Section 167.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Hull Requirements, Construction and Arrangement of Nautical School Ships § 167.20-10 Means of...

  4. 46 CFR 167.20-10 - Means of escape.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Means of escape. 167.20-10 Section 167.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Hull Requirements, Construction and Arrangement of Nautical School Ships § 167.20-10 Means of...

  5. 46 CFR 167.20-10 - Means of escape.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Means of escape. 167.20-10 Section 167.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Hull Requirements, Construction and Arrangement of Nautical School Ships § 167.20-10 Means of...

  6. 46 CFR 167.20-10 - Means of escape.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Means of escape. 167.20-10 Section 167.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Hull Requirements, Construction and Arrangement of Nautical School Ships § 167.20-10 Means of...

  7. 46 CFR 167.20-10 - Means of escape.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Means of escape. 167.20-10 Section 167.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Hull Requirements, Construction and Arrangement of Nautical School Ships § 167.20-10 Means of...

  8. 12. CLOSEUP VIEW FROM NORTHWEST, SHOWING DETAILS OF FIRE ESCAPE ...

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

    12. CLOSE-UP VIEW FROM NORTHWEST, SHOWING DETAILS OF FIRE ESCAPE NEAR CORNER OF MILLS HALL MAIN WING NORTH WALL, AND MILLS HALL NORTH WING WEST WALL. - Mills Hall, Mills College, 5000 MacArthur Boulevard, Oakland, Alameda County, CA

  9. Magnetic Field Influence on Atmospheric Escape and Planetary Evolution

    NASA Astrophysics Data System (ADS)

    Driscoll, P. E.; Bercovici, D.

    2012-12-01

    Planetary magnetic fields are maintained by a convective dynamo within the deep interior but their influence extends all the way up to the magnetopause, where the solar wind is deflect around the planet. The presence of a magnetic field is thought to influence the atmosphere-solar wind interaction in a variety of ways, but there is no clear consensus as to whether it impedes or facilitates volatile loss to space. Escape of planetary atmospheres to space is of central importance to studying the evolution of planetary climates, volatile exchange with the interior, and interaction with the space environment. Out of the terrestrial planets Earth has by far the largest surface hydrogen inventory (mainly in the form of liquid water) and furthest magnetopause at ~10 Earth radii. Evidence from volatile concentrations and isotopic ratios imply that Mars and Venus have both lost a significant amount of H over their history, and have maintained little to no magnetic barrier, respectively, to hold off the erosive solar wind. Venus is a particularly interesting case because it is most similar to Earth in mass and density, yet has no detectable magnetic field and an isotopic D/H ratio that implies the loss of a significant amount of water in the past. Is the decline of Venus' dynamo related to the loss of hydrogen from its atmosphere? Is the stability of Earth's unusually large volatile reservoir over billions of years related to the presence of a strong magnetic field over that period of time? We explore conditions under which the presence of a magnetic barrier at the top of the atmosphere may operate as an additional limit to escape. We derive a model for magnetic field limited escape that depends on the terrestrial number density, area, scale height, and loss time scale at the magnetopause. This model predicts rapid escape when magnetic field is weak and magnetopause altitude is low, and a decrease in escape as magnetic field strength increases. This coupling between field

  10. Plasma-induced Escape and Alterations of Planetary Atmospheres

    NASA Astrophysics Data System (ADS)

    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

  11. [Transposition of Great Artery].

    PubMed

    Konuma, Takeshi; Shimpo, Hideto

    2015-07-01

    Transposition of the great artery is one of common congenital cardiac disease resulting cyanosis. Death occurs easily in untreated patients with transposition and intact ventricular septal defect (VSD) in infancy at a few days of age when posterior descending coronary artery (PDA) closed. Since there are 2 parallel circulations, flow from pulmonary to systemic circulation is necessary for systemic oxygenation, and Balloon atrial septostomy or prostaglandin infusion should be performed especially if patient do not have VSD. Although the advent of fetal echocardiography, it is difficult to diagnose the transposition of the great arteries (TGA) as abnormality of great vessels is relatively undistinguishable. The diagnosis of transposition is in itself an indication for surgery, and arterial switch procedure is performed in the case the left ventricle pressure remains more than 2/3 of systemic pressure. Preoperative diagnosis is important as associated anomalies and coronary artery branching patterns are important to decide the operative indication and timing of surgery.

  12. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein.

    PubMed

    Bates, John T; Keefer, Christopher J; Slaughter, James C; Kulp, Daniel W; Schief, William R; Crowe, James E

    2014-04-01

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (Kon) for binding to RSV F protein, while alteration of dissociation rate (Koff) did not significantly affect neutralizing activity. Interestingly, linkage of reduced Kon with reduced potency mirrored the effect of increased Kon found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants.

  13. Modelling the role of immunity in reversion of viral antigenic sites.

    PubMed

    Chan, Carmen H S; Sanders, Lloyd P; Tanaka, Mark M

    2016-03-01

    Antigenic sites in viral pathogens exhibit distinctive evolutionary dynamics due to their role in evading recognition by host immunity. Antigenic selection is known to drive higher rates of non-synonymous substitution; less well understood is why differences are observed between viruses in their propensity to mutate to a novel or previously encountered amino acid. Here, we present a model to explain patterns of antigenic reversion and forward substitution in terms of the epidemiological and molecular processes of the viral population. We develop an analytical three-strain model and extend the analysis to a multi-site model to predict characteristics of observed sequence samples. Our model provides insight into how the balance between selection to escape immunity and to maintain viability is affected by the rate of mutational input. We also show that while low probabilities of reversion may be due to either a low cost of immune escape or slowly decaying host immunity, these two scenarios can be differentiated by the frequency patterns at antigenic sites. Comparison between frequency patterns of human influenza A (H3N2) and human RSV-A suggests that the increased rates of antigenic reversion in RSV-A is due to faster decaying immunity and not higher costs of escape. PMID:26723535

  14. Recording Field Potentials From Zebrafish Larvae During Escape Responses

    PubMed Central

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

    2014-01-01

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

  15. Escape manoeuvres in the spiny dogfish (Squalus acanthias).

    PubMed

    Domenici, Paolo; Standen, Emily M; Levine, Robert P

    2004-06-01

    The locomotor performance of dogfish during escape responses was observed by means of high-speed video. Dogfish show C-type escape responses that are comparable with those shown previously in teleosts. Dogfish show high variability of turning rates of the anterior part of the body (head to centre of mass), i.e. with peak values from 434 to 1023 deg. s(-1). We suggest that this variability may be due to the presence of two types of escape manoeuvres, i.e. responses with high and low turning rates, as previously found in a teleost species. Fast responses (i.e. with high maximum turning rates, ranging between 766 and 1023 deg. s(-1)) showed significantly higher locomotor performance than slow responses (i.e. with low maximum turning rates, ranging between 434 and 593 deg. s(-1)) in terms of distance covered, speed and acceleration, although no differences were found in the turning radius of the centre of mass during the escape manoeuvres. The existence of two types of escape responses would have implications in terms of both neural control and muscular activation patterns. When compared with literature data for the locomotor performance of bony fishes, dogfish showed relatively low speed and acceleration, comparable turning rates and a turning radius that is in the low part of the range when compared with teleosts, indicating relatively high manoeuvrability. The locomotor performance observed in dogfish is consistent with their morphological characteristics: (1) low locomotor performance associated with low thrust developed by their relatively small posterior depth of section and (2) relatively high manoeuvrability associated with their high flexibility.

  16. Erratum: The Escape of Ionizing Photons from the Galaxy

    NASA Astrophysics Data System (ADS)

    Bland-Hawthorn, J.; Maloney, P. R.

    2001-04-01

    In the Letter ``The Escape of Ionizing Photons from the Galaxy'' by J. Bland-Hawthorn & P. R. Maloney (ApJ, 510, L33 [1999]), there is an error in Figure 4 that bears on the derived escape fraction of ionizing photons from star-forming regions in the Galaxy's disk. For the quoted distance (55 kpc) of the Magellanic Stream, the predicted emission measures should be reduced by a factor of (20/55)2. Our derived value of fesc~6%, the escape fraction normal to the disk, must be raised by the inverse of this factor, which makes it unlikely that the Stream Hα arises from UV produced by the Galaxy's young stellar disk. This is exacerbated by new Hα observations that show that the Stream is even brighter than originally thought (Weiner, Vogel, & Williams 2001). Bland-Hawthorn & Putman (2001) discuss possible sources of ionization for the Magellanic Stream. We note with interest that high-velocity clouds have now been detected in Hα (e.g., Tufte, Reynolds, & Haffner 1998). Some of these have well-established distance bounds. Bland-Hawthorn & Putman (2001) and Weiner et al. (2001) find that the observed Hα is roughly consistent with fesc~5%, although the present uncertainties are about a factor of 2. It should be noted that fesc refers to the escape fraction normal to the disk. The escape fraction averaged over 4π sr, fesc, is about a factor of 3 smaller and depends on the details of the opacity model (Bland-Hawthorn 1998, Appendix 1). The present uncertainties on fesc for the Galaxy mean that we cannot determine whether star-forming regions dominate the extragalactic UV background (cf. Shull et al. 1999).

  17. The Great Lakes whitefish

    USGS Publications Warehouse

    Van Oosten, John; Elliot, Charles

    1942-01-01

    In every one of the Great Lakes- Ontario, Erie, Huron, Michigan, and Superior- the most valuable fishes are declining, and there is no evidence that this trend will be reversed. Under existing conditions of a diversity of regulations that vary between states and between the two countries, and with the present methods of fishing, the Great Lakes fisheries are doomed. This chapter deals with the common whitefish, a valuable species which many believe to be the next that will go unless positive action is forthcoming soon.

  18. The Great Salt Lake

    USGS Publications Warehouse

    Hassibe, W.R.; Keck, W.G.

    1991-01-01

    The western part of the conterminous United States is often thought of as being a desert without any large bodies of water. In the desert area of western Utah, however, lies Great Salt Lake, which in 1986 covered approximately 2,300 square miles and contained 30 million acre-feet of water (an acre-foot is the amount of water necessary to cover 1 acre of land with water 1 foot in depth or about 326,000 gallons). To emphasize its size, the Great Salt Lake is the largest lake west of the Mississippi River, larger than the states of Rhode Island and Delaware.

  19. A DNA-Device that Mediates Selective Endosomal Escape and Intracellular Delivery of Drugs and Biologicals

    PubMed Central

    Muro, Silvia

    2014-01-01

    Design of materials to aid intracellular delivery of agents can greatly improve medical treatments. While DNA is a molecule difficult to introduce into cells, DNA can be engineered into devices capable of intracellular delivery. Yet, transport mediated by DNA-devices void of other structural material, with size greater than that associated with non-specific penetration, and with targeting capacity enough to overcome non-specific pathways has not been achived. This study demonstrates that this is possible. Submicrometer (200-nm) dendrimers built of DNA (nucleodendrimers (NDs)) are coupled to antibodies against selected cell-surface receptors and compared to polymer nanoparticles (NPs). NDs and NPs bind specifically to cells expressing these targets and efficiently enter cells via the pathway associated with the selected receptor. While NPs traffic to perinuclear endo-lysosomes, NDs remain scattered throughout the cell, suggesting endosomal escape. This is confirmed in vitro, where NDs disrupt membranous vesicles at endosomal-like pH and in cell culture, where they: provide endosomal escape of model drugs, sugars, proteins, and nucleic acids; allow access to other intracellular compartments; result in measurable effects of cargoes; and do not cause cytotoxicity. Therefore, these DNA-nanodevices can be used to selectively overcome intracellular barriers, underscoring the growing range of applications of DNA materials. PMID:25018687

  20. A DNA-Device that Mediates Selective Endosomal Escape and Intracellular Delivery of Drugs and Biologicals.

    PubMed

    Muro, Silvia

    2014-05-21

    Design of materials to aid intracellular delivery of agents can greatly improve medical treatments. While DNA is a molecule difficult to introduce into cells, DNA can be engineered into devices capable of intracellular delivery. Yet, transport mediated by DNA-devices void of other structural material, with size greater than that associated with non-specific penetration, and with targeting capacity enough to overcome non-specific pathways has not been achived. This study demonstrates that this is possible. Submicrometer (200-nm) dendrimers built of DNA (nucleodendrimers (NDs)) are coupled to antibodies against selected cell-surface receptors and compared to polymer nanoparticles (NPs). NDs and NPs bind specifically to cells expressing these targets and efficiently enter cells via the pathway associated with the selected receptor. While NPs traffic to perinuclear endo-lysosomes, NDs remain scattered throughout the cell, suggesting endosomal escape. This is confirmed in vitro, where NDs disrupt membranous vesicles at endosomal-like pH and in cell culture, where they: provide endosomal escape of model drugs, sugars, proteins, and nucleic acids; allow access to other intracellular compartments; result in measurable effects of cargoes; and do not cause cytotoxicity. Therefore, these DNA-nanodevices can be used to selectively overcome intracellular barriers, underscoring the growing range of applications of DNA materials.

  1. [Neuropsychiatric sequelae of viral meningitis in adults].

    PubMed

    Damsgaard, Jesper; Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter Derek Christian

    2011-10-10

    Viral meningitis is considered to be a benign illness with only mild symptoms. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. However, retrospective studies have demonstrated that patients suffering from viral meningitis may experience cognitive impairment following the acute course of infection. Larger controlled studies are needed to elucidate the potential neuropsychiatric adverse outcome of viral meningitis.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    ERIC Educational Resources Information Center

    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…

  4. Great Expectations. [Lesson Plan].

    ERIC Educational Resources Information Center

    Devine, Kelley

    Based on Charles Dickens' novel "Great Expectations," this lesson plan presents activities designed to help students understand the differences between totalitarianism and democracy; and a that a writer of a story considers theme, plot, characters, setting, and point of view. The main activity of the lesson involves students working in groups to…

  5. The Great Mathematician Project

    ERIC Educational Resources Information Center

    Goldberg, Sabrina R.

    2013-01-01

    The Great Mathematician Project (GMP) introduces both mathematically sophisticated and struggling students to the history of mathematics. The rationale for the GMP is twofold: first, mathematics is a uniquely people-centered discipline that is used to make sense of the world; and second, students often express curiosity about the history of…

  6. The Great Lakes.

    ERIC Educational Resources Information Center

    Seasons, 1987

    1987-01-01

    The Great Lakes are one of the world's greatest reserviors of fresh water, the foundation of Ontario's economic development, a primary force in ecological systems, and a base for pleasure and recreation. These lakes and their relationship with people of Canada and the United States can be useful as a subject for teaching the impact of human…

  7. 1 Great Question

    ERIC Educational Resources Information Center

    Nethery, Carrie

    2011-01-01

    In this article, the author presents an ideal question that can take an art teacher and his or her students through all the levels of thought in Bloom's taxonomy--perfect for modeling the think-aloud process: "How many people is the artist inviting into this picture?" This great question always helps the students look beyond the obvious and dig…

  8. Great Barrier Reef

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A better than average view of the Great Barrier Reef was captured by SeaWiFS on a recent overpass. There is sunglint northeast of the reef and there appears to be some sort of filamentous bloom in the Capricorn Channel.

  9. Endogenous Viral Elements in Animal Genomes

    PubMed Central

    Katzourakis, Aris; Gifford, Robert J.

    2010-01-01

    Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs) derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized. PMID:21124940

  10. Cellular sensing of viral DNA and viral evasion mechanisms.

    PubMed

    Orzalli, Megan H; Knipe, David M

    2014-01-01

    Mammalian cells detect foreign DNA introduced as free DNA or as a result of microbial infection, leading to the induction of innate immune responses that block microbial replication and the activation of mechanisms that epigenetically silence the genes encoded by the foreign DNA. A number of DNA sensors localized to a variety of sites within the cell have been identified, and this review focuses on the mechanisms that detect viral DNA and how the resulting responses affect viral infections. Viruses have evolved mechanisms that inhibit these host sensors and signaling pathways, and the study of these antagonistic viral strategies has provided insight into the mechanisms of these host responses. The field of cellular sensing of foreign DNA is in its infancy, but our currently limited knowledge has raised a number of important questions for study.

  11. Viral evasion of a bacterial suicide system by RNA-based molecular mimicry enables infectious altruism.

    PubMed

    Blower, Tim R; Evans, Terry J; Przybilski, Rita; Fineran, Peter C; Salmond, George P C

    2012-01-01

    Abortive infection, during which an infected bacterial cell commits altruistic suicide to destroy the replicating bacteriophage and protect the clonal population, can be mediated by toxin-antitoxin systems such as the Type III protein-RNA toxin-antitoxin system, ToxIN. A flagellum-dependent bacteriophage of the Myoviridae, ΦTE, evolved rare mutants that "escaped" ToxIN-mediated abortive infection within Pectobacterium atrosepticum. Wild-type ΦTE encoded a short sequence similar to the repetitive nucleotide sequence of the RNA antitoxin, ToxI, from ToxIN. The ΦTE escape mutants had expanded the number of these "pseudo-ToxI" genetic repeats and, in one case, an escape phage had "hijacked" ToxI from the plasmid-borne toxIN locus, through recombination. Expression of the pseudo-ToxI repeats during ΦTE infection allowed the phage to replicate, unaffected by ToxIN, through RNA-based molecular mimicry. This is the first example of a non-coding RNA encoded by a phage that evolves by selective expansion and recombination to enable viral suppression of a defensive bacterial suicide system. Furthermore, the ΦTE escape phages had evolved enhanced capacity to transduce replicons expressing ToxIN, demonstrating virus-mediated horizontal transfer of genetic altruism.

  12. Computational mechanics of viral capsids.

    PubMed

    Gibbons, Melissa M; Perotti, Luigi E; Klug, William S

    2015-01-01

    Viral capsids undergo significant mechanical deformations during their assembly, maturation, and infective life-span. In order to characterize the mechanics of viral capsids, their response to applied external forces is analyzed in several experimental studies using, for instance, Atomic Force Microscope (AFM) indentation experiments. In recent years, a broader approach to study the mechanics of viral capsids has leveraged the theoretical tools proper of continuum mechanics. Even though the theory of continuum elasticity is most commonly used to study deformable bodies at larger macroscopic length scales, it has been shown that this very rich theoretical field can still offer useful insights into the mechanics of viral structures at the nanometer scale. Here we show the construction of viral capsid continuum mechanics models starting from different forms of experimental data. We will discuss the kinematics assumptions, the issue of the reference configuration, the material constitutive laws, and the numerical discretization necessary to construct a complete Finite Element capsid mechanical model. Some examples in the second part of the chapter will show the predictive capabilities of the constructed models and underline useful practical aspects related to efficiency and accuracy. We conclude each example by collecting several key findings discovered by simulating AFM indentation experiments using the constructed numerical models.

  13. Viral metagenomics and blood safety.

    PubMed

    Sauvage, V; Eloit, M

    2016-02-01

    The characterization of the human blood-associated viral community (also called blood virome) is essential for epidemiological surveillance and to anticipate new potential threats for blood transfusion safety. Currently, the risk of blood-borne agent transmission of well-known viruses (HBV, HCV, HIV and HTLV) can be considered as under control in high-resource countries. However, other viruses unknown or unsuspected may be transmitted to recipients by blood-derived products. This is particularly relevant considering that a significant proportion of transfused patients are immunocompromised and more frequently subjected to fatal outcomes. Several measures to prevent transfusion transmission of unknown viruses have been implemented including the exclusion of at-risk donors, leukocyte reduction of donor blood, and physicochemical treatment of the different blood components. However, up to now there is no universal method for pathogen inactivation, which would be applicable for all types of blood components and, equally effective for all viral families. In addition, among available inactivation procedures of viral genomes, some of them are recognized to be less effective on non-enveloped viruses, and inadequate to inactivate higher viral titers in plasma pools or derivatives. Given this, there is the need to implement new methodologies for the discovery of unknown viruses that may affect blood transfusion. Viral metagenomics combined with High Throughput Sequencing appears as a promising approach for the identification and global surveillance of new and/or unexpected viruses that could impair blood transfusion safety. PMID:26778104

  14. Great Lakes Energy Institute

    SciTech Connect

    Alexander, J. Iwan

    2012-11-18

    The vision of the Great Lakes Energy Institute is to enable the transition to advanced, sustainable energy generation, storage, distribution and utilization through coordinated research, development, and education. The Institute will place emphasis on translating leading edge research into next generation energy technology. The Institute’s research thrusts focus on coordinated research in decentralized power generation devices (e.g. fuel cells, wind turbines, solar photovoltaic devices), management of electrical power transmission and distribution, energy storage, and energy efficiency.

  15. The great intimidators.

    PubMed

    Kramer, Roderick M

    2006-02-01

    After Disney's Michael Eisner, Miramax's Harvey Weinstein, and Hewlett-Packard's Carly Fiorina fell from their heights of power, the business media quickly proclaimed thatthe reign of abrasive, intimidating leaders was over. However, it's premature to proclaim their extinction. Many great intimidators have done fine for a long time and continue to thrive. Their modus operandi runs counter to a lot of preconceptions about what it takes to be a good leader. They're rough, loud, and in your face. Their tactics include invading others' personal space, staging tantrums, keeping people guessing, and possessing an indisputable command of facts. But make no mistake--great intimidators are not your typical bullies. They're driven by vision, not by sheer ego or malice. Beneath their tough exteriors and sharp edges are some genuine, deep insights into human motivation and organizational behavior. Indeed, these leaders possess political intelligence, which can make the difference between paralysis and successful--if sometimes wrenching--organizational change. Like socially intelligent leaders, politically intelligent leaders are adept at sizing up others, but they notice different things. Those with social intelligence assess people's strengths and figure out how to leverage them; those with political intelligence exploit people's weaknesses and insecurities. Despite all the obvious drawbacks of working under them, great intimidators often attract the best and brightest. And their appeal goes beyond their ability to inspire high performance. Many accomplished professionals who gravitate toward these leaders want to cultivate a little "inner intimidator" of their own. In the author's research, quite a few individuals reported having positive relationships with intimidating leaders. In fact, some described these relationships as profoundly educational and even transformational. So before we throw out all the great intimidators, the author argues, we should stop to consider what

  16. Not so Great Lakes?

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    In 1965, Frank Sinatra won the Grammy Award for his album, “September of My Years” “Early Bird,” the first commercial communications satellite, was launched; and Dr. Martin Luther King, Jr. was arrested in Selma, Alabama, during demonstrations against voter-registration rules.The year 1965 was also the last time water levels in the U.S. Great Lakes were as low as they are now.

  17. Not so Great Lakes?

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    In 1965, Frank Sinatra won the Grammy Award for his album, "September of My Years;" "Early Bird," the first commercial communications satellite, was launched; and Dr. Martin Luther King, Jr. was arrested in Selma, Alabama, during demonstrations against voter-registration rules.The year 1965 was also the last time water levels in the U.S. Great Lakes were as low as they are now.

  18. The great intimidators.

    PubMed

    Kramer, Roderick M

    2006-02-01

    After Disney's Michael Eisner, Miramax's Harvey Weinstein, and Hewlett-Packard's Carly Fiorina fell from their heights of power, the business media quickly proclaimed thatthe reign of abrasive, intimidating leaders was over. However, it's premature to proclaim their extinction. Many great intimidators have done fine for a long time and continue to thrive. Their modus operandi runs counter to a lot of preconceptions about what it takes to be a good leader. They're rough, loud, and in your face. Their tactics include invading others' personal space, staging tantrums, keeping people guessing, and possessing an indisputable command of facts. But make no mistake--great intimidators are not your typical bullies. They're driven by vision, not by sheer ego or malice. Beneath their tough exteriors and sharp edges are some genuine, deep insights into human motivation and organizational behavior. Indeed, these leaders possess political intelligence, which can make the difference between paralysis and successful--if sometimes wrenching--organizational change. Like socially intelligent leaders, politically intelligent leaders are adept at sizing up others, but they notice different things. Those with social intelligence assess people's strengths and figure out how to leverage them; those with political intelligence exploit people's weaknesses and insecurities. Despite all the obvious drawbacks of working under them, great intimidators often attract the best and brightest. And their appeal goes beyond their ability to inspire high performance. Many accomplished professionals who gravitate toward these leaders want to cultivate a little "inner intimidator" of their own. In the author's research, quite a few individuals reported having positive relationships with intimidating leaders. In fact, some described these relationships as profoundly educational and even transformational. So before we throw out all the great intimidators, the author argues, we should stop to consider what

  19. Escape rate in the gene transcriptional regulatory system with time delay

    NASA Astrophysics Data System (ADS)

    Zeng, Chun-Hua; Xie, Chong-Wei

    2008-09-01

    The escape rate in the gene transcriptional regulatory system with time delay in the presence of cross-correlation noises is studied. The expression of the escape rate is derived under the condition of small delay time. Based on the escape rate, we investigated the effects of both cross-correlation intensity (λ) and delay time (τ) on the escape rate. Our results indicate that: (i) under positively correlated noises action (i.e. λ> 0), the escape rate exhibits one minimum value as the intensities of the multiplicative and additive noises vary, namely the suppression effect. However, for the case of uncorrelated noises (λ=0) and negatively correlated noises (λ<0), the suppression phenomenon disappears. (ii) λ and τ have opposite effects on the escape rate of the system, i.e. under positively correlated noises action, an increase of λ can intensify the suppression of the escape rate, but an increase of τ can weaken the suppression of the escape rate.

  20. 20. DETAIL VIEW IN 18FOOT LOCK, ESCAPE TRAINING TANK, SHOWING ...

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

    20. DETAIL VIEW IN 18-FOOT LOCK, ESCAPE TRAINING TANK, SHOWING DOOR INTO TANK AT RIGHT - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  1. Great Salt Lake, Utah

    USGS Publications Warehouse

    Stephens, Doyle W.; Gardner, Joe F.

    1999-01-01

    This document is intended as a source of general information and facts about Great Salt Lake, Utah. This U.S. Geological Survey information sheet answers frequently asked questions about Great Salt Lake. Topics include: History, salinity, brine shrimp, brine flies, migratory birds, and recreation. Great Salt Lake, the shrunken remnant of prehistoric Lake Bonneville, has no outlet. Dissolved salts accumulate in the lake by evaporation. Salinity south of the causeway has ranged from 6 percent to 27 percent over a period of 22 years (2 to 7 times saltier than the ocean). The high salinity supports a mineral industry that extracts about 2 million tons of salt from the lake each year. The aquatic ecosystem consists of more than 30 species of organisms. Harvest of its best-known species, the brine shrimp, annually supplies millions of pounds of food for the aquaculture industry worldwide. The lake is used extensively by millions of migratory and nesting birds and is a place of solitude for people. All this occurs in a lake that is located at the bottom of a 35,000-square-mile drainage basin that has a human population of more than 1.5 million.

  2. Great Basin Paleontological Bibliography

    USGS Publications Warehouse

    Blodgett, Robert B.; Zhang, Ning; Hofstra, Albert H.; Morrow, Jared R.

    2007-01-01

    Introduction This work was conceived as a derivative product for 'The Metallogeny of the Great Basin' project of the Mineral Resources Program of the U.S. Geological Survey. In the course of preparing a fossil database for the Great Basin that could be accessed from the Internet, it was determined that a comprehensive paleontological bibliography must first be compiled, something that had not previously been done. This bibliography includes published papers and abstracts as well as unpublished theses and dissertations on fossils and stratigraphy in Nevada and adjoining portions of California and Utah. This bibliography is broken into first-order headings by geologic age, secondary headings by taxonomic group, followed by ancillary topics of interest to both paleontologists and stratigraphers; paleoecology, stratigraphy, sedimentary petrology, paleogeography, tectonics, and petroleum potential. References were derived from usage of Georef, consultation with numerous paleontologists and geologists working in the Great Basin, and literature currently on hand with the authors. As this is a Web-accessible bibliography, we hope to periodically update it with new citations or older references that we have missed during this compilation. Hence, the authors would be grateful to receive notice of any new or old papers that the readers think should be added. As a final note, we gratefully acknowledge the helpful reviews provided by A. Elizabeth J. Crafford (Anchorage, Alaska) and William R. Page (USGS, Denver, Colorado).

  3. Noncoding RNPs of viral origin.

    PubMed

    Steitz, Joan; Borah, Sumit; Cazalla, Demian; Fok, Victor; Lytle, Robin; Mitton-Fry, Rachel; Riley, Kasandra; Samji, Tasleem

    2011-03-01

    Like their host cells, many viruses produce noncoding (nc)RNAs. These show diversity with respect to time of expression during viral infection, length and structure, protein-binding partners and relative abundance compared with their host-cell counterparts. Viruses, with their limited genomic capacity, presumably evolve or acquire ncRNAs only if they selectively enhance the viral life cycle or assist the virus in combating the host's response to infection. Despite much effort, identifying the functions of viral ncRNAs has been extremely challenging. Recent technical advances and enhanced understanding of host-cell ncRNAs promise accelerated insights into the RNA warfare mounted by this fascinating class of RNPs. PMID:20719877

  4. Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

    PubMed Central

    Mehraj, Vikram; Routy, Jean-Pierre

    2015-01-01

    l-Tryptophan (l-Trp) is an essential amino acid that possesses diverse metabolic, neurological, and immunological roles spanning from the synthesis of proteins, neurotransmitter serotonin, and neurohormone melatonin, to its degradation into immunosuppressive catabolites by indoleamine-2, 3-dioxygenase (IDO) in the kynurenine pathway (KP). Trp catabolites, by activating aryl hydrocarbon receptor (AhR), play an important role in antimicrobial defense and immune regulation. IDO/AhR acts as a double-edged sword by both depleting l-Trp to starve the invaders and by contributing to the state of immunosuppression with microorganisms that were not cleared during acute infection. Pathogens experiencing Trp deprivation by IDO-mediated degradation include certain bacteria, parasites, and less likely viruses. However, chronic viral infections highjack the host immune response to create a state of disease tolerance via kynurenine catabolites. This review covers the latest data involving chronic viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes, and cytomegalovirus (CMV) and their cellular interplay with Trp catabolites. Strategies developed by viruses to escape immune control also represent new avenues for therapeutic interventions based on Trp metabolism. PMID:26309411

  5. Conventional and unconventional mechanisms for capping viral mRNA.

    PubMed

    Decroly, Etienne; Ferron, François; Lescar, Julien; Canard, Bruno

    2012-01-01

    In the eukaryotic cell, capping of mRNA 5' ends is an essential structural modification that allows efficient mRNA translation, directs pre-mRNA splicing and mRNA export from the nucleus, limits mRNA degradation by cellular 5'-3' exonucleases and allows recognition of foreign RNAs (including viral transcripts) as 'non-self'. However, viruses have evolved mechanisms to protect their RNA 5' ends with either a covalently attached peptide or a cap moiety (7-methyl-Gppp, in which p is a phosphate group) that is indistinguishable from cellular mRNA cap structures. Viral RNA caps can be stolen from cellular mRNAs or synthesized using either a host- or virus-encoded capping apparatus, and these capping assemblies exhibit a wide diversity in organization, structure and mechanism. Here, we review the strategies used by viruses of eukaryotic cells to produce functional mRNA 5'-caps and escape innate immunity. PMID:22138959

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  8. Escape of heated ions upstream of quasi-parallel shocks

    NASA Technical Reports Server (NTRS)

    Edmiston, J. P.; Kennel, C. F.; Eichler, D.

    1982-01-01

    A simple theoretical criterion by which quasi-parallel and quasi-perpendicular collisionless shocks may be distinguished is proposed on the basis of an investigation of the free escape of ions from the post-shock plasma into the region upstream of a fast collisionless shock. It was determined that the accessibility of downstream ions to the upstream region depends on upstream magnetic field shock normal angle, in addition to the upstream plasma parameters, with post-shock ions escaping upstream for shock normal angles of less than 45 deg, in agreement with the observed transition between quasi-parallel and quasi-perpendicular shock structure. Upstream ion distribution functions resembling those of observed intermediate ions and beams are also calculated.

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

    PubMed Central

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

    2007-01-01

    Fishes show a remarkable diversity of shapes which have been associated with their swimming abilities and anti-predator adaptations. The crucian carp (Carassius carassius) provides an extreme example of phenotypic plasticity in body shape which makes it a unique model organism for evaluating the relationship between body form and function in fishes. In crucian carp, a deep body is induced by the presence of pike (Esox lucius), and this results in lower vulnerability to gape-limited predators, such as pike itself. Here, we demonstrate that deep-bodied crucian carp attain higher speed, acceleration and turning rate during anti-predator responses than shallow-bodied crucian carp. Therefore, a predator-induced morphology in crucian carp enhances their escape locomotor performance. The deep-bodied carp also show higher percentage of muscle mass. Therefore, their superior performance in escape swimming may be due to a combination of higher muscle power and higher thrust. PMID:17971327

  10. Ionospheric Flow and Escape of Ions from Titan and Venus

    NASA Technical Reports Server (NTRS)

    Hartle, R. E.; Intriligator, D. S.; Grebowsky, Joseph M.; Vondrak, Richard R. (Technical Monitor)

    2001-01-01

    Knowledge gained from measurements and models is used to study the high-speed plasmas interacting with the atmospheres and ionospheres of Titan and Venus. Considering the similarities of the interactions, comparative analysis is used to support the interpretations of observations made at each body. Ionospheric flow inferred to exist by analysis of measurements made from the Pioneer Venus Orbiter supports the interpretation of similar flow in the ionosphere of Titan. The concept that cold ions escape from the ionosphere of Venus is supported by the Voyager I observation that cold ions escape down the magnetic tail of Titan. Pickup O+ ion energy distributions observed at their source in the ionosheath of Venus are shown to be influenced by finite gyroradius effects. The signatures of such effects are expected to be retained as the ions move into the wakes of Titan and Venus.

  11. Fractionation of noble gases by thermal escape from accreting planetesimals

    NASA Technical Reports Server (NTRS)

    Donahue, T. M.

    1986-01-01

    Assuming solar initial elemental and isotopic ratios and a determination of the degree of fractionation occurring by competition between gravitational binding and escape, a model is developed for selective noble gas loss through escape during the growth of planetesimals to form the terrestrial planets. Of the two classes of planetesimals that can form on a time scale that is consistent with modern accretion models, one is depleted in neon while the other is neon-rich. The mechanism is noted to be capable of accounting for all known properties of the noble gas volatiles on the terrestrial planets, with only one exception, namely the Ar-36/Ar-38 ratios for Mars and the earth, which are much lower than observed.

  12. Planetary loss from light ion escape on Venus

    NASA Technical Reports Server (NTRS)

    Hartle, R. E.; Grebowsky, J. M.

    1995-01-01

    Using Pioneer Venus data, hydrogen and deuterium ions are shown to escape from the hydrogen bulge region in the nightside ionosphere. The polarization electric field propels these light ions upward through the ionosphere and into the ion-exosphere, where H(+) and D(+) continue to be accelerated away from Venus and move into the ionotail and beyond. The vertical flow speeds of H(+) and D(+) are found to be about the same; therefore, selective escape between H(+) and D(+) is negligible for this mechanism. Present day planetary loss rates of about 8.6 x 10(exp 25)/s and 3.2 X 10(exp 23)/s were obtained for H(+) and D(+), respectively. Such rates, persisting over a few billion years, should have significantly affected the planetary water budget.

  13. Fixation and escape times in stochastic game learning

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  14. The production and escape of nitrogen atoms on Mars

    NASA Astrophysics Data System (ADS)

    Fox, J. L.

    1993-02-01

    Updated rate coefficients and a revised ionosphere-thermosphere model are used to compute the production rates and densities of odd nitrogen species in the Martian atmosphere. Computed density profiles for N(4S), N(2D), N(2P), and NO are presented. The model NO densities are found to be about a factor of 2-3 less than those measured by the Viking 1 mass spectrometer. Revised values for the escape rates of N atoms from dissociative recombination and ionospheric reactions are also computed. Dissociative recombination is found to be comparable in importance to photodissociation at low solar activity, but it is still the most important escape mechanism for N-14 at high solar activity.

  15. Failed Escape: Solid Surfaces Prevent Tumbling of Escherichia coli

    NASA Astrophysics Data System (ADS)

    Molaei, Mehdi; Barry, Michael; Stocker, Roman; Sheng, Jian

    2014-08-01

    Understanding how bacteria move close to surfaces is crucial for a broad range of microbial processes including biofilm formation, bacterial dispersion, and pathogenic infections. We used digital holographic microscopy to capture a large number (>103) of three-dimensional Escherichia coli trajectories near and far from a surface. We found that within 20 μm from a surface tumbles are suppressed by 50% and reorientations are largely confined to surface-parallel directions, preventing escape of bacteria from the near-surface region. A hydrodynamic model indicates that the tumble suppression is likely due to a surface-induced reduction in the hydrodynamic force responsible for the flagellar unbundling that causes tumbling. These findings imply that tumbling does not provide an effective means to escape trapping near surfaces.

  16. Corona-like atmospheric escape from KBOs. I. Gas dynamics

    NASA Astrophysics Data System (ADS)

    Levi, Amit; Podolak, Morris

    2009-08-01

    We show that for low temperatures ( T˜30 K) and small, but non-negligible, gravitational fields the hydrodynamic escape of gas can be treated by Parker's theory of coronal expansion [Parker, E.N., 1963. Interplanetary Dynamical Processes. Interscience Publishers, New York]. We apply this theory to gas escape from Kuiper belt objects. We derive limits on the density and radius of the bodies for which this theory is applicable, and show how the flow depends on the mean molecular weight and internal degrees of freedom of the gas molecules. We use these results to explain the CH 4 dichotomy seen on KBOs [Schaller, E.L., Brown, M.E., 2007. Astrophys. J., 659, L61-L64].

  17. Viral metagenomics: a tool for virus discovery and diversity in aquaculture.

    PubMed

    Alavandi, S V; Poornima, M

    2012-09-01

    Viruses are abundant biological entities on earth and the emergence of viral pathogens has become a serious threat to aquaculture and fisheries worldwide. However, our response to viral pathogens has been largely reactive, in the sense that a new pathogen is usually not discovered until it has already reached epidemic proportions. Current diagnostic methods such as PCR, immunological assays and pan-viral microarrays are limited in their ability to identify novel viruses. In this context, the knowledge on the diversity of viruses in healthy and disease situations becomes important for understanding their role on the health of animals in aquaculture species. Viral metagenomics, which involves viral purification and shotgun sequencing, has proven to be useful for understanding viral diversity and describing novel viruses in new diseases and has been recognized as an important tool for discovering novel viruses in human and veterinary medicine. With the advancements in sequencing technology and development of bioinformatics tools for nucleic acid sequence assembly and annotation, information on novel viruses and diversity of viruses in marine ecosystems has been rapidly expanding through viral metagenomics. Novel circoviruses and RNA viruses in Tampa bay pink shrimp, annelovirus in sea lion, picornavirus in ringed seals and several new viruses of marine animals have been recently described using viral metagenomics and this tool has been also recently used in describing viral diversity in aquaculture ponds. Further, a large amount of information has been generated on the diversity of viruses in the marine environment using viral metagenomics during the last decade. There exists a great potential with viral metagenomics for discovering novel viruses in asymptomatic marine candidate animals of aquaculture/mariculture, some of which may assume pathogenic status under high density culture and stress. Additionally, viral metagenomics can help our understanding of viruses

  18. The Role of Endosomal Escape and Mitogen-Activated Protein Kinases in Adenoviral Activation of the Innate Immune Response

    PubMed Central

    Smith, Jeffrey S.; Xu, Zhili; Tian, Jie; Palmer, Donna J.; Ng, Philip; Byrnes, Andrew P.

    2011-01-01

    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. PMID:22046344

  19. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing

    PubMed Central

    Neff, C. Preston; Gibbert, Kathrin; Dietze, Kirsten K.; Werner, Tanja; Liu, Jia; Chen, Lieping; Lang, Karl S.; Palmer, Brent E.; Dittmer, Ulf; Zelinskyy, Gennadiy

    2015-01-01

    Cytotoxic CD8+ T Lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV) or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells. PMID:26484769

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

    PubMed Central

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

    2009-01-01

    The cerci of the cockroach are covered with identified sensory hairs, which detect air movements. The sensory neurons which innervate these hairs synapse with giant interneurons (GIs) in the terminal ganglion which in turn synapse with interneurons and leg motorneurons in thoracic ganglia. This neural circuit mediates the animal's escape behavior. The transcription factor Engrailed (En) is expressed only in the medially born sensory neurons, which suggested it could work as a positional determinant of sensory neuron identity. Previously, we used dsRNA interference to abolish En expression, and found that the axonal arborization and synaptic outputs of an identified En-positive sensory neuron changed so that it came to resemble a nearby En-negative cell, which was itself unaffected. We thus demonstrated directly that En controls synaptic choice, as well as axon projections. Is escape behavior affected as a result of this mis-wiring? We recently showed that adult cockroaches keep each escape unpredictable by running along one of a set of preferred escape trajectories (ETs) at fixed angles from the direction of the threatening stimulus. The probability of selecting a particular ET is influenced by wind direction. In this present study we show that early instar juvenile cockroaches also use those same ETs. En knockout significantly perturbs the animals' perception of posterior wind, altering the choice of ETs to one more appropriate for anterior wind. This is the first time that it has been shown that knockout of a transcription factor controlling synaptic connectivity can alter the perception of a directional stimulus. PMID:19494140