Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies.

PubMed

Krumm, Stefanie A; Mohammed, Hajer; Le, Khoa M; Crispin, Max; Wrin, Terri; Poignard, Pascal; Burton, Dennis R; Doores, Katie J

2016-02-02

Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. Furthermore, we show that the V3 loop is important in facilitating promiscuous binding to glycans within the mannose-patch. These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch.

MAVEN in situ measurements of photochemical escape of oxygen from Mars

NASA Astrophysics Data System (ADS)

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

2016-04-01

One of the primary goals of the MAVEN mission is to characterize rates of atmospheric escape from Mars at the present epoch and relate those escape rates to solar drivers. One of the known escape processes is photochemical escape, where a) an exothermic chemical reaction in the atmosphere results in an upward-traveling neutral particle whose velocity exceeds planetary escape velocity and b) the particle is not prevented from escaping through subsequent collisions. At Mars, photochemical escape of oxygen is expected to be a significant channel for atmospheric escape, particularly in the early solar system when extreme ultraviolet (EUV) fluxes were much higher. Thus characterizing this escape process and its variability with solar drivers is central to understanding the role escape to space has played in Mars' climate evolution. We use near-periapsis (<400 km altitude) data from three MAVEN instruments: the Langmuir Probe and Waves (LPW) instrument measures electron density and temperature, the Suprathermal And Thermal Ion Composition (STATIC) experiment measures ion temperature and the Neutral Gas and Ion Mass Spectrometer (NGIMS) measures neutral and ion densities. For each profile of in situ measurements, we make several calculations, each as a function of altitude. The first uses electron and temperatures and simulates the dissociative recombination of both O2+ and CO2+ to calculate the probability distribution for the initial energies of the resulting hot oxygen atoms. The second is a Monte Carlo hot atom transport model that takes that distribution of initial O energies and the measured neutral density profiles and calculates the probability that a hot atom born at that altitude will escape. The third takes the measured electron and ion densities and electron temperatures and calculates the production rate of hot O atoms. We then multiply together the profiles of hot atom production and escape probability to get profiles of the production rate of escaping atoms. We integrate with respect to altitude to give us the escape flux of hot oxygen atoms for that periapsis pass. We have sufficient coverage in solar zenith angle (SZA) to estimate total escape rates for two intervals with the obvious assumption that escape rates are the same at all points with the same SZA. We estimate total escape rates of 3.5-5.8 x 1025 s-1 for Ls = 289° to 319° and 1.6-2.6 x 1025 s-1 for Ls = 326° to 348°. The latter is the most directly comparable to previous model-based estimates and is roughly in line with several of them. Total photochemical loss over Mars history is not very useful to calculate from such escape fluxes derived over a limited area and under limited conditions. A thicker atmosphere and much higher solar EUV in the past may change the dynamics of escape dramatically. In the future, we intend to use 3-D Monte Carlo models of global atmospheric escape, in concert with our in situ and remote measurements, to fully characterize photochemical escape under current conditions and carefully extrapolate back in time using further simulations with new boundary conditions.

Stabilizing effect of driving and dissipation on quantum metastable states

NASA Astrophysics Data System (ADS)

Valenti, Davide; Carollo, Angelo; Spagnolo, Bernardo

2018-04-01

We investigate how the combined effects of strong Ohmic dissipation and monochromatic driving affect the stability of a quantum system with a metastable state. We find that, by increasing the coupling with the environment, the escape time makes a transition from a regime in which it is substantially controlled by the driving, displaying resonant peaks and dips, to a regime of frequency-independent escape time with a peak followed by a steep falloff. The escape time from the metastable state has a nonmonotonic behavior as a function of the thermal-bath coupling, the temperature, and the frequency of the driving. The quantum noise-enhanced stability phenomenon is observed in the investigated system.

The Receptor-Binding Site of the Measles Virus Hemagglutinin Protein Itself Constitutes a Conserved Neutralizing Epitope

PubMed Central

Ohno, Shinji; Sakai, Kouji; Ito, Yuri; Fukuhara, Hideo; Komase, Katsuhiro; Brindley, Melinda A.; Rota, Paul A.; Plemper, Richard K.; Maenaka, Katsumi; Takeda, Makoto

2013-01-01

Here, we provide direct evidence that the receptor-binding site of measles virus (MV) hemagglutinin protein itself forms an effective conserved neutralizing epitope (CNE). Several receptor-interacting residues constitute the CNE. Thus, viral escape from neutralization has to be associated with loss of receptor-binding activity. Since interactions with both the signaling lymphocyte activation molecule (SLAM) and nectin4 are critical for MV pathogenesis, its escape, which results from loss of receptor-binding activity, should not occur in nature. PMID:23283964

Routes to formation of highly excited neutral atoms in the break-up of strongly driven hydrogen molecule

NASA Astrophysics Data System (ADS)

Emmanouilidou, Agapi

2012-06-01

We present a theoretical quasiclassical treatment of the formation, during Coulomb explosion, of highly excited neutral H atoms for strongly-driven hydrogen molecule. This process, where after the laser field is turned off, one electron escapes to the continuum while the other occupies a Rydberg state, was recently reported in an experimental study in Phys. Rev. Lett 102, 113002 (2009). We find that two-electron effects are important in order to correctly account for all pathways leading to highly excited neutral hydrogen formation [1]. We identify two pathways where the electron that escapes to the continuum does so either very quickly or after remaining bound for a few periods of the laser field. These two pathways of highly excited neutral H formation have distinct traces in the probability distribution of the escaping electron momentum components. [4pt] [1] A. Emmanouilidou, C. Lazarou, A. Staudte and U. Eichmann, Phys. Rev. A (Rapid) 85 011402 (2012).

Longitudinal Analysis of Early HIV-1-Specific Neutralizing Activity in an Elite Neutralizer and in Five Patients Who Developed Cross-Reactive Neutralizing Activity

PubMed Central

Euler, Zelda; van den Kerkhof, Tom L. G. M.; van Gils, Marit J.; Burger, Judith A.; Edo-Matas, Diana; Phung, Pham; Wrin, Terri

2012-01-01

We previously established that at 3 years postseroconversion, ∼30% of HIV-infected individuals have cross-reactive neutralizing activity (CrNA) in their sera. Here we studied the kinetics with which CrNA develops and how these relate to the development of autologous neutralizing activity as well as viral escape and diversification. For this purpose, sera from five individuals with CrNA and one elite neutralizer that were obtained at three monthly intervals in the first year after seroconversion and at multiple intervals over the disease course were tested for neutralizing activity against an established multiclade panel of six viruses. The same serum samples, as well as sera from three individuals who lacked CrNA, were tested for their neutralizing activities against autologous clonal HIV-1 variants from multiple time points covering the disease course from seroconversion onward. The elite neutralizer already had CrNA at 9.8 months postseroconversion, in contrast with the findings for the other five patients, in whom CrNA was first detected at 20 to 35 months postseroconversion and peaked around 35 months postseroconversion. In all patients, CrNA coincided with neutralizing activity against autologous viruses that were isolated <12 months postseroconversion, while viruses from later time points had already escaped autologous neutralizing activity. Also, the peak in gp160 sequence diversity coincided with the peak of CrNA titers. Individuals who lacked CrNA had lower peak autologous neutralizing titers, viral escape, and sequence diversity than individuals with CrNA. A better understanding of the underlying factors that determine the presence of CrNA or even an elite neutralizer phenotype may aid in the design of an HIV-1 vaccine. PMID:22156522

Generalized Jeans' Escape of Pick-Up Ions in Quasi-Linear Relaxation

NASA Technical Reports Server (NTRS)

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

2011-01-01

Jeans escape is a well-validated formulation of upper atmospheric escape that we have generalized to estimate plasma escape from ionospheres. It involves the computation of the parts of particle velocity space that are unbound by the gravitational potential at the exobase, followed by a calculation of the flux carried by such unbound particles as they escape from the potential well. To generalize this approach for ions, we superposed an electrostatic ambipolar potential and a centrifugal potential, for motions across and along a divergent magnetic field. We then considered how the presence of superthermal electrons, produced by precipitating auroral primary electrons, controls the ambipolar potential. We also showed that the centrifugal potential plays a small role in controlling the mass escape flux from the terrestrial ionosphere. We then applied the transverse ion velocity distribution produced when ions, picked up by supersonic (i.e., auroral) ionospheric convection, relax via quasi-linear diffusion, as estimated for cometary comas [1]. The results provide a theoretical basis for observed ion escape response to electromagnetic and kinetic energy sources. They also suggest that super-sonic but sub-Alfvenic flow, with ion pick-up, is a unique and important regime of ion-neutral coupling, in which plasma wave-particle interactions are driven by ion-neutral collisions at densities for which the collision frequency falls near or below the gyro-frequency. As another possible illustration of this process, the heliopause ribbon discovered by the IBEX mission involves interactions between the solar wind ions and the interstellar neutral gas, in a regime that may be analogous [2].

Estimating Collisionally-Induced Escape Rates of Light Neutrals from Early Mars

NASA Astrophysics Data System (ADS)

Gacesa, M.; Zahnle, K. J.

2016-12-01

Collisions of atmospheric gases with hot oxygen atoms constitute an important non-thermal mechanism of escape of light atomic and molecular species at Mars. In this study, we present revised theoretical estimates of non-thermal escape rates of neutral O, H, He, and H2 based on recent atmospheric density profiles obtained from the NASA Mars Atmosphere and Volatile Evolution (MAVEN) mission and related theoretical models. As primary sources of hot oxygen, we consider dissociative recombination of O2+ and CO2+ molecular ions. We also consider hot oxygen atoms energized in primary and secondary collisions with energetic neutral atoms (ENAs) produced in charge-exchange of solar wind H+ and He+ ions with atmospheric gases1,2. Scattering of hot oxygen and atmospheric species of interest is modeled using fully-quantum reactive scattering formalism3. This approach allows us to construct distributions of vibrationally and rotationally excited states and predict the products' emission spectra. In addition, we estimate formation rates of excited, translationally hot hydroxyl molecules in the upper atmosphere of Mars. The escape rates are calculated from the kinetic energy distributions of the reaction products using an enhanced 1D model of the atmosphere for a range of orbital and solar parameters. Finally, by considering different scenarios, we estimate the influence of these escape mechanisms on the evolution of Mars's atmosphere throughout previous epochs and their impact on the atmospheric D/H ratio. M.G.'s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Ames Research Center, administered by Universities Space Research Association under contract with NASA. 1N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere", Astroph. J., 790, 98 (2014) 2M. Gacesa, N. Lewkow, and V. Kharchenko, "Non-thermal production and escape of OH from the upper atmosphere of Mars", arXiv:1607.03602 (2016) 3M. Gacesa and V. Kharchenko, "Non-thermal escape of molecular hydrogen from Mars", Geophys. Res. Lett., 39, L10203 (2012).

Neutral ISM, Ly α , and Lyman-continuum in the Nearby Starburst Haro 11

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivera-Thorsen, T. Emil; Östlin, Göran; Hayes, Matthew

2017-03-01

Star-forming galaxies are believed to be a major source of Lyman continuum (LyC) radiation responsible for reionizing the early universe. Direct observations of escaping ionizing radiation have however been sparse and with low escape fractions. In the local universe, only 10 emitters have been observed, with typical escape fractions of a few percent. The mechanisms regulating this escape need to be strongly evolving with redshift in order to account for the epoch of reionization. Gas content and star formation feedback are among the main suspects, known to both regulate neutral gas coverage and evolve with cosmic time. In this paper,more » we reanalyze Hubble Space Telescope ( HST )-Cosmic Origins Spectrograph (COS) spectrocopy of the first detected local LyC leaker, Haro 11. We examine the connection between LyC leakage and Ly α line shape, and feedback-influenced neutral interstellar medium (ISM) properties like kinematics and gas distribution. We discuss the two extremes of an optically thin, density bounded ISM and a riddled, optically thick, ionization bounded ISM, and how Haro 11 fits into theoretical predictions. We find that the most likely ISM model is a clumpy neutral medium embedded in a highly ionized medium with a combined covering fraction of unity and a residual neutral gas column density in the ionized medium high enough to be optically thick to Ly α , but low enough to be at least partly transparent to LyC and undetected in Si ii. This suggests that star formation feedback and galaxy-scale interaction events play a major role in opening passageways for ionizing radiation through the neutral medium.« less

Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses

PubMed Central

Schein, Catherine H; Zhou, Bin; Braun, Werner

2005-01-01

Background Flaviviruses, which include Dengue (DV) and West Nile (WN), mutate in response to immune system pressure. Identifying escape mutants, variant progeny that replicate in the presence of neutralizing antibodies, is a common way to identify functionally important residues of viral proteins. However, the mutations typically occur at variable positions on the viral surface that are not essential for viral replication. Methods are needed to determine the true targets of the neutralizing antibodies. Results Stereophysicochemical variability plots (SVPs), 3-D images of protein structures colored according to variability, as determined by our PCPMer program, were used to visualize residues conserved in their physical chemical properties (PCPs) near escape mutant positions. The analysis showed 1) that escape mutations in the flavivirus envelope protein are variable residues by our criteria and 2) two escape mutants found at the same position in many flaviviruses sit above clusters of conserved residues from different regions of the linear sequence. Conservation patterns in T-cell epitopes in the NS3- protease suggest a similar mechanism of immune system evasion. Conclusion The SVPs add another dimension to structurally defining the binding sites of neutralizing antibodies. They provide a useful aid for determining antigenically important regions and designing vaccines. PMID:15845145

Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lingshu; Shi, Wei; Chappell, James D.

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ~35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specificmore » and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections. IMPORTANCEMERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using structurally defined probes for the MERS-CoV spike glycoprotein (S), the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized nonhuman primates (NHPs). MAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining MAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed MAbs. These data suggest that antibody responses to multiple domains on CoV spike protein may improve immunity and will guide future vaccine and therapeutic development efforts.« less

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.

Structural Basis of HCV Neutralization by Human Monoclonal Antibodies Resistant to Viral Neutralization Escape

PubMed Central

Krey, Thomas; Meola, Annalisa; Keck, Zhen-yong; Damier-Piolle, Laurence; Foung, Steven K. H.; Rey, Felix A.

2013-01-01

The high mutation rate of hepatitis C virus allows it to rapidly evade the humoral immune response. However, certain epitopes in the envelope glycoproteins cannot vary without compromising virus viability. Antibodies targeting these epitopes are resistant to viral escape from neutralization and understanding their binding-mode is important for vaccine design. Human monoclonal antibodies HC84-1 and HC84-27 target conformational epitopes overlapping the CD81 receptor-binding site, formed by segments aa434–446 and aa610–619 within the major HCV glycoprotein E2. No neutralization escape was yet observed for these antibodies. We report here the crystal structures of their Fab fragments in complex with a synthetic peptide comprising aa434–446. The structures show that the peptide adopts an α-helical conformation with the main contact residues F442 and Y443 forming a hydrophobic protrusion. The peptide retained its conformation in both complexes, independently of crystal packing, indicating that it reflects a surface feature of the folded glycoprotein that is exposed similarly on the virion. The same residues of E2 are also involved in interaction with CD81, suggesting that the cellular receptor binds the same surface feature and potential escape mutants critically compromise receptor binding. In summary, our results identify a critical structural motif at the E2 surface, which is essential for virus propagation and therefore represents an ideal candidate for structure-based immunogen design for vaccine development. PMID:23696737

Photochemical escape of oxygen from Mars: constraints from MAVEN in situ measurements

NASA Astrophysics Data System (ADS)

Lillis, R. J.; Deighan, J.; Fox, J. L.; Bougher, S. W.; Lee, Y.; Cravens, T.; Rahmati, A.; Mahaffy, P. R.; Andersson, L.; Combi, M. R.; Benna, M.; Jakosky, B. M.; Gröller, H.

2016-12-01

One of the primary goals of the MAVEN mission is to characterize rates of atmospheric escape from Mars at the present epoch and relate those escape rates to solar drivers. Photochemical escape of oxygen is expected to be a significant channel for atmospheric loss, particularly in the early solar system when extreme ultraviolet (EUV) fluxes were much higher. We use near-periapsis (<400 km altitude) data from three instruments. The Langmuir Probe and Waves (LPW) instrument measures electron density and temperature, the Suprathermal And Thermal Ion Composition (STATIC) experiment measures ion temperature and the Neutral Gas and Ion Mass Spectrometer (NGIMS) measures neutral and ion densities. For each profile of in situ measurements, we make a series of calculations, each as a function of altitude. The first uses electron and ion temperatures to calculate the probability distribution for initial energies of hot O atoms. The second calculates the probability that a hot atom born at that altitude will escape. The third takes calculates the production rate of the hot O atoms. We then multiply together the profiles of hot atom production and escape probability to get profiles of the production rate of escaping atoms. We integrate with respect to altitude to give us the escape flux of hot oxygen atoms for that periapsis pass. We will present escape fluxes and derived escape rates from the first Mars year of data collected. Total photochemical loss over time is not very useful to calculate from such escape fluxes derived from current conditions because a thicker atmosphere and much higher solar EUV in the past may change the dynamics of escape dramatically. In the future, we intend to use 3-D Monte Carlo models of global atmospheric escape, in concert with our in situ and remote measurements, to fully characterize photochemical escape under current conditions and carefully extrapolate back in time using further simulations with new boundary conditions.

Auroral zone effects on hydrogen geocorona structure and variability

NASA Technical Reports Server (NTRS)

Moore, T. E.; Biddle, A. P.; Waite, J. H., Jr.; Killeen, T. L.

1985-01-01

The effect of diurnal and magnetospheric modulations on the structure of the hydrogen geocorona is analyzed on the basis of recent observations. Particular attention is given to the enhancement of neutral escape by plasma effects, including the recently observed phenomenon of low-altitude ion acceleration. It is found that, while significant fluxes of neutral H should be produced by transverse ion acceleration in the auroral zone, the process is probably insufficient to account for the observed polar depletion of hydrogen atoms. Analysis of recent exospheric temperature measurements from the Dynamics Explorer-2 satellite suggest that neutral heating in and near the high latitude cusp may be the major contributor to depleted atomic hydrogen densities at high latitudes. Altitude profiles of the production rates for escaping neutral hydrogen atoms during periods of maximum, minimum, and typical solar activity are provided.

In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

PubMed

Aasa-Chapman, Marlén M I; Cheney, Kelly M; Hué, Stéphane; Forsman, Anna; O'Farrell, Stephen; Pellegrino, Pierre; Williams, Ian; McKnight, Áine

2011-01-01

The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies.

Antibody neutralization of retargeted measles viruses

PubMed Central

Lech, Patrycja J.; Pappoe, Roland; Nakamura, Takafumi; Tobin, Gregory J.; Nara, Peter L.; Russell, Stephen J.

2014-01-01

The measles virus (MV) vaccine lineage is a promising oncolytic but prior exposure to the measles vaccine or wild-type MV strains limits treatment utility due to the presence of anti-measles antibodies. MV entry can be redirected by displaying a polypeptide ligand on the Hemagglutinin (H) C-terminus. We hypothesized that retargeted MV would escape neutralization by monoclonal antibodies (mAbs) recognizing the H receptor-binding surface and be less susceptible to neutralization by human antisera. Using chimeric H proteins, with and without mutations that ablate MV receptor binding, we show that retargeted MVs escape mAbs that target the H receptor-binding surface by virtue of mutations that ablate infection via SLAM and CD46. However, C-terminally displayed domains do not mediate virus entry in the presence of human antibodies that bind to the underlying H domain. In conclusion, utility of retargeted oncolytic measles viruses does not extend to evasion of human serum neutralization. PMID:24725950

Interaction of reflected ions with the firehose marginally stable current sheet - Implications for plasma sheet convection

NASA Technical Reports Server (NTRS)

Pritchett, P. L.; Coroniti, F. V.

1992-01-01

The firehose marginally stable current sheet, which may model the flow away from the distant reconnection neutral line, assumes that the accelerated particles escape and never return to re-encounter the current region. This assumption fails on the earthward side where the accelerated ions mirror in the geomagnetic dipole field and return to the current sheet at distances up to about 30 R(E) down the tail. Two-dimensional particle simulations are used to demonstrate that the reflected ions drive a 'shock-like' structure in which the incoming flow is decelerated and the Bz field is highly compressed. These effects are similar to those produced by adiabatic choking of steady convection. Possible implications of this interaction for the dynamics of the tail are considered.

MAGNETIC FLUX CANCELATION AS THE TRIGGER OF SOLAR QUIET-REGION CORONAL JETS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panesar, Navdeep K.; Sterling, Alphonse C.; Moore, Ronald L.

We report observations of 10 random on-disk solar quiet-region coronal jets found in high-resolution extreme ultraviolet (EUV) images from the Solar Dynamics Observatory ( SDO )/Atmospheric Imaging Assembly and having good coverage in magnetograms from the SDO /Helioseismic and Magnetic Imager (HMI). Recent studies show that coronal jets are driven by the eruption of a small-scale filament (called a minifilament ). However, the trigger of these eruptions is still unknown. In the present study, we address the question: what leads to the jet-driving minifilament eruptions? The EUV observations show that there is a cool-transition-region-plasma minifilament present prior to each jetmore » event and the minifilament eruption drives the jet. By examining pre-jet evolutionary changes in the line of sight photospheric magnetic field, we observe that each pre-jet minifilament resides over the neutral line between majority-polarity and minority-polarity patches of magnetic flux. In each of the 10 cases, the opposite-polarity patches approach and merge with each other (flux reduction between 21% and 57%). After several hours, continuous flux cancelation at the neutral line apparently destabilizes the field holding the cool-plasma minifilament to erupt and undergo internal reconnection, and external reconnection with the surrounding coronal field. The external reconnection opens the minifilament field allowing the minifilament material to escape outward, forming part of the jet spire. Thus, we found that each of the 10 jets resulted from eruption of a minifilament following flux cancelation at the neutral line under the minifilament. These observations establish that magnetic flux cancelation is usually the trigger of quiet-region coronal jet eruptions.« less

Titan's gas and plasma torus

NASA Technical Reports Server (NTRS)

Eviatar, A.; Podolak, M.

1983-01-01

The implications of the Voyager observations for a steady state model of a torus of hydrogen and nitrogen neutral gas and plasma are assessed. Constraints are placed on the nitrogen neutral density, the neutral hydrogen and nitrogen escape fluxes (from Titan), and the diffusion rate in terms of observed or inferred quantities. The results obtained are consistent with the Voyager observations.

Neutral ISM, Lyα, and Lyman-continuum in the Nearby Starburst Haro11

NASA Astrophysics Data System (ADS)

Rivera-Thorsen, T. Emil; Östlin, Göran; Hayes, Matthew; Puschnig, Johannes

2017-03-01

Star-forming galaxies are believed to be a major source of Lyman continuum (LyC) radiation responsible for reionizing the early universe. Direct observations of escaping ionizing radiation have however been sparse and with low escape fractions. In the local universe, only 10 emitters have been observed, with typical escape fractions of a few percent. The mechanisms regulating this escape need to be strongly evolving with redshift in order to account for the epoch of reionization. Gas content and star formation feedback are among the main suspects, known to both regulate neutral gas coverage and evolve with cosmic time. In this paper, we reanalyze Hubble Space Telescope (HST)-Cosmic Origins Spectrograph (COS) spectrocopy of the first detected local LyC leaker, Haro 11. We examine the connection between LyC leakage and Lyα line shape, and feedback-influenced neutral interstellar medium (ISM) properties like kinematics and gas distribution. We discuss the two extremes of an optically thin, density bounded ISM and a riddled, optically thick, ionization bounded ISM, and how Haro 11 fits into theoretical predictions. We find that the most likely ISM model is a clumpy neutral medium embedded in a highly ionized medium with a combined covering fraction of unity and a residual neutral gas column density in the ionized medium high enough to be optically thick to Lyα, but low enough to be at least partly transparent to LyC and undetected in Si II. This suggests that star formation feedback and galaxy-scale interaction events play a major role in opening passageways for ionizing radiation through the neutral medium. Based on observations with HST-COS, program GO 13017, obtained from the Mikulski Archive for Space Telescopes (MAST). STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555. Support for MAST for non-HST data is provided by the NASA Office of Space Science via grant NNX09AF08G and by other grants and contracts.

Calculation of low-Z impurity pellet induced fluxes of charge exchange neutral particles escaping from magnetically confined toroidal plasmas.

PubMed

Goncharov, P R; Ozaki, T; Sudo, S; Tamura, N; Tolstikhina, I Yu; Sergeev, V Yu

2008-10-01

Measurements of energy- and time-resolved neutral hydrogen and helium fluxes from an impurity pellet ablation cloud, referred to as pellet charge exchange or PCX experiments, can be used to study local fast ion energy distributions in fusion plasmas. The estimation of the local distribution function f(i)(E) of fast ions entering the cloud requires knowledge of both the fraction F(0)(E) of incident ions exiting the cloud as neutral atoms and the attenuation factor A(E,rho) describing the loss of fast atoms in the plasma. Determination of A(E,rho), in turn, requires the total stopping cross section sigma(loss) of neutral atoms in the plasma and the Jacobian reflecting the measurement geometry and the magnetic surface shape. The obtained functions F(0)(E) and A(E,rho) enter multiplicatively into the probability density for escaping neutral particle kinetic energy. A general calculation scheme has been developed and realized as a FORTRAN code, which is to be applied for the calculation of f(i)(E) from PCX experimental results obtained with low-Z impurity pellets.

Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope.

PubMed

Tharakaraman, Kannan; Watanabe, Satoru; Chan, Kuan Rong; Huan, Jia; Subramanian, Vidya; Chionh, Yok Hian; Raguram, Aditya; Quinlan, Devin; McBee, Megan; Ong, Eugenia Z; Gan, Esther S; Tan, Hwee Cheng; Tyagi, Anu; Bhushan, Shashi; Lescar, Julien; Vasudevan, Subhash G; Ooi, Eng Eong; Sasisekharan, Ram

2018-05-09

Following the recent emergence of Zika virus (ZIKV), many murine and human neutralizing anti-ZIKV antibodies have been reported. Given the risk of virus escape mutants, engineering antibodies that target mutationally constrained epitopes with therapeutically relevant potencies can be valuable for combating future outbreaks. Here, we applied computational methods to engineer an antibody, ZAb_FLEP, that targets a highly networked and therefore mutationally constrained surface formed by the envelope protein dimer. ZAb_FLEP neutralized a breadth of ZIKV strains and protected mice in distinct in vivo models, including resolving vertical transmission and fetal mortality in infected pregnant mice. Serial passaging of ZIKV in the presence of ZAb_FLEP failed to generate viral escape mutants, suggesting that its epitope is indeed mutationally constrained. A single-particle cryo-EM reconstruction of the Fab-ZIKV complex validated the structural model and revealed insights into ZAb_FLEP's neutralization mechanism. ZAb_FLEP has potential as a therapeutic in future outbreaks. Copyright © 2018. Published by Elsevier Inc.

Antibody neutralization of retargeted measles viruses.

PubMed

Lech, Patrycja J; Pappoe, Roland; Nakamura, Takafumi; Tobin, Gregory J; Nara, Peter L; Russell, Stephen J

2014-04-01

The measles virus (MV) vaccine lineage is a promising oncolytic but prior exposure to the measles vaccine or wild-type MV strains limits treatment utility due to the presence of anti-measles antibodies. MV entry can be redirected by displaying a polypeptide ligand on the Hemagglutinin (H) C-terminus. We hypothesized that retargeted MV would escape neutralization by monoclonal antibodies (mAbs) recognizing the H receptor-binding surface and be less susceptible to neutralization by human antisera. Using chimeric H proteins, with and without mutations that ablate MV receptor binding, we show that retargeted MVs escape mAbs that target the H receptor-binding surface by virtue of mutations that ablate infection via SLAM and CD46. However, C-terminally displayed domains do not mediate virus entry in the presence of human antibodies that bind to the underlying H domain. In conclusion, utility of retargeted oncolytic measles viruses does not extend to evasion of human serum neutralization. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Comment on "A hydrogen-rich early Earth atmosphere".

PubMed

Catling, David C

2006-01-06

Tian et al. (Reports, 13 May 2005, p. 1014) proposed a hydrogen-rich early atmosphere with slow hydrogen escape from a cold thermosphere. However, their model neglects the ultraviolet absorption of all gases other than H2. The model also neglects Earth's magnetic field, which affects the temperature and density of ions and promotes nonthermal escape of neutral hydrogen.

Influenza virus resistance to human neutralizing antibodies.

PubMed

Crowe, James E

2012-01-01

The human antibody repertoire has an exceptionally large capacity to recognize new or changing antigens through combinatorial and junctional diversity established at the time of V(D)J recombination and through somatic hypermutation. Influenza viruses exhibit a relentless capacity to escape the human antibody response by altering the amino acids of their surface proteins in hypervariable domains that exhibit a high level of structural plasticity. Both parties in this high-stakes game of shape shifting drive structural evolution of their functional proteins (the B cell receptor/antibody on one side and the viral hemagglutinin and neuraminidase proteins on the other) using error-prone polymerase systems. It is likely that most of the genetic mutations that occur in these systems are deleterious, resulting in the failure of the B cell or virus with mutations to propagate in the immune repertoire or viral quasispecies. A subset of mutations is tolerated in functional surface proteins that enter the B cell or virus progeny pool. In both cases, selection occurs in the population of mutated and unmutated species. In cases where the functional avidity of the B cell receptor is increased significantly, that clone may be selected for preferential expansion. In contrast, an influenza virus that "escapes" the inhibitory effect of secreted antibodies may represent a high proportion of the progeny virus in that host. The recent paper by O'Donnell et al. [C. D. O'Donnell et al., mBio 3(3):e00120-12, 2012] identifies a mechanism for antibody resistance that does not require escape from binding but rather achieves a greater efficiency in replication.

An inter-residue network model to identify mutational-constrained regions on the Ebola coat glycoprotein

PubMed Central

Quinlan, Devin S.; Raman, Rahul; Tharakaraman, Kannan; Subramanian, Vidya; del Hierro, Gabriella; Sasisekharan, Ram

2017-01-01

Recently, progress has been made in the development of vaccines and monoclonal antibody cocktails that target the Ebola coat glycoprotein (GP). Based on the mutation rates for Ebola virus given its natural sequence evolution, these treatment strategies are likely to impose additional selection pressure to drive acquisition of mutations in GP that escape neutralization. Given the high degree of sequence conservation among GP of Ebola viruses, it would be challenging to determine the propensity of acquiring mutations in response to vaccine or treatment with one or a cocktail of monoclonal antibodies. In this study, we analyzed the mutability of each residue using an approach that captures the structural constraints on mutability based on the extent of its inter-residue interaction network within the three-dimensional structure of the trimeric GP. This analysis showed two distinct clusters of highly networked residues along the GP1-GP2 interface, part of which overlapped with epitope surfaces of known neutralizing antibodies. This network approach also permitted us to identify additional residues in the network of the known hotspot residues of different anti-Ebola antibodies that would impact antibody-epitope interactions. PMID:28397835

Substitution at aspartic acid 1128 in the SARS coronavirus spike glycoprotein mediates escape from a S2 domain-targeting neutralizing monoclonal antibody.

PubMed

Ng, Oi-Wing; Keng, Choong-Tat; Leung, Cynthia Sau-Wai; Peiris, J S Malik; Poon, Leo Lit Man; Tan, Yee-Joo

2014-01-01

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941-50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111-1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.

Antibody-Dependent Cell-Mediated Viral Inhibition Emerges after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys Coincident with gp140-Binding Antibodies and Is Effective against Neutralization-Resistant Viruses▿

PubMed Central

Asmal, Mohammed; Sun, Yue; Lane, Sophie; Yeh, Wendy; Schmidt, Stephen D.; Mascola, John R.; Letvin, Norman L.

2011-01-01

Antibody-dependent cell-mediated viral inhibition (ADCVI) is an attractive target for vaccination because it takes advantage of both the anamnestic properties of an adaptive immune response and the rapid early response characteristics of an innate immune response. Effective utilization of ADCVI in vaccine strategies will depend on an understanding of the natural history of ADCVI during acute and chronic human immunodeficiency virus type 1 (HIV-1) infection. We used the simian immunodeficiency virus (SIV)-infected rhesus monkey as a model to study the kinetics of ADCVI in early infection, the durability of ADCVI through the course of infection, and the effectiveness of ADCVI against viruses with envelope mutations that are known to confer escape from antibody neutralization. We demonstrate the development of ADCVI, capable of inhibiting viral replication 100-fold, within 3 weeks of infection, preceding the development of a comparable-titer neutralizing antibody response by weeks to months. The emergence of ADCVI was temporally associated with the emergence of gp140-binding antibodies, and in most animals, ADCVI persisted through the course of infection. Highly evolved viral envelopes from viruses isolated at late time points following infection that were resistant to plasma neutralization remained susceptible to ADCVI, suggesting that the epitope determinants of neutralization escape are not shared by antibodies that mediate ADCVI. These findings suggest that despite the ability of SIV to mutate and adapt to multiple immunologic pressures during the course of infection, SIV envelope may not escape the binding of autologous antibodies that mediate ADCVI. PMID:21450829

European SpaceCraft for the study of Atmospheric Particle Escape (ESCAPE): a planetary mission to Earth, proposed in response to the ESA M5-call

NASA Astrophysics Data System (ADS)

Dandouras, I.; Yamauchi, M.; Rème, H.; De Keyser, J.; Marghitu, O.; Fazakerley, A.; Grison, B.; Kistler, L.; Milillo, A.; Nakamura, R.; Paschalidis, N.; Paschalis, A.; Pinçon, J.-L.; Sakanoi, T.; Wieser, M.; Wurz, P.; Yoshikawa, I.; Häggström, I.; Liemohn, M.; Tian, F.

2017-09-01

ESCAPE is a mission proposed in response to the ESA-M5 call that will quantitatively estimate the amount of escaping particles of the major atmospheric components (nitrogen and oxygen), as neutral and ionised species, escaping from the Earth as a magnetised planet. The goal is to understand the importance of each escape mechanism, its dependence on solar and geomagnetic activity, and to infer the history of the Earth's atmospheric composition over a long (geological scale) time period. Since the solar EUV and solar wind conditions during solar maximum at present are comparable to the solar minimum conditions 1-2 billion years ago, the escaping amount and the isotope and N/O ratios should be obtained as a function of external forcing (solar and geomagnetic conditions) to allow a scaling to the past. The result will be used as a reference to understand the atmospheric/ionospheric evolution of magnetised planets, which is essential for habitability.

How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin.

PubMed

Doud, Michael B; Lee, Juhye M; Bloom, Jesse D

2018-04-11

Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin's receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin's stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.

Non-thermal escape rates of atmospheric H and D from Mars using MAVEN data

NASA Astrophysics Data System (ADS)

Gacesa, M.; Zahnle, K. J.

2017-12-01

Geological evidence suggests that an ocean of liquid water existed on Mars until at least middle to late Noachian era (4.1 to 3.8 Ga) and possibly, at least episodically, as late as Hesperian. Between 67% and 87% of the total primordial amount of water, equal to about 70 to 110 meters equivalent (spread over the entire Mars' surface), is believed to have escape to space, while about 35 meters remains on or beneath the surface as water ice. Establishing better constraints on these numbers and identifying the responsible atmospheric loss processes remains the major objective of NASA's Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. The ratio of atmospheric Deuterium and Hydrogen (D/H) on Mars is one of the best indicators of water loss to space. While majority of H and D escape through thermal Jeans escape, up to 10% of D can escape to space via non-thermal mechanisms, such as collisions with superthermal neutral atoms. In this study, we present new estimates of non-thermal escape rates of light molecules of interest to the water evolution, including H2, HD, OH, and OD, based on recent measurements of atmospheric density and temperature profiles by MAVEN. The escape mechanisms considered include photochemical sources of hot O, as well as collisions with energetic neutral atoms produced in charge-exchange of solar wind ions with atmospheric gases1,2. Energy transport and escape rates are modeled using quantum reactive scattering formalism3 and seasonal variations are illustrated. Finally, a simple estimate of the role of the non-thermal escape mechanisms in previous eras is given. We conclude that D escape rates can be affected by the non-thermal processes with consequences on the estimates of primordial water inventory based on the D/H ratio. [1] N. Lewkow and V. Kharchenko, Astroph. J., 790, 98 (2014) [2] M. Gacesa, N. Lewkow, V. Kharchenko, Icarus 284, 90 (2017) [3] M. Gacesa and V. Kharchenko, Geophys. Res. Lett., 39, L10203 (2012)

The OSS and Project SAFEHAVEN

DTIC Science & Technology

2000-01-01

would act to secretly transfer blocs of industrial and fiscal capital to neutral countries, thereby escaping confiscation and the reparations bill. 9...sensing, defeat, would act to transfer secretly blocs of industrial and fiscal capital to neu tral countries, thereby escaping confiscation and the...economic and fiscal lines of substance, SAFE- HAVEN brought out these differences in a forum in which they were incapable of resolution. Jockeying for

Dust escape from Io

NASA Astrophysics Data System (ADS)

Flandes, Alberto

2004-08-01

The Dust ballerina skirt is a set of well defined streams composed of nanometric sized dust particles that escape from the Jovian system and may be accelerated up to >=200 km/s. The source of this dust is Jupiter's moon Io, the most volcanically active body in the Solar system. The escape of dust grains from Jupiter requires first the escape of these grains from Io. This work is basically devoted to explain this escape given that the driving of dust particles to great heights and later injection into the ionosphere of Io may give the particles an equilibrium potential that allow the magnetic field to accelerate them away from Io. The grain sizes obtained through this study match very well to the values required for the particles to escape from the Jovian system.

Characterization of human monoclonal antibodies that neutralize multiple poliovirus serotypes.

PubMed

Puligedda, Rama Devudu; Kouiavskaia, Diana; Al-Saleem, Fetweh H; Kattala, Chandana Devi; Nabi, Usman; Yaqoob, Hamid; Bhagavathula, V Sandeep; Sharma, Rashmi; Chumakov, Konstantin; Dessain, Scott K

2017-10-04

Following the eradication of wild poliovirus (PV), achieving and maintaining a polio-free status will require eliminating potentially pathogenic PV strains derived from the oral attenuated vaccine. For this purpose, a combination of non-cross-resistant drugs, such as small molecules and neutralizing monoclonal antibodies (mAbs), may be ideal. We previously isolated chimpanzee and human mAbs capable of neutralizing multiple PV types (cross-neutralization). Here, we describe three additional human mAbs that neutralize types 1 and 2 PV and one mAb that neutralizes all three types. Most bind conformational epitopes and have unusually long heavy chain complementarity determining 3 domains (HC CDR3). We assessed the ability of the mAbs to neutralize A12 escape mutant PV strains, and found that the neutralizing activities of the mAbs were disrupted by different amino acid substitutions. Competitive binding studies further suggested that the specific mAb:PV interactions that enable cross-neutralization differ among mAbs and serotypes. All of the cloned mAbs bind PV in the vicinity of the "canyon", a circular depression around the 5-fold axis of symmetry through which PV recognizes its cellular receptor. We were unable to generate escape mutants to two of the mAbs, suggesting that their epitopes are important for the PV life cycle. These data indicate that PV cross-neutralization involves binding to highly conserved structures within the canyon that binds to the cellular receptor. These may be facilitated by the long HC CDR3 domains, which may adopt alternative binding configurations. We propose that the human and chimpanzee mAbs described here could have potential as anti-PV therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploring potential Pluto-generated neutral tori

NASA Astrophysics Data System (ADS)

Smith, Howard T.; Hill, Matthew; KollMann, Peter; McHutt, Ralph

2015-11-01

The NASA New Horizons mission to Pluto is providing unprecedented insight into this mysterious outer solar system body. Escaping molecular nitrogen is of particular interest and possibly analogous to similar features observed at moons of Saturn and Jupiter. Such escaping N2 has the potential of creating molecular nitrogen and N (as a result of molecular dissociation) tori or partial toroidal extended particle distributions. The presence of these features would present the first confirmation of an extended toroidal neutral feature on a planetary scale in our solar system. While escape velocities are anticipated to be lower than those at Enceladus, Io or even Europa, particle lifetimes are much longer in Pluto’s orbit because as a result of much weaker solar interaction processes along Pluto’s orbit (on the order of tens of years). Thus, with a ~248 year orbit, Pluto may in fact be generating an extended toroidal feature along it orbit.For this work, we modify and apply our 3-D Monte Carlo neutral torus model (previously used at Saturn, Jupiter and Mercury) to study/analyze the theoretical possibility and scope of potential Pluto-generated neutral tori. Our model injects weighted particles and tracks their trajectories under the influence of all gravitational fields with interactions with other particles, solar photons and Pluto collisions. We present anticipated N2 and N tori based on current estimates of source characterization and environmental conditions. We also present an analysis of sensitivity to assumed initial conditions. Such results can provide insight into the Pluto system as well as valuable interpretation of New Horizon’s observational data.

HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.

PubMed

Klein, Florian; Halper-Stromberg, Ariel; Horwitz, Joshua A; Gruell, Henning; Scheid, Johannes F; Bournazos, Stylianos; Mouquet, Hugo; Spatz, Linda A; Diskin, Ron; Abadir, Alexander; Zang, Trinity; Dorner, Marcus; Billerbeck, Eva; Labitt, Rachael N; Gaebler, Christian; Marcovecchio, Paola; Incesu, Reha-Baris; Eisenreich, Thomas R; Bieniasz, Paul D; Seaman, Michael S; Bjorkman, Pamela J; Ravetch, Jeffrey V; Ploss, Alexander; Nussenzweig, Michel C

2012-12-06

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy, the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.

THE LYMAN ALPHA REFERENCE SAMPLE. V. THE IMPACT OF NEUTRAL ISM KINEMATICS AND GEOMETRY ON Lyα ESCAPE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivera-Thorsen, Thøger E.; Hayes, Matthew; Östlin, Göran

2015-05-20

We present high-resolution far-UV spectroscopy of the 14 galaxies of the Lyα Reference Sample; a sample of strongly star-forming galaxies at low redshifts (0.028 < z < 0.18). We compare the derived properties to global properties derived from multi-band imaging and 21 cm H i interferometry and single-dish observations, as well as archival optical SDSS spectra. Besides the Lyα line, the spectra contain a number of metal absorption features allowing us to probe the kinematics of the neutral ISM and evaluate the optical depth and and covering fraction of the neutral medium as a function of line of sight velocity.more » Furthermore, we show how this, in combination with the precise determination of systemic velocity and good Lyα spectra, can be used to distinguish a model in which separate clumps together fully cover the background source, from the “picket fence” model named by Heckman et al. We find that no one single effect dominates in governing Lyα radiative transfer and escape. Lyα escape in our sample coincides with a maximum velocity-binned covering fraction of ≲0.9 and bulk outflow velocities of ≳50 km s{sup −1}, although a number of galaxies show these characteristics and yet little or no Lyα escape. We find that Lyα peak velocities, where available, are not consistent with a strong backscattered component, but rather with a simpler model of an intrinsic emission line overlaid by a blueshifted absorption profile from the outflowing wind. Finally, we find a strong anticorrelation between Hα equivalent width and maximum velocity-binned covering factor, and propose a heuristic explanatory model.« less

Two Regimes of Interaction of a Hot Jupiter’s Escaping Atmosphere with the Stellar Wind and Generation of Energized Atomic Hydrogen Corona

NASA Astrophysics Data System (ADS)

Shaikhislamov, I. F.; Khodachenko, M. L.; Lammer, H.; Kislyakova, K. G.; Fossati, L.; Johnstone, C. P.; Prokopov, P. A.; Berezutsky, A. G.; Zakharov, Yu. P.; Posukh, V. G.

2016-12-01

The interaction of escaping the upper atmosphere of a hydrogen-rich non-magnetized analog of HD 209458b with a stellar wind (SW) of its host G-type star at different orbital distances is simulated with a 2D axisymmetric multi-fluid hydrodynamic (HD) model. A realistic Sun-like spectrum of X-ray and ultraviolet radiation, which ionizes and heats the planetary atmosphere, together with hydrogen photochemistry, as well as stellar-planetary tidal interaction are taken into account to generate self-consistently an atmospheric HD outflow. Two different regimes of the planetary and SW interaction have been modeled. These are: (1) the “captured by the star” regime, when the tidal force and pressure gradient drive the planetary material beyond the Roche lobe toward the star, and (2) the “blown by the wind” regime, when sufficiently strong SW confines the escaping planetary atmosphere and channels it into the tail. The model simulates in detail the HD interaction between the planetary atoms, protons and the SW, as well as the production of energetic neutral atoms (ENAs) around the planet due to charge exchange between planetary atoms and stellar protons. The revealed location and shape of the ENA cloud, either as a paraboloid shell between the ionopause and bowshock (for the “blown by the wind” regime), or a turbulent layer at the contact boundary between the planetary stream and SW (for the “captured by the star” regime) are of importance for the interpretation of Lyα absorption features in exoplanetary transit spectra and characterization of the plasma environments.

DNA replication stress as a hallmark of cancer.

PubMed

Macheret, Morgane; Halazonetis, Thanos D

2015-01-01

Human cancers share properties referred to as hallmarks, among which sustained proliferation, escape from apoptosis, and genomic instability are the most pervasive. The sustained proliferation hallmark can be explained by mutations in oncogenes and tumor suppressors that regulate cell growth, whereas the escape from apoptosis hallmark can be explained by mutations in the TP53, ATM, or MDM2 genes. A model to explain the presence of the three hallmarks listed above, as well as the patterns of genomic instability observed in human cancers, proposes that the genes driving cell proliferation induce DNA replication stress, which, in turn, generates genomic instability and selects for escape from apoptosis. Here, we review the data that support this model, as well as the mechanisms by which oncogenes induce replication stress. Further, we argue that DNA replication stress should be considered as a hallmark of cancer because it likely drives cancer development and is very prevalent.

The Sodium Tail of the Moon

NASA Technical Reports Server (NTRS)

Matta, M.; Smith, S.; Baumgardner, J.; Wilson, J.; Martinis, C.; Mendillo, M.

2009-01-01

During the few days centered about new Moon, the lunar surface is optically hidden from Earth-based observers. However, the Moon still offers an observable: an extended sodium tail. The lunar sodium tail is the escaping "hot" component of a coma-like exosphere of sodium generated by photon-stimulated desorption, solar wind sputtering and meteoroid impact. Neutral sodium atoms escaping lunar gravity experience solar radiation pressure that drives them into the anti-solar direction forming a comet-like tail. During new Moon time, the geometry of the Sun, Moon and Earth is such that the anti-sunward sodium flux is perturbed by the terrestrial gravitational field resulting in its focusing into a dense core that extends beyond the Earth. An all-sky camera situated at the El Leoncito Observatory (CASLEO) in Argentina has been successfully imaging this tail through a sodium filter at each lunation since April 2006. This paper reports on the results of the brightness of the lunar sodium tail spanning 31 lunations between April 2006 and September 2008. Brightness variability trends are compared with both sporadic and shower meteor activity, solar wind proton energy flux and solar near ultra violet (NUV) patterns for possible correlations. Results suggest minimal variability in the brightness of the observed lunar sodium tail, generally uncorrelated with any single source, yet consistent with a multi-year period of minimal solar activity and non-intense meteoric fluxes.

Progress Toward an Neutral Yb Frequency Standard

NASA Astrophysics Data System (ADS)

Cramer, Claire; Hong, Tao; Nagourney, Warren; Fortson, Norval

2004-05-01

We report recent progress toward a direct observation of the ^1S_0^ -- ^3P0 clock transition at 578 nm in atomic Yb and review the experimental path to an optical frequency standard based on neutral Yb confined in a Stark-free optical lattice. Lamb-Dicke confinement in an optical lattice at the ``magic wavelength'' (λ _M) at which ground and excited state light shifts cancel will free the spectrum from Doppler and recoil shifts, providing an optimal environment for a clock consisting of an ensemble of cold, trapped atoms. In^171Yb the ^3P0 level has a hfs induced lifetime of 21 s. With this isotope in a Stark-free lattice at λ M ng 750 nm, perturbations to the clock energy levels can be held below the mHz level, providing an accuracy of a few parts in 10^18[1]. To observe the clock transition we use a shelving scheme that creates a leak in a MOT on the ^1S_0^ -- ^1P1 transition. A laser resonant with the clock transition drives atoms into the ^3P0 state, in which they can escape the MOT, leading to an observable decrease in MOT fluorescence. [1] S. Porsev and A. Derevianko, to be published in PRA

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

PubMed Central

Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

2015-01-01

ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as a result of increasing population immunity. We show that single amino acid substitutions near the receptor binding site were sufficient to escape from antibodies specific for A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified substitutions in A(H1N1)pdm09 viruses that support escape from population immunity but also suggested that the number of potential escape variants is limited by previous exposure to seasonal A(H1N1) viruses. PMID:25609810

Construction of a hepatitis B virus neutralizing chimeric monoclonal antibody recognizing escape mutants of the viral surface antigen (HBsAg).

PubMed

Golsaz-Shirazi, Forough; Amiri, Mohammad Mehdi; Farid, Samira; Bahadori, Motahareh; Bohne, Felix; Altstetter, Sebastian; Wolff, Lisa; Kazemi, Tohid; Khoshnoodi, Jalal; Hojjat-Farsangi, Mohammad; Chudy, Michael; Jeddi-Tehrani, Mahmood; Protzer, Ulrike; Shokri, Fazel

2017-08-01

Hepatitis B virus (HBV) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. Over 248 million patients are currently suffering from chronic HBV infection worldwide and annual mortality rate of this infection is 686000. The "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis B surface antigen (HBsAg), and antibodies against this region can neutralize the virus and are protective against all subtypes. We have recently generated a murine anti-HBs monoclonal antibody (4G4), which can neutralize HBV infection in HepaRG cells and recognize most of the escape mutant forms of HBsAg. Here, we describe the production and characterization of the chimeric human-murine antibody 4G4 (c-4G4). Variable region genes of heavy and light chains of the m-4G4 were cloned and fused to constant regions of human kappa and IgG1 by splice overlap extension (SOE) PCR. The chimeric antibody was expressed in Chinese Hamster Ovary (CHO)-K1 cells and purified from culture supernatant. Competition ELISA proved that both antibodies bind the same epitope within HBsAg. Antigen-binding studies using ELISA and Western blot showed that c-4G4 has retained the affinity and specificity of the parental murine antibody, and displayed a similar pattern of reactivity to 13 escape mutant forms of HBsAg. Both, the parental and c-4G4 showed a comparably high HBV neutralization capacity in cell culture even at the lowest concentration (0.6μg/ml). Due to the ability of c-4G4 to recognize most of the sub-genotypes and escape mutants of HBsAg, this antibody either alone or in combination with other anti-HBs antibodies could be considered as a potent alternative for Hepatitis B immune globulin (HBIG) as an HBV infection prophylactic or for passive immunotherapy against HBV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Energy Deposition and Escape Fluxes Induced by Energetic Solar Wind Ions and ENAs Precipitating into Mars Atmosphere: Accurate Consideration of Energy Transfer Collisions

NASA Astrophysics Data System (ADS)

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

2014-12-01

Formation and evolution of neutral fluxes of atoms and molecules escaping from the Mars atmosphere have been investigated for the sputtering and photo-chemical mechanisms. Energy and momentum transfer in collisions between the atmospheric gas and fast atoms and molecules have been considered using our recently obtained angular and energy dependent cross sections[1]. We have showed that accurate angular dependent collision cross sections are critical for the description of the energy relaxation of precipitating keV energetic ions/ENAs and for computations of altitude profiles of the fast atom and molecule production rates in recoil collisions. Upward and escape fluxes of the secondary energetic He and O atoms and H2, N2, CO and CO2 molecules, induced by precipitating ENAs, have been determined and their non-thermal energy distribution functions have been computed at different altitudes for different solar conditions. Precipitation and energy deposition of the energetic H2O molecules and products of their dissociations into the Mars atmosphere in the Comet C/2013 A1 (Siding Spring) - Mars interaction have been modeled using accurate cross sections. Reflection of precipitating ENAs by the Mars atmosphere has been analyzed in detail. [1] N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere, ApJ, v.790, p.98 (2014).

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewkow, N. R.; Kharchenko, V.

2014-08-01

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

Impact ionization study

NASA Technical Reports Server (NTRS)

Whipple, E. C., Jr.

1982-01-01

The impact ionization phenomenon which was observed on certain spacecraft was studied. The phenomenon occurs when a neutral atom, molecule, or ion strikes a surface with sufficient kinetic energy that either the incident neutral or atoms on the surface are ionized, with subsequent escape of ions and/or electrons. The released ions and electrons can interfere with measurements on the spacecraft by confusing interpretation of the data. On the other hand, there is the possibility that the effect could be developed into a diagnostic tool for investigating neutral atmospheric species or for studying physical processes on spacecraft surfaces.

Triton: topside ionosphere and nitrogen escape.

PubMed

Yung, Y L; Lyons, J R

1990-09-01

The principal ion in the ionosphere of Triton is N+. Energetic electrons of magnetospheric origin are the primary source of ionization, with a smaller contribution due to photoionization. To explain the topside plasma scale height, we postulate that N+ ions escape from Triton. The loss rate is 3.4 x 10(7) cm-2 s-1 or 7.9 x 10(24) ions s-1. Dissociative recombination of N2+ produces neutral exothermic fragments that can escape from Triton. The rate is estimated to be 8.6 x 10(6) N cm-2 s-1 or 2.0 x 10(24) atoms s-1. Implications for the magnetosphere of Neptune and Triton's evolution are discussed.

A Quantitative Quasispecies Theory-Based Model of Virus Escape Mutation Under Immune Selection

DTIC Science & Technology

2012-01-01

immune pressure, and their capacity for rapid escape mutation underlies many of the difficulties in combating pathogens, including HIV -1. In a typical...interpreted as the total number of virions within a finite sys- tem. The HIV -1 viral load during the acute infection phase can reach up to 104 ∼ 106...therefore models both the de- crease of the mean fitness away from WT and the distribution of neutral, deleterious, and beneficial mutants for a

Therapeutic and protective efficacy of a dengue antibody against Zika infection in rhesus monkeys.

PubMed

Abbink, Peter; Larocca, Rafael A; Dejnirattisai, Wanwisa; Peterson, Rebecca; Nkolola, Joseph P; Borducchi, Erica N; Supasa, Piyada; Mongkolsapaya, Juthathip; Screaton, Gavin R; Barouch, Dan H

2018-06-01

Strategies to treat Zika virus (ZIKV) infection in dengue virus (DENV)-endemic areas are urgently needed. Here we show that a DENV-specific antibody against the E-dimer epitope (EDE) potently cross-neutralizes ZIKV and provides robust therapeutic efficacy as well as prophylactic efficacy against ZIKV in rhesus monkeys. Viral escape was not detected, suggesting a relatively high bar to escape. These data demonstrate the potential for antibody-based therapy and prevention of ZIKV.

Emergent lineages of mumps virus suggest the need for a polyvalent vaccine.

PubMed

May, Meghan; Rieder, Courtney A; Rowe, Rebecca J

2018-01-01

Mumps outbreaks among vaccinated patients have become increasingly common in recent years. While there are multiple conditions driving this re-emergence, convention has suggested that these outbreaks are associated with waning immunity rather than vaccine escape. Molecular evidence from both the ongoing American and Dutch outbreaks in conjunction with recent structural biology studies challenge this convention, and suggest that emergent lineages of mumps virus exhibit key differences in antigenic epitopes from the vaccine strain employed: Jeryl-Lynn 5. The American and Dutch 2016-2017 outbreak lineages were examined using computational biology through the lens of diversity in immunogenic epitopes. Findings are discussed and the laboratory evidence indicating neutralization of heterologous mumps strains by serum from vaccinated individuals is reviewed. Taken together, it is concluded that the number of heterologous epitopes occurring in mumps virus in conjunction with waning immunity is facilitating small outbreaks in vaccinated patients, and that consideration of a polyvalent mumps vaccine is warranted. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Charge Exchange Contribution to the Decay of the Ring Current, Measured by Energetic Neutral Atoms (ENAs)

NASA Technical Reports Server (NTRS)

Jorgensen, A. M.; Henderson, M. G.; Roelof, E. C.; Reeves, G. D.; Spence, H. E.

2001-01-01

In this paper we calculate the contribution of charge exchange to the decay of the ring current. Past works have suggested that charge exchange of ring current protons is primarily responsible for the decay of the ring current during the late recovery phase, but there is still much debate about the fast decay of the early recovery phase. We use energetic neutral atom (ENA) measurements from Polar to calculate the total ENA energy escape. To get the total ENA escape we apply a forward modeling technique, and to estimate the total ring current energy escape we use the Dessler-Parker-Sckopke relationship. We find that during the late recovery phase of the March 10, 1998 storm ENAs with energies greater than 17.5 keV can account for 75% of the estimated energy loss from the ring current. During the fast recovery the measured ENAs can only account for a small portion of the total energy loss. We also find that the lifetime of the trapped ions is significantly shorter during the fast recovery phase than during the late recovery phase, suggesting that different processes are operating during the two phases.

Monte Carlo simulation of neutral-beam injection for mirror fusion reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Ronald Lee

1979-01-01

Computer simulation techniques using the Monte Carlo method have been developed for application to the modeling of neutral-beam intection into mirror-confined plasmas of interest to controlled thermonuclear research. The energetic (10 to 300 keV) neutral-beam particles interact with the target plasma (T i ~ 10 to 100 keV) through electron-atom and ion-atom collisional ionization as well as ion-atom charge-transfer (charge-exchange) collisions to give a fractional trapping of the neutral beam and a loss of charge-transfer-produced neutrals which escape to bombard the reactor first wall. Appropriate interaction cross sections for these processes are calculated for the assumed anisotropic, non-Maxwellian plasma ionmore » phase-space distributions.« less

Potent Autologous and Heterologous Neutralizing Antibody Responses Occur in HIV-2 Infection across a Broad Range of Infection Outcomes

PubMed Central

Aasa-Chapman, Marlén; Cotten, Matthew; Hué, Stéphane; Robinson, James; Bibollet-Ruche, Frederic; Sarge-Njie, Ramu; Berry, Neil; Jaye, Assan; Aaby, Peter; Whittle, Hilton; Rowland-Jones, Sarah; Weiss, Robin

2012-01-01

Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (n = 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC50], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC50s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection. PMID:22072758

Modelling the ionosphere of gas-giant exoplanets irradiated by low-mass stars

NASA Astrophysics Data System (ADS)

Chadney, J.; Galand, M.; Unruh, Y.; Koskinen, T.; Sanz-Forcada, J.

2015-10-01

The composition and structure of the upper atmosphere of Extrasolar Giant Planets (EGPs) are affected by the high-energy spectrum of the host star from soft X-rays to Extreme UltraViolet (EUV) (0.1-10 nm). This emission depends on the activity level of the star, which is primarily determined by its age [1]. In this study, we focus upon EGPs orbiting K- and M-dwarf stars of different ages. XUV spectra for these stars are constructed using a coronal model [2]. These spectra are used to drive both a thermospheric [3] and an ionospheric model, providing densities of neutral and ion species. Ionisation is included through photo-ionisation and electronimpact processes. The former is calculated by solving the Lambert-Beer law, while the latter is calculated from a supra-thermal electron transport model [4]. Planets orbiting far from the star are found to undergo Jeans escape, whereas close-orbiting planets undergo hydrodynamic escape. The critical orbital distance of transition between the two regimes is dependent on the level of stellar activity. We also find that EGP ionospheres at all orbital distances considered (0.1-1 AU) and around all stars selected (eps Eri, AD Leo, AU Mic) are dominated by the long-lived H+ ion. In addition, planets in the Jeans escape regime also have a layer in which H3 + is the major ion at the base of the ionosphere. For fast-rotating planets, densities of short-lived H3 + undergo significant diurnal variations, their peak value being determined by the stellar X-ray flux. In contrast, densities of longer-lived H+ show very little day/night variability and their value is determined by the level of stellar EUV flux. The H3 + peak in EGPs in the hydrodynamic escape regime under strong stellar illumination is pushed to altitudes below the homopause, where this ion is likely to be destroyed through reactions with heavy species (e.g., hydrocarbons, water). Infrared emissions from H3 + shall also be discussed, as well as the impact of stellar variability.

Charge exchange, ENAs and the loss of planetary ions at Mars

NASA Astrophysics Data System (ADS)

Kallio, E.; Janhunen, P.; Säles, T.

Neither Mars nor Venus has a strong global intrinsic magnetic field and therefore the solar wind can flow close to the planets in high neutral density regions. Because of the formed direct interaction between the atmosphere/exosphere and the solar wind, the ionized atmospheric neutrals can be picked up by the solar wind. Charge exchange between solar wind protons and planetary neutrals, instead, produce energetic neutral hydrogen atoms (H-ENA) which are the manifestation of the direct interaction between the solar wind and planetary neutrals. Picked-up planetary O+ ions in turn form energetic neutral oxygen atoms (O-ENA) via charge exchange process. The ion escape, H-ENAs, O-ENAs and electrons will be investigated at Mars and Venus by two identical instruments: ASPERA-3 on MarsExpress (measurements started in Jan. 2004) and ASPERA-4 on VenusExpress (2006). We present a self-consistent, three-dimensional quasi-neutral hybrid (ions are particles, electrons a fluid) simulation to study Mars/Venus-solar wind interaction in general and ASPERA-3/4 measurements in particular. Our model includes three ion species (H+, O+, O2+), and contains charge exchange, ion-neutral and chemical reactions. We show results of quasi-neutral hybrid model runs that we have used to study the escape of planetary ions, the effects of planetary ions on the Martian plasma environment and the production and properties of fast hydrogen(H) and oxygen(O) ENAs near Mars. We also compare these hydrogen ENA images with the hydrogen ENA images that has been derived from an empirical flow model by line-of-sight integration. The advantage of the analytical gas dynamic like flow model is that it is computationally so fast that it provides a possibility to perform an ENA inversion, that is, to derive global plasma parameters from the measured ENA image.

Enhanced Endosomal Escape by Light-Fueled Liquid-Metal Transformer.

PubMed

Lu, Yue; Lin, Yiliang; Chen, Zhaowei; Hu, Quanyin; Liu, Yang; Yu, Shuangjiang; Gao, Wei; Dickey, Michael D; Gu, Zhen

2017-04-12

Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.

Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation

PubMed Central

Donaldson, Eric F.; Corti, Davide; Swanstrom, Jesica; Debbink, Kari; Lanzavecchia, Antonio; Baric, Ralph S.

2012-01-01

Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009). NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd immunity is a driving force in norovirus molecular evolution. PMID:22615565

Effect of Surface Properties on Liposomal siRNA Delivery

PubMed Central

Xia, Yuqiong; Tian, Jie; Chen, Xiaoyuan

2015-01-01

Liposomes are one of the most widely investigated carriers for siRNA delivery. The surface properties of liposomal carriers, including the surface charge, PEGylation, and ligand modification can significantly affect the gene silencing efficiency. Three barriers of systemic siRNA delivery (long blood circulation, efficient tumor penetration and efficient cellular uptake/endosomal escape) are analyzed on liposomal carriers with different surface charges, PEGylations and ligand modifications. Cationic formulations dominate siRNA delivery and neutral formulations also have good performance while anionic formulations are generally not proper for siRNA delivery. The PEG dilemma (prolonged blood circulation vs. reduced cellular uptake/endosomal escape) and the side effect of repeated PEGylated formulation (accelerated blood clearance) were discussed. Effects of ligand modification on cationic and neutral formulations were analyzed. Finally, we summarized the achievements in liposomal siRNA delivery, outlined existing problems and provided some future perspectives. PMID:26695117

The Relation Between Death Attitude and Distress: Tolerance, Aggression, and Anger.

PubMed

Esnaashari, Fatemeh; Kargar, Flor Rezaei

2018-06-01

The aim of this research was to determine the relation between death attitude and distress tolerance and aggression and anger. For this, 135 subjects among 7,535 professional and specialist members of the Iran National Library were selected using convenience sampling method. They replied to Death Attitudes Profile-Revised, distress tolerance questionnaire, and aggression questionnaire. The results showed that the attitudes of approach acceptance, neutral acceptance, and escape acceptance had positive relation to distress tolerance and negative relation to aggression and anger while the attitudes of fear of death and death avoidance had negative relation to distress tolerance and positive relation to aggression and anger. Furthermore, all death attitudes predicted distress tolerance. But only the attitudes of approach acceptance, escape acceptance, fear of death, and death avoidance predicted aggression, and only approach acceptance, neutral acceptance, fear of death, and death avoidance predicted anger.

The mean free path of hydrogen ionizing photons during the epoch of reionization

NASA Astrophysics Data System (ADS)

Rahmati, Alireza; Schaye, Joop

2018-05-01

We use the Aurora radiation-hydrodynamical simulations to study the mean free path (MFP) for hydrogen ionizing photons during the epoch of reionization. We directly measure the MFP by averaging the distance 1 Ry photons travel before reaching an optical depth of unity along random lines-of-sight. During reionization the free paths tend to end in neutral gas with densities near the cosmic mean, while after reionization the end points tend to be overdense but highly ionized. Despite the increasing importance of discrete, over-dense systems, the cumulative contribution of systems with NHI ≲ 1016.5 cm-2 suffices to drive the MFP at z ≈ 6, while at earlier times higher column densities are more important. After reionization the typical size of HI systems is close to the local Jeans length, but during reionization it is much larger. The mean free path for photons originating close to galaxies, {MFP_{gal}}, is much smaller than the cosmic MFP. After reionization this enhancement can remain significant up to starting distances of ˜1 comoving Mpc. During reionization, however, {MFP_{gal}} for distances ˜102 - 103 comoving kpc typically exceeds the cosmic MFP. These findings have important consequences for models that interpret the intergalactic MFP as the distance escaped ionizing photons can travel from galaxies before being absorbed and may cause them to under-estimate the required escape fraction from galaxies, and/or the required emissivity of ionizing photons after reionization.

Applying antibody-sensitive hypervariable region 1-deleted hepatitis C virus to the study of escape pathways of neutralizing human monoclonal antibody AR5A

PubMed Central

Velázquez-Moctezuma, Rodrigo; Bukh, Jens

2017-01-01

Hepatitis C virus (HCV) is a major cause of end-stage liver diseases. With 3–4 million new HCV infections yearly, a vaccine is urgently needed. A better understanding of virus escape from neutralizing antibodies and their corresponding epitopes are important for this effort. However, for viral isolates with high antibody resistance, or antibodies with moderate potency, it remains challenging to induce escape mutations in vitro. Here, as proof-of-concept, we used antibody-sensitive HVR1-deleted (ΔHVR1) viruses to generate escape mutants for a human monoclonal antibody, AR5A, targeting a rare cross-genotype conserved epitope. By analyzing the genotype 1a envelope proteins (E1/E2) of recovered Core-NS2 recombinant H77/JFH1ΔHVR1 and performing reverse genetic studies we found that resistance to AR5A was caused by substitution L665W, also conferring resistance to the parental H77/JFH1. The mutation did not induce viral fitness loss, but abrogated AR5A binding to HCV particles and intracellular E1/E2 complexes. Culturing J6/JFH1ΔHVR1 (genotype 2a), for which fitness was decreased by L665W, with AR5A generated AR5A-resistant viruses with the substitutions I345V, L665S, and S680T, which we introduced into J6/JFH1 and J6/JFH1ΔHVR1. I345V increased fitness but had no effect on AR5A resistance. L665S impaired fitness and decreased AR5A sensitivity, while S680T combined with L665S compensated for fitness loss and decreased AR5A sensitivity even further. Interestingly, S680T alone had no fitness effect but sensitized the virus to AR5A. Of note, H77/JFH1L665S was non-viable. The resistance mutations did not affect cell-to-cell spread or E1/E2 interactions. Finally, introducing L665W, identified in genotype 1, into genotypes 2–6 parental and HVR1-deleted variants (not available for genotype 4a) we observed diverse effects on viral fitness and a universally pronounced reduction in AR5A sensitivity. Thus, we were able to take advantage of the neutralization-sensitive HVR1-deleted viruses to rapidly generate escape viruses aiding our understanding of the divergent escape pathways used by HCV to evade AR5A. PMID:28231271

Ion current in a magnetic neutral region - Generation of an incipient magnetopause

NASA Technical Reports Server (NTRS)

Whipple, E. C.; Silevitch, M. B.

1982-01-01

The current contributed by ions trapped in the vicinity of a magnetic X line is calculated. The three dimensional configuration of the neutral region is found to be critical in determining the current in that the escape mechanism and trapping times depend on the three-dimensional aspects. A trapping criterion is defined. In the neutral region the ions can gain substantial kinetic energy, and the current will change the X line configuration in such a way that there will be a positive feedback effect, rapidly forming an extended magnetopauselike structure for even very small incident plasma densities.

SOURCES AND SINKS OF NEUTRALS AND PLASMA IN THE SATURNIAN MAGNETOSPHERE (Invited)

NASA Astrophysics Data System (ADS)

Richardson, J. D.

2009-12-01

This talk will review current knowledge on the source and sinks of plasm and energy in Saturn's magnetosphere. Enceladus dominates the water group source, with most of the material escaping from the plume near the southern pole. The relatively low corotation energy in this region results in less energy being available to heat electrons. The electrons are too cold to ionize the neutrals and the inner magnetosphere is dominated by neutrals. In addition, Saturn's atmosphere is a large source of neutral H, the rings contribute O2, and Titan is a source whose magnitude is controversial. In the inner magnetosphere most particles and energy are removed as fast neutrals; transport is more important further out and may be dominated by fingers of inflow and outflow as at Jupiter.

Mars H Escape is potentially dominated by a high-altitude water source

NASA Astrophysics Data System (ADS)

Chaffin, Michael; Deighan, Justin; Schneider, Nick; Stewart, Ian

2017-04-01

H escape from the Mars atmosphere has removed a large part of Mars' initial water inventory. Until recently, this escape was thought to be slow and steady, sourced from long-lived molecular hydrogen whose lightness and volatility in comparison with water allow it to penetrate the upper atmosphere. Contradicting this thinking, observations from the Hubble Space Telescope and Mars Express, as well as more recent MAVEN measurements, indicate that H escape varies by at least a factor of ten over the Mars year and is largest in Southern Summer near perihelion. At the largest rates, H escape exceeds the ability of molecular hydrogen to supply the escape fluxes observed. At the same time in Southern Summer, Mars Express solar occultations have shown unexpectedly large concentrations of water at high altitude, potentially providing a source of escaping H unaccounted for in standard models. Here we show via photochemical modeling that the presence of this high altitude water can partially explain the large escape rates observed in Southern Summer. We further show that this escaping H is not in immediate balance with O escape, and therefore that short-term atmospheric dynamics can drive long-term variations in the oxidation balance and volatile content of planetary atmospheres. Future simultaneous observations by MAVEN, Mars Express, and the Trace Gas Orbiter may provide a direct test of this mechanism.

Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants

PubMed Central

Purtha, Whitney E.; Tedder, Thomas F.; Johnson, Syd

2011-01-01

Memory B cells (MBCs) and long-lived plasma cells (LLPCs) persist after clearance of infection, yet the specific and nonredundant role MBCs play in subsequent protection is unclear. After resolution of West Nile virus infection in mice, we demonstrate that LLPCs were specific for a single dominant neutralizing epitope, such that immune serum poorly inhibited a variant virus that encoded a mutation at this critical epitope. In contrast, a large fraction of MBC produced antibody that recognized both wild-type (WT) and mutant viral epitopes. Accordingly, antibody produced by the polyclonal pool of MBC neutralized WT and variant viruses equivalently. Remarkably, we also identified MBC clones that recognized the mutant epitope better than the WT protein, despite never having been exposed to the variant virus. The ability of MBCs to respond to variant viruses in vivo was confirmed by experiments in which MBCs were adoptively transferred or depleted before secondary challenge. Our data demonstrate that class-switched MBC can respond to variants of the original pathogen that escape neutralization of antibody produced by LLPC without a requirement for accumulating additional somatic mutations. PMID:22162833

Modeling Mercury

NASA Astrophysics Data System (ADS)

Burger, M. H.; Killen, R. M.; M, N.; Sarantos, M.; Crider, D. H.; Vervak, R. J.

2009-04-01

Mercury has a tenuous exosphere created by the combined effects of solar radiation and micrometeoroid bombardment on the surface and the interaction of the solar wind with Mercury's magnetic field and surface. Observations of this exosphere provide essential data necessary for understanding the composition and evolution of Mercury's surface, as well as the interaction between Mercury's magnetosphere with the solar wind. The sodium component of the exosphere has been well observed from the ground (see review by Killen et al., 2007). These observations have revealed a highly variable and inhomogeneous exosphere with emission often peaking in the polar regions. Radiation acceleration drives exospheric escape producing a sodium tail pointing away from the sun which has been detected up to 1400 Mercury radii from the planet (Potter et al. 2002; Baumgardner et al. 2008). Calcium has also been observed in Mercury's exosphere showing a distribution distinct from sodium, although also variable (Killen et al. 2005). During the first two encounters with Mercury by MESSENGER, observations of the exosphere were made by the UltraViolet and Visible Spectrometer (UVVS) channel of the Mercury Atmospheric and Surface Composition Spectrometer (MASCS). Sodium and calcium emission were detected during both flybys, and magnesium was detected for the first time in Mercury's exosphere during the second flyby. The spatial distributions of these species showed significant, unexpected differences which suggest differences in the mechanisms responsible for releasing them from the surface. We present a Monte-Carlo model of sodium, magnesium, and calcium in Mercury's exosphere. The important source mechanisms for ejecting these species from the surface are sputtering by solar wind ions, photon-stimulated desorption, and micrometeoroid impact vaporization. Thermal desorption on the dayside does not supply enough energy to significantly populate the exosphere, although it does play a role in redistributing volatiles over the surface. In addition, atomic calcium can be produced from the dissociation of Ca-bearing molecules, such as CaO, which can be formed in impact vapors. The primary loss processes are the escape of neutrals ejected with sufficient energy and photoionization. The former process is supplemented by radiation pressure which accelerates neutrals anti-sunward such that escaping neutrals form a tail pointing away from the sun. Because Mercury's heliocentric distance and radial velocity vary during its orbit, both loss processes are functions of Mercury's true anomaly. We also consider the spatial distribution of the surface source. Impact vaporization is roughly isotropic over the surface, although there may be a leading/trailing asymmetry in the impact rate due to Mercury's orbital motion. Sputtering is confined to regions where the solar wind can impact the surface, which is shielded somewhat by the internal magnetic field. The surface regions vulnerable depend on the solar wind conditions. References: Baumgardner et al., GRL, 35, L03201, 2008. Killen, R.M. et al., Space Sci. Rev. 132, 433-509, 2007. Killen, R.M. et al., Icarus, 173, 300-311, 2005. Potter et al., Meteoritics & Planetary Sci., 37, 1165, 2002.

Keep Away from Danger: Dangerous Objects in Dynamic and Static Situations

PubMed Central

Anelli, Filomena; Nicoletti, Roberto; Bolzani, Roberto; Borghi, Anna M.

2013-01-01

Behavioral and neuroscience studies have shown that objects observation evokes specific affordances (i.e., action possibilities) and motor responses. Recent findings provide evidence that even dangerous objects can modulate the motor system evoking aversive affordances. This sounds intriguing since so far the majority of behavioral, brain imaging, and transcranial magnetic stimulation studies with painful and dangerous stimuli strictly concerned the domain of pain, with the exception of evidence suggesting sensitivity to objects’ affordances when neutral objects are located in participants’ peripersonal space. This study investigates whether the observation of a neutral or dangerous object in a static or dynamic situation differently influences motor responses, and the time-course of the dangerous objects’ processing. In three experiments we manipulated: object dangerousness (neutral vs. dangerous); object category (artifact vs. natural); manual response typology (press vs. release a key); object presentation (Experiment 1: dynamic, Experiments 2 and 3: static); object movement direction (Experiment 1: away vs. toward the participant) or size (Experiments 2 and 3: big vs. normal vs. small). The task required participants to decide whether the object was an artifact or a natural object, by pressing or releasing one key. Results showed a facilitation for neutral over dangerous objects in the static situation, probably due to an affordance effect. Instead, in the dynamic condition responses were modulated by the object movement direction, with a dynamic affordance effect elicited by neutral objects and an escape-avoidance effect provoked by dangerous objects (neutral objects were processed faster when they moved toward-approached the participant, whereas dangerous objects were processed faster when they moved away from the participant). Moreover, static stimuli influenced the manual response typology. These data indicate the emergence of dynamic affordance and escaping-avoidance effects. PMID:23847512

Keep away from danger: dangerous objects in dynamic and static situations.

PubMed

Anelli, Filomena; Nicoletti, Roberto; Bolzani, Roberto; Borghi, Anna M

2013-01-01

Behavioral and neuroscience studies have shown that objects observation evokes specific affordances (i.e., action possibilities) and motor responses. Recent findings provide evidence that even dangerous objects can modulate the motor system evoking aversive affordances. This sounds intriguing since so far the majority of behavioral, brain imaging, and transcranial magnetic stimulation studies with painful and dangerous stimuli strictly concerned the domain of pain, with the exception of evidence suggesting sensitivity to objects' affordances when neutral objects are located in participants' peripersonal space. This study investigates whether the observation of a neutral or dangerous object in a static or dynamic situation differently influences motor responses, and the time-course of the dangerous objects' processing. In three experiments we manipulated: object dangerousness (neutral vs. dangerous); object category (artifact vs. natural); manual response typology (press vs. release a key); object presentation (Experiment 1: dynamic, Experiments 2 and 3: static); object movement direction (Experiment 1: away vs. toward the participant) or size (Experiments 2 and 3: big vs. normal vs. small). The task required participants to decide whether the object was an artifact or a natural object, by pressing or releasing one key. Results showed a facilitation for neutral over dangerous objects in the static situation, probably due to an affordance effect. Instead, in the dynamic condition responses were modulated by the object movement direction, with a dynamic affordance effect elicited by neutral objects and an escape-avoidance effect provoked by dangerous objects (neutral objects were processed faster when they moved toward-approached the participant, whereas dangerous objects were processed faster when they moved away from the participant). Moreover, static stimuli influenced the manual response typology. These data indicate the emergence of dynamic affordance and escaping-avoidance effects.

Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

PubMed Central

Asfor, Amin S.; Upadhyaya, Sasmita; Knowles, Nick J.; King, Donald P.; Paton, David J.

2014-01-01

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design. PMID:24584474

Analyzing the Signatures of High Red-shift Hydrogen: The Lyman Alpha and 21cm Emission Lines

NASA Astrophysics Data System (ADS)

Hansen, Matthew

Hydrogen line emission is an important window on galaxy formation due to the large abundance of neutral hydrogen in the early Universe. This dissertation comprises two theoretical/computational studies of two types of hydrogen line emission: Lyman alpha emission and escape from young stellar populations, and 21cm radiation from neutral hydrogen clouds at the time of the first luminous objects. The Lyman alpha research concerns the radiative transfer of resonant line radiation from a central source escaping from a multi-phase medium appropriate to young star forming regions. To analyze the properties of this novel radiative transfer problem I develop new theoretical formulations of the problem, substantiated by physically accurate monte carlo simulations of photon scattering and absorption through multi-phase gas geometries. I find that the escape fraction of resonant line photons from young star forming regions--ionized gas filled with neutral hydrogen clouds with low dust content--can exceed the continuum photon escape fraction by up to an order of magnitude. Additionally, I study the effect of gas outflow on the line profile of escaping resonant photons. In light of these results, I discuss why a young normal stellar populations surrounded by a clumpy multi-phase gas outflow can explain the Lyman alpha spectra seen from high red-shift Lyman Alpha Emitters (LAEs). The 21cm research concerns the ionization evolution of the Intergalactic Medium (IGM) during the era of the first luminous objects in the Universe. Large radio-array observatories are currently being built to specifically detect the red-shifted 21cm radiation from neutral hydrogen at red-shifts z ˜ 12 - - 6; the output will be three dimensional maps of ionized regions across the plane of the sky at various red-shift depths. The signal in the resulting ionization maps will be limited by observational noise, mainly from foreground galactic emission in radio frequencies. The research presented here is a unique approach to data mining the planned observational ionization map data. I develop the one-point statistics of the observed 21cm intensity appropriate for the IGM at high red-shifts using a mixture model technique. I show that physically interesting parameters of such mixture models, such as the total ionized gas fraction at a given red-shift slice, can be estimated by applying Maximum Likelihood Expectation to the mixture model of the observed 21cm intensity distribution. The confidence intervals on the expected model parameters are rigorously calculated, and applied to expected detection capabilities of the planned radio-array observatories. I find that at least one of the observatories, the Low Frequency Array (LOFAR), will be able to statistically detect the evolution of the total ionized gas fraction with good precision.

TIMING APPARATUS

DOEpatents

Bennett, A.E.; Geisow, J.C.H.

1956-04-17

The timing device comprises an escapement wheel and pallet, a spring drive to rotate the escapement wheel to a zero position, means to wind the pretensioned spring proportional to the desired signal time, and a cam mechanism to control an electrical signal switch by energizing the switch when the spring has been wound to the desired position, and deenergizing it when it reaches the zero position. This device produces an accurately timed signal variably witain the control of the operator.

Social Status-Dependent Shift in Neural Circuit Activation Affects Decision Making.

PubMed

Miller, Thomas H; Clements, Katie; Ahn, Sungwoo; Park, Choongseok; Hye Ji, Eoon; Issa, Fadi A

2017-02-22

In a social group, animals make behavioral decisions that fit their social ranks. These behavioral choices are dependent on the various social cues experienced during social interactions. In vertebrates, little is known of how social status affects the underlying neural mechanisms regulating decision-making circuits that drive competing behaviors. Here, we demonstrate that social status in zebrafish ( Danio rerio ) influences behavioral decisions by shifting the balance in neural circuit activation between two competing networks (escape and swim). We show that socially dominant animals enhance activation of the swim circuit. Conversely, social subordinates display a decreased activation of the swim circuit, but an enhanced activation of the escape circuit. In an effort to understand how social status mediates these effects, we constructed a neurocomputational model of the escape and swim circuits. The model replicates our findings and suggests that social status-related shift in circuit dynamics could be mediated by changes in the relative excitability of the escape and swim networks. Together, our results reveal that changes in the excitabilities of the Mauthner command neuron for escape and the inhibitory interneurons that regulate swimming provide a cellular mechanism for the nervous system to adapt to changes in social conditions by permitting the animal to select a socially appropriate behavioral response. SIGNIFICANCE STATEMENT Understanding how social factors influence nervous system function is of great importance. Using zebrafish as a model system, we demonstrate how social experience affects decision making to enable animals to produce socially appropriate behavior. Based on experimental evidence and computational modeling, we show that behavioral decisions reflect the interplay between competing neural circuits whose activation thresholds shift in accordance with social status. We demonstrate this through analysis of the behavior and neural circuit responses that drive escape and swim behaviors in fish. We show that socially subordinate animals favor escape over swimming, while socially dominants favor swimming over escape. We propose that these differences are mediated by shifts in relative circuit excitability. Copyright © 2017 the authors 0270-6474/17/372137-12$15.00/0.

Structure of Rotavirus Outer-Layer Protein VP7 Bound with a Neutralizing Fab

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aoki, Scott T.; Settembre, Ethan C.; Trask, Shane D.

2009-06-17

Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free calcium ions (Ca{sup 2+}) dissociates VP7 trimers into monomers, releasing VP7 from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure at 3.4 angstrom resolution of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which contains two Ca{sup 2+} sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab ismore » sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.« less

Wind Enhanced Escape, Ion Pickup and the Evolution of Water on Mars

NASA Technical Reports Server (NTRS)

Hartle, Richard

1999-01-01

Preferential loss of hydrogen over deuterium from Mars has produced a deuterium rich atmosphere possessing a D/B ratio 5.2 times that of terrestrial water. Rayleigh fractionation is applied, constrained by the deuterium enrichment factor, to determine the magnitudes of ancient and present water reservoirs on the planet. The dominant lose mechanisms of R and D from the current atmosphere are thought to be thermal escape and solar wind ion pickup of the neutral and ion forms of theme constituents, respectively. During an earlier martian epoch, only thermal escape was significant because Mars had a terrestrial sized magnetosphere that protected the atmosphere from solar wind scavenging processes. The magnitudes of present and ancient water reservoirs are estimated when thermal escape is considered alone and subsequently when the effects of ion pickup are added. The escape fluxes of R and D are significantly increased above the respective Jeans fluxes when the effects of thermospheric winds and planetary rotation are accounted for at the exobase. Such wind enhanced escape also increases as the mass of an escaping constituent increases; thus, the increase in the escape flux of D is greater than that of H. When the fractionation process is also constrained by the D/H ratio observed in hydrous minerals of SNC meteorites, an ancient crustal reservoir of Martian water in derived, tens of meters in global-equivalent depth, considerably exceeding that obtained with no winds. The reservoir becomes even larger when ion pickup processes are added.

European SpaceCraft for the study of Atmospheric Particle Escape (ESCAPE): a mission proposed in response to the ESA M5-call

NASA Astrophysics Data System (ADS)

Dandouras, Iannis; Yamauchi, Masatoshi; Rème, Henri; De Keyser, Johan; Marghitu, Octav; Fazakerley, Andrew; Grison, Benjamin; Kistler, Lynn; Milillo, Anna; Nakamura, Rumi; Paschalidis, Nikolaos; Paschalis, Antonis; Pinçon, Jean-Louis; Sakanoi, Takeshi; Wieser, Martin; Wurz, Peter; Yoshikawa, Ichiro; Häggström, Ingemar; Liemohn, Mike; Tian, Feng

2017-04-01

ESCAPE is a mission proposed in response to the ESA-M5 call that will quantitatively estimate the amount of escaping particles of the major atmospheric components (nitrogen and oxygen), as neutral and ionised species, escaping from the Earth as a magnetised planet. The spatial distribution and temporal variability of the flux of these species and their isotopic composition will be for the first time systematically investigated in an extended altitude range, from the exobase/upper ionosphere (500 km altitude) up to the magnetosphere. The goal is to understand the importance of each escape mechanism, its dependence on solar and geomagnetic activity, and to infer the history of the Earth's atmosphere over a long (geological scale) time period. Since the solar EUV and solar wind conditions during solar maximum at present are comparable to the solar minimum conditions 1-2 billion years ago, the escaping amount and the isotope and N/O ratios should be obtained as a function of external forcing (solar and geomagnetic conditions) to allow a scaling to the past. The result will be used as a reference to understand the atmospheric/ionospheric evolution of magnetised planets. To achieve this goal, a slowly spinning spacecraft is proposed equipped with a suite of instruments developed and supplied by an international consortium. These instruments will detect the upper atmosphere and magnetosphere escaping populations by a combination of in-situ measurements and of remote-sensing observations.

Composition and evolution of the atmosphere of Venus

NASA Technical Reports Server (NTRS)

Donahue, Thomas (Principal Investigator)

1996-01-01

The contract year started by analyzing Jovian atmospheric data acquired by the Galileo Probe Mass Spectrometer (GPMS). Two Venus hydrogen projects got underway as well. The first study strives to understand how to reconcile the standard treatment of the evolution of the H2O and HDO resevoirs on Venus over 4.5 Gyr in the presence of H and D escape and injection by comets. The second study is calculating the charge exchange contribution to hydrogen loss rates, using realistic models for exospheric H, H(+), D, D(+), and ion temperature from PV data. This report includes the following papers as attachments and supporting data: 'The Galileo Probe Mass Spectrometer: Composition of Jupiter's Atmosphere'; 'Chemical Composition Measurements of the Atmosphere of Jupiter with the Galileo Probe Mass Spectrometer'; 'Ion/Neutral Escape of Hydrogen and Deuterium: Evolution of Water'; 'Hydrogen and Deuterium in the Thermosphere of Venus: Solar Cycle Variations and Escape'; and 'Solar Cycle Variations in H(+) and D(+) Densities in the Venus Ionosphere: Implications for Escape'.

Examining the possibility of magnetic protection of Proxima b's atmosphere

NASA Astrophysics Data System (ADS)

Garcia-Sage, K.; Glocer, A.; Drake, J. J.; Gronoff, G.; Cohen, O.

2017-12-01

It is commonly believed that magnetic field provides protection of the planet's atmosphere from space weather effects. However, escape of the ionosphere along open magnetic field lines at the poles may under certain conditions be quite large and involve the escape of heavy ions like O+. The EUV spectrum of the star, in particular, produces ionization and heating that enhances escape. We calculate the field-aligned ionospheric escape for a reconstructed spectrum from Proxima Centauri. The EUV flux at the orbit of Proxima b is two orders of magnitude higher than at Earth. We model the resulting mass loss rates, assuming an Earth-like atmosphere and magnetic field. we also show uncertainties due to neutral atmospheric temperatures and polar cap size. We show that for high levels of stellar activity, the mass loss timescales for an Earth-like atmosphere are less than the age of the Proxima Centauri system, casting doubt on the idea that a magnetic field can protect a planet from space weather-driven atmospheric loss.

Does a threat appeal moderate reckless driving? A terror management theory perspective.

PubMed

Ben-Ari, O T; Florian, V; Mikulincer, M

2000-01-01

A series of two studies examined the effects of threat appeals on reckless driving from a terror management theory perspective. In both studies, all the participants (N = 109) reported on the relevance of driving to their self-esteem, and, then, half of them were exposed to a road trauma film and the remaining to a neutral film. In Study 1, the dependent variable was the self-report of intentions to drive recklessly in hypothetical scenarios. In Study 2, the dependent variable was actual behavior (driving speed) in a driving simulator. Findings indicated that a road trauma film led to less reported intentions of reckless driving, but to higher driving speed than a neutral film. These effects were only found among participants who perceived driving as relevant to their self-esteem. The discussion emphasized the self-enhancing mechanisms proposed by the terror management theory.

Analysis of Titan's neutral upper atmosphere from Cassini Ion Neutral Mass Spectrometer measurements in the Closed Source Neutral mode

NASA Astrophysics Data System (ADS)

Cui, Jun

In this thesis I present an in-depth study of the distribution of various neutral species in Titan's upper atmosphere, at altitudes between 950 and 1,500 km for abundant species (N 2 , CH 4 as well as their isotopes) and between 950 and 1,200 km for most minor species. However, the study of the H 2 distribution on Titan is extended to an altitude as high as 6,000 km in the exosphere. The analysis is based on a large sample of Cassini/INMS (Ion Neutral Mass Spectrometer) measurements in the CSN (Closed Source Neutral) mode, obtained during 15 close flybys of Titan. The densities of abundant species including N 2 , CH 4 and H 2 are determined directly from their main channels. However, to untangle the overlapping cracking patterns of minor species, the technique of Singular Value Decomposition (SVD) is used to determine simultaneously the densities of various hydrocarbons, nitriles and oxygen compounds. All minor species except for 40 Ar present density enhancements measured during the outbound legs. This can be interpreted as a result of wall effects, which could be either adsorption/desorption or heterogeneous surface chemistry on the chamber walls. In the thesis, I use a simple model to describe the observed time behavior of minor species. Results on their atmospheric abundances are provided both in terms of direct inbound measurements assuming ram pressure enhancement and values corrected for wall adsorption/desorption. Among all minor species of photochemical interest, the INMS data provide direct observational evidences for C 2 H 2 , C 2 H 4 , C 2 H 6 , CH 3 C 2 H, C 4 H 2 , C 6 H 6 , HC 3 N and C 2 N 2 in Titan's upper atmosphere. Upper limits are put for other minor species. The globally averaged distribution of N 2 , CH 4 and H 2 are each modeled with the diffusion approximation. The N 2 profile suggests an average thermospheric temperature of 154 K. The CH 4 and H 2 distribution constrains their fluxes to be 3.0 × 10 9 cm -2 s -1 and 1.3 × 10 10 cm -2 s -1 , referred to Titan's surface. The H 2 escape flux is about a factor of ~3 higher than the Jeans value, which is interpreted as enhanced thermal escape driven primarily by an upward conductive heat flux. Such a conclusion is based on kinetic model calculations in the 13-moment approximation that require energy continuity at the upper boundary. On the other hand, a proper interpretation of the observed CH 4 escape has to rely on the detailed nonthermal processes, which are still unknown at the present time. The INMS observations of the nitrogen isotope ratio implies 14 N/ 15 N=131.6 near Titan's surface. The profile of carbon isotope ratio combining INMS and GCMS results implies that both CH 4 and its isotope escape from Titan's exobase with roughly the same drift velocity, in contrast to the Jeans case which requires that CH 4 escapes with a much larger velocity due to its smaller mass. The INMS data also suggest horizontal/diurnal variations of temperature and neutral gas distribution in Titan's thermosphere. The equatorial regions, the ramside, as well as the nightside hemisphere of Titan appear to be warmer and present some evidences for the depletion of light species such as CH 4 . Meridional variations of most heavy species are also observed, with a trend of depletion toward the north pole. Though some of the above variations might be interpreted by either the solar-driven models or plasma-driven models, a physical scenario that reconciles all the observed horizontal/diurnal variations in a consistent way is still missing, With a careful evaluation of the effect of restricted sampling, some of the features shown in the INMS data are more likely to be observational biases.

Analysis of variola and vaccinia virus neutralization assays for smallpox vaccines.

PubMed

Hughes, Christine M; Newman, Frances K; Davidson, Whitni B; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Yan, Lihan; Frey, Sharon E; Belshe, Robert B; Karem, Kevin L; Damon, Inger K

2012-07-01

Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

Modeling the near-Earth interaction between ring current ions and exospheric neutrals: escape through energetic neutral atoms (ENAs)

NASA Astrophysics Data System (ADS)

LLera, K.; Goldstein, J.; McComas, D. J.; Valek, P. W.

2016-12-01

The two major loss processes for ring current decay are precipitation and energetic neutral atoms (ENAs). Since the exospheric neutral density increases with decreasing altitudes, precipitating ring current ions (reaching down to 200 - 800 km in altitude) also produce low-altitude ENA signatures that can be stronger than the ring current emission at equatorial distances ( 2 - 9 Re). The higher density results in multiple collisions between the ring current ions and exospheric oxygen. The affect on hydrogen ions is the focus of this study. Since the H particle sustains energy loss ( 36 eV) at each neutralizing or re-ionizing interaction, the escaped ENAs do not directly reflect the ring current properties. We model the energy loss due to multiple charge exchange and electron stripping interactions of 1 - 100 keV precipitating ring current ions undergo before emerging as low-altitude ENAs. The H particle is either an ion or an ENA throughout the simulation. Their lifetime is analytically determined by the length of one mean free path. We track the ion state with Lorentz motion while the ENA travels ballistically across the geomagnetic field. Our simulations show the energy loss is greater than 20% for hydrogen ring current ions below 30 keV (60 keV for the simulations that wander equatorward). This is the first quantification of the energy loss associated with the creation of low-altitude ENAs. Our model (currently constrained in the meridional plane) has revealed characteristics on how precipitation is affected by the near-Earth neutral exosphere. This ion-neutral interaction removes particles from the loss cone but promotes loss through ENA generation. These findings should be implemented in models predicting the ring current decay and used as an analysis tool to reconstruct the ring current population from observed low-altitude ENAs.

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

DOE PAGES

Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.; ...

2015-09-09

The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

Energetic neutral particles from Jupiter and Saturn

NASA Astrophysics Data System (ADS)

Cheng, A. F.

1986-04-01

The Voyager 1 spacecraft has detected energetic neutral particles escaping from the magnetospheres of Jupiter and Saturn. These energetic neutrals are created in charge exchange reactions between radiation belt ions and ambient atoms or molecules in the magnetosphere. If the Io torus is assumed to be the dominant Jovian source region for energetic neutrals, the Voyager observations can be used to infer upper limits to the average ion intensities there below about 200 keV. No readily interpretable in-situ measurements are available in the Io torus at these energies. The middle and outer Jovian magnetospheres may also be a significant source of energetic neutrals. At Saturn, the observed neutral particle count rates are too high to be explained by charge exchange between fast protons and H atoms of the Titan torus. Most of the energetic neutrals may be produced by charge exchanges between heavy ions and a neutral cloud containing H2O in Saturn's inner magnetosphere. If so, the Voyager measurements of energetic neutral fluxes would be the first detected emissions from this region of Saturn's magnetosphere.

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

PubMed Central

Wu, Xueling; Parast, Adam B.; Richardson, Barbra A.; Nduati, Ruth; John-Stewart, Grace; Mbori-Ngacha, Dorothy; Rainwater, Stephanie M. J.; Overbaugh, Julie

2006-01-01

Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies biz, 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission. PMID:16378985

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.

The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

The Lyman Alpha Reference Sample. V. The Impact of Neutral ISM Kinematics and Geometry on Lyα Escape

NASA Astrophysics Data System (ADS)

Rivera-Thorsen, Thøger E.; Hayes, Matthew; Östlin, Göran; Duval, Florent; Orlitová, Ivana; Verhamme, Anne; Mas-Hesse, J. Miguel; Schaerer, Daniel; Cannon, John M.; Otí-Floranes, Héctor; Sandberg, Andreas; Guaita, Lucia; Adamo, Angela; Atek, Hakim; Herenz, E. Christian; Kunth, Daniel; Laursen, Peter; Melinder, Jens

2015-05-01

We present high-resolution far-UV spectroscopy of the 14 galaxies of the Lyα Reference Sample; a sample of strongly star-forming galaxies at low redshifts (0.028 < z < 0.18). We compare the derived properties to global properties derived from multi-band imaging and 21 cm H i interferometry and single-dish observations, as well as archival optical SDSS spectra. Besides the Lyα line, the spectra contain a number of metal absorption features allowing us to probe the kinematics of the neutral ISM and evaluate the optical depth and and covering fraction of the neutral medium as a function of line of sight velocity. Furthermore, we show how this, in combination with the precise determination of systemic velocity and good Lyα spectra, can be used to distinguish a model in which separate clumps together fully cover the background source, from the “picket fence” model named by Heckman et al. We find that no one single effect dominates in governing Lyα radiative transfer and escape. Lyα escape in our sample coincides with a maximum velocity-binned covering fraction of ≲0.9 and bulk outflow velocities of ≳50 km s-1, although a number of galaxies show these characteristics and yet little or no Lyα escape. We find that Lyα peak velocities, where available, are not consistent with a strong backscattered component, but rather with a simpler model of an intrinsic emission line overlaid by a blueshifted absorption profile from the outflowing wind. Finally, we find a strong anticorrelation between Hα equivalent width and maximum velocity-binned covering factor, and propose a heuristic explanatory model. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with programs GO 11522, GO 11727, GO 12027, and GO 12583.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaikhislamov, I. F.; Prokopov, P. A.; Berezutsky, A. G.

The interaction of escaping the upper atmosphere of a hydrogen-rich non-magnetized analog of HD 209458b with a stellar wind (SW) of its host G-type star at different orbital distances is simulated with a 2D axisymmetric multi-fluid hydrodynamic (HD) model. A realistic Sun-like spectrum of X-ray and ultraviolet radiation, which ionizes and heats the planetary atmosphere, together with hydrogen photochemistry, as well as stellar-planetary tidal interaction are taken into account to generate self-consistently an atmospheric HD outflow. Two different regimes of the planetary and SW interaction have been modeled. These are: (1) the “ captured by the star ” regime, whenmore » the tidal force and pressure gradient drive the planetary material beyond the Roche lobe toward the star, and (2) the “ blown by the wind ” regime, when sufficiently strong SW confines the escaping planetary atmosphere and channels it into the tail. The model simulates in detail the HD interaction between the planetary atoms, protons and the SW, as well as the production of energetic neutral atoms (ENAs) around the planet due to charge exchange between planetary atoms and stellar protons. The revealed location and shape of the ENA cloud, either as a paraboloid shell between the ionopause and bowshock (for the “ blown by the wind ” regime), or a turbulent layer at the contact boundary between the planetary stream and SW (for the “ captured by the star ” regime) are of importance for the interpretation of Ly α absorption features in exoplanetary transit spectra and characterization of the plasma environments.« less

Spatial Distribution of Io's Neutral Oxygen Cloud Observed by Hisaki

NASA Astrophysics Data System (ADS)

Koga, Ryoichi; Tsuchiya, Fuminori; Kagitani, Masato; Sakanoi, Takeshi; Yoneda, Mizuki; Yoshioka, Kazuo; Yoshikawa, Ichiro; Kimura, Tomoki; Murakami, Go; Yamazaki, Atsushi; Smith, H. Todd; Bagenal, Fran

2018-05-01

We report on the spatial distribution of a neutral oxygen cloud surrounding Jupiter's moon Io and along Io's orbit observed by the Hisaki satellite. Atomic oxygen and sulfur in Io's atmosphere escape from the exosphere mainly through atmospheric sputtering. Some of the neutral atoms escape from Io's gravitational sphere and form neutral clouds around Jupiter. The extreme ultraviolet spectrograph called EXCEED (Extreme Ultraviolet Spectroscope for Exospheric Dynamics) installed on the Japan Aerospace Exploration Agency's Hisaki satellite observed the Io plasma torus continuously in 2014-2015, and we derived the spatial distribution of atomic oxygen emissions at 130.4 nm. The results show that Io's oxygen cloud is composed of two regions, namely, a dense region near Io and a diffuse region with a longitudinally homogeneous distribution along Io's orbit. The dense region mainly extends on the leading side of Io and inside of Io's orbit. The emissions spread out to 7.6 Jupiter radii (RJ). Based on Hisaki observations, we estimated the radial distribution of the atomic oxygen number density and oxygen ion source rate. The peak atomic oxygen number density is 80 cm-3, which is spread 1.2 RJ in the north-south direction. We found more oxygen atoms inside Io's orbit than a previous study. We estimated the total oxygen ion source rate to be 410 kg/s, which is consistent with the value derived from a previous study that used a physical chemistry model based on Hisaki observations of ultraviolet emission ions in the Io plasma torus.

The Neutral Gas and Ion Mass Spectrometer on the Mars Atmosphere and Volatile Evolution Mission

NASA Technical Reports Server (NTRS)

Mahaffy, Paul R.; Benna, Mehdi; King, Todd; Harpold, Daniel N.; Arvey, Robert; Barciniak, Michael; Bendt, Mirl; Carrigan, Daniel; Errigo, Therese; Holmes, Vincent;

Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs.

PubMed

Kosik, Ivan; Ince, William L; Gentles, Lauren E; Oler, Andrew J; Kosikova, Martina; Angel, Matthew; Magadán, Javier G; Xie, Hang; Brooke, Christopher B; Yewdell, Jonathan W

2018-01-01

Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies. Antibody-free propagation following antigenic escape rapidly selected viruses with mutations that modulated receptor binding avidity through the addition of N-linked glycans to the HA globular domain. These findings expand our understanding of the viral mechanisms that maintain fitness during antigenic evolution to include glycan addition, and highlight the immense power of high-definition virus population sequencing to reveal novel viral adaptive mechanisms.

Methane in the lunar exosphere: Implications for solar wind carbon escape

NASA Astrophysics Data System (ADS)

Hodges, R. Richard

2016-07-01

A positive identification of methane in the lunar exosphere has been made in data from the neutral mass spectrometer on the Lunar Atmosphere and Dust Environment Explorer (LADEE) spacecraft. Like argon-40, methane is adsorbed on the lunar surface during nighttime. However, higher activation energies for methane delay its desorption at sunrise by about an hour local time, creating a postsunrise bulge with peak concentration of approximately 400-450 molecules cm-3 at a reference altitude of 12 km, which is just above the highest topographic feature on the Moon. The rate of escape of carbon as methane derived from the LADEE data is estimated to be in the range 1.5-4.5 × 1021 s-1. A lower bound for solar carbon escape derived separately from Apollo sample analyses is 3.4 × 1021 s-1.

Specific features of measuring the isotopic composition of hydrogen ions in ITER plasma by using neutral particle diagnostics under neutral beam injection conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Afanasyev, V. I.; Goncharov, P. R., E-mail: p.goncharov@spbstu.ru; Mironov, M. I.

2015-12-15

Results of numerical simulation of signals from neutral particle analyzers under injection of the heating and diagnostic neutral beams in different operating modes of the ITER tokamak are presented. The distribution functions of fast ions in plasma are simulated, and the corresponding neutral particle fluxes escaping from the plasma along the line of sight of the analyzers are calculated. It is shown that the injection of heating deuterium (D{sup 0}) beams results in the appearance of an intense background signal hampering measurements of the ratio between the densities of deuterium and tritium fuel ions in plasma in the thermal energymore » range. The injection of a diagnostic hydrogen (H{sup 0}) beam does not affect measurements owing to the high mass resolution of the analyzers.« less

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

DOE PAGES

Rocha, Cheila; Calado, Rita; Borrego, Pedro; ...

2013-10-24

Background: therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4 + T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected atmore » birth. As a result, CD4 + T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4 + T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Finally, our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.« less

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocha, Cheila; Calado, Rita; Borrego, Pedro

Background: therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4 + T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected atmore » birth. As a result, CD4 + T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4 + T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Finally, our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.« less

Neutral escape at Mars induced by the precipitation of high-energy protons and hydrogen atoms of the solar wind origin

NASA Astrophysics Data System (ADS)

Shematovich, Valery I.

2017-04-01

One of the first surprises of the NASA MAVEN mission was the observation by the SWIA instrument of a tenuous population of protons with solar wind energies travelling anti-sunward near periapsis, at altitudes of 150-250 km (Halekas et al., 2015). While the penetration of solar wind protons to low altitude is not completely unexpected given previous Mars Express results, this population maintains exactly the same velocity as the solar wind observed. From previous studies it was known that some fraction of the solar wind can interact with the extended corona of Mars. By charge exchange with the neutral particles in this corona, some fraction of the incoming solar wind protons can gain an electron and become an energetic neutral hydrogen atom. Once neutral, these particles penetrate through the Martian induced magnetosphere with ease, with free access to the collisional atmosphere/ionosphere. The origin, kinetics and transport of the suprathermal O atoms in the transition region (from thermosphere to exosphere) of the Martian upper atmosphere due to the precipitation of the high-energy protons and hydrogen atoms are discussed. Kinetic energy distribution functions of suprathermal and superthermal (ENA) oxygen atoms formed in the Martian upper atmosphere were calculated using the kinetic Monte Carlo model (Shematovich et al., 2011, Shematovich, 2013) of the high-energy proton and hydrogen atom precipitation into the atmosphere. These functions allowed us: (a) to estimate the non-thermal escape rates of neutral oxygen from the Martian upper atmosphere, and (b) to compare with available MAVEN measurements of oxygen corona. Induced by precipitation the escape of hot oxygen atoms may become dominant under conditions of extreme solar events - solar flares and coronal mass ejections, - as it was shown by recent observations of the NASA MAVEN spacecraft (Jakosky et al., 2015). This work is supported by the RFBR project and by the Basic Research Program of the Praesidium of the Russian Academy of Sciences (Program 1.7). References Shematovich, Solar System Res., 2013, v.47, 437. Shematovich et al., J. Geophys. Res., 2011, v.116, A11320. Halekas et al., Geophys. Res. Lett., 2015, v. 42. doi:10.1002/2015GL064781. Jakosky et al., Science, 2015, v. 350, Issue 6261, aad0210:1-7.

Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate

PubMed Central

Keck, Zhen-yong; Xia, Jinming; Wang, Yong; Wang, Wenyan; Krey, Thomas; Prentoe, Jannick; Carlsen, Thomas; Li, Angela Ying-Jian; Patel, Arvind H.; Lemon, Stanley M.; Bukh, Jens; Rey, Felix A.; Foung, Steven K. H.

2012-01-01

The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1–6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1–6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418–446 and aa611–616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434–446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410–425. The isolation of four HC-84 HMAbs binding to the peptide, aa434–446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus. PMID:22511875

Antigenic Drift Defines a New D4 Subgenotype of Measles Virus.

PubMed

Muñoz-Alía, Miguel Ángel; Muller, Claude P; Russell, Stephen J

2017-06-01

The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes. IMPORTANCE Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope (NE). The subgenotype D4.2 viruses have a higher predominance in countries with intermediary levels of vaccine coverage. Our studies demonstrate that subgenotype D4.2 lacks epitopes associated with half of the known antigenic sites, which significantly impacts our understanding of measles virus evolution. Copyright © 2017 American Society for Microbiology.

Antigenic Drift Defines a New D4 Subgenotype of Measles Virus

PubMed Central

Muller, Claude P.

2017-01-01

ABSTRACT The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes. IMPORTANCE Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope (NE). The subgenotype D4.2 viruses have a higher predominance in countries with intermediary levels of vaccine coverage. Our studies demonstrate that subgenotype D4.2 lacks epitopes associated with half of the known antigenic sites, which significantly impacts our understanding of measles virus evolution. PMID:28356529

An atomic and molecular fluid model for efficient edge-plasma transport simulations at high densities

NASA Astrophysics Data System (ADS)

Rognlien, Thomas; Rensink, Marvin

2016-10-01

Transport simulations for the edge plasma of tokamaks and other magnetic fusion devices requires the coupling of plasma and recycling or injected neutral gas. There are various neutral models used for this purpose, e.g., atomic fluid model, a Monte Carlo particle models, transition/escape probability methods, and semi-analytic models. While the Monte Carlo method is generally viewed as the most accurate, it is time consuming, which becomes even more demanding for device simulations of high densities and size typical of fusion power plants because the neutral collisional mean-free path becomes very small. Here we examine the behavior of an extended fluid neutral model for hydrogen that includes both atoms and molecules, which easily includes nonlinear neutral-neutral collision effects. In addition to the strong charge-exchange between hydrogen atoms and ions, elastic scattering is included among all species. Comparisons are made with the DEGAS 2 Monte Carlo code. Work performed for U.S. DoE by LLNL under Contract DE-AC52-07NA27344.

Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses

PubMed Central

Tabor, Kathryn M.; Bergeron, Sadie A.; Horstick, Eric J.; Jordan, Diana C.; Aho, Vilma; Porkka-Heiskanen, Tarja; Haspel, Gal

2014-01-01

Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish. PMID:24848468

The Escaping Upper Atmospheres of Hot Jupiters

NASA Astrophysics Data System (ADS)

Davidson, Eric; Jones, Gabrielle; Uribe, Ana; Carson, Joseph

2017-01-01

Hot Jupiters are massive gaseous planets which orbit closely to their parent star. The strong stellar irradiation at these small orbital separations causes the temperature of the upper atmosphere of the planet to rise. This can cause the planet's atmosphere to escape into space, creating an exoplanet outflow. We ascertained which factors determine the presence and structure of these outflows by creating one dimensional simulations of the density, pressure, velocity, optical depth, and neutral fraction of hot Jupiter atmospheres. This was done for planets of masses and radii ranging from 0.5-1.5 Mj and 0.5-1.5 Rj. We found the outflow rate to be highest for a planet of 0.5 Mj and 1.5 Rj at 5.3×10-14 Mj/Yr. We also found that the higher the escape velocity, the lower the chance of the planet having an outflow.

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.

PubMed

Moody, M Anthony; Gao, Feng; Gurley, Thaddeus C; Amos, Joshua D; Kumar, Amit; Hora, Bhavna; Marshall, Dawn J; Whitesides, John F; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey E; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Finzi, Andrés; Vandergrift, Nathan A; Alam, S Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia D; Kamanga, Gift; Cohen, Myron S; Sam, Noel E; Kapiga, Saidi; Gray, Elin S; Tumba, Nancy L; Morris, Lynn; Zolla-Pazner, Susan; Gorny, Miroslaw K; Mascola, John R; Hahn, Beatrice H; Shaw, George M; Sodroski, Joseph G; Liao, Hua-Xin; Montefiori, David C; Hraber, Peter T; Korber, Bette T; Haynes, Barton F

2015-09-09

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses. Copyright © 2015 Elsevier Inc. All rights reserved.

Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys.

PubMed

Oswald, Wendelien B; Geisbert, Thomas W; Davis, Kelly J; Geisbert, Joan B; Sullivan, Nancy J; Jahrling, Peter B; Parren, Paul W H I; Burton, Dennis R

2007-01-01

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.

Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains.

PubMed

Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B; Harrison, Stephen C

2014-07-15

Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus-antibody "arms race." Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus-antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule.

Photochemical escape of oxygen from Mars: First results from MAVEN in situ data

NASA Astrophysics Data System (ADS)

Lillis, Robert J.; Deighan, Justin; Fox, Jane L.; Bougher, Stephen W.; Lee, Yuni; Combi, Michael R.; Cravens, Thomas E.; Rahmati, Ali; Mahaffy, Paul R.; Benna, Mehdi; Elrod, Meredith K.; McFadden, James P.; Ergun, Robert. E.; Andersson, Laila; Fowler, Christopher M.; Jakosky, Bruce M.; Thiemann, Ed; Eparvier, Frank; Halekas, Jasper S.; Leblanc, François; Chaufray, Jean-Yves

2017-03-01

Photochemical escape of atomic oxygen is thought to be one of the dominant channels for Martian atmospheric loss today and played a potentially major role in climate evolution. Mars Atmosphere and Volatile Evolution Mission (MAVEN) is the first mission capable of measuring, in situ, the relevant quantities necessary to calculate photochemical escape fluxes. We utilize 18 months of data from three MAVEN instruments: Langmuir Probe and Waves, Neutral Gas and Ion Mass Spectrometer, and SupraThermal And Thermal Ion Composition. From these data, we calculate altitude profiles of the production rate of hot oxygen atoms from the dissociative recombination of O2+ and the probability that such atoms will escape the Mars atmosphere. From this, we determine escape fluxes for 815 periapsis passes. Derived average dayside hot O escape rates range from 1.2 to 5.5 × 1025 s-1, depending on season and EUV flux, consistent with several pre-MAVEN predictions and in broad agreement with estimates made with other MAVEN measurements. Hot O escape fluxes do not vary significantly with dayside solar zenith angle or crustal magnetic field strength but depend on CO2 photoionization frequency with a power law whose exponent is 2.6 ± 0.6, an unexpectedly high value which may be partially due to seasonal and geographic sampling. From this dependence and historical EUV measurements over 70 years, we estimate a modern-era average escape rate of 4.3 × 1025 s-1. Extrapolating this dependence to early solar system, EUV conditions gives total losses of 13, 49, 189, and 483 mbar of oxygen over 1-3 and 3.5 Gyr, respectively, with uncertainties significantly increasing with time in the past.

Multi-species analysis of ion distributions at Mars

NASA Astrophysics Data System (ADS)

Curry, S.; Liemohn, M. W.; Fang, X.; Ma, Y.; Johnson, B.; Bougher, S. W.; Dong, C.

2012-12-01

This study focuses on using the Mars Test Particle simulation to compare observations with virtual detections of O+, O2+, CO2+, and H+ in an orbital configuration in the Mars space environment. These planetary pick-up ions are formed when the solar wind directly interacts with the neutral atmosphere, causing the ions to be accelerated by the background convective electric field. The subsequent mass loading and ion escape are still the subject of great interest, specifically with respect to which species dominates ion loss from Mars. Modeling efforts and observations have found different results; some conclude that O+ is the most dominant escaping ion while others conclude that O2+ has the larger total loss rate. Furthermore, mass loss might actually favor CO2+ because of its tri-atomic structure. To address this unresolved issue, this study will present velocity space distributions for different species and discuss fluxes and escape rates using different modeling parameters. The simulation will also illustrate individual particle traces, which reveal the origin and trajectories of the different ion species. Finally, results from different solar conditions will be presented with respect to ion fluxes and energies as well as overall escape in order to robustly describe the physical processes controlling planetary ion distributions and atmospheric escape.

Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierce, Brian G.; Boucher, Elisabeth N.; Piepenbrink, Kurt H.

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, asmore » well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines. IMPORTANCEHepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that is the target of broadly neutralizing antibodies.In vivoresults in mice indicated that these antigens elicited epitope-specific neutralizing antibodies, with various degrees of potency and breadth. These promising results suggest that a rational design approach can be used to generate an effective vaccine for this virus.« less

Noise-induced phase space transport in two-dimensional Hamiltonian systems.

PubMed

Pogorelov, I V; Kandrup, H E

1999-08-01

First passage time experiments were used to explore the effects of low amplitude noise as a source of accelerated phase space diffusion in two-dimensional Hamiltonian systems, and these effects were then compared with the effects of periodic driving. The objective was to quantify and understand the manner in which "sticky" chaotic orbits that, in the absence of perturbations, are confined near regular islands for very long times, can become "unstuck" much more quickly when subjected to even very weak perturbations. For both noise and periodic driving, the typical escape time scales logarithmically with the amplitude of the perturbation. For white noise, the details seem unimportant: Additive and multiplicative noise typically have very similar effects, and the presence or absence of a friction related to the noise by a fluctuation-dissipation theorem is also largely irrelevant. Allowing for colored noise can significantly decrease the efficacy of the perturbation, but only when the autocorrelation time, which vanishes for white noise, becomes so large that there is little power at frequencies comparable to the natural frequencies of the unperturbed orbit. Similarly, periodic driving is relatively inefficient when the driving frequency is not comparable to these natural frequencies. This suggests that noise-induced extrinsic diffusion, like modulational diffusion associated with periodic driving, is a resonance phenomenon. The logarithmic dependence of the escape time on amplitude reflects the fact that the time required for perturbed and unperturbed orbits to diverge a given distance scales logarithmically in the amplitude of the perturbation.

Multiplexed screening of natural humoral immunity identifies antibodies at fine specificity for complex and dynamic viral targets.

PubMed

McCutcheon, Krista M; Gray, Julia; Chen, Natalie Y; Liu, Keyi; Park, Minha; Ellsworth, Stote; Tripp, Ralph A; Tompkins, S Mark; Johnson, Scott K; Samet, Shelly; Pereira, Lenore; Kauvar, Lawrence M

2014-01-01

Viral entry targets with therapeutic neutralizing potential are subject to multiple escape mechanisms, including antigenic drift, immune dominance of functionally irrelevant epitopes, and subtle variations in host cell mechanisms. A surprising finding of recent years is that potent neutralizing antibodies to viral epitopes independent of strain exist, but are poorly represented across the diverse human population. Identifying these antibodies and understanding the biology mediating the specific immune response is thus difficult. An effective strategy for meeting this challenge is to incorporate multiplexed antigen screening into a high throughput survey of the memory B cell repertoire from immune individuals. We used this approach to discover suites of cross-clade antibodies directed to conformational epitopes in the stalk region of the influenza A hemagglutinin (HA) protein and to select high-affinity anti-peptide antibodies to the glycoprotein B (gB) of human cytomegalovirus. In each case, our screens revealed a restricted VH and VL germline usage, including published and previously unidentified gene families. The in vivo evolution of paratope specificity with optimal neutralizing activity was understandable after correlating biological activities with kinetic binding and epitope recognition. Iterative feedback between antigen probe design based on structure and function information with high throughput multiplexed screening demonstrated a generally applicable strategy for efficient identification of safe, native, finely tuned antibodies with the potential for high genetic barriers to viral escape.

Virtual driving and risk taking: do racing games increase risk-taking cognitions, affect, and behaviors?

PubMed

Fischer, Peter; Kubitzki, Jörg; Guter, Stephanie; Frey, Dieter

2007-03-01

Research has consistently shown that aggressive video console and PC games elicit aggressive cognitions, affect, and behaviors. Despite the increasing popularity of racing (driving) games, nothing is known about the psychological impact of this genre. This study investigated whether playing racing games affects cognitions, affect, and behaviors that can promote risk taking in actual road traffic situations. In Study 1, the authors found that the frequency of playing racing games was positively associated with competitive driving, obtrusive driving, and car accidents; a negative association with cautious driving was observed. To determine cause and effect, in Study 2, the authors manipulated whether participants played 1 of 3 racing games or 1 of 3 neutral games. Participants who played a racing game subsequently reported a higher accessibility of cognitions and affect positively associated with risk taking than did participants who played a neutral game. Finally, on a more behavioral level, in Study 3, the authors found that men who played a racing game subsequently took higher risks in computer-simulated critical road traffic situations than did men who played a neutral game. Theoretical and practical implications are discussed. ((c) 2007 APA, all rights reserved).

XUV-Exposed, Non-Hydrostatic Hydrogen-Rich Upper Atmospheres of Terrestrial Planets. Part II: Hydrogen Coronae and Ion Escape

PubMed Central

Lammer, Helmut; Holmström, Mats; Panchenko, Mykhaylo; Odert, Petra; Erkaev, Nikolai V.; Leitzinger, Martin; Khodachenko, Maxim L.; Kulikov, Yuri N.; Güdel, Manuel; Hanslmeier, Arnold

2013-01-01

Abstract We studied the interactions between the stellar wind plasma flow of a typical M star, such as GJ 436, and the hydrogen-rich upper atmosphere of an Earth-like planet and a “super-Earth” with a radius of 2 REarth and a mass of 10 MEarth, located within the habitable zone at ∼0.24 AU. We investigated the formation of extended atomic hydrogen coronae under the influences of the stellar XUV flux (soft X-rays and EUV), stellar wind density and velocity, shape of a planetary obstacle (e.g., magnetosphere, ionopause), and the loss of planetary pickup ions on the evolution of hydrogen-dominated upper atmospheres. Stellar XUV fluxes that are 1, 10, 50, and 100 times higher compared to that of the present-day Sun were considered, and the formation of high-energy neutral hydrogen clouds around the planets due to the charge-exchange reaction under various stellar conditions was modeled. Charge-exchange between stellar wind protons with planetary hydrogen atoms, and photoionization, lead to the production of initially cold ions of planetary origin. We found that the ion production rates for the studied planets can vary over a wide range, from ∼1.0×1025 s−1 to ∼5.3×1030 s−1, depending on the stellar wind conditions and the assumed XUV exposure of the upper atmosphere. Our findings indicate that most likely the majority of these planetary ions are picked up by the stellar wind and lost from the planet. Finally, we estimated the long-time nonthermal ion pickup escape for the studied planets and compared them with the thermal escape. According to our estimates, nonthermal escape of picked-up ionized hydrogen atoms over a planet's lifetime within the habitable zone of an M dwarf varies between ∼0.4 Earth ocean equivalent amounts of hydrogen (EOH) to <3 EOH and usually is several times smaller in comparison to the thermal atmospheric escape rates. Key Words: Stellar activity—Low-mass stars—Early atmospheres—Earth-like exoplanets—Energetic neutral atoms—Ion escape—Habitability. Astrobiology 13, 1030–1048. PMID:24283926

INMS Titan Observations

NASA Astrophysics Data System (ADS)

Waite, J. H., Jr.; Niemann, H.; Yelle, R. V.; Kasprzak, W. T.; Cravens, T. E.; Luhmann, J. G.; McNutt, R. L.; Ip, W.-H.; De La Haye, V.; Ledvina, S.; Mueller-Wordarg, I.; Borggren, N.

2005-08-01

The Ion Neutral Mass Spectrometer (INMS) aboard the Cassini Orbiter has obtained the first in situ composition measurements of the neutral densities of molecular nitrogen, methane, hydrogen, argon, and a host of stable carbon-nitrile ion and neutral compounds in the first and sixth flybys of Titan. The bulk composition and thermal structure of the moon's upper atmosphere appear to vary with latitude and local time. The new data set provides strong evidence for atmospheric waves in the upper atmosphere and for the existence of a warm, chemically complex corona. Furthermore, the data set provides direct measurements of isotopes of nitrogen, carbon, and argon, which reveal interesting clues about the evolution of the atmosphere. The atmosphere likely formed from outgassing as planetesimals composed of silicates, water ice, clathrates of methane, and ammonia hydrates coalesced. Subsequent photochemistry and/or shock-induced chemistry likely converted the atmospheric nitrogen into molecular nitrogen, which is inferred by the absence (<0.6 ppm) of 36Ar in the INMS data. (Ice clathrate delivery of N2 would have presumably also delivered 36Ar to the proto Titan.) The decrease of the 14N to 15N isotopic ratio with respect to the terrestrial value allows us to suggest an early atmosphere >1.5 to 100 times more substantial that was lost via escape over the intervening 4.5 billion years. Carbon in the form of methane has continued to outgas over time from the interior (as inferred from the elevated 12C to 13C ratio as compared to terrestrial values) with much of its subsequent photolysis products being deposited in the form of complex hydrocarbons on the surface ( 5 x 1027 s-1 as estimated from the H2 escape rate of 6.1 ± 0.2 x 109 cm-2 s-1 measured by INMS). This talk will highlight the composition, vertical structure, wave processes, and escape of Titan's atmosphere.

Numerical Simulations of Turbulent Molecular Clouds Regulated by Radiation Feedback Forces. II. Radiation-Gas Interactions and Outflows

NASA Astrophysics Data System (ADS)

Raskutti, Sudhir; Ostriker, Eve C.; Skinner, M. Aaron

2017-12-01

Momentum deposition by radiation pressure from young, massive stars may help to destroy molecular clouds and unbind stellar clusters by driving large-scale outflows. We extend our previous numerical radiation hydrodynamic study of turbulent star-forming clouds to analyze the detailed interaction between non-ionizing UV radiation and the cloud material. Our simulations trace the evolution of gas and star particles through self-gravitating collapse, star formation, and cloud destruction via radiation-driven outflows. These models are idealized in that we include only radiation feedback and adopt an isothermal equation of state. Turbulence creates a structure of dense filaments and large holes through which radiation escapes, such that only ˜50% of the radiation is (cumulatively) absorbed by the end of star formation. The surface density distribution of gas by mass as seen by the central cluster is roughly lognormal with {σ }{ln{{Σ }}}=1.3{--}1.7, similar to the externally projected surface density distribution. This allows low surface density regions to be driven outwards to nearly 10 times their initial escape speed {v}{esc}. Although the velocity distribution of outflows is broadened by the lognormal surface density distribution, the overall efficiency of momentum injection to the gas cloud is reduced because much of the radiation escapes. The mean outflow velocity is approximately twice the escape speed from the initial cloud radius. Our results are also informative for understanding galactic-scale wind driving by radiation, in particular, the relationship between velocity and surface density for individual outflow structures and the resulting velocity and mass distributions arising from turbulent sources.

Compact Starburst Galaxies with Fast Outflows: Spatially Resolved Stellar Mass Profiles

NASA Astrophysics Data System (ADS)

Gottlieb, Sophia; Diamond-Stanic, Aleksandar; Lipscomb, Charles; Ohene, Senyo; Rines, Josh; Moustakas, John; Sell, Paul; Tremonti, Christy; Coil, Alison; Rudnick, Gregory; Hickox, Ryan C.; Geach, James; Kepley, Amanda

2018-01-01

Powerful galactic winds driven by stellar feedback and black hole accretion are thought to play an important role in regulating star formation in galaxies. In particular, strong stellar feedback from supernovae, stellar winds, radiation pressure, and cosmic rays is required by simulations of star-forming galaxies to prevent the vast majority of baryons from cooling and collapsing to form stars. However, it remains unclear whether these stellar processes play a significant role in expelling gas and shutting down star formation in massive progenitors of quiescent galaxies. What are the limits of stellar feedback? We present multi-band photometry with HST/WFC3 (F475W, F814W, F160W) for a dozen compact starburst galaxies at z~0.6 with half-light radii that suggest incredibly large central escape velocities. These massive galaxies are driving fast (>1000 km/s) outflows that have been previously attributed to stellar feedback associated with the compact (r~100 pc) starburst. But how compact is the stellar mass? In the context of the stellar feedback hypothesis, it is unclear whether these fast outflows are being driven at velocities comparable to the escape velocity of an incredibly dense stellar system (as predicted by some models of radiation-pressure winds) or at velocities that exceed the central escape velocity by large factor. Our spatially resolved measurements with HST show that the stellar mass is more extended than the light, and this requires that the physical mechanism responsible for driving the winds must be able to launch gas at velocities that are factors of 5-10 beyond the central escape velocity.

Reactor refueling containment system

DOEpatents

Gillett, J.E.; Meuschke, R.E.

1995-05-02

A method of refueling a nuclear reactor is disclosed whereby the drive mechanism is disengaged and removed by activating a jacking mechanism that raises the closure head. The area between the barrier plate and closure head is exhausted through the closure head penetrations. The closure head, upper drive mechanism, and bellows seal are lifted away and transported to a safe area. The barrier plate acts as the primary boundary and each drive and control rod penetration has an elastomer seal preventing excessive tritium gases from escaping. The individual instrumentation plugs are disengaged allowing the corresponding fuel assembly to be sealed and replaced. 2 figs.

Reactor refueling containment system

DOEpatents

Gillett, James E.; Meuschke, Robert E.

1995-01-01

A method of refueling a nuclear reactor whereby the drive mechanism is disengaged and removed by activating a jacking mechanism that raises the closure head. The area between the barrier plate and closure head is exhausted through the closure head penetrations. The closure head, upper drive mechanism, and bellows seal are lifted away and transported to a safe area. The barrier plate acts as the primary boundary and each drive and control rod penetration has an elastomer seal preventing excessive tritium gases from escaping. The individual instrumentation plugs are disengaged allowing the corresponding fuel assembly to be sealed and replaced.

Mass Loss Near the Eddington Limit

NASA Astrophysics Data System (ADS)

Bjorkman, J. E.

2005-09-01

We investigate whether ``continuum'' opacity near the Fe peak at log T = 5.2 can produce the great eruption of η Car. Our simple estimates show that η Car can be super-Eddington (Γ >1) well below the photosphere. The super-Eddington region is sufficiently extended that it can drive a very large mass loss rate (a few 0.1 M⊙ yr-1) to well above the escape speed (several 100 km s-1). Furthermore once initiated, it appears plausible that continuum-driving may ``run away,'' approaching the photon tiring limit. This suggests continuum-driving may be capable of producing the great eruption.

Investigating the Consequences of Interference between Multiple CD8+ T Cell Escape Mutations in Early HIV Infection

PubMed Central

Garcia, Victor; Feldman, Marcus W.; Regoes, Roland R.

2016-01-01

During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV’s genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains –an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction– could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation-associated selective coefficients posed by interference effects cannot simply be overcome by improved sampling frequencies or sizes. This problem is a consequence of the fundamental shortcomings of current estimation techniques under interference regimes. Hence, accounting for the stochastic nature of competition between mutations demands novel estimation methodologies based on the analysis of HIV strains, rather than mutation frequencies. PMID:26829720

The Hepatitis C Virus Glycan Shield and Evasion of the Humoral Immune Response

PubMed Central

Helle, François; Duverlie, Gilles; Dubuisson, Jean

2011-01-01

Despite the induction of effective immune responses, 80% of hepatitis C virus (HCV)-infected individuals progress from acute to chronic hepatitis. In contrast to the cellular immune response, the role of the humoral immune response in HCV clearance is still subject to debate. Indeed, HCV escapes neutralizing antibodies in chronically infected patients and reinfection has been described in human and chimpanzee. Studies of antibody-mediated HCV neutralization have long been hampered by the lack of cell-culture-derived virus and the absence of a small animal model. However, the development of surrogate models and recent progress in HCV propagation in vitro now enable robust neutralization assays to be performed. These advances are beginning to shed some light on the mechanisms of HCV neutralization. This review summarizes the current state of knowledge of the viral targets of anti-HCV-neutralizing antibodies and the mechanisms that enable HCV to evade the humoral immune response. The recent description of the HCV glycan shield that reduces the immunogenicity of envelope proteins and masks conserved neutralizing epitopes at their surface constitutes the major focus of this review. PMID:22069522

Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences.

PubMed

Love, Tanzy M T; Thurston, Sally W; Keefer, Michael C; Dewhurst, Stephen; Lee, Ha Youn

2010-06-01

The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stainmore » electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design.« less

Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

PubMed Central

Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Ndabambi, Nonkululeko; Druz, Aliaksandr; Williamson, Carolyn

2017-01-01

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design. PMID:28076415

Constraints on Mars Hydrogen loss from MAVEN: processes and present-day rates

NASA Astrophysics Data System (ADS)

Chaffin, M.; Deighan, J.; Stewart, I. F.; Schneider, N. M.; Chaufray, J. Y.; Jain, S.; Thiemann, E.; Mayyasi, M.; Clarke, J. T.; Crismani, M. M. J.; Stiepen, A.; Montmessin, F.; Epavier, F.; McClintock, B.; Holsclaw, G.; Jakosky, B. M.

2017-12-01

The surface of Mars today is dessicated and oxidized, despite a large body of evidence indicating that the planet was wet and redox neutral early in its history. H escape has the potential to explain both conditions, but until recently there was no long-term monitoring of H loss at Mars. The presence of MAVEN at Mars since late 2014 has established a seasonal record of H escape via airglow measurements of coronal hydrogen and the flux of energetic particles whose production is mediated by the H corona. H escape appears from multiple proxies to be more than an order of magnitude larger in Southern summer than Northern summer, potentially as a consequence of enhanced water transport to the middle atmosphere. This newly described escape channel potentially dominates water loss from Mars today and over its history, and may be the most important control on the chemistry of the atmosphere and surface. I will present an overview of MAVEN measurements of H loss, focusing on contributions made by the Imaging Ultraviolet Spectrograph, and discuss how photochemical models of the atmosphere may need to be adjusted to incorporate new mechanisms for H loss.

Persistent infection of macaques with simian-human immunodeficiency viruses.

PubMed Central

Li, J T; Halloran, M; Lord, C I; Watson, A; Ranchalis, J; Fung, M; Letvin, N L; Sodroski, J G

1995-01-01

Chimeric simian-human immunodeficiency viruses (SHIV) containing the human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some cases, vpu genes were inoculated into eight cynomolgus monkeys. Viruses could be consistently recovered from the CD8-depleted peripheral blood lymphocytes of all eight animals for at least 2 months. After this time, virus isolation varied among the animals, with viruses continuing to be isolated from some animals beyond 600 days after inoculation. The level of viral RNA in plasma during acute infection and the frequency of virus isolation after the initial 2-month period were higher for the Vpu-positive viruses. All of the animals remained clinically healthy, and the absolute numbers of CD4-positive lymphocytes were stable. Antibodies capable of neutralizing HIV-1 were generated at high titers in animals exhibiting the greatest consistency of virus isolation. Strain-specific HIV-1-neutralizing antibodies were initially elicited, and then more broadly neutralizing antibodies were elicited. env sequences from two viruses isolated more than a year after infection were analyzed. In the Vpu-negative SHIV, for which virus loads were lower, a small amount of env variation, which did not correspond to that found in natural HIV-1 variants, was observed. By contrast, in the Vpu-positive virus, which was consistently isolated from the host animal, extensive variation of the envelope glycoproteins in the defined variable gp120 regions was observed. Escape from neutralization by CD4 binding site monoclonal antibodies was observed for the viruses with the latter envelope glycoproteins, and the mechanism of escape appears to involve decreased binding of the antibody to the monomeric gp120 glycoproteins. The consistency with which SHIV infection of cynomolgus monkeys is initiated and the similarities in the neutralizing antibody response to SHIV and HIV-1 support the utility of this model system for the study of HIV-1 prophylaxis. PMID:7474126

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Saturn Ring

NASA Image and Video Library

2007-12-12

Like Earth, Saturn has an invisible ring of energetic ions trapped in its magnetic field. This feature is known as a "ring current." This ring current has been imaged with a special camera on Cassini sensitive to energetic neutral atoms. This is a false color map of the intensity of the energetic neutral atoms emitted from the ring current through a processed called charged exchange. In this process a trapped energetic ion steals and electron from cold gas atoms and becomes neutral and escapes the magnetic field. The Cassini Magnetospheric Imaging Instrument's ion and neutral camera records the intensity of the escaping particles, which provides a map of the ring current. In this image, the colors represent the intensity of the neutral emission, which is a reflection of the trapped ions. This "ring" is much farther from Saturn (roughly five times farther) than Saturn's famous icy rings. Red in the image represents the higher intensity of the particles, while blue is less intense. Saturn's ring current had not been mapped before on a global scale, only "snippets" or areas were mapped previously but not in this detail. This instrument allows scientists to produce movies (see PIA10083) that show how this ring changes over time. These movies reveal a dynamic system, which is usually not as uniform as depicted in this image. The ring current is doughnut shaped but in some instances it appears as if someone took a bite out of it. This image was obtained on March 19, 2007, at a latitude of about 54.5 degrees and radial distance 1.5 million kilometres (920,000 miles). Saturn is at the center, and the dotted circles represent the orbits of the moon's Rhea and Titan. The Z axis points parallel to Saturn's spin axis, the X axis points roughly sunward in the sun-spin axis plane, and the Y axis completes the system, pointing roughly toward dusk. The ion and neutral camera's field of view is marked by the white line and accounts for the cut-off of the image on the left. The image is an average of the activity over a (roughly) 3-hour period. http://photojournal.jpl.nasa.gov/catalog/PIA10094

Crystal engineering of a zwitterionic drug to neutral cocrystals: a general solution for floxacins.

PubMed

Gunnam, Anilkumar; Suresh, Kuthuru; Ganduri, Ramesh; Nangia, Ashwini

2016-10-18

The transformation of zwitterionic Sparfloxacin (SPX) to the neutral form is achieved by cocrystallization. Neutral forms of drugs are important for higher membrane permeability, while zwitterions are more soluble in water. The twin advantages of higher solubility/dissolution rate and good stability of neutral SPX are achieved in a molecular cocrystal compared to its zwitterionic SPX hydrate. The amine-phenol supramolecular synthon drives cocrystal formation, with the paraben ester acting as a "proton migrator" for the ionic to neutral transformation.

INDIRECT EVIDENCE FOR ESCAPING IONIZING PHOTONS IN LOCAL LYMAN BREAK GALAXY ANALOGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2015-09-10

A population of early star-forming galaxies is the leading candidate for the re-ionization of the universe. It is still unclear, however, what conditions and physical processes would enable a significant fraction of the ionizing (Lyman continuum) photons to escape from these gas-rich galaxies. In this paper we present the results of the analysis of Hubble Space Telescope Cosmic Origins Spectrograph far-UV (FUV) spectroscopy plus ancillary multi-waveband data of a sample of 22 low-redshift galaxies that are good analogs to typical star-forming galaxies at high redshift. We measure three parameters that provide indirect evidence of the escape of ionizing radiation (leakiness):more » (1) the residual intensity in the cores of saturated interstellar low-ionization absorption lines, which indicates incomplete covering by that gas in the galaxy; (2) the relative amount of blueshifted Lyα line emission, which can indicate the existence of holes in the neutral hydrogen on the front-side of the galaxy outflow, and (3) the relative weakness of the [S ii] optical emission lines that trace matter-bounded H ii regions. We show that our residual intensity measures are only negligibly affected by infilling from resonance emission lines. We find all three diagnostics agree well with one another. We use these diagnostics to rank-order our sample in terms of likely leakiness, noting that a direct measure of escaping Lyman continuum has recently been made for one of the leakiest members of our sample. We then examine the correlations between our ranking and other proposed diagnostics of leakiness. We find a good correlation with the equivalent width of the Lyα emission line, but no significant correlations with either the flux ratio of the [O iii]/[O ii] emission lines or the ratio of star-formation rates derived from the (dust-corrected) FUV and Hα luminosities. Turning to galaxy properties, we find the strongest correlations with leakiness are with the compactness of the star-forming region (Star formation rate/area) and the speed of the galactic outflow. This suggests that extreme feedback—a high intensity of ionizing radiation and strong pressure from both radiation and a hot galactic wind—combines to create significant holes in the neutral gas. These results not only shed new light on the physical mechanisms that can allow ionizing radiation to escape from intensely star-forming galaxies, they also provide indirect observational indicators that can be used at high redshift where direct measurements of escaping Lyman continuum radiation are impossible.« less

Radiative lifetimes for 29 N2+ and implications for planetary escape and isotope enrichment

NASA Astrophysics Data System (ADS)

Guberman, Steven L.

2017-07-01

The Viking missions to Mars found that 15N/14N is enhanced by a factor of 1.62 compared to Earth and it was suggested that the cause was dissociative recombination (DR) of N2+. The high kinetic energy imparted to N in DR drives atmospheric escape. More recent models of the Martian ionosphere show that much of the N2+ is vibrationally excited. If DR of vibrationally excited 29N2+ is important, the energetics are such that the isotope enhancement would be greatly reduced. Here I show that at the Mars exobase electron temperature and density, the excited vibrational levels of 29N2+ radiate before they can recombine. The isotope enhancement arising from DR is due entirely to DR of 28N2+ with a small contribution to 14N escape arising from DR of the ground vibrational level of 29N2+.

Towards a Genetic Definition of Cancer-Associated Inflammation

PubMed Central

Prendergast, George C.; Metz, Richard; Muller, Alexander J.

2010-01-01

Chronic inflammation drives the development of many cancers, but a genetic definition of what constitutes ‘cancer-associated’ inflammation has not been determined. Recently, a mouse genetic study revealed a critical role for the immune escape mediator indoleamine 2,3-dioxygenase (IDO) in supporting inflammatory skin carcinogenesis. IDO is generally regarded as being immunosuppressive; however, there was no discernable difference in generalized inflammatory processes in IDO-null mice under conditions where tumor development was significantly suppressed, implicating IDO as key to establishing the pathogenic state of ‘cancer-associated’ inflammation. Here we review recent findings and their potential implications to understanding the relationship between immune escape and inflammation in cancer. Briefly, we propose that genetic pathways of immune escape in cancer are synonymous with pathways that define ‘cancer-associated’ inflammation and that these processes may be identical rather than distinct, as generally presumed, in terms of their genetic definition. PMID:20228228

A facility to study the particles released by ion sputtering process

NASA Astrophysics Data System (ADS)

de Angelis, E.; di Lellis, A. M.; Vannaroni, G.; Orsini, S.; Mangano, V.; Milillo, A.; Massetti, S.; Mura, A.; Vertolli, N.

2007-08-01

Research on the planetary surface erosion and planetary evolution could be enriched with the detection of the escaping material, in terms of energy and direction, caused by ions sputtering. A complete study of emitted neutral distribution from which infers the processes occurring on the impacted surface requires dedicated instrumentation, tailored on the peculiarity on the low energy profile of the sputtered signal. We propose a comprehensive facility at INAF/IFSI in Rome intended to provide the opportunity to investigate the interaction of selectable ion beam with planetary analogues through the detection of sputtered neutral atoms. The laboratory is equipped with a high volume UHV chamber, ion selectable sources in the range 0 to 10 keV, a set of 3D sample/sensor orientation motion actuation motors down to 1/100 deg resolution. The laboratory will support a set of neutral sensor heads sets derived from the Emitted for Low Energetic Neutral Atoms (ELENA) instrument under development for the ESA BepiColombo Mercury mission able to detect neutral atoms (few eV-up to 5 keV).

Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency.

PubMed

Bournazos, Stylianos; Gazumyan, Anna; Seaman, Michael S; Nussenzweig, Michel C; Ravetch, Jeffrey V

2016-06-16

Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) suppress viremia in animal models of HIV-1 and humans. To achieve potent activity without the emergence of viral escape mutants, co-administration of different bNAbs is necessary to target distinct epitopes essential for viral fitness. Here, we report the development of bispecific anti-Env neutralizing antibodies (biNAbs) with potent activity. Synergistic activity of biNAbs was achieved by combining an engineered hinge domain of IgG3 to increase Fab domain flexibility necessary for hetero-bivalent binding to the Env trimer while retaining the functional properties of the IgG1-Fc. Compared to unmodified biNAbs, hinge domain variants exhibited substantially improved neutralization activity, with particular combinations showing evidence of synergistic neutralization potency in vitro and enhanced in vivo therapeutic activity in HIV-1-infected humanized mice. These findings suggest innovative strategies for generating biNAbs with enhanced neutralization breadth and potency, representing ideal candidate molecules for the control of HIV-1 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Prediction of Protection against Asian Enterovirus 71 Outbreak Strains by Cross-neutralizing Capacity of Serum from Dutch Donors, The Netherlands

PubMed Central

Koen, Gerrit; van Eijk, Hetty; Koekkoek, Sylvie M.; de Jong, Menno D.; Wolthers, Katja C.

2016-01-01

Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from donors in the Netherlands against EV-71 strains isolated in Europe and in Asia. All IVIg batches and 41%, 79%, and 65% of serum samples from children ≤5 years of age, women of childbearing age, and HIV-positive men, respectively, showed high neutralizing activity against a Dutch C1 strain, confirming widespread circulation of EV-71 in the Netherlands. Asian B3–4 and C4 strains were efficiently cross-neutralized, predicting possible protection against extensive circulation and associated outbreaks of those types in Europe. However, C2 and C5 strains that had few mutations in the capsid region consistently escaped neutralization, emphasizing the importance of monitoring antigenic diversity among circulating EV-71 strains. PMID:27533024

Current profile redistribution driven by neutral beam injection in a reversed-field pinch

NASA Astrophysics Data System (ADS)

Parke, E.; Anderson, J. K.; Brower, D. L.; Den Hartog, D. J.; Ding, W. X.; Johnson, C. A.; Lin, L.

2016-05-01

Neutral beam injection in reversed-field pinch (RFP) plasmas on the Madison Symmetric Torus [Dexter et al., Fusion Sci. Technol. 19, 131 (1991)] drives current redistribution with increased on-axis current density but negligible net current drive. Internal fluctuations correlated with tearing modes are observed on multiple diagnostics; the behavior of tearing mode correlated structures is consistent with flattening of the safety factor profile. The first application of a parametrized model for island flattening to temperature fluctuations in an RFP allows inferrence of rational surface locations for multiple tearing modes. The m = 1, n = 6 mode is observed to shift inward by 1.1 ± 0.6 cm with neutral beam injection. Tearing mode rational surface measurements provide a strong constraint for equilibrium reconstruction, with an estimated reduction of q0 by 5% and an increase in on-axis current density of 8% ± 5%. The inferred on-axis current drive is consistent with estimates of fast ion density using TRANSP [Goldston et al., J. Comput. Phys. 43, 61 (1981)].

Autonomous Soft Robotic Fish Capable of Escape Maneuvers Using Fluidic Elastomer Actuators.

PubMed

Marchese, Andrew D; Onal, Cagdas D; Rus, Daniela

2014-03-01

In this work we describe an autonomous soft-bodied robot that is both self-contained and capable of rapid, continuum-body motion. We detail the design, modeling, fabrication, and control of the soft fish, focusing on enabling the robot to perform rapid escape responses. The robot employs a compliant body with embedded actuators emulating the slender anatomical form of a fish. In addition, the robot has a novel fluidic actuation system that drives body motion and has all the subsystems of a traditional robot onboard: power, actuation, processing, and control. At the core of the fish's soft body is an array of fluidic elastomer actuators. We design the fish to emulate escape responses in addition to forward swimming because such maneuvers require rapid body accelerations and continuum-body motion. These maneuvers showcase the performance capabilities of this self-contained robot. The kinematics and controllability of the robot during simulated escape response maneuvers are analyzed and compared with studies on biological fish. We show that during escape responses, the soft-bodied robot has similar input-output relationships to those observed in biological fish. The major implication of this work is that we show soft robots can be both self-contained and capable of rapid body motion.

Structural Basis for Escape of Human Astrovirus from Antibody Neutralization: Broad Implications for Rational Vaccine Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogdanoff, Walter A.; Perez, Edmundo I.; López, Tomás

ABSTRACT Human astroviruses are recognized as a leading cause of viral diarrhea worldwide in children, immunocompromised patients, and the elderly. There are currently no vaccines available to prevent astrovirus infection; however, antibodies developed by healthy individuals during previous infection correlate with protection from reinfection, suggesting that an effective vaccine could be developed. In this study, we investigated the molecular mechanism by which several strains of human astrovirus serotype 2 (HAstV-2) are resistant to the potent HAstV-2-neutralizing monoclonal antibody PL-2 (MAb PL-2). Sequencing of the HAstV-2 capsid genes reveals mutations in the PL-2 epitope within the capsid's spike domain. To understandmore » the molecular basis for resistance from MAb PL-2 neutralization, we determined the 1.35-Å-resolution crystal structure of the capsid spike from one of these HAstV-2 strains. Our structure reveals a dramatic conformational change in a loop within the PL-2 epitope due to a serine-to-proline mutation, locking the loop in a conformation that sterically blocks binding and neutralization by MAb PL-2. We show that mutation to serine permits loop flexibility and recovers MAb PL-2 binding. Importantly, we find that HAstV-2 capsid spike containing a serine in this loop is immunogenic and elicits antibodies that neutralize all HAstV-2 strains. Taken together, our results have broad implications for rational selection of vaccine strains that do not contain prolines in antigenic loops, so as to elicit antibodies against diverse loop conformations. IMPORTANCEHuman astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. In this study, we investigated how several strains of HAstV are resistant to a virus-neutralizing monoclonal antibody. We determined the crystal structure of the capsid protein spike domain from one of these HAstV strains and found that a single amino acid mutation induces a structural change in a loop that is responsible for antibody binding. Our findings reveal how viruses can escape antibody neutralization and provide insight for the rational design of vaccines to elicit diverse antibodies that provide broader protection from infection.« less

Fast-ion transport in qmin>2, high- β steady-state scenarios on DIII-D

DOE PAGES

Holcomb, C. T.; Heidbrink, W. W.; Ferron, J. R.; ...

2015-05-22

The results from experiments on DIII-D [J. L. Luxon, Fusion Sci. Technol. 48, 828 (2005)] aimed at developing high β steady-state operating scenarios with high-qminqmin confirm that fast-ion transport is a critical issue for advanced tokamak development using neutral beam injection current drive. In DIII-D, greater than 11 MW of neutral beam heating power is applied with the intent of maximizing β N and the noninductive current drive. However, in scenarios with q min>2 that target the typical range of q 95= 5–7 used in next-step steady-state reactor models, Alfvén eigenmodes cause greater fast-ion transport than classical models predict. Thismore » enhanced transport reduces the absorbed neutral beam heating power and current drive and limits the achievable β N. Conversely similar plasmas except with q min just above 1 have approximately classical fast-ion transport. Experiments that take q min>3 plasmas to higher β P with q 95= 11–12 for testing long pulse operation exhibit regimes of better than expected thermal confinement. Compared to the standard high-q min scenario, the high β P cases have shorter slowing-down time and lower ∇β fast, and this reduces the drive for Alfvénic modes, yielding nearly classical fast-ion transport, high values of normalized confinement, β N, and noninductive current fraction. These results suggest DIII-D might obtain better performance in lower-q 95, high-q min plasmas using broader neutral beam heating profiles and increased direct electron heating power to lower the drive for Alfvén eigenmodes.« less

Fast-ion transport in q{sub min}>2, high-β steady-state scenarios on DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holcomb, C. T.; Heidbrink, W. W.; Collins, C.

2015-05-15

Results from experiments on DIII-D [J. L. Luxon, Fusion Sci. Technol. 48, 828 (2005)] aimed at developing high β steady-state operating scenarios with high-q{sub min} confirm that fast-ion transport is a critical issue for advanced tokamak development using neutral beam injection current drive. In DIII-D, greater than 11 MW of neutral beam heating power is applied with the intent of maximizing β{sub N} and the noninductive current drive. However, in scenarios with q{sub min}>2 that target the typical range of q{sub 95}= 5–7 used in next-step steady-state reactor models, Alfvén eigenmodes cause greater fast-ion transport than classical models predict. Thismore » enhanced transport reduces the absorbed neutral beam heating power and current drive and limits the achievable β{sub N}. In contrast, similar plasmas except with q{sub min} just above 1 have approximately classical fast-ion transport. Experiments that take q{sub min}>3 plasmas to higher β{sub P} with q{sub 95}= 11–12 for testing long pulse operation exhibit regimes of better than expected thermal confinement. Compared to the standard high-q{sub min} scenario, the high β{sub P} cases have shorter slowing-down time and lower ∇β{sub fast}, and this reduces the drive for Alfvénic modes, yielding nearly classical fast-ion transport, high values of normalized confinement, β{sub N}, and noninductive current fraction. These results suggest DIII-D might obtain better performance in lower-q{sub 95}, high-q{sub min} plasmas using broader neutral beam heating profiles and increased direct electron heating power to lower the drive for Alfvén eigenmodes.« less

Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability.

PubMed

Tahara, Maino; Bürckert, Jean-Philippe; Kanou, Kazuhiko; Maenaka, Katsumi; Muller, Claude P; Takeda, Makoto

2016-08-02

Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors.

Mars Exospheric studies with MENCA on a Mars Orbiter

NASA Astrophysics Data System (ADS)

Bhardwaj, Anil; Menca Team

2012-07-01

The study of Martian exosphere is important for understanding the escape rate of Martian atmosphere and its impact on Mars' climate change. The neutral density distribution and the composition of Martian exosphere still remain largely unexplored. There are no in-situ measurements of the Martian exosphere; only a few remote sensing measurements have been made and some modelling studies are carried out. We proposed to fly a neutral mass spectrometer, namely "MENCA" (Mars Exospheric Neutral Composition Analyser) to explore the Martian exospheric neutral density and composition at an altitude of ~500 km and above from the surface of Mars, and to study its radial and diurnal variations. MENCA is based on the technique of quadrupole mass spectrometry and has the mass range of 1-300 amu with unit mass resolution. (*) MENCA Team includes: S.V. Mohankumar, T. P. Das, P. Sreelatha, P. Pradeepkumar, B. Sunder, Amarnath Nandi, Neha Naik, G. Supriya, Vipin K. Yadav, M. B. Dhanya, R. Satheesh Thampi, G. P. Padmanabhan

Measurement of fast minority /sub 3/He/sup + +/ energy distribution during ICRF heating

DOEpatents

Post, D.E. Jr.; Grisham, L.R.; Medley, S.S.

A method and means for measuring the fast /sub 3/He/sup + +/ distribution during /sub 3/He/sup + +/ minority Ion Cyclotron Resonance Frequency (ICRF) heating is disclosed. The present invention involves the use of 10 to 100 keV beams of neutral helium atoms to neutralize the fast /sub 3/He/sup + +/ ions in a heated plasma by double charge exchange (/sub 3/He/sup + +/ + /sub 4/He/sup 0/ ..-->.. /sub 3/He/sup 0/ + /sub 4/He/sup + +/). The neutralized fast /sub 3/He/sup 0/ atoms then escape from the hot plasma confined by a magnetic field and are detected by conventional neutral particle analyzing means. This technique permits the effectiveness of the coupling of the ion cyclotron waves to the /sub 3/He/sup + +/ minority ions to be accurately measured. The present invention is particularly adapted for use in evaluating the effectiveness of the intermediate coupling between the RF heating and the /sub 3/He/sup + +/ in an energetic toroidal plasma.

The Third Indochina Conflict: Cambodia’s Total War

DTIC Science & Technology

2014-12-12

Military Region. NR National Road. OMZ Operational Military Zone. PAVN People’s Army of Vietnam. PMC Provincial Military Command. PRK People’s......of the Khmer Rouge regime escaped to the Cambodian-Thai border and started a resistance movement aimed at deposing the PRK and driving out the

Single-Chain Fv-Based Anti-HIV Proteins: Potential and Limitations

PubMed Central

West, Anthony P.; Galimidi, Rachel P.; Gnanapragasam, Priyanthi N. P.

2012-01-01

The existence of very potent, broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) offers the potential for prophylaxis against HIV-1 infection by passive immunization or gene therapy. Both routes permit the delivery of modified forms of IgGs. Smaller reagents are favored when considering ease of tissue penetration and the limited capacities of gene therapy vectors. Immunoadhesin (single-chain fragment variable [scFv]-Fc) forms of IgGs are one class of relatively small reagent that has been explored for delivery by adeno-associated virus. Here we investigated the neutralization potencies of immunoadhesins compared to those of their parent IgGs. For the antibodies VRC01, PG9, and PG16, the immunoadhesins showed modestly reduced potencies, likely reflecting reduced affinities compared to those of the parent IgG, and the VRC01 immunoadhesin formed dimers and multimers with reduced neutralization potencies. Although scFv forms of neutralizing antibodies may exhibit affinity reductions, they provide a means of building reagents with multiple activities. Attachment of the VRC01 scFv to PG16 IgG yielded a bispecific reagent whose neutralization activity combined activities from both parent antibodies. Although the neutralization activity due to each component was partially reduced, the combined reagent is attractive since fewer strains escaped neutralization. PMID:22013046

Generation and Characterization of Monoclonal Antibodies against a Cyclic Variant of Hepatitis C Virus E2 Epitope 412-422

PubMed Central

Sandomenico, Annamaria; Leonardi, Antonio; Berisio, Rita; Sanguigno, Luca; Focà, Giuseppina; Focà, Annalia; Ruggiero, Alessia; Doti, Nunzianna; Muscariello, Livio; Barone, Daniela; Farina, Claudio; Owsianka, Ania; Vitagliano, Luigi

2016-01-01

ABSTRACT The hepatitis C virus (HCV) E2 envelope glycoprotein is crucial for virus entry into hepatocytes. A conserved region of E2 encompassing amino acids 412 to 423 (epitope I) and containing Trp420, a residue critical for virus entry, is recognized by several broadly neutralizing antibodies. Peptides embodying this epitope I sequence adopt a β-hairpin conformation when bound to neutralizing monoclonal antibodies (MAbs) AP33 and HCV1. We therefore generated new mouse MAbs that were able to bind to a cyclic peptide containing E2 residues 412 to 422 (C-epitope I) but not to the linear counterpart. These MAbs bound to purified E2 with affinities of about 50 nM, but they were unable to neutralize virus infection. Structural analysis of the complex between C-epitope I and one of our MAbs (C2) showed that the Trp420 side chain is largely buried in the combining site and that the Asn417 side chain, which is glycosylated in E2 and solvent exposed in other complexes, is slightly buried upon C2 binding. Also, the orientation of the cyclic peptide in the antibody-combining site is rotated by 180° compared to the orientations of the other complexes. All these structural features, however, do not explain the lack of neutralization activity. This is instead ascribed to the high degree of selectivity of the new MAbs for the cyclic epitope and to their inability to interact with the epitope in more flexible and extended conformations, which recent data suggest play a role in the mechanisms of neutralization escape. IMPORTANCE Hepatitis C virus (HCV) remains a major health care burden, affecting almost 3% of the global population. The conserved epitope comprising residues 412 to 423 of the viral E2 glycoprotein is a valid vaccine candidate because antibodies recognizing this region exhibit potent neutralizing activity. This epitope adopts a β-hairpin conformation when bound to neutralizing MAbs. We explored the potential of cyclic peptides mimicking this structure to elicit anti-HCV antibodies. MAbs that specifically recognize a cyclic variant of the epitope bind to soluble E2 with a lower affinity than other blocking antibodies and do not neutralize virus. The structure of the complex between one such MAb and the cyclic epitope, together with new structural data showing the linear peptide bound to neutralizing MAbs in extended conformations, suggests that the epitope displays a conformational flexibility that contributes to neutralization escape. Such features can be of major importance for the design of epitope-based anti-HCV vaccines. PMID:26819303

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2012 CFR

2012-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2011 CFR

2011-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2014 CFR

2014-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2013 CFR

2013-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

Measurements of Lyman-Alpha Escape From HST Far-UV Spectral SNAP Survey of 33 Starforming Galaxies: Initial Results

NASA Astrophysics Data System (ADS)

Redwine, Keith

2018-01-01

This thesis will describe and analyze far-UV spectra from nearby starforming galaxies to investigate how line features like the hydrogen Lyman-alpha (Lyα) line at 1216 Å are related to the local properties of the host galaxy. It has been suggested that Lyα can be used as a proxy for the escape of Lyman continuum (LyC) radiation, the escape of of which from bright regions of galaxies is of particular interest. Most notably, the reionization epoch of neutral atomic hydrogen in the universe over a redshift range from z∼6 to z∼12, was highly dependent on the flux of ionizing LyC photons in the interstellar and intergalactic media. Expanding our understanding of the dynamics of the Lyα escape fraction (fLyα) from the local environment of its emission could be key to determining a total LyC escape fraction (fLyC) across all morphologies of galaxies. The wide range of Lyα emitters and absorbors (occasionally both) of this Cycle 22 SNAP survey observed by the Cosmic Origins Spectrograph (COS) onboard Hubble Space Telescope (HST) provides a unique look at far-UV spectra in candidate LyC emitters. Lyα profiles are easily observable in short exposures, and line features discernable in the low-resolution G140L mode can inform and guide future observations by COS or other FUV spectroscopy.

How does ionizing radiation escape from galaxies?

NASA Astrophysics Data System (ADS)

Orlitova, Ivana

2016-10-01

Search for sources that reionized the Universe from z 15 to z 6 is one of the main drivers of present-day astronomy. Low-mass star-forming galaxies are the most favoured sources of ionizing photons, but the searches of escaping Lyman continuum (LyC) have not been extremely successful. Our team has recently detected prominent LyC escape from five Green Pea galaxies at redshift 0.3, using the HST/COS spectrograph, which represents a significant breakthrough. We propose here to study the LyC escape of the strongest among these leakers, J1152, with spatial resolution. From the comparison of the ionizing and non-ionizing radiation maps, and surface brightness profiles, we will infer the major mode in which LyC is escaping: from the strongest starburst, from the galaxy edge, through a hole along our line-of-sight, through clumpy medium, or directly from all the production sites due to highly ionized medium in the entire galaxy. In parallel, we will test the predictive power of two highly debated indirect indicators of LyC leakage: the [OIII]5007/[OII]3727 ratio, and Lyman-alpha. We predict that their spatial distribution should closely follow that of the ionizing continuum if column densities of the neutral gas are low. This combined study, which relies on the HST unique capabilities, will bring crucial information on the structure of the leaking galaxies, provide constraints for hydrodynamic simulations, and will lead to efficient future searches for LyC leakers across a large range of redshifts.

Immune Escape Mutations Detected within HIV-1 Epitopes Associated with Viral Control During Treatment Interruption

PubMed Central

Schweighardt, Becky; Wrin, Terri; Meiklejohn, Duncan A.; Spotts, Gerald; Petropoulos, Christos J.; Nixon, Douglas F.; Hecht, Frederick M.

2010-01-01

We analyzed immune responses in chronically HIV-infected individuals who took part in a treatment interruption (TI) trial designed for patients who initiated anti-retroviral therapy within 6 months of seroconversion. In the two subjects that exhibited the best viral control, we detected CD8+ T cell responses against 1-2 Gag epitopes during the early weeks of TI and a subsequent increase in the number of epitopes recognized by the later time points. Each of these subjects developed mutations within the epitopes targeted by the highest magnitude responses. In the subject with the worst viral control, we detected responses against two Gag epitopes throughout the entire TI and no Gag mutations. The magnitude of these responses increased dramatically with time, greatly exceeding those detected in the virologic controllers. The highest levels of contemporaneous autologous neutralizing antibody activity were detected in the virologic controllers, and a subsequent escape mutation developed within the envelope gene of one controller that abrogated the response. These data suggest that immune escape mutations are a sign of viral control during TI, and that the absence of immune escape mutations in the presence of high-levels of viral replication indicates the lack of an effective host immune response. PMID:19910798

Biomechanical and ergonomic assessment of urban transit operators.

PubMed

Albert, Wayne J; Everson, Donald; Rae, Michelle; Callaghan, Jack P; Croll, Jim; Kuruganti, Usha

2014-01-01

The prevalence of neck and low back musculoskeletal injuries in transit operators has been shown to be high; with work absences exceeding double the National average. There is a lack of biomechanical data generated from field researches to inform on musculoskeletal risk associated with transportation and driving occupations. Instead there has been a reliance on simulated driving and questionnaire-based research. This study was designed to examine the musculoskeletal and biomechanical stresses experienced by urban bus drivers. The main objective was to obtain a baseline understanding of sitting posture, muscle activiation and subjective ratings of stress during regular driving tasks. Fifteen urban city bus drivers were recruited for this study. Bus drivers drove the same 65-minute bus route once, at the same time of day, in the same preselected bus. Wireless surface electromyography monitored muscular activity of the drivers' neck, upper trapezius, and erector spinae and video analysis and seat pressure mapping was used to monitor changes in driving posture. A health and lifestyle questionnaire was administered to record specific neck and back pain experienced by drivers as well as to provide lifestyle habits. Drivers were found to exhibit non-neutral postures for less than 30% of the time while conducting routine tasks of turning and stopping for passenger loading and unloading. The neck posture was the greatest concern in terms of non-neutral posture and this was supported by the higher muscle activation to the neck musculature. There was significant posture adjustment made during the one-hour driving period with the adjustments increasing with driving time. Activities associated with bus driving appear to require the use of non-neutral postures an increase in muscle activation. Significant postural adjustments were needed over the one-hour observation period suggesting that the musculoskeletal demands may increase over a regular 12-hour shift.

The Structure of Titan’s N2 and CH4 Coronae

NASA Astrophysics Data System (ADS)

Jiang, Fayu; Cui, Jun; Xu, Jiyao

2017-12-01

In this study, we analyze the structures of Titan’s N2 and CH4 coronae using a large data set acquired by the Ion Neutral Mass Spectrometer (INMS) instrument on board Cassini. The N2 and CH4 densities measured from the exobase up to 2000 km imply a mean exobase temperature of 146 K and 143 K, respectively, which is lower than the mean upper atmospheric temperature by 4 and 7 K. This indicates that on average, Titan possesses a subthermal rather than suprathermal corona. A careful examination reveals that the variability in corona structure is not very likely to be solar driven. Within the framework of the collisionless kinetic model, we investigate how the CH4 energy distribution near the exobase could be constrained if strong CH4 escape occurs on Titan. Several functional forms for the CH4 energy distribution are attempted, assuming two representative CH4 escape rates of 1.2× {10}25 s-1 and 2.2× {10}27 s-1. We find that the double Maxwellian and power-law distributions can reproduce the shape of the CH4 corona structure as well as the imposed CH4 escape rate. In both cases, the escape rate is contributed by a suprathermal CH4 population on the high-energy tail, with a number fraction below 5% and a characteristic energy of 0.1-0.6 eV per suprathermal CH4 molecule. The coexistence of the subthermal CH4 corona revealed by the INMS data and substantial CH4 escape suggested by some previous works could be reconciled by a significant departure in the exobase CH4 energy distribution from ideal Maxwellian that enhances escape and causes a noticeable redistribution of the corona structure.

On charge exchange and knock-on processes in the exosphere of Io

NASA Technical Reports Server (NTRS)

Ip, W.-H.

1982-01-01

One direct consequence of magnetospheric interaction of Io is the strong dynamical coupling of its neutral atmosphere with the corotating plasma. The absorption of the thermal ions and the associated neutral injection is an improtant issue not yet explored. As far as nonthermal escape of the neutral atmosphere is concerned, three processes stand out. That is, apart from sputtering, exospheric interactions like atom-ion knock-on collision and charge exchange recombination could be a significant source of the neutral clouds in the Jovian system. Using a current electrodynamic model of Io, both the absorption rate of the corotating thermal plasma and the production rates of new exospheric ions and the fast neutrals are considered. It is found that the source strength of the neutral atoms and molecules with speeds of about 100 km/sec could amount to 10 to the 26th/sec whereas exospheric neutrals emitted at lower speed (of about 10 km/sec) amounts to 4 x 10 to the 25th/sec. The generation of the new ions in connection with the streaming of the magnetospheric plasma around Io could also produce an asymmetric sputtering with a neutral flux of about 10 to the 27th/sec emitted from the region of Io which faces Jupiter. These results may be related to a number of sodium observations.

Dynamics of Ion Beam Charge Neutralization by Ferroelectric Plasma Sources

NASA Astrophysics Data System (ADS)

Stepanov, Anton D.; Gilson, Erik P.; Grisham, Larry R.; Kaganovich, Igor D.; Davidson, Ronald C.; Ji, Qing; Persaud, Arun; Seidl, Peter A.; Schenkel, Thomas

2016-10-01

Ferroelectric Plasma Sources (FEPSs) can generate plasma that provides effective space-charge neutralization of intense high-perveance ion beams. Here we present experimental results on charge neutralization of a high-perveance 38 keV Ar+ beam by a FEPS plasma. By comparing the measured beam radius with the envelope model for space-charge expansion, it is shown that a charge neutralization fraction of 98% is attainable. The transverse electrostatic potential of the ion beam is reduced from 15 V before neutralization to 0.3 V, implying that the energy of the neutralizing electrons is below 0.3 eV. Near-complete charge neutralization is established 5 μs after the driving pulse is applied to the FEPS, and can last for 35 μs. It is argued that the duration of neutralization is much longer than a reasonable lifetime of the plasma produced in the sub- μs surface discharge. Measurements of current flow in the driving circuit of the FEPS suggest that plasma can be generated for tens of μs after the high voltage pulse is applied. This is confirmed by fast photography of the plasma in the 1-meter long FEPS on NDCX-II, where effective charge neutralization of the beam was achieved with the optimized FEPS timing. This work was supported by the Office of Science of the US Department of Energy under contracts DE-AC0209CH11466 (PPPL) and DE-AC0205CH11231 (LBNL).

HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

PubMed Central

Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina; Turk, Gabriela; Rubio, Andrea E.; Pampuro, Sandra; Gomez-Carrillo, Manuel; Bautista, Christian; Deluchi, Gabriel; Benetucci, Jorge; Lasala, María Beatriz; Lourtau, Leonardo; Losso, Marcelo Horacio; Perez, Héctor; Cahn, Pedro; Salomón, Horacio

2008-01-01

Background Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. Methodology/Principal Findings We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. Conclusions Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. PMID:18941505

Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability.

PubMed

Bougher, S; Jakosky, B; Halekas, J; Grebowsky, J; Luhmann, J; Mahaffy, P; Connerney, J; Eparvier, F; Ergun, R; Larson, D; McFadden, J; Mitchell, D; Schneider, N; Zurek, R; Mazelle, C; Andersson, L; Andrews, D; Baird, D; Baker, D N; Bell, J M; Benna, M; Brain, D; Chaffin, M; Chamberlin, P; Chaufray, J-Y; Clarke, J; Collinson, G; Combi, M; Crary, F; Cravens, T; Crismani, M; Curry, S; Curtis, D; Deighan, J; Delory, G; Dewey, R; DiBraccio, G; Dong, C; Dong, Y; Dunn, P; Elrod, M; England, S; Eriksson, A; Espley, J; Evans, S; Fang, X; Fillingim, M; Fortier, K; Fowler, C M; Fox, J; Gröller, H; Guzewich, S; Hara, T; Harada, Y; Holsclaw, G; Jain, S K; Jolitz, R; Leblanc, F; Lee, C O; Lee, Y; Lefevre, F; Lillis, R; Livi, R; Lo, D; Ma, Y; Mayyasi, M; McClintock, W; McEnulty, T; Modolo, R; Montmessin, F; Morooka, M; Nagy, A; Olsen, K; Peterson, W; Rahmati, A; Ruhunusiri, S; Russell, C T; Sakai, S; Sauvaud, J-A; Seki, K; Steckiewicz, M; Stevens, M; Stewart, A I F; Stiepen, A; Stone, S; Tenishev, V; Thiemann, E; Tolson, R; Toublanc, D; Vogt, M; Weber, T; Withers, P; Woods, T; Yelle, R

2015-11-06

The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability. Copyright © 2015, American Association for the Advancement of Science.

Extinction Correction Significantly Influences the Estimate of the Lyα Escape Fraction

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

Energy transfer in O collisions with He isotopes and helium escape from Mars

NASA Astrophysics Data System (ADS)

Bovino, S.; Zhang, P.; Kharchenko, V.; Dalgarno, A.

2010-12-01

Helium is one of the dominant constituents in the upper atmosphere of Mars [1]. Thermal (Jeans’) escape of He is negligible on Mars [2] and major mechanism of escape is related to the collisional ejection of He atoms by energetic oxygen. Collisional ejection dominates over ion-related mechanisms [3] and evaluation of the escape flux of neutral He becomes an important issue. The dissociative recombination of O2+ is considered to be the major source of energetic oxygen atoms [4]. We report accurate data on energy-transfer collisions between hot oxygen atoms and the atmospheric helium gas. Angular dependent scattering cross sections for elastic collisions of O(3P) and O(1D) atoms with helium gas have been calculated quantum mechanically and found to be surprisingly similar. Cross sections, computed for collisions with both helium isotopes, 3He and 4He, have been used to construct the kernel of the Boltzmann equation, describing the energy relaxation of hot oxygen atoms. Computed rates of energy transfer in O + He collisions have been used to evaluate the flux of He atoms escaping from the Mars atmosphere at different solar conditions. We have identified atmospheric layers mostly responsible for production of the He escape flux. Our results are consistent with recent data from Monte Carlo simulations of the escape of O atoms: strong angular anisotropy of atomic cross sections leads to an increased transparency of the upper atmosphere for escaping O flux [5] and stimulate the collisional ejection of He atoms. References [1] Krasnopolsky, V. A., and G. R. Gladstone (2005), Helium on Mars and Venus: EUVE observations and modeling, Icarus, 176, 395. [2] Chassefiere E. and F. Leblanc (2004), Mars atmospheric escape and evolution; interaction with the solar wind, Planetary and Space Science, 52, 1039 [3] Krasnopolsky, V. (2010), Solar activity variations of thermospheric temperatures on Mars and a problem of CO in the lower atmoshpere, Icarus, 207, 638. [4] Fox, J. L. (1995), On the escape of oxygen and hydrogen from Mars, Geophy. Rev. Lett., 20, 1847. [5] Krestyanikova, M. A. and V. I. Shematovich (2006), Stochastic models of hot planetary and satellite coronas: a hot oxygen corona of Mars, Solar System Research, 40, 384.

Epitope Dampening Monotypic Measles Virus Hemagglutinin Glycoprotein Results in Resistance to Cocktail of Monoclonal Antibodies

PubMed Central

Lech, Patrycja J.; Tobin, Gregory J.; Bushnell, Ruth; Gutschenritter, Emily; Pham, Linh D.; Nace, Rebecca; Verhoeyen, Els; Cosset, François-Loïc; Muller, Claude P.; Russell, Stephen J.; Nara, Peter L.

2013-01-01

The measles virus (MV) is serologically monotypic. Life-long immunity is conferred by a single attack of measles or following vaccination with the MV vaccine. This is contrary to viruses such as influenza, which readily develop resistance to the immune system and recur. A better understanding of factors that restrain MV to one serotype may allow us to predict if MV will remain monotypic in the future and influence the design of novel MV vaccines and therapeutics. MV hemagglutinin (H) glycoprotein, binds to cellular receptors and subsequently triggers the fusion (F) glycoprotein to fuse the virus into the cell. H is also the major target for neutralizing antibodies. To explore if MV remains monotypic due to a lack of plasticity of the H glycoprotein, we used the technology of Immune Dampening to generate viruses with rationally designed N-linked glycosylation sites and mutations in different epitopes and screened for viruses that escaped monoclonal antibodies (mAbs). We then combined rationally designed mutations with naturally selected mutations to generate a virus resistant to a cocktail of neutralizing mAbs targeting four different epitopes simultaneously. Two epitopes were protected by engineered N-linked glycosylations and two epitopes acquired escape mutations via two consecutive rounds of artificial selection in the presence of mAbs. Three of these epitopes were targeted by mAbs known to interfere with receptor binding. Results demonstrate that, within the epitopes analyzed, H can tolerate mutations in different residues and additional N-linked glycosylations to escape mAbs. Understanding the degree of change that H can tolerate is important as we follow its evolution in a host whose immunity is vaccine induced by genotype A strains instead of multiple genetically distinct wild-type MVs. PMID:23300970

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo

PubMed Central

Freund, Natalia T.; Horwitz, Joshua A.; Nogueira, Lilian; Sievers, Stuart A.; Scharf, Louise; Scheid, Johannes F.; Gazumyan, Anna; Liu, Cassie; Velinzon, Klara; Goldenthal, Ariel; Sanders, Rogier W.; Moore, John P.; Bjorkman, Pamela J.; Seaman, Michael S.; Walker, Bruce D.; Klein, Florian; Nussenzweig, Michel C.

2015-01-01

The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC80 value of 0.42 μg/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans. PMID:26516768

Simulation of field-induced molecular dissociation in atom-probe tomography: Identification of a neutral emission channel

NASA Astrophysics Data System (ADS)

Zanuttini, David; Blum, Ivan; Rigutti, Lorenzo; Vurpillot, François; Douady, Julie; Jacquet, Emmanuelle; Anglade, Pierre-Matthieu; Gervais, Benoit

2017-06-01

We investigate the dynamics of dicationic metal-oxide molecules under large electric-field conditions, on the basis of ab initio calculations coupled to molecular dynamics. Applied to the case of ZnO2 + in the field of atom probe tomography (APT), our simulation reveals the dissociation into three distinct exit channels. The proportions of these channels depend critically on the field strength and on the initial molecular orientation with respect to the field. For typical field strength used in APT experiments, an efficient dissociation channel leads to emission of neutral oxygen atoms, which escape detection. The calculated composition biases and their dependence on the field strength show remarkable consistency with recent APT experiments on ZnO crystals. Our work shows that bond breaking in strong static fields may lead to significant neutral atom production, and therefore to severe elemental composition biases in measurements.

Dynamics of ion beam charge neutralization by ferroelectric plasma sources

DOE PAGES

Stepanov, Anton D.; Gilson, Erik P.; Grisham, Larry R.; ...

2016-04-27

Ferroelectric Plasma Sources (FEPSs) can generate plasma that provides effective space-charge neutralization of intense high-perveance ion beams, as has been demonstrated on the Neutralized Drift Compression Experiment NDCX-I and NDCX-II. This article presents experimental results on charge neutralization of a high-perveance 38 keV Ar + beam by a plasma produced in a FEPS discharge. By comparing the measured beam radius with the envelope model for space-charge expansion, it is shown that a charge neutralization fraction of 98% is attainable with sufficiently dense FEPS plasma. The transverse electrostatic potential of the ion beam is reduced from 15V before neutralization to 0.3more » V, implying that the energy of the neutralizing electrons is below 0.3 eV. Measurements of the time-evolution of beam radius show that near-complete charge neutralization is established similar to –5 μs after the driving pulse is applied to the FEPS and can last for 35 μs. It is argued that the duration of neutralization is much longer than a reasonable lifetime of the plasma produced in the sub-mu s surface discharge. Measurements of current flow in the driving circuit of the FEPS show the existence of electron emission into vacuum, which lasts for tens of mu s after the high voltage pulse is applied. Lastly, it is argued that the beam is neutralized by the plasma produced by this process and not by a surface discharge plasma that is produced at the instant the high-voltage pulse is applied.« less

Detection of Escaping Lyman Continuum Radiation in Two Local Starbursts Using FUSE

NASA Astrophysics Data System (ADS)

Leitet, E.; Bergvall, N.; Andersson, B.-G.; Zackrisson, E.

2007-05-01

Dwarf galaxies may play a significant role in the reionization history of the universe, and as such also for the history of structure formation. These galaxies are however too faint to be observed at high redshifts, and it is therefore important to establish the amount of Lyman continuum (LyC) radiation that escape local starbursting dwarf galaxies. The amount of leakage is important to know also in order to improve models of star formation and spectral evolution of galaxies, which if neglected, might lead to false conclusions about the properties of the galaxies themself. Previous attempts to directly observe the leakage of hydrogen-ionizing radiation from local galaxies has before this resulted only in one successful case. In Bergvall et al. (2006 A&A 448, 513) an escape fraction of 4-10 % for the blue compact galaxy Haro 11, was found. In this work the detection and quantification of the LyC escape fractions for two additional local starburst galaxies using the Far Ultraviolet Spectroscopic Explorer, FUSE, is presented. The detections were made using FUSE archival data reduced with the latest, and much improved, pipeline. The LyC continuum can be seen as a faint structure between the Lyman limit of the target galaxies and the Milky Way. From line profile fitting it was found that both galaxies have high column densities of neutral gas, indicating that the LyC radiation is escaping through holes in the ISM. The escape fractions are calculated using spectral evolutionary models, based on the f(900Å), f(960Å) and f(Ha) fluxes. The fact that LyC leakage now is detected in three local starbursting dwarf galaxies is going to have a deep impact on future research on structure formation and galaxy evolution. The next challenge would be to statistically determine the escape fraction in extended surveys of starbursting dwarf galaxies.

Computer Labs Report to the Holodeck

ERIC Educational Resources Information Center

Raths, David

2011-01-01

In many ways, specialized computer labs are the black holes of IT organizations. Budgets, equipment, employees--even space itself--are sucked in. Given a choice, many IT shops would engage warp drive and escape their gravitational pull forever. While Captain Kirk might have looked to Scotty for a fix to the problem, colleges and universities are…

Anomalous barrier escape: The roles of noise distribution and correlation.

PubMed

Hu, Meng; Zhang, Jia-Ming; Bao, Jing-Dong

2017-05-28

We study numerically and analytically the barrier escape dynamics of a particle driven by an underlying correlated Lévy noise for a smooth metastable potential. A "quasi-monochrome-color" Lévy noise, i.e., the first-order derivative variable of a linear second-order differential equation subjected to a symmetric α-stable white Lévy noise, also called the harmonic velocity Lévy noise, is proposed. Note that the time-integral of the noise Green function of this kind is equal to zero. This leads to the existence of underlying negative time correlation and implies that a step in one direction is likely followed by a step in the other direction. By using the noise of this kind as a driving source, we discuss the competition between long flights and underlying negative correlations in the metastable dynamics. The quite rich behaviors in the parameter space including an optimum α for the stationary escape rate have been found. Remarkably, slow diffusion does not decrease the stationary rate while a negative correlation increases net escape. An approximate expression for the Lévy-Kramers rate is obtained to support the numerically observed dependencies.

Anomalous barrier escape: The roles of noise distribution and correlation

NASA Astrophysics Data System (ADS)

Hu, Meng; Zhang, Jia-Ming; Bao, Jing-Dong

2017-05-01

We study numerically and analytically the barrier escape dynamics of a particle driven by an underlying correlated Lévy noise for a smooth metastable potential. A "quasi-monochrome-color" Lévy noise, i.e., the first-order derivative variable of a linear second-order differential equation subjected to a symmetric α-stable white Lévy noise, also called the harmonic velocity Lévy noise, is proposed. Note that the time-integral of the noise Green function of this kind is equal to zero. This leads to the existence of underlying negative time correlation and implies that a step in one direction is likely followed by a step in the other direction. By using the noise of this kind as a driving source, we discuss the competition between long flights and underlying negative correlations in the metastable dynamics. The quite rich behaviors in the parameter space including an optimum α for the stationary escape rate have been found. Remarkably, slow diffusion does not decrease the stationary rate while a negative correlation increases net escape. An approximate expression for the Lévy-Kramers rate is obtained to support the numerically observed dependencies.

Wabble gear drive mechanism. [for aerospace environments

NASA Technical Reports Server (NTRS)

Winiarski, F. J. (Inventor)

1967-01-01

The wabble gear principle was applied in the design of a driving mechanism for controlling spacecraft solar panels. The moving elements, other than the output gear, are contained within a hermetically sealed package to prevent escape of lubricants and ingestion of contaminant particles. The driving gear contains one more tooth than the output gear on a concave, conical pitch surface of slightly larger apex angle. The two gears mesh face to face such that engagement takes place at one point along the circumference. The driving gear is not permitted to rotate by virtue of its attachment through the bellows which permits flexure in the pitch and yaw position, but not in roll. As the bearing carrier rotates, the inclined mounting of the bearing causes the driving gear to perform a wabbling, irrotational motion. This wabbling motion causes the contact point between the output gear and the driving gear to traverse around the circumference of the gears once per revolution of the bearing carrier.

An Industry-Scale Mass Marking Technique for Tracing Farmed Fish Escapees

PubMed Central

Warren-Myers, Fletcher; Dempster, Tim; Fjelldal, Per Gunnar; Hansen, Tom; Swearer, Stephen E.

2015-01-01

Farmed fish escape and enter the environment with subsequent effects on wild populations. Reducing escapes requires the ability to trace individuals back to the point of escape, so that escape causes can be identified and technical standards improved. Here, we tested if stable isotope otolith fingerprint marks delivered during routine vaccination could be an accurate, feasible and cost effective marking method, suitable for industrial-scale application. We tested seven stable isotopes, 134Ba, 135Ba, 136Ba, 137Ba, 86Sr, 87Sr and 26Mg, on farmed Atlantic salmon reared in freshwater, in experimental conditions designed to reflect commercial practice. Marking was 100% successful with individual Ba isotopes at concentrations as low as 0.001 µg. g-1 fish and for Sr isotopes at 1 µg. g-1 fish. Our results suggest that 63 unique fingerprint marks can be made at low cost using Ba (0.0002 – 0.02 $US per mark) and Sr (0.46 – 0.82 $US per mark) isotopes. Stable isotope fingerprinting during vaccination is feasible for commercial application if applied at a company level within the world’s largest salmon producing nations. Introducing a mass marking scheme would enable tracing of escapees back to point of origin, which could drive greater compliance, better farm design and improved management practices to reduce escapes. PMID:25738955

Current profile redistribution driven by neutral beam injection in a reversed-field pinch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parke, E.; Department of Physics, University of Wisconsin-Madison 1150 University Ave., Madison, Wisconsin 53706; Anderson, J. K.

2016-05-15

Neutral beam injection in reversed-field pinch (RFP) plasmas on the Madison Symmetric Torus [Dexter et al., Fusion Sci. Technol. 19, 131 (1991)] drives current redistribution with increased on-axis current density but negligible net current drive. Internal fluctuations correlated with tearing modes are observed on multiple diagnostics; the behavior of tearing mode correlated structures is consistent with flattening of the safety factor profile. The first application of a parametrized model for island flattening to temperature fluctuations in an RFP allows inferrence of rational surface locations for multiple tearing modes. The m = 1, n = 6 mode is observed to shift inward by 1.1 ± 0.6 cm withmore » neutral beam injection. Tearing mode rational surface measurements provide a strong constraint for equilibrium reconstruction, with an estimated reduction of q{sub 0} by 5% and an increase in on-axis current density of 8% ± 5%. The inferred on-axis current drive is consistent with estimates of fast ion density using TRANSP [Goldston et al., J. Comput. Phys. 43, 61 (1981)].« less

Importance of Ambipolar Electric Field in the Ion Loss from Mars- Results from a Multi-fluid MHD Model with the Electron Pressure Equation Included

NASA Astrophysics Data System (ADS)

Ma, Y.; Dong, C.; van der Holst, B.; Nagy, A. F.; Bougher, S. W.; Toth, G.; Cravens, T.; Yelle, R. V.; Jakosky, B. M.

2017-12-01

The multi-fluid (MF) magnetohydrodynamic (MHD) model of Mars is further improved by solving an additional electron pressure equation. Through the electron pressure equation, the electron temperature is calculated based on the effects from various electrons related heating and cooling processes (e.g. photo-electron heating, electron-neutral collision and electron-ion collision), and thus the improved model is able to calculate the electron temperature and the electron pressure force self-consistently. Electron thermal conductivity is also considered in the calculation. Model results of a normal case with electron pressure equation included (MFPe) are compared in detail to an identical case using the regular MF model to identify the effect of the improved physics. We found that when the electron pressure equation is included, the general interaction patterns are similar to that of the case with no electron pressure equation. The model with electron pressure equation predicts that electron temperature is much larger than the ion temperature in the ionosphere, consistent with both Viking and MAVEN observations. The inclusion of electron pressure equation significantly increases the total escape fluxes predicted by the model, indicating the importance of the ambipolar electric field(electron pressure gradient) in driving the ion loss from Mars.

Charge Neutralization Drives the Shape Reconfiguration of DNA Nanotubes.

PubMed

Liu, Pi; Zhao, Yan; Liu, Xiaoguo; Sun, Jixue; Xu, Dede; Li, Yang; Li, Qian; Wang, Lihua; Yang, Sichun; Fan, Chunhai; Lin, Jianping

2018-05-04

Reconfiguration of membrane protein channels for gated transport is highly regulated under physiological conditions. However, a mechanistic understanding of such channels remains challenging owing to the difficulty in probing subtle gating-associated structural changes. Herein, we show that charge neutralization can drive the shape reconfiguration of a biomimetic 6-helix bundle DNA nanotube (6HB). Specifically, 6HB adopts a compact state when its charge is neutralized by Mg 2+ ; whereas Na + switches it to the expanded state, as revealed by MD simulations, small-angle X-ray scattering (SAXS), and FRET characterization. Furthermore, partial neutralization of the DNA backbone charges by chemical modification renders 6HB compact and insensitive to ions, suggesting an interplay between electrostatic and hydrophobic forces in the channels. This system provides a platform for understanding the structure-function relationship of biological channels and designing rules for the shape control of DNA nanostructures in biomedical applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hraber, Peter; Korber, Bette; Wagh, Kshitij

Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

Fusion loop peptide of the West Nile virus envelope protein is essential for pathogenesis and is recognized by a therapeutic cross-reactive human monoclonal antibody.

PubMed

Sultana, Hameeda; Foellmer, Harald G; Neelakanta, Girish; Oliphant, Theodore; Engle, Michael; Ledizet, Michel; Krishnan, Manoj N; Bonafé, Nathalie; Anthony, Karen G; Marasco, Wayne A; Kaplan, Paul; Montgomery, Ruth R; Diamond, Michael S; Koski, Raymond A; Fikrig, Erol

2009-07-01

West Nile virus is an emerging pathogen that can cause fatal neurological disease. A recombinant human mAb, mAb11, has been described as a candidate for the prevention and treatment of West Nile disease. Using a yeast surface display epitope mapping assay and neutralization escape mutant, we show that mAb11 recognizes the fusion loop, at the distal end of domain II of the West Nile virus envelope protein. Ab mAb11 cross-reacts with all four dengue viruses and provides protection against dengue (serotypes 2 and 4) viruses. In contrast to the parental West Nile virus, a neutralization escape variant failed to cause lethal encephalitis (at higher infectious doses) or induce the inflammatory responses associated with blood-brain barrier permeability in mice, suggesting an important role for the fusion loop in viral pathogenesis. Our data demonstrate that an intact West Nile virus fusion loop is critical for virulence, and that human mAb11 targeting this region is efficacious against West Nile virus infection. These experiments define the molecular determinant on the envelope protein recognized by mAb11 and demonstrate the importance of this region in causing West Nile encephalitis.

Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability

PubMed Central

Tahara, Maino; Bürckert, Jean-Philippe; Kanou, Kazuhiko; Maenaka, Katsumi; Muller, Claude P.; Takeda, Makoto

2016-01-01

Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors. PMID:27490564

A nebula of gases from Io surrounding Jupiter.

PubMed

Krimigis, Stamatios M; Mitchell, Donald G; Hamilton, Douglas C; Dandouras, Jannis; Armstrong, Thomas P; Bolton, Scott J; Cheng, Andrew F; Gloeckler, George; Hsieh, K C; Keath, Edwin P; Krupp, Norbert; Lagg, Andreas; Lanzerotti, Louis J; Livi, Stefano; Mauk, Barry H; McEntire, Richard W; Roelof, Edmond C; Wilken, Berend; Williams, Donald J

2002-02-28

Several planetary missions have reported the presence of substantial numbers of energetic ions and electrons surrounding Jupiter; relativistic electrons are observable up to several astronomical units (au) from the planet. A population of energetic (>30[?]keV) neutral particles also has been reported, but the instrumentation was not able to determine the mass or charge state of the particles, which were subsequently labelled energetic neutral atoms. Although images showing the presence of the trace element sodium were obtained, the source and identity of the neutral atoms---and their overall significance relative to the loss of charged particles from Jupiter's magnetosphere---were unknown. Here we report the discovery by the Cassini spacecraft of a fast (>103[?]km[?]s-1) and hot magnetospheric neutral wind extending more than 0.5[?]au from Jupiter, and the presence of energetic neutral atoms (both hot and cold) that have been accelerated by the electric field in the solar wind. We suggest that these atoms originate in volcanic gases from Io, undergo significant evolution through various electromagnetic interactions, escape Jupiter's magnetosphere and then populate the environment around the planet. Thus a 'nebula' is created that extends outwards over hundreds of jovian radii.

Limits of neutral drift: lessons from the in vitro evolution of two ribozymes.

PubMed

Petrie, Katherine L; Joyce, Gerald F

2014-10-01

The relative contributions of adaptive selection and neutral drift to genetic change are unknown but likely depend on the inherent abundance of functional genotypes in sequence space and how accessible those genotypes are to one another. To better understand the relative roles of selection and drift in evolution, local fitness landscapes for two different RNA ligase ribozymes were examined using a continuous in vitro evolution system under conditions that foster the capacity for neutral drift to mediate genetic change. The exploration of sequence space was accelerated by increasing the mutation rate using mutagenic nucleotide analogs. Drift was encouraged by carrying out evolution within millions of separate compartments to exploit the founder effect. Deep sequencing of individuals from the evolved populations revealed that the distribution of genotypes did not escape the starting local fitness peak, remaining clustered around the sequence used to initiate evolution. This is consistent with a fitness landscape where high-fitness genotypes are sparse and well isolated, and suggests, at least in this context, that neutral drift alone is not a primary driver of genetic change. Neutral drift does, however, provide a repository of genetic variation upon which adaptive selection can act.

Comparative pick-up ion distributions at Mars and Venus: Consequences for atmospheric deposition and escape

NASA Astrophysics Data System (ADS)

Curry, Shannon M.; Luhmann, Janet; Ma, Yingjuan; Liemohn, Michael; Dong, Chuanfei; Hara, Takuya

2015-09-01

Without the shielding of a substantial intrinsic dipole magnetic field, the atmospheres of Mars and Venus are particularly susceptible to similar atmospheric ion energization and scavenging processes. However, each planet has different attributes and external conditions controlling its high altitude planetary ion spatial and energy distributions. This paper describes analogous test particle simulations in background MHD fields that allow us to compare the properties and fates, precipitation or escape, of the mainly O+ atmospheric pick-up ions at Mars and Venus. The goal is to illustrate how atmospheric and planetary scales affect the upper atmospheres and space environments of our terrestrial planet neighbors. The results show the expected convection electric field-related hemispheric asymmetries in both precipitation and escape, where the degree of asymmetry at each planet is determined by the planetary scale and local interplanetary field strength. At Venus, the kinetic treatment of O+ reveals a strong nightside source of precipitation while Mars' crustal fields complicate the simple asymmetry in ion precipitation and drive a dayside source of precipitation. The pickup O+ escape pattern at both Venus and Mars exhibits low energy tailward escape, but Mars exhibits a prominent, high energy 'polar plume' feature in the hemisphere of the upward convection electric field while the Venus ion wake shows only a modest poleward concentration. The overall escape is larger at Venus than Mars (2.1 ×1025 and 4.3 ×1024 at solar maximum, respectively), but the efficiency (likelihood) of O+ escaping is 2-3 times higher at Mars. The consequences of these comparisons for pickup ion related atmospheric energy deposition, loss rates, and detection on spacecraft including PVO, VEX, MEX and MAVEN are considered. In particular, both O+ precipitation and escape show electric field controlled asymmetries that grow with energy, while the O+ fluxes and energy spectra at selected spatial locations show characteristic signatures of the pickup related acceleration and precipitation.

Measurements of Ion-Neutral Coupling in the Auroral F Region in Response to Increases in Particle Precipitation

NASA Astrophysics Data System (ADS)

Kiene, A.; Bristow, W. A.; Conde, M. G.; Hampton, D. L.

2018-05-01

Neutral winds are a key factor in the dynamics of the ionosphere-thermosphere system. Previous observations have shown that neutral and ion flows are strongly coupled during periods of auroral activity when ion drag forcing can become the dominant force driving neutral wind flow. This is primarily due to increases in ion density due to enhanced particle precipitation as well as associated increases the strength of the electric fields that drive ion motions. Due to this strong coupling, numerical simulations of neutral dynamics have difficulty reproducing neutral wind observations when they are driven by modeled precipitation and modeled convection. It is therefore desirable whenever possible to have concurrent coincident measurements of auroral precipitation and ion convection. Recent advancements in high-resolution fitting of Super Dual Auroral Radar Network ion convection data have enabled the generation of steady maps of ion drifts over Alaska, coinciding with several optics sites. The Super Dual Auroral Radar Network measurements are compared with scanning Doppler imager neutral wind measurements at similar altitude, providing direct comparisons of ion and neutral velocities over a wide field and for long periods throughout the night. Also present are a digital all-sky imager and a meridian spectrograph, both of which provide measurements of auroral intensity on several wavelengths. In this study, we combine these data sets to present three case studies that show significant correlation between increases in F region precipitation and enhancements in ion-neutral coupling in the evening sector. We investigate the time scales over which the coupling takes place and compare our findings to previous measurements.

The emotional side of cognitive distraction: Implications for road safety.

PubMed

Chan, Michelle; Singhal, Anthony

2013-01-01

Driver distraction is estimated to be one of the leading causes of motor vehicle accidents. However, little is known about the role of emotional distraction on driving, despite evidence that attention is highly biased toward emotion. In the present study, we used a dual-task paradigm to examine the potential for driver distraction from emotional information presented on roadside billboards. This purpose was achieved using a driving simulator and three different types of emotional information: neutral words, negative emotional words, and positive emotional words. Participants also responded to target words while driving and completed a surprise free recall task of all the words at the end of the study. The findings suggest that driving performance is differentially affected by the valence (negative versus positive) of the emotional content. Drivers had lower mean speeds when there were emotional words compared to neutral words, and this slowing effect lasted longer when there were positive words. This may be due to distraction effects on driving behavior, which are greater for positive arousing stimuli. Moreover, when required to process non-emotional target stimuli, drivers had faster mean speeds in conditions where the targets were interspersed with emotional words compared to neutral words, and again, these effects lasted longer when there were positive words. On the other hand, negative information led to better memory recall. These unique effects may be due to separate processes in the human attention system, particularly related to arousal mechanisms and their interaction with emotion. We conclude that distraction that is emotion-based can modulate attention and decision-making abilities and have adverse impacts on driving behavior for several reasons. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of candidate vaccine approaches for MERS-CoV

DOE PAGES

Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; ...

2015-07-28

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanismsmore » were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.« less

Evaluation of candidate vaccine approaches for MERS-CoV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lingshu; Shi, Wei; Joyce, M. Gordon

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanismsmore » were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.« less

Cosmic ray interactions with lunar materials - Nature and composition of species formed

NASA Technical Reports Server (NTRS)

Mukherjee, N. R.

1976-01-01

The paper discusses the effect of cosmic-ray proton interactions with lunar material, the nature and composition of the species resulting from these interactions, and the contribution of these species to the lunar atmosphere. It is shown that hydrogen atoms resulting from cosmic-ray proton neutralization escape into the atmosphere mostly as H2, that only a small fraction of the very small amount of OH and H2O produced by cosmic-ray protons escapes into the atmosphere, and that cosmic-ray protons play a very minor role, as compared with solar-wind protons, in producing lunar atmospheric hydrogen and hydrogenated species. It is concluded that the atmospheric contributions of H2, H, OH, and H2O produced by cosmic-ray protons are about three orders of magnitude less than those due to solar-wind protons.

Relationships between trip motivations and selected variables among Allegheny National forest visitors

Treesearch

Alan R. Graefe; Brijesh Thapa; John J. Confer; James D. Absher

2000-01-01

To meet visitors’ needs, managers must understand the motivations driving visitors to wilderness areas. This paper compares the motivations of different segments of Allegheny National Forest users. Factor analysis identified 5 motivation factors (social, escape, fun, nature and learning), with two items retained as single item dimensions (close to home and challenge)....

Guerrilla Counterintelligence: Insurgent Approaches to Neutralizing Adversary Intelligence Operations

DTIC Science & Technology

2009-01-01

guard that managed to escape. Before attacking a town or population center, a list of traitors and h. “persecutors” and their addresses should be...threats to security and who require an overview of U.S. intelligence potential. Abu Bakr Naji’s Management of Savagery offers some more specific...dangers to the movement in the event a mujahid is captured by the enemy are manifest and obvious. Management of Strategy considers some options for

Occupational Strength Testing Related to Gender-Neutral Issues in Naval Aviation: A Selected Bibliography.

DTIC Science & Technology

1995-02-01

the deficiency in using the DoD survey in designing escape system tests covering female aviators. Further, analysis of two existing anthropometric...sinusoidally in all 5 contractions with a peak endurance midway through the ovulatory phase and the lowest endurance mid-way through the luteal phase...goals, and identifies deficiencies in the crewstation layout of mockups and aircraft undergoing development. 96 Reilly, R. R.; Zedeck, S.; Tenopyr, M. L

Collisional Evolution of the Enceladus Neutral Cloud

NASA Technical Reports Server (NTRS)

Cassidy, T. A.; Johnson, R. E.; Hendrix, A. R.

2011-01-01

Water vapor ejected from Saturn's small moon Enceladus easily escapes its meager gravity to form a Saturn-encircling cloud with a low collision rate. Observations show that the cloud is quite broad in the radial direction, and we show here that collisions, though quite rare, may be largely responsible for this radial spreading. We modeled this cloud using the Direct Simulation Monte Carlo method, as fluid methods would be inappropriate for such a tenuous gas.

Fitness-Balanced Escape Determines Resolution of Dynamic Founder Virus Escape Processes in HIV-1 Infection

PubMed Central

Sunshine, Justine E.; Larsen, Brendan B.; Maust, Brandon; Casey, Ellie; Deng, Wenje; Chen, Lennie; Westfall, Dylan H.; Kim, Moon; Zhao, Hong; Ghorai, Suvankar; Lanxon-Cookson, Erinn; Rolland, Morgane; Collier, Ann C.; Maenza, Janine; Mullins, James I.

2015-01-01

ABSTRACT To understand the interplay between host cytotoxic T-lymphocyte (CTL) responses and the mechanisms by which HIV-1 evades them, we studied viral evolutionary patterns associated with host CTL responses in six linked transmission pairs. HIV-1 sequences corresponding to full-length p17 and p24 gag were generated by 454 pyrosequencing for all pairs near the time of transmission, and seroconverting partners were followed for a median of 847 days postinfection. T-cell responses were screened by gamma interferon/interleukin-2 (IFN-γ/IL-2) FluoroSpot using autologous peptide sets reflecting any Gag variant present in at least 5% of sequence reads in the individual's viral population. While we found little evidence for the occurrence of CTL reversions, CTL escape processes were found to be highly dynamic, with multiple epitope variants emerging simultaneously. We found a correlation between epitope entropy and the number of epitope variants per response (r = 0.43; P = 0.05). In cases in which multiple escape mutations developed within a targeted epitope, a variant with no fitness cost became fixed in the viral population. When multiple mutations within an epitope achieved fitness-balanced escape, these escape mutants were each maintained in the viral population. Additional mutations found to confer escape but undetected in viral populations incurred high fitness costs, suggesting that functional constraints limit the available sites tolerable to escape mutations. These results further our understanding of the impact of CTL escape and reversion from the founder virus in HIV infection and contribute to the identification of immunogenic Gag regions most vulnerable to a targeted T-cell attack. IMPORTANCE Rapid diversification of the viral population is a hallmark of HIV-1 infection, and understanding the selective forces driving the emergence of viral variants can provide critical insight into the interplay between host immune responses and viral evolution. We used deep sequencing to comprehensively follow viral evolution over time in six linked HIV transmission pairs. We then mapped T-cell responses to explore if mutations arose due to adaption to the host and found that escape processes were often highly dynamic, with multiple mutations arising within targeted epitopes. When we explored the impact of these mutations on replicative capacity, we found that dynamic escape processes only resolve with the selection of mutations that conferred escape with no fitness cost to the virus. These results provide further understanding of the complicated viral-host interactions that occur during early HIV-1 infection and may help inform the design of future vaccine immunogens. PMID:26223634

Optimized AAV rh.10 Vectors That Partially Evade Neutralizing Antibodies during Hepatic Gene Transfer

PubMed Central

Selot, Ruchita; Arumugam, Sathyathithan; Mary, Bertin; Cheemadan, Sabna; Jayandharan, Giridhara R.

2017-01-01

Of the 12 common serotypes used for gene delivery applications, Adeno-associated virus (AAV)rh.10 serotype has shown sustained hepatic transduction and has the lowest seropositivity in humans. We have evaluated if further modifications to AAVrh.10 at its phosphodegron like regions or predicted immunogenic epitopes could improve its hepatic gene transfer and immune evasion potential. Mutant AAVrh.10 vectors were generated by site directed mutagenesis of the predicted targets. These mutant vectors were first tested for their transduction efficiency in HeLa and HEK293T cells. The optimal vector was further evaluated for their cellular uptake, entry, and intracellular trafficking by quantitative PCR and time-lapse confocal microscopy. To evaluate their potential during hepatic gene therapy, C57BL/6 mice were administered with wild-type or optimal mutant AAVrh.10 and the luciferase transgene expression was documented by serial bioluminescence imaging at 14, 30, 45, and 72 days post-gene transfer. Their hepatic transduction was further verified by a quantitative PCR analysis of AAV copy number in the liver tissue. The optimal AAVrh.10 vector was further evaluated for their immune escape potential, in animals pre-immunized with human intravenous immunoglobulin. Our results demonstrate that a modified AAVrh.10 S671A vector had enhanced cellular entry (3.6 fold), migrate rapidly to the perinuclear region (1 vs. >2 h for wild type vectors) in vitro, which further translates to modest increase in hepatic gene transfer efficiency in vivo. More importantly, the mutant AAVrh.10 vector was able to partially evade neutralizing antibodies (~27–64 fold) in pre-immunized animals. The development of an AAV vector system that can escape the circulating neutralizing antibodies in the host will substantially widen the scope of gene therapy applications in humans. PMID:28769791

A Mechanistic Understanding of Allosteric Immune Escape Pathways in the HIV-1 Envelope Glycoprotein

PubMed Central

Sethi, Anurag; Tian, Jianhui; Derdeyn, Cynthia A.; Korber, Bette; Gnanakaran, S.

2013-01-01

The HIV-1 envelope (Env) spike, which consists of a compact, heterodimeric trimer of the glycoproteins gp120 and gp41, is the target of neutralizing antibodies. However, the high mutation rate of HIV-1 and plasticity of Env facilitates viral evasion from neutralizing antibodies through various mechanisms. Mutations that are distant from the antibody binding site can lead to escape, probably by changing the conformation or dynamics of Env; however, these changes are difficult to identify and define mechanistically. Here we describe a network analysis-based approach to identify potential allosteric immune evasion mechanisms using three known HIV-1 Env gp120 protein structures from two different clades, B and C. First, correlation and principal component analyses of molecular dynamics (MD) simulations identified a high degree of long-distance coupled motions that exist between functionally distant regions within the intrinsic dynamics of the gp120 core, supporting the presence of long-distance communication in the protein. Then, by integrating MD simulations with network theory, we identified the optimal and suboptimal communication pathways and modules within the gp120 core. The results unveil both strain-dependent and -independent characteristics of the communication pathways in gp120. We show that within the context of three structurally homologous gp120 cores, the optimal pathway for communication is sequence sensitive, i.e. a suboptimal pathway in one strain becomes the optimal pathway in another strain. Yet the identification of conserved elements within these communication pathways, termed inter-modular hotspots, could present a new opportunity for immunogen design, as this could be an additional mechanism that HIV-1 uses to shield vulnerable antibody targets in Env that induce neutralizing antibody breadth. PMID:23696718

Random perturbations of a periodically driven nonlinear oscillator: escape from a resonance zone

NASA Astrophysics Data System (ADS)

Lingala, Nishanth; Sri Namachchivaya, N.; Pavlyukevich, Ilya

2017-04-01

For nonlinear oscillators, frequency of oscillations depends on the oscillation amplitude. When a nonlinear oscillator is periodically driven, the phase space consists of many resonance zones where the oscillator frequency and the driving frequency are commensurable. It is well known that, a small subset of initial conditions can lead to capture in one of the resonance zones. In this paper we study the effect of weak noise on the escape from a resonance zone. Using averaging techniques we obtain the mean exit time from a resonance zone and study the dependence of the exit rate on the parameters of the oscillator. Paper dedicated to Professor Peter W Sauer of University of Illinois on the occasion of his 70th birthday.

Autoresonant Control of Elliptical Non-neutral Plasmas

NASA Astrophysics Data System (ADS)

Friedland, Lazar

1999-11-01

It is shown that placing a magnetized non-neutral plasma column in a weak oscillating transverse quadrupolar potential with chirped oscillation frequency allows excitation and control of the ellipticity and rotation phase of the plasma cross section. For a given chirp rate of the driving frequency, the phenomenon has a sharp threshold on the amplitude of the perturbing potential. The effect is analogous to that reported in controlling Kirchhoff vortices in fluid dynamics [1]. The ellipticity of the plasma cross section is manipulated by using autoresonance (nonlinear phase locking) in the system between the ExB drifting plasma particles and adiabatically varying driving potential. A similar idea was used recently in controlling the l=1 diocotron mode in a non-neutral plasma [2]. [1] L. Friedland, Phys. Rev. E59, 4106 (1999). [2] J. Fajans, E. Gilson, and L. Friedland, Phys. Rev. Lett. 82, 4444 (1999).

Low-redshift Lyman continuum leaking galaxies with high [O III]/[O II] ratios

NASA Astrophysics Data System (ADS)

Izotov, Y. I.; Worseck, G.; Schaerer, D.; Guseva, N. G.; Thuan, T. X.; Fricke, K. J.; Verhamme, A.; Orlitová, I.

2018-05-01

We present observations with the Cosmic Origins Spectrograph onboard the Hubble Space Telescope of five star-forming galaxies at redshifts z in the range 0.2993 - 0.4317 and with high emission-line flux ratios O32 = [O III]λ5007/[O II]λ3727 ˜ 8 - 27 aiming to detect the Lyman continuum (LyC) emission. We detect LyC emission in all galaxies with the escape fractions fesc(LyC) in a range of 2 - 72 per cent. A narrow Lyα emission line with two peaks in four galaxies and with three peaks in one object is seen in medium-resolution COS spectra with a velocity separation between the peaks Vsep varying from ˜153 km s-1 to ˜ 345 km s-1. We find a general increase of the LyC escape fraction with increasing O32 and decreasing stellar mass M⋆, but with a large scatter of fesc(LyC). A tight anti-correlation is found between fesc(LyC) and Vsep making Vsep a good parameter for the indirect determination of the LyC escape fraction. We argue that one possible source driving the escape of ionizing radiation is stellar winds and radiation from hot massive stars.

Virtual Genomes in Flux: An Interplay of Neutrality and Adaptability Explains Genome Expansion and Streamlining

PubMed Central

Cuypers, Thomas D.; Hogeweg, Paulien

2012-01-01

The picture that emerges from phylogenetic gene content reconstructions is that genomes evolve in a dynamic pattern of rapid expansion and gradual streamlining. Ancestral organisms have been estimated to possess remarkably rich gene complements, although gene loss is a driving force in subsequent lineage adaptation and diversification. Here, we study genome dynamics in a model of virtual cells evolving to maintain homeostasis. We observe a pattern of an initial rapid expansion of the genome and a prolonged phase of mutational load reduction. Generally, load reduction is achieved by the deletion of redundant genes, generating a streamlining pattern. Load reduction can also occur as a result of the generation of highly neutral genomic regions. These regions can expand and contract in a neutral fashion. Our study suggests that genome expansion and streamlining are generic patterns of evolving systems. We propose that the complex genotype to phenotype mapping in virtual cells as well as in their biological counterparts drives genome size dynamics, due to an emerging interplay between adaptation, neutrality, and evolvability. PMID:22234601

Neutral Beam Development for the Lockheed Martin Compact Fusion Reactor

NASA Astrophysics Data System (ADS)

Ebersohn, Frans; Sullivan, Regina

2017-10-01

The Compact Fusion Reactor project at Lockheed Martin Skunk Works is developing a neutral beam injection system for plasma heating. The neutral beam plasma source consists of a high current lanthanum hexaboride (LaB6) hollow cathode which drives an azimuthal cusp discharge similar to gridded ion thrusters. The beam is extracted with a set of focusing grids and is then neutralized in a chamber pumped with Titanium gettering. The design, testing, and analyses of individual components are presented along with the most current full system results. The goal of this project is to advance in-house neutral beam expertise at Lockheed Martin to aid in operation, procurement, and development of neutral beam technology. ©2017 Lockheed Martin Corporation. All Rights Reserved.

Space Weather at Mars: 3-D studies using one-way coupling between the Multi-fluid MHD, M-GITM and M-AMPS models

NASA Astrophysics Data System (ADS)

Dong, Chuanfei

This dissertation presents numerical simulation results of the solar wind interaction with the Martian upper atmosphere by using three comprehensive 3-D models: the Mars Global Ionosphere Thermosphere Model (M-GITM), the Mars exosphere Monte Carlo model Adaptive Mesh Particle Simulator (M-AMPS), and the BATS-R-US Mars multi-fluid MHD (MF-MHD) model. The coupled framework has the potential to provide improved predictions for ion escape rates for comparison with future data to be returned by the MAVEN mission (2014-2016) and thereby improve our understanding of present day escape processes. Estimates of ion escape rates over Mars history must start from properly validated models that can be extrapolated into the past. This thesis aims to build a model library for the NASA Mars Atmosphere and Volatile EvolutioN (MAVEN) mission, which will thus enhance the science return from the MAVEN mission. In this thesis, we aim to address the following four main scientific questions by adopting the one-way coupled framework developed here: (1) What are the Martian ion escape rates at the current epoch and ancient times? (2) What controls the ion escape processes at the current epoch? How are the ion escape variations connected to the solar cycle, crustal field orientation and seasonal variations? (3) How do the variable 3-D cold neutral thermosphere and hot oxygen corona affect the solar wind-Mars interaction? (4) How does the Martian atmosphere respond to extreme variations (e.g., ICMEs) in the solar wind and its interplanetary environment? These questions are closely related to the primary scientific goals of NASA's MAVEN mission and European Space Agency's Mars Express (MEX) mission. We reasonably answer all these four questions at the end of this thesis by employing the one-way coupled framework and comparing the simulation results with both MEX and MAVEN observational data.

XUV-Exposed, Non-Hydrostatic Hydrogen-Rich Upper Atmospheres of Terrestrial Planets. Part I: Atmospheric Expansion and Thermal Escape

PubMed Central

Lammer, Helmut; Odert, Petra; Kulikov, Yuri N.; Kislyakova, Kristina G.; Khodachenko, Maxim L.; Güdel, Manuel; Hanslmeier, Arnold; Biernat, Helfried

2013-01-01

Abstract The recently discovered low-density “super-Earths” Kepler-11b, Kepler-11f, Kepler-11d, Kepler-11e, and planets such as GJ 1214b represent the most likely known planets that are surrounded by dense H/He envelopes or contain deep H2O oceans also surrounded by dense hydrogen envelopes. Although these super-Earths are orbiting relatively close to their host stars, they have not lost their captured nebula-based hydrogen-rich or degassed volatile-rich steam protoatmospheres. Thus, it is interesting to estimate the maximum possible amount of atmospheric hydrogen loss from a terrestrial planet orbiting within the habitable zone of late main sequence host stars. For studying the thermosphere structure and escape, we apply a 1-D hydrodynamic upper atmosphere model that solves the equations of mass, momentum, and energy conservation for a planet with the mass and size of Earth and for a super-Earth with a size of 2 REarth and a mass of 10 MEarth. We calculate volume heating rates by the stellar soft X-ray and extreme ultraviolet radiation (XUV) and expansion of the upper atmosphere, its temperature, density, and velocity structure and related thermal escape rates during the planet's lifetime. Moreover, we investigate under which conditions both planets enter the blow-off escape regime and may therefore experience loss rates that are close to the energy-limited escape. Finally, we discuss the results in the context of atmospheric evolution and implications for habitability of terrestrial planets in general. Key Words: Stellar activity—Low-mass stars—Early atmospheres—Earth-like exoplanets—Energetic neutral atoms—Ion escape—Habitability. Astrobiology 13, 1011–1029. PMID:24251443

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

PubMed Central

Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Çuburu, Nicolas

2013-01-01

BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. PMID:23843634

Collision cross sections and diffusion parameters for H and D in atomic oxygen. [in upper earth and Venus atmospheres

NASA Technical Reports Server (NTRS)

Hodges, R. R., Jr.

1993-01-01

Modeling the behavior of H and D in planetary exospheres requires detailed knowledge of the differential scattering cross sections for all of the important neutral-neutral and ion-neutral collision processes affecting these species over their entire ranges of interaction energies. In the upper atmospheres of Earth, Venus, and other planets as well, the interactions of H and D with atomic oxygen determine the rates of diffusion of escaping hydrogen isotopes through the thermosphere, the velocity distributions of exospheric atoms that encounter the upper thermosphere, the lifetimes of exospheric orbiters with periapsides near the exobase, and the transfer of momentum in collisions with hot O. The nature of H-O and D-O collisions and the derivation of a data base consisting of phase shifts and the differential, total, and momentum transfer cross sections for these interactions in the energy range 0.001 - 10 eV are discussed. Coefficients of mutual diffusion and thermal diffusion factors are calculated for temperatures of planetary interest.

Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

PubMed

Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

2016-05-01

HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. Copyright © 2016 Elsevier Inc. All rights reserved.

Turbomolecular Pumps for Holding Gases in Open Containers

NASA Technical Reports Server (NTRS)

Keller, John W.; Lorenz, John E.

2010-01-01

Proposed special-purpose turbomolecular pumps denoted turbotraps would be designed, along with mating open containers, to prevent the escape of relatively slowly (thermal) moving gas molecules from the containers while allowing atoms moving at much greater speeds to pass through. In the original intended applications, the containers would be electron-attachment cells, and the contained gases would be vapors of alkali metal atoms moving at thermal speeds that would be of the order of a fraction of 300 meters per second. These cells would be parts of apparatuses used to measure fluxes of neutral atoms incident at kinetic energies in the approximate range of 10 eV to 10 keV (corresponding to typical speeds of the order of 40,000 m/s and higher). The incident energetic neutral atoms would pass through the cells, wherein charge-exchange reactions with the alkali metal atoms would convert the neutral atoms to negative ions, which, in turn, could then be analyzed by use of conventional charged-particle optics.

Low energy ion distribution measurements in Madison Symmetric Torus plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Titus, J. B., E-mail: jtitus@cepast.famu.edu; Mezonlin, E. D.; Johnson, J. A.

2014-06-15

Charge-exchange neutrals contain information about the contents of a plasma and can be detected as they escape confinement. The Florida A and M University compact neutral particle analyzer (CNPA), used to measure the contents of neutral particle flux, has been reconfigured, calibrated, and installed on the Madison Symmetric Torus (MST) for high temperature deuterium plasmas. The energy range of the CNPA has been extended to cover 0.34–5.2 keV through an upgrade of the 25 detection channels. The CNPA has been used on all types of MST plasmas at a rate of 20 kHz throughout the entire discharge (∼70 ms). Plasma parameter scans showmore » that the ion distribution is most dependent on the plasma current. Magnetic reconnection events throughout these scans produce stronger poloidal electric fields, stronger global magnetic modes, and larger changes in magnetic energy all of which heavily influence the non-Maxwellian part of the ion distribution (the fast ion tail)« less

Unique Resistance of I/LnJ Mice to a Retrovirus Is Due to Sustained Interferon γ–dependent Production of Virus-neutralizing Antibodies

PubMed Central

Purdy, Alexandra; Case, Laure; Duvall, Melody; Overstrom-Coleman, Max; Monnier, Nilah; Chervonsky, Alexander; Golovkina, Tatyana

2003-01-01

Selection of immune escape variants impairs the ability of the immune system to sustain an efficient antiviral response and to control retroviral infections. Like other retroviruses, mouse mammary tumor virus (MMTV) is not efficiently eliminated by the immune system of susceptible mice. In contrast, MMTV-infected I/LnJ mice are capable of producing IgG2a virus-neutralizing antibodies, sustain this response throughout their life, and secrete antibody-coated virions into the milk, thereby preventing infection of their progeny. Antibodies were produced in response to several MMTV variants and were cross-reactive to them. Resistance to MMTV infection was recessive and was dependent on interferon (IFN)-γ production, because I/LnJ mice with targeted deletion of the INF-γ gene failed to produce any virus-neutralizing antibodies. These findings reveal a novel mechanism of resistance to retroviral infection that is based on a robust and sustained IFN-γ–dependent humoral immune response. PMID:12538662

The PhotoElectron Boundary as observed by MAVEN instruments

NASA Astrophysics Data System (ADS)

Garnier, P.; Steckiewicz, M.; Mazelle, C. X.; Xu, S.; Mitchell, D. L.; Holmberg, M.; Halekas, J. S.; Andersson, L.; Brain, D.; Connerney, J. E. P.; Espley, J. R.; Lillis, R. J.; Luhmann, J. G.; Savaud, J. A.; Jakosky, B. M.

2017-12-01

Photoelectron peaks in the 20-30 eV energy range are commonly observed in planetary atmospheres (Earth, Mars, Titan...), produced by the intense photoionization from solar 30.4 nm photons. At Mars, these photoelectrons result from the ionization of CO2 and O atmospheric neutrals, and are known to escape the planet down its tail, making them tracers for the atmospheric escape (Frahm et al., 2006). Furthermore, their presence or absence allows us to define the so-called PhotoElectron Boundary (PEB), that separates the sunlit photoelectron-dominated ionosphere from the solar wind controlled environment, as initially observed by the Mars Global Surveyor (MGS) MAG/ER instrument (Mitchell et al. (2000, 2001). We provide here a detailed statistical analysis of the location and properties of the PEB based on the Mars Atmosphere and Volatile Evolution (MAVEN) mission electron and magnetic field data. Our dataset includes 1696 dayside PEB crossings obtained from September 2014 until May 2016 (the observations of escaping photoelectrons in the wake being not included). The PEB appears as mostly sensitive to the solar wind dynamic and crustal magnetic fields pressures, for which a quantitative dependance is derived and compared with two other important boundaries : the bow shock and magnetic pileup boundary. The PEB altitude is highly variable, leading to a variable wake cross section for escape (up to +- 50%), which is important for deriving global escape rates from in situ photoelectron escape rates. The PEB is not always sharp, and is, despite a strong variability, characterized on average by : a magnetic field topology typical for the edge of the Magnetic Pile Up Region above it, more field aligned fluxes above than below, and a clear change of the altitude dependence of both electron fluxes and total density (that appears different from the ionopause). The PEB thus appears as a transition region between two plasma and field configurations which is determined by the draping topology of the interplanetary magnetic field around Mars and strongly influenced by the crustal field sources below, and whose dynamics also impacts the estimation of ionospheric plasma escape rate.

Lyman Continuum Escape Fraction of Star-forming Dwarf Galaxies at z ˜ 1

NASA Astrophysics Data System (ADS)

Rutkowski, Michael J.; Scarlata, Claudia; Haardt, Francesco; Siana, Brian; Henry, Alaina; Rafelski, Marc; Hayes, Matthew; Salvato, Mara; Pahl, Anthony J.; Mehta, Vihang; Beck, Melanie; Malkan, Matthew; Teplitz, Harry I.

2016-03-01

To date, no direct detection of Lyman continuum emission has been measured for intermediate-redshift (z˜ 1) star-forming galaxies. We combine Hubble Space Telescope grism spectroscopy with GALEX UV and ground-based optical imaging to extend the search for escaping Lyman continuum to a large (˜600) sample of z˜ 1 low-mass ({log}(\\bar{M}) ≃ 9.3{M}⊙ ), moderately star-forming (\\bar{{{\\Psi }}} ≲ 10{M}⊙ yr-1) galaxies selected initially on Hα emission. The characteristic escape fraction of LyC from star-forming galaxies (SFGs) that populate this parameter space remains weakly constrained by previous surveys, but these faint (sub-L⋆) SFGs are assumed to play a significant role in the reionization of neutral hydrogen in the intergalactic medium (IGM) at high redshift z\\gt 6. We do not make an unambiguous detection of escaping LyC radiation from this z˜ 1 sample, individual non-detections to constrain the absolute Lyman continuum escape fraction, {f}{esc} \\lt 2.1% (3σ). We measure an upper limit of {f}{esc} \\lt 9.6% from a sample of SFGs selected on high Hα equivalent width (EW \\gt 200 {{\\mathringA }}), which are thought to be close analogs of high redshift sources of reionization. For reference, we also present an emissivity-weighted escape fraction that is useful for measuring the general contribution SFGs to the ionizing UV background. In the discussion, we consider the implications of these intermediate redshift constraints for the reionization of hydrogen in the IGM at high (z\\gt 6) redshift. If we assume our z˜ 1 SFGs, for which we measure this emissivity-weighted {f}{esc}, are analogs to the high redshift sources of reionization, we find it is difficult to reconcile reionization by faint ({M}{UV}≲ -13) SFGs with a low escape fraction ({f}{esc} \\lt 3%), with constraints from independent high redshift observations. If {f}{esc} evolves with redshift, reionization by SFGs may be consistent with observations from Planck.

Heating and current drive on NSTX

NASA Astrophysics Data System (ADS)

Wilson, J. R.; Batchelor, D.; Carter, M.; Hosea, J.; Ignat, D.; LeBlanc, B.; Majeski, R.; Ono, M.; Phillips, C. K.; Rogers, J. H.; Schilling, G.

1997-04-01

Low aspect ratio tokamaks pose interesting new challenges for heating and current drive. The NSTX (National Spherical Tokamak Experiment) device to be built at Princeton is a low aspect ratio toroidal device that has the achievement of high toroidal beta (˜45%) and non-inductive operation as two of its main research goals. To achieve these goals significant auxiliary heating and current drive systems are required. Present plans include ECH (Electron cyclotron heating) for pre-ionization and start-up assist, HHFW (high harmonic fast wave) for heating and current drive and eventually NBI (neutral beam injection) for heating, current drive and plasma rotation.

Magnetic Flux Cancelation as the Trigger of Solar Coronal Jets in Coronal Holes

NASA Astrophysics Data System (ADS)

Panesar, Navdeep K.; Sterling, Alphonse C.; Moore, Ronald L.

2018-02-01

We investigate in detail the magnetic cause of minifilament eruptions that drive coronal-hole jets. We study 13 random on-disk coronal-hole jet eruptions, using high-resolution X-ray images from the Hinode/X-ray telescope(XRT), EUV images from the Solar Dynamics Observatory (SDO)/Atmospheric Imaging Assembly (AIA), and magnetograms from the SDO/Helioseismic and Magnetic Imager (HMI). For all 13 events, we track the evolution of the jet-base region and find that a minifilament of cool (transition-region-temperature) plasma is present prior to each jet eruption. HMI magnetograms show that the minifilaments reside along a magnetic neutral line between majority-polarity and minority-polarity magnetic flux patches. These patches converge and cancel with each other, with an average cancelation rate of ∼0.6 × 1018 Mx hr‑1 for all 13 jets. Persistent flux cancelation at the neutral line eventually destabilizes the minifilament field, which erupts outward and produces the jet spire. Thus, we find that all 13 coronal-hole-jet-driving minifilament eruptions are triggered by flux cancelation at the neutral line. These results are in agreement with our recent findings for quiet-region jets, where flux cancelation at the underlying neutral line triggers the minifilament eruption that drives each jet. Thus, from that study of quiet-Sun jets and this study of coronal-hole jets, we conclude that flux cancelation is the main candidate for triggering quiet-region and coronal-hole jets.

Scandinavian neuroscience during the Nazi era.

PubMed

Kondziella, Daniel; Hansen, Klaus; Zeidman, Lawrence A

2013-07-01

Although Scandinavian neuroscience has a proud history, its status during the Nazi era has been overlooked. In fact, prominent neuroscientists in German-occupied Denmark and Norway, as well as in neutral Sweden, were directly affected. Mogens Fog, Poul Thygesen (Denmark) and Haakon Sæthre (Norway) were resistance fighters, tortured by the Gestapo: Thygesen was imprisoned in concentration camps and Sæthre executed. Jan Jansen (Norway), another neuroscientist resistor, escaped to Sweden, returning under disguise to continue fighting. Fritz Buchthal (Denmark) was one of almost 8000 Jews escaping deportation by fleeing from Copenhagen to Sweden. In contrast, Carl Værnet (Denmark) became a collaborator, conducting inhuman experiments in Buchenwald concentration camp, and Herman Lundborg (Sweden) and Thorleif Østrem (Norway) advanced racial hygiene in order to maintain the "superior genetic pool of the Nordic race." Compared to other Nazi-occupied countries, there was a high ratio of resistance fighters to collaborators and victims among the neuroscientists in Scandinavia.

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

DOE PAGES

Hraber, Peter; Korber, Bette; Wagh, Kshitij; ...

2015-10-21

Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

Opiorphin causes a panicolytic-like effect in rat panic models mediated by μ-opioid receptors in the dorsal periaqueductal gray.

PubMed

Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Bonfim, Antonio Joaquim; Kitayama, Mariana; Graeff, Frederico Guilherme; Zangrossi, Hélio; Audi, Elisabeth Aparecida

2016-02-01

Reported evidence indicates that endogenous opioid peptides regulate the expression of escape behavior in rats, a panic-related defensive response, through μ-opioid receptors (MORs) in the dorsal periaqueductal gray (dPAG). These peptides are rapidly catabolized by degrading enzymes, including neutral endopeptidase (NEP) and aminopeptidase N (APN). Opiorphin is a peptide inhibitor of both NEP and APN and potentiates the action of endogenous enkephalins. This study evaluated the effects of intravenous and intra-dPAG administration of opiorphin on escape responses in the elevated T-maze and in a dPAG electrical stimulation test in rats. We also evaluated the involvement of MORs in the effects of opiorphin using the selective MOR antagonist CTOP. A dose of 2.0 mg/kg, i.v., of opiorphin impaired escape performance in both tests. Similar effects were observed with intra-dPAG administration of 5.0 nmol of opiorphin. Local pretreatment with 1.0 nmol CTOP antagonized the anti-escape effects of intra-dPAG opiorphin in both tests, as well as the effect of systemically administered opiorphin (2.0 mg/kg, i.v.) in the electrical stimulation test. These results indicate that opiorphin has an antipanic-like effect that is mediated by MORs in the dPAG. They may open new perspectives for the development of opiorphin analogues with greater bioavailability and physicochemical characteristics in the pursuit of new medications for the treatment of panic disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stellar Ablation of Planetary Atmospheres

NASA Technical Reports Server (NTRS)

Moore, Thomas E.; Horwitz, J. L.

2007-01-01

We review observations and theories of the solar ablation of planetary atmospheres, focusing on the terrestrial case where a large magnetosphere holds off the solar wind, so that there is little direct atmospheric impact, but also couples the solar wind electromagnetically to the auroral zones. We consider the photothermal escape flows known as the polar wind or refilling flows, the enhanced mass flux escape flows that result from localized solar wind energy dissipation in the auroral zones, and the resultant enhanced neutral atom escape flows. We term these latter two escape flows the "auroral wind." We review observations and theories of the heating and acceleration of auroral winds, including energy inputs from precipitating particles, electromagnetic energy flux at magnetohydrodynamic and plasma wave frequencies, and acceleration by parallel electric fields and by convection pickup processes also known as "centrifugal acceleration." We consider also the global circulation of ionospheric plasmas within the magnetosphere, their participation in magnetospheric disturbances as absorbers of momentum and energy, and their ultimate loss from the magnetosphere into the downstream solar wind, loading reconnection processes that occur at high altitudes near the magnetospheric boundaries. We consider the role of planetary magnetization and the accumulating evidence of stellar ablation of extrasolar planetary atmospheres. Finally, we suggest and discuss future needs for both the theory and observation of the planetary ionospheres and their role in solar wind interactions, to achieve the generality required for a predictive science of the coupling of stellar and planetary atmospheres over the full range of possible conditions.

Evolution dynamics of a model for gene duplication under adaptive conflict

NASA Astrophysics Data System (ADS)

Ancliff, Mark; Park, Jeong-Man

2014-06-01

We present and solve the dynamics of a model for gene duplication showing escape from adaptive conflict. We use a Crow-Kimura quasispecies model of evolution where the fitness landscape is a function of Hamming distances from two reference sequences, which are assumed to optimize two different gene functions, to describe the dynamics of a mixed population of individuals with single and double copies of a pleiotropic gene. The evolution equations are solved through a spin coherent state path integral, and we find two phases: one is an escape from an adaptive conflict phase, where each copy of a duplicated gene evolves toward subfunctionalization, and the other is a duplication loss of function phase, where one copy maintains its pleiotropic form and the other copy undergoes neutral mutation. The phase is determined by a competition between the fitness benefits of subfunctionalization and the greater mutational load associated with maintaining two gene copies. In the escape phase, we find a dynamics of an initial population of single gene sequences only which escape adaptive conflict through gene duplication and find that there are two time regimes: until a time t* single gene sequences dominate, and after t* double gene sequences outgrow single gene sequences. The time t* is identified as the time necessary for subfunctionalization to evolve and spread throughout the double gene sequences, and we show that there is an optimum mutation rate which minimizes this time scale.

Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies.

PubMed

Muñoz-Alía, Miguel Angel; Casasnovas, José M; Celma, María Luisa; Carabaña, Juan; Liton, Paloma B; Fernandez-Muñoz, Rafael

2017-05-15

Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia) which are essential for MV multiplication. In contrast, two MV-H neutralization epitopes, showed a genotype-specific neutralization escape due to a single amino acid change, that we mapped in the "noose" antigenic site, or an enhanced neutralization epitope (antigenic site IIa). The monoclonal antibody (mAb) neutralization potency correlated with its binding affinity and was mainly driven by kinetic dissociation rate (k off ). We developed an immunoassay for mAb binding to MV-H in its native hetero-oligomeric structure with MV-F on the surface of a MV productive steady-state persistently infected (p.i.) human cell lines, and a competitive-binding assay with serum from individuals with past infection by different MV genotypes. Binding assays revealed that a broad neutralization epitope, in RBS antigenic site, a genotype specific neutralization epitopes, in noose and IIa sites, were immunogenic in natural infection and vaccination and may elicit long-lasting humoral immunity that might contribute to explain MV immunogenic stability. These results support the design of improved measles vaccines, broad-spectrum prophylactic or therapeutic antibodies and MV-used in oncolytic therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Morphology of the Saturn Magnetospheric Neutral gas

NASA Astrophysics Data System (ADS)

Shemansky, D. E.

2009-05-01

Although it has been known that Saturn's magnetospheric volume is filled with neutral gas, from the time of the Voyager encounters and subsequent HST observations, the Cassini Mission was essential for revealing the depth of complexity in the source processes and structure of this system. The state of the magnetosphere is unique, containing a plasma environment quenched by neutral gas from the top of the atmosphere to beyond the bow shock with neutral/plasma mixing ratios in the range 100 to ˜ 3000. The dominant neutral species identified in the magnetosphere by remote sensing are atomic hydrogen and oxygen, OH and H2O . Atomic hydrogen was mapped using the Voyager UVS and found to have an asymmetric distribution in local time, filling the entire magnetosphere, with a broad latitudinal distribution. These observations were followed by the measurement of the OH spectrum using the HST FOS. The definition of the HST distribution was limited to a few points in the system, showing a peak near 3. Saturn radii (RS ) from system center. Atomic oxygen was detected and mapped using the Cassini UVIS system, showing orbital asymmetry and temporal variation, with a substantially broader distribution than OH. All of the observed species emissions from the magnetosphere are produced by solar photon fluorescence, the ambient plasma volume being too low in density and temperature to generate measurable particle excited emission. H2O has been measured in Cassini UVIS stellar occultations at the south polar plumes at Enceladus, with a total mass injection rate that is the same order needed to maintain the oxygen population. The oxygen distribution, however, indicates that sources other than Enceladus may be contributing. Virtually all of the atomic hydrogen in the system is attributed to escape from the top of the Saturn atmosphere. The complexity of this process was graphically revealed in the Cassini UVIS system higher resolution images showing a plume of atoms in ballistic and escaping orbits emerging from the sub-solar atmosphere at about -13 deg latitude, with a FWHM of about 20 deg. The total flux in H atoms is high enough to account for the heating required to maintain the temperature at the top of the atmosphere. There is only a crude understanding of this phenomenon, that evidently requires electrodynamic forcing in hydrogen physical chemistry in the vicinity of the exobase.

Microelectromechanical timer

DOEpatents

Polosky, Marc A.; Garcia, Ernest J.; Plummer, David W.

2001-01-01

A microminiature timer having an optical readout is disclosed. The timer can be formed by surface micromachining or LIGA processes on a silicon substrate. The timer includes an integral motor (e.g. an electrostatic motor) that can intermittently wind a mainspring to store mechanical energy for driving a train of meshed timing gears at a rate that is regulated by a verge escapement. Each timing gear contains an optical encoder that can be read out with one or more light beams (e.g. from a laser or light-emitting diode) to recover timing information. In the event that electrical power to the timer is temporarily interrupted, the mechanical clock formed by the meshed timing gears and verge escapement can continue to operate, generating accurate timing information that can be read out when the power is restored.

Statistical observations of martian 20-30 eV photoelectrons by MAVEN/SWEA

NASA Astrophysics Data System (ADS)

Garnier, P.; Steckiewicz, M.; Andre, N.; Mazelle, C. X.; Sauvaud, J. A.; Sakai, S.; Cravens, T.; Mitchell, D. L.; Lillis, R. J.; Espley, J. R.; Brain, D.; Andersson, L.; Jakosky, B. M.

2016-12-01

Photoelectron peaks in the 20-30 eV energy range are commonly observed in planetary atmospheres, produced by intense photoionization from solar 30.4 nm photons. At Mars, these photoelectrons are known to escape the planet down its tail (Frahm et al., 2006). Assuming overall charge neutrality, the number of corresponding electrons must be identical to the number of ion charges escaping the planet. Studying the photoelectrons is thus important to understand and quantify the erosion of the martian atmosphere. Moreover, the photoelectrons also play a significant role for the heating and ionization of the atmosphere. The MAVEN (Mars Atmosphere and Volatile EvolutioN) spacecraft has provided detailed observations of the Martian environment for the last two years thanks to its unique orbital coverage and comprehensive plasma instrument suite. The low periapsis altitudes (down to 125 km altitude) and combined presence of an electron spectrometer (Solar Wind Electron Analyzer, SWEA) and of a magnetometer (MAG) provide a unique opportunity to investigate the source region of the photoelectrons and their transport and escape down the tail. We will present statistical results of an automatic detection of 20-30 eV photoelectrons at Mars, based on a simple algorithm using three levels of confidence. More than 150,000 spectra (each averaged over 30s) revealed clear photoelectron peaks from October 2014 to May 2016. The analysis reveals several interesting features such as: the evolution of the peak shape from their source region to higher altitudes, the influence of the magnetic field topology on photoelectron transport, a clear dusk-dawn asymmetry in agreement with the recently-discovered neutral density asymmetry, the statistical influence of the EUV and solar wind parameters and the location of the photoelectron boundary. These results will also be compared with an electron transport code (Sakai et al., 2015, 2016) to better constrain the photoelectron production and transport.

Hepatitis C Virus Evasion Mechanisms from Neutralizing Antibodies

PubMed Central

Di Lorenzo, Caterina; Angus, Allan G. N.; Patel, Arvind H.

2011-01-01

Hepatitis C virus (HCV) represents a major public health problem, affecting 3% of the world’s population. The majority of infected individuals develop chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. To date, a vaccine is not available and current therapy is limited by resistance, adverse effects and high costs. Although it is very well established that cell-mediated immunity is necessary for viral clearance, the importance of host antibodies in clearing HCV infection is being increasingly recognized. Indeed, recent studies indicate that neutralizing antibodies are induced in the early phase of infection by patients who subsequently clear viral infection. Conversely, patients who do not clear the virus develop high titers of neutralizing antibodies during the chronic stage. Surprisingly, these antibodies are not able to control HCV infection. HCV has therefore developed mechanisms to evade immune elimination, allowing it to persist in the majority of infected individuals. A detailed understanding of the mechanisms by which the virus escapes immune surveillance is therefore necessary if novel preventive and therapeutic treatments have to be designed. This review summarizes the current knowledge of the mechanisms used by HCV to evade host neutralizing antibodies. PMID:22163345

Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

PubMed Central

Schanz, Merle; Reynell, Lucy; Günthard, Huldrych F.; Rusert, Peter; Trkola, Alexandra

2012-01-01

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo. PMID:22496655

The thermodynamics of endosomal escape and DNA release from lipoplexes.

PubMed

Avital, Yotam Y; Grønbech-Jensen, Niels; Farago, Oded

2016-01-28

Complexes of cationic and neutral lipids and DNA (lipoplexes) are emerging as promising vectors for gene therapy applications. Their appeal stems from their non pathogenic nature and the fact that they self-assemble under conditions of thermal equilibrium. Lipoplex adhesion to the cell plasma membrane initiates a three-stage process termed transfection, consisting of (i) endocytosis, (ii) lipoplex breakdown, and (iii) DNA release followed by gene expression. As successful transfection requires lipoplex degradation, it tends to be hindered by the lipoplex thermodynamic stability; nevertheless, it is known that the transfection process may proceed spontaneously. Here, we use a simple model to study the thermodynamic driving forces governing transfection. We demonstrate that after endocytosis [stage (i)], the lipoplex becomes inherently unstable. This instability, which is triggered by interactions between the cationic lipids of the lipoplex and the anionic lipids of the enveloping plasma membrane, is entropically controlled involving both remixing of the lipids and counterions release. Our detailed calculation shows that the free energy gain during stage (ii) is approximately linear in Φ+, the mole fraction of cationic lipids in the lipoplex. This free energy gain, ΔF, reduces the barrier for fusion between the enveloping and the lipoplex bilayers, which produces a hole allowing for DNA release [stage (iii)]. The linear relationship between ΔF and the fraction of cationic lipids explains the experimentally observed exponential increase of transfection efficiency with Φ+ in lamellar lipoplexes.

Escape from washing out of baryon number in a two-zero-texture general Zee model compatible with the large mixing angle MSW solution

NASA Astrophysics Data System (ADS)

Hasegawa, K.; Lim, C. S.; Ogure, K.

2003-09-01

We propose a two-zero-texture general Zee model, compatible with the large mixing angle Mikheyev-Smirnov-Wolfenstein solution. The washing out of the baryon number does not occur in this model for an adequate parameter range. We check the consistency of a model with the constraints coming from flavor changing neutral current processes, the recent cosmic microwave background observation, and the Z-burst scenario.

Probing the Martian Exosphere and Neutral Escape Using Pickup Ions Measured by MAVEN

NASA Astrophysics Data System (ADS)

Rahmati, A.; Larson, D. E.; Cravens, T.; Halekas, J. S.; Lillis, R. J.; McFadden, J. P.; Mitchell, D. L.; Thiemann, E.; Connerney, J. E. P.; Dunn, P.; DiBraccio, G. A.; Espley, J. R.; Eparvier, F. G.; Jakosky, B. M.

2016-12-01

Soon after the MAVEN (Mars Atmosphere and Volatile EvolutioN) spacecraft started orbiting Mars in September 2014, the SEP (Solar Energetic Particle), SWIA (Solar Wind Ion Analyzer), and STATIC (Supra-Thermal and Thermal Ion Composition) instruments onboard the spacecraft started detecting planetary pickup ions. SEP can measure energetic (>50 keV) oxygen pickup ions, the source of which is the extended hot oxygen exosphere of Mars. Model results show that these pickup ions originate from tens of Martian radii upstream of Mars and are energized by the solar wind motional electric field as they gyrate back towards Mars. SEP is blind to pickup hydrogen, as the low energy threshold for detection of hydrogen in SEP is 20 keV; well above the maximum pickup hydrogen energy, which is four times the solar wind proton energy. SWIA and STATIC, on the other hand, can detect both pickup oxygen and pickup hydrogen with energies below 30 keV and created closer to Mars. During the times when MAVEN is outside the Martian bow shock and in the upstream undisturbed solar wind, the solar wind velocity measured by SWIA and the solar wind (or interplanetary) magnetic field measured by the MAG (magnetometer) instrument can be used to model pickup oxygen and hydrogen fluxes near Mars. Solar wind flux measurements of the SWIA instrument are used in calculating charge-exchange frequencies, and data from the EUVM (Extreme Ultraviolet Monitor) and SWEA (Solar Wind Electron Analyzer) instruments are also used in calculating photo-ionization and electron impact frequencies of neutral species in the Martian exosphere. By comparing SEP, SWIA, and STATIC measured pickup ion fluxes with model results, the Martian thermal hydrogen and hot oxygen neutral densities can be probed outside the bow shock, which would place constraints on estimates of oxygen and hydrogen neutral escape rates. We will present model-data comparisons of pickup ions measured outside the Martian bow shock. Our analysis reveals an order of magnitude density change with Mars season in the hydrogen exosphere, whereas the hot oxygen exosphere densities vary less than a factor of 2.

What You May Not See Might Slow You Down Anyway: Masked Images and Driving

PubMed Central

Lewis-Evans, Ben; de Waard, Dick; Jolij, Jacob; Brookhuis, Karel A.

2012-01-01

Many theories of driver behaviour suggest that unconscious or implicit emotions play a functional role in the shaping and control of behaviour. This has not been experimentally tested however. Therefore, in this study the effects of emotive masked images on driver behaviour were examined. While driving a simulator, participants were repeatedly exposed to negative or neutral emotionally laden target images that were sandwich masked by emotionally neutral images. These images were encountered across two different trials each of which consisted of 3–4 minutes of driving on a rural road. The results indicate an effect of the negative target images primarily in reducing the extent of familiarisation occurring between the first and second experimental drives. This is evident in a reduced decrease in heart rate and a reduced increase in high band heart rate variability and actual travelling speed from the first to second drives if the negative target image was presented in the second drive. In addition to these findings there was no clear effect of the target image on subjective ratings of effort or feelings of risk. There was however an effect of gender, with the majority of the effects found in the study being limited to the larger female dataset. These findings suggest that unconscious or implicit emotional stimuli may well influence driver behaviour without explicit awareness. PMID:22279549

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

NASA Astrophysics Data System (ADS)

Pace, D. C.; Austin, M. E.; Bardoczi, L.; Collins, C. S.; Crowley, B.; Davis, E.; Du, X.; Ferron, J.; Grierson, B. A.; Heidbrink, W. W.; Holcomb, C. T.; McKee, G. R.; Pawley, C.; Petty, C. C.; Podestà, M.; Rauch, J.; Scoville, J. T.; Spong, D. A.; Thome, K. E.; Van Zeeland, M. A.; Varela, J.; Victor, B.

2018-05-01

An engineering upgrade to the neutral beam system at the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)] enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic ( E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2 MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities and results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Austin, Max E.; Bardoczi, Laszlo; Collins, Cami S.

Here, an engineering upgrade to the neutral beam system at the DIII-D tokamak enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic (E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities andmore » results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.« less

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

DOE PAGES

Austin, Max E.; Bardoczi, Laszlo; Collins, Cami S.; ...

2018-04-20

Here, an engineering upgrade to the neutral beam system at the DIII-D tokamak enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic (E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities andmore » results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.« less

Combination Antimicrobial Nanocomposite Materials for Neutralization of Biological Threat Agents (PREPRINT)

DTIC Science & Technology

2008-09-01

AFRL-RX-TY-TP-2008-4601 PREPRINT COMBINATION ANTIMICROBIAL NANOCOMPOSITE MATERIALS FOR NEUTRALIZATION OF BIOLOGICAL THREAT AGENTS...AIRBASE TECHNOLOGIES DIVISION MATERIALS AND MANUFACTURING DIRECTORATE AIR FORCE RESEARCH LABORATORY AIR FORCE MATERIEL COMMAND 139 BARNES DRIVE, SUITE 2...a composite material that combines the protein and inorganic components. The process can be mimicked in vitro to some degree, providing methods for

Interactive Ion-Neutral Dynamics in the Low Latitude Evening Ionosphere

NASA Astrophysics Data System (ADS)

Evonosky, W. R.; Richmond, A. D.; Fang, T. W.; Maute, A. I.

2015-12-01

Neutral winds in the ionosphere drive global electrodynamic phenomena which alter theupper-atmosphere so significantly that they can affect the orbit of satellites andground-to-spacecraft communications. Understanding these winds and what drives them is centralto prediction and risk management associated with such a dynamic upper atmosphere. This studyexamined the relationship between accelerations acting on neutral winds in the ionosphere and theformation of a vertical shear of those winds in low latitudes (between ±30 magnetic) and earlyevening local times (16-22 LT). Accelerations were calculated using variables output by thethermosphere ionosphere electrodynamics general circulation model (TIEGCM) under differentsolar activity and night-time ionization conditions and visualized both spatially and temporally. Ingeneral, with acceleration values averaged along magnetic latitudes between ±30 degrees(inclusive) and only considering medium solar activity conditions, we found that the ionosphereexhibits distinct layering defined by the dominant accelerations in each layer. We also found hintsthat during different night-time ionization levels, ion drag acceleration tends to remain constantwhile ion and neutral velocities change to conserve the difference between them. When consideringspecific latitudes and solar conditions, previously unreported structures appear which involveinteractions between the ion drag and viscous forces.

Centering Single Cells in Microgels via Delayed Crosslinking Supports Long-Term 3D Culture by Preventing Cell Escape.

PubMed

Kamperman, Tom; Henke, Sieger; Visser, Claas Willem; Karperien, Marcel; Leijten, Jeroen

2017-06-01

Single-cell-laden microgels support physiological 3D culture conditions while enabling straightforward handling and high-resolution readouts of individual cells. However, their widespread adoption for long-term cultures is limited by cell escape. In this work, it is demonstrated that cell escape is predisposed to off-center encapsulated cells. High-speed microscopy reveals that cells are positioned at the microgel precursor droplets' oil/water interface within milliseconds after droplet formation. In conventional microencapsulation strategies, the droplets are typically gelled immediately after emulsification, which traps cells in this off-center position. By delaying crosslinking, driving cells toward the centers of microgels is succeeded. The centering of cells in enzymatically crosslinked microgels prevents their escape during at least 28 d. It thereby uniquely enables the long-term culture of individual cells within <5-µm-thick 3D uniform hydrogel coatings. Single cell analysis of mesenchymal stem cells in enzymatically crosslinked microgels reveals unprecedented high cell viability (>90%), maintained metabolic activity (>70%), and multilineage differentiation capacity (>60%) over a period of 28 d. The facile nature of this microfluidic cell-centering method enables its straightforward integration into many microencapsulation strategies and significantly enhances control, reproducibility, and reliability of 3D single cell cultures. © 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effects of taboo-related distraction on driving performance.

PubMed

Chan, Michelle; Madan, Christopher R; Singhal, Anthony

2016-07-01

Roadside billboards containing negative and positive emotional content have been shown to influence driving performance, however, the impact of highly arousing taboo information is unknown. Taboo information more reliably evokes emotional arousal and can lead to greater attentional capture due to its inherent 'shock value.' The objective of the present study was to examine driver distraction associated with four types of information presented on roadside billboards: highly arousing taboo words, moderately arousing positive and negative words, and non-arousing neutral words. Participants viewed blocks of taboo, positive, negative and neutral words presented on roadside billboards while operating a driving simulator. They also responded to target (household-related) words by pressing a button on the steering wheel. At the end of the session, a surprise recall task was completed for all the words they saw while driving. Results showed that taboo words captured the most attention as revealed by better memory recall compared to all the other word types. Interestingly, taboo words were associated with better lane control compared to the other word types. We suggest that taboo-related arousal can enhance attentional focus during a complex task like simulated driving. That is, in a highly arousing situation, attention is selectively narrowed to the road ahead, resulting in better lane control. Copyright © 2016 Elsevier B.V. All rights reserved.

HST/COS Observations Of Lyman-α Emission From =0.03 Star Forming Galaxies

NASA Astrophysics Data System (ADS)

Wofford, Aida; Leitherer, C.; Salzer, J.; COS Science Team

2012-01-01

Although HI Lyman-alpha (Lyα, 1216 Å) is expected to be the strongest recombination line in HII nebulae, it is resonantly scattered by neutral hydrogen and is easily destroyed by dust. And yet, some star-forming galaxies show Lyα in emission. As evidenced by high dispersion HST/GHRS+STIS FUV spectroscopy of a handful of local (z<0.03) galaxies, the velocity shift between the neutral gas and the ionized gas plays a key role in driving the observed Lyα escape. We present HST/COS/G130M 1150-1450 Å (observed-frame) spectroscopy of 20 new targets located at a mean redshift of =0.03. The targets were selected from the KISSR survey on the basis of their GALEX FUV continuum luminosity. The observations cover the central 1-2 kpc of each galaxy, a wide range in metallicity ([O/H]=-0.83 to 0.38), and at least two orders of magnitude in FUV continuum luminosity. Seven objects show Lyα emission in the form of a P-Cygni or double-peaked profile. For 6/7 of the latter objects we are able to show that the emission is accompanied of O I gas outflows with speeds of up to 200 km/s. Two objects have Lyα luminosities comparable to the GALEX Lyα luminosities of targets at =0.3, but we find no Lyα emitters with EW(Lyα)>20 Å, such as those discovered with GALEX at z=0.2-0.35. We compare the observed Lyα/Hα line intensity ratios with predictions from dust-free cases A and B recombination under normal HII region conditions. We find evidence of O I gas inflow in the most metal-poor objects. This work is supported by NASA grant N1317.

Modeling Ultraviolet Emissions Near Io

NASA Technical Reports Server (NTRS)

Linker, Jon A.

2000-01-01

In this report, we describe work awarded to Science Applications International Corporation, for the period 6/l/99 to 5/31/00. During this time period, we have investigated the interaction of Io, Jupiter's innermost Galilean satellite, with the Io plasma torus, and the role this interaction plays in producing ultraviolet (UV) emissions from neutral oxygen and sulfur. Io, the innermost of Jupiter's Galilean satellites, plays a unique role in the jovian magnetosphere. Neutral material that escapes from Io is ionized to form the lo torus, a dense, heavy-ion plasma that corotates with Jupiter and interacts with Io. Io supplies not only the torus, but is a major source of plasma for the entire magnetosphere. Ionization and charge-exchange of neutrals near lo strongly influences the plasma interaction, and Io's neutral atmosphere plays an important role in the generation of currents that couple Io to Jupiter. There have been no in situ measurements of the neutral density near Io, but remote observations of neutrals near lo have been performed for many years. Recent observations from the Hubble Space Telescope (HST) have shown detailed structure in UV emissions from neutral species near Io. Electron-impact of the neutrals by the Io torus plasma is the primary mechanism responsible for exciting these emissions. Previously, we have modeled the Io plasma environment using three-dimensional magnetohydrodynamic (MHD) simulations, and we have shown that the interaction between Io and the plasma torus plays an important role in producing the morphology of the observed emissions. In the past year, we have extended these studies to use both UV observations and Galileo particle and field measurements to investigate the Io interaction.

Escape of Hydrogen from the Exosphere of Mars

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Remote Sensing of Icy Galilean Moon Surface and Atmospheric Composition Using Low Energy (1 eV-4 keV) Neutral Atom Imaging

NASA Technical Reports Server (NTRS)

Collier, M. R.; Sittler, E.; Chornay, D.; Cooper, J. F.; Coplan, M.; Johnson, R. E.

2004-01-01

We describe a low energy neutral atom imager suitable for composition measurements Europa and other icy Galilean moons in the Jovian magnetosphere. This instrument employs conversion surface technology and is sensitive to either neutrals converted to negative ions, neutrals converted to positive ions and the positive ions themselves depending on the power supply. On a mission such as the Jupiter Icy Moons Orbiter (JIMO), two back-to-back sensors would be flown with separate power supplies fitted to the neutral atom and iodneutral atom sides. This will allow both remote imaging of 1 eV < E < 4 keV neutrals from icy moon surfaces and atmospheres, and in situ measurements of ions at similar energies in the moon ionospheres and Jovian magnetospheric plasma. The instrument provides composition measurements of the neutrals and ions that enter the spectrometer with a mass resolution dependent on the time-of-flight subsystem and capable of resolving molecules. The lower energy neutrals, up to tens of eV, arise from atoms and molecules sputtered off the moon surfaces and out of the moon atmospheres by impacts of more energetic (keV to MeV) ions from the magnetosphere. Direct Simulation Monte Carlo (DSMC) models are used to convert measured neutral abundances to compositional distributions of primary and trace species in the sputtered surfaces and atmospheres. The escaping neutrals can also be detected as ions after photo- or plasma-ionization and pickup. Higher energy, keV neutrals come from charge exchange of magnetospheric ions in the moon atmospheres and provide information on atmospheric structure. At the jovicentric orbits of the icy moons the presence of toroidal gas clouds, as detected at Europa's orbit, provide M e r opportunities to analyze both the composition of neutrals and ions originating from the moon surfaces, and the characteristics of magnetospheric ions interacting with neutral cloud material. Charge exchange of low energy ions near the moons, and directional distributions of the resultant neutrals, allow indirect global mapping of magnetic field structures around the moons. Temporal variation of the magnetic structures can be linked to induced magnetic fields associated with subsurface oceans.

The impact of antigenic drift of influenza A virus on human herd immunity: Sero-epidemiological study of H1N1 in healthy Thai population in 2009.

PubMed

Kanai, Yuta; Boonsathorn, Naphatsawan; Chittaganpitch, Malinee; Bai, Guirong; Li, Yonggang; Kase, Tetsuo; Takahashi, Kazuo; Okuno, Yoshinobu; Jampangern, Wipawee; Ikuta, Kazuyoshi; Sawanpanyalert, Pathom

2010-07-26

To examine the effect of the antigenic drift of H1N1 influenza viruses on herd immunity, neutralization antibodies from 744 sera from Thai healthy volunteers in 2008-2009, who had not been vaccinated for at least the last 5 years, were investigated by microneutralization (MN) and hemagglutination inhibition (HI) assays. Significantly higher MN titers were observed for the H1N1 Thai isolate in 2006 than in 2008. The results indicate that the antigenically drifted virus effectively escaped herd immunity. Since the low neutralization activity of herd immunity against drifted viruses is an important factor for viruses to spread efficiently, continuous sero-epidemiological study is required for public health. Copyright 2010 Elsevier Ltd. All rights reserved.

The Lyman continuum escape fraction of low mass star-forming galaxies at z~1.

NASA Astrophysics Data System (ADS)

Rutkowski, Michael J.; Scarlata, Claudia; Haardt, Francesco; Siana, Brian D.; Rafelski, Marc; Henry, Alaina L.; Hayes, Matthew; Salvato, Mara; Pahl, Anthony; Mehta, Vihang; Beck, Melanie; Malkan, Matthew Arnold; Teplitz, Harry I.

2016-01-01

Star-forming galaxies (SFGs) in the high redshift universe (z>6) are believed to ionize neutral hydrogen in the intergalactic medium during the epoch of reionization. We tested this assumption by studying likely analogs of these SFGs in archival HST grism spectroscopy with GALEX UV and ground-based optical images at the redshift range in which we can directly measure the rest-frame Lyman continuum (λ<912Å, LyC) emission. We selected ~1400 SFGs for study on the presence of strong Hα emission and strongly selected against those SFGs whose GALEX FUV photometry could be contaminated by low redshift interlopers along the line of sight to produce a sample of ~600 z~1 SFGs. We made no unambiguous detection of escaping Lyman continuum radiation in individual galaxies in this sample, and stacked the individual non-detections in order to constrain the absolute Lyman continuum escape fraction, fesc<2% (3σ). We sub-divided this sample and stacked SFGs to measure upper limits to fesc with respect to stellar mass,luminosity and relative orientation. For z~1 high Hα equivalent width (EW>200Å) SFGs, we found for the first time an upper limit to fesc<9%. We discuss the implications of these limits for the ionizing emissivity of high redshift SFGs during the epoch of reionization. We conclude that reionization by SFGs is only marginally consistent with independent Planck observations of the CMB electron scattering opacity unless the LyC escape fraction of SFGs increases with redshift and an unobserved population of faint (MUV<-13 AB) SFGs contributes significantly to the UV background.

Experimental evidence on microwave induced electron losses from ECRIS plasma

NASA Astrophysics Data System (ADS)

Sakildien, M.; Tarvainen, O.; Kronholm, R.; Izotov, I.; Skalyga, V.; Kalvas, T.; Jones, P.; Koivisto, H.

2018-06-01

The balance between warm and hot (>1 keV) electron density and their losses from the magnetic confinement system of an Electron Cyclotron Resonance Ion Source (ECRIS) plasma is considered to be one of the main factors determining the rate of the high charge state ion production. One of the key loss channels for heated electrons is thought to be induced by the injected microwaves. While this loss mechanism, referred to as rf-induced pitch angle scattering, has been studied theoretically and with computational tools, direct experimental evidence of its significance in minimum-B ECRIS plasmas remains limited. In this work, experimental evidence of microwave induced electron losses in the axial direction is presented in both continuous wave (CW) and pulsed operation of a 14 GHz ECRIS. In the CW mode, the experiment was carried out by comparing the characteristic X-ray emission from the plasma volume and from the surface of the biased disc located in the flux of the escaping electron at the axial magnetic mirror. Parametric sweeps of magnetic field, neutral gas pressure, and microwave power were conducted to determine their effect on electron losses. In the pulsed mode, the experiment was conducted by measuring the flux of escaping electrons through aluminum foils of different thicknesses providing some energy resolution. Both diagnostics support the view that rf-induced losses account for up to 70% of total hot electron losses and their importance depends on the source parameters, especially power and neutral gas pressure.

Photochemistry of Triton's atmosphere and ionosphere.

PubMed

Krasnopolsky, V A; Cruikshank, D P

1995-10-25

The photochemistry of 32 neutral and 21 ion species in Triton's atmosphere is considered. Parent species N2, CH4, and CO (with a mixing ratio of 3 x 10(-4) in our basic model) sublime from the ice with rates of 40, 208, and 0.3 g/cm2/b.y., respectively. Chemistry below 50 km is driven mostly by photolysis of methane by the solar and interstellar medium Lyman-alpha photons, producing hydrocarbons C2H4, C2H6, and C2H2 which form haze particles with precipitation rates of 135, 28, and 1.3 g/cm2/b.y., respectively. Some processes are discussed which increase the production of HCN (by an order of magnitude to a value of 29 g/cm2/b.y.) and involve indirect photolysis of N2 by neutrals. Reanalysis of the measured methane profiles gives an eddy diffusion coefficient K = 4 x 10(3) cm2/s above the tropopause and a more accurate methane number density near the surface, (3.1 +/- 0.8) x 10(11) cm-3. Chemistry above 200 km is driven by the solar EUV radiation (lambda < 1000 angstroms) and by precipitation of magnetospheric electrons with a total energy input of 10(8) W (based on thermal balance calculations). The most abundant photochemical species are N, H2, H, O, and C. They escape with the total rates of 7.7 x 10(24) s-1, 4.5 x 10(25) s-1, 2.4 x 10(25) s-1, 4.4 x 10(22) s-1, and 1.1 x 10(24) s-1, respectively. Atomic species are transported to a region of 50-200 km and drive the chemistry there. Ionospheric chemistry explains the formation of an E region at 150-240 km with HCO+ as a major ion, and of an F region above 240 km with a peak at 320 km and C+ as a major ion. The ionosphere above 500 km consists of almost equal densities of C+ and N+ ions. The model profiles agree with the measured atomic nitrogen and electron density profiles. A number of other models with varying rate coefficients of some reactions, differing properties of the haze particles (chemically passive or active), etc., were developed. These models show that there are four basic unknown values which have strong impacts on the composition and structure of the atmosphere and ionosphere. These values and their plausible ranges are the CO mixing ratio fco = 10(-4)-10(-3), the magnetospheric electron energy input (1 +/- 0.5) x 10(8) W, the rate coefficient of charge-exchange reaction N2(+) + C k = 10(-11)-10(-10) cm3/s, and the ion escape velocity Vi approximately equal to 150 cm/s.

Survey of heating and current drive for K-DEMO

NASA Astrophysics Data System (ADS)

Mikkelsen, D. R.; Kessel, C. E.; Poli, F. M.; Bertelli, N.; Kim, K.

2018-03-01

We present calculations of heating and current drive by neutral injection and by electromagnetic waves in the ion cyclotron, helicon, lower hybrid, and electron cyclotron frequency ranges for the steady state burn conditions in a K-DEMO configuration with I_p=12.3 MA, a  =  2.1 m, R_o=6.8 m, B_o=7.4 T, \

Beyond ITER: neutral beams for a demonstration fusion reactor (DEMO) (invited).

PubMed

McAdams, R

2014-02-01

In the development of magnetically confined fusion as an economically sustainable power source, International Tokamak Experimental Reactor (ITER) is currently under construction. Beyond ITER is the demonstration fusion reactor (DEMO) programme in which the physics and engineering aspects of a future fusion power plant will be demonstrated. DEMO will produce net electrical power. The DEMO programme will be outlined and the role of neutral beams for heating and current drive will be described. In particular, the importance of the efficiency of neutral beam systems in terms of injected neutral beam power compared to wallplug power will be discussed. Options for improving this efficiency including advanced neutralisers and energy recovery are discussed.

On geometric factors for neutral particle analyzers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stagner, L.; Heidbrink, W. W.

2014-11-15

Neutral particle analyzers (NPA) detect neutralized energetic particles that escape from plasmas. Geometric factors relate the counting rate of the detectors to the intensity of the particle source. Accurate geometric factors enable quick simulation of geometric effects without the need to resort to slower Monte Carlo methods. Previously derived expressions [G. R. Thomas and D. M. Willis, “Analytical derivation of the geometric factor of a particle detector having circular or rectangular geometry,” J. Phys. E: Sci. Instrum. 5(3), 260 (1972); J. D. Sullivan, “Geometric factor and directional response of single and multi-element particle telescopes,” Nucl. Instrum. Methods 95(1), 5–11 (1971)]more » for the geometric factor implicitly assume that the particle source is very far away from the detector (far-field); this excludes applications close to the detector (near-field). The far-field assumption does not hold in most fusion applications of NPA detectors. We derive, from probability theory, a generalized framework for deriving geometric factors that are valid for both near and far-field applications as well as for non-isotropic sources and nonlinear particle trajectories.« less

The DYNAMO Orbiter Project: High Resolution Mapping of Gravity/Magnetic Fields and In Situ Investigation of Mars Atmospheric Escape

NASA Technical Reports Server (NTRS)

Smrekar, S.; Chassefiere, E.; Forget, F.; Reme, H.; Mazelle, C.; Blelly, P. -L.; Acuna, M.; Connerney, J.; Purucker, M.; Lin, R.

2000-01-01

Dynamo is a small Mars orbiter planned to be launched in 2005 or 2007, in the frame of the NASA/CNES Mars exploration program. It is aimed at improving gravity and magnetic field resolution, in order to better understand the magnetic, geologic and thermal history of Mars, and at characterizing current atmospheric escape, which is still poorly constrained. These objectives are achieved by using a low periapsis orbit, similar to the one used by the Mars Global Surveyor spacecraft during its aerobraking phases. The proposed periapsis altitude for Dynamo of 120-130 km, coupled with the global distribution of periapses to be obtained during one Martian year of operation, through about 5000 low passes, will produce a magnetic/gravity field data set with approximately five times the spatial resolution of MGS. Low periapsis provides a unique opportunity to investigate the chemical and dynamical properties of the deep ionosphere, thermosphere, and the interaction between the atmosphere and the solar wind, therefore atmospheric escape, which may have played a crucial role in removing atmosphere, and water, from the planet. There is much room for debate on the importance of current atmosphere escape processes in the evolution of the Martian atmosphere, as early "exotic" processes including hydrodynamic escape and impact erosion are traditionally invoked to explain the apparent sparse inventory of present-day volatiles. Yet, the combination of low surface gravity and the absence of a substantial internally generated magnetic field have undeniable effects on what we observe today. In addition to the current losses in the forms of Jeans and photochemical escape of neutrals, there are solar wind interaction-related erosion mechanisms because the upper atmosphere is directly exposed to the solar wind. The solar wind related loss rates, while now comparable to those of a modest comet, nonetheless occur continuously, with the intriguing possibility of important cumulative and/or enhanced effects over the several billion years of the solar system's life. If the detailed history of the Martian internal field could be traced back, and the current escape processes could be understood well enough to model the expected stronger losses under early Sun conditions, one could go a long way toward constraining this part of the mysterious history of Mars' atmosphere.

Genetic variation of loci potentially under selection confounds species-genetic diversity correlations in a fragmented habitat.

PubMed

Bertin, Angeline; Gouin, Nicolas; Baumel, Alex; Gianoli, Ernesto; Serratosa, Juan; Osorio, Rodomiro; Manel, Stephanie

2017-01-01

Positive species-genetic diversity correlations (SGDCs) are often thought to result from the parallel influence of neutral processes on genetic and species diversity. Yet, confounding effects of non-neutral mechanisms have not been explored. Here, we investigate the impact of non-neutral genetic diversity on SGDCs in high Andean wetlands. We compare correlations between plant species diversity and genetic diversity (GD) calculated with and without loci potentially under selection (outlier loci). The study system includes 2188 specimens from five species (three common aquatic macroinvertebrate and two dominant plant species) that were genotyped for 396 amplified fragment length polymorphism loci. We also appraise the importance of neutral processes on SGDCs by investigating the influence of habitat fragmentation features. Significant positive SGDCs were detected for all five species (mean SGDC = 0.52 ± 0.05). While only a few outlier loci were detected in each species, they resulted in significant decreases in GD and in SGDCs. This supports the hypothesis that neutral processes drive species-genetic diversity relationships in high Andean wetlands. Unexpectedly, the effects on genetic diversity GD of the habitat fragmentation characteristics in this study increased with the presence of outlier loci in two species. Overall, our results reveal pitfalls in using habitat features to infer processes driving SGDCs and show that a few loci potentially under selection are enough to cause a significant downward bias in SGDC. Investigating confounding effects of outlier loci thus represents a useful approach to evidence the contribution of neutral processes on species-genetic diversity relationships. © 2016 John Wiley & Sons Ltd.

Evidence of a potential receptor-binding site on the Nipah virus G protein (NiV-G): identification of globular head residues with a role in fusion promotion and their localization on an NiV-G structural model.

PubMed

Guillaume, Vanessa; Aslan, Hamide; Ainouze, Michelle; Guerbois, Mathilde; Wild, T Fabian; Buckland, Robin; Langedijk, Johannes P M

2006-08-01

As a preliminary to the localization of the receptor-binding site(s) on the Nipah virus (NiV) glycoprotein (NiV-G), we have undertaken the identification of NiV-G residues that play a role in fusion promotion. To achieve this, we have used two strategies. First, as NiV and Hendra virus (HeV) share a common receptor and their cellular tropism is similar, we hypothesized that residues functioning in receptor attachment could be conserved between their respective G proteins. Our initial strategy was to target charged residues (which can be expected to be at the surface of the protein) conserved between the NiV-G and HeV-G globular heads. Second, we generated NiV variants that escaped neutralization by anti-NiV-G monoclonal antibodies (MAbs) that neutralize NiV both in vitro and in vivo, likely by blocking receptor attachment. The sequencing of such "escape mutants" identified NiV-G residues present in the epitopes to which the neutralizing MAbs are directed. Residues identified via these two strategies whose mutation had an effect on fusion promotion were localized on a new structural model for the NiV-G protein. Our results suggest that seven NiV-G residues, including one (E533) that was identified using both strategies, form a contiguous site on the top of the globular head that is implicated in ephrinB2 binding. This site commences near the shallow depression in the center of the top surface of the globular head and extends to the rim of the barrel-like structure on the top loops of beta-sheet 5. The topology of this site is strikingly similar to that proposed to form the SLAM receptor site on another paramyxovirus attachment protein, that of the measles virus hemagglutinin.

Evidence of a Potential Receptor-Binding Site on the Nipah Virus G Protein (NiV-G): Identification of Globular Head Residues with a Role in Fusion Promotion and Their Localization on an NiV-G Structural Model

PubMed Central

Guillaume, Vanessa; Aslan, Hamide; Ainouze, Michelle; Guerbois, Mathilde; Fabian Wild, T.; Buckland, Robin; Langedijk, Johannes P. M.

2006-01-01

As a preliminary to the localization of the receptor-binding site(s) on the Nipah virus (NiV) glycoprotein (NiV-G), we have undertaken the identification of NiV-G residues that play a role in fusion promotion. To achieve this, we have used two strategies. First, as NiV and Hendra virus (HeV) share a common receptor and their cellular tropism is similar, we hypothesized that residues functioning in receptor attachment could be conserved between their respective G proteins. Our initial strategy was to target charged residues (which can be expected to be at the surface of the protein) conserved between the NiV-G and HeV-G globular heads. Second, we generated NiV variants that escaped neutralization by anti-NiV-G monoclonal antibodies (MAbs) that neutralize NiV both in vitro and in vivo, likely by blocking receptor attachment. The sequencing of such “escape mutants” identified NiV-G residues present in the epitopes to which the neutralizing MAbs are directed. Residues identified via these two strategies whose mutation had an effect on fusion promotion were localized on a new structural model for the NiV-G protein. Our results suggest that seven NiV-G residues, including one (E533) that was identified using both strategies, form a contiguous site on the top of the globular head that is implicated in ephrinB2 binding. This site commences near the shallow depression in the center of the top surface of the globular head and extends to the rim of the barrel-like structure on the top loops of β-sheet 5. The topology of this site is strikingly similar to that proposed to form the SLAM receptor site on another paramyxovirus attachment protein, that of the measles virus hemagglutinin. PMID:16840334

The role of plasma/neutral source and loss processes in shaping the giant planet magnetospheres

NASA Astrophysics Data System (ADS)

Delamere, P. A.

2014-12-01

The giant planet magnetospheres are filled with neutral and ionized gases originating from satellites orbiting deep within the magnetosphere. The complex chemical and physical pathways for the flow of mass and energy in this partially ionized plasma environment is critical for understanding magnetospheric dynamics. The flow of mass at Jupiter and Saturn begins, primarily, with neutral gases emanating from Io (~1000 kg/s) and Enceladus (~200 kg/s). In addition to ionization losses, the neutral gases are absorbed by the planet, its rings, or escape at high speeds from the magnetosphere via charge exchange reactions. The net result is a centrifugally confined torus of plasma that is transported radially outward, distorting the magnetic field into a magnetodisc configuration. Ultimately the plasma is lost to the solar wind. A critical parameter for shaping the magnetodisc and determining its dynamics is the radial plasma mass transport rate (~500 kg/s and ~50 kg/s for Jupiter and Saturn respectively). Given the plasma transport rates, several simple properties of the giant magnetodiscs can be estimated including the physical scale of the magnetosphere, the magnetic flux transport, and the magnitude of azimuthal magnetic field bendback. We will discuss transport-related magnetic flux conservation and the mystery of plasma heating—two critical issues for shaping the giant planet magnetospheres.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLellan, Jason S.; Chen, Man; Chang, Jung-San

Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants and elderly people. Currently there is no effective vaccine against RSV, but passive prophylaxis with neutralizing antibodies reduces hospitalizations. To investigate the mechanism of antibody-mediated RSV neutralization, we undertook structure-function studies of monoclonal antibody 101F, which binds a linear epitope in the RSV fusion glycoprotein. Crystal structures of the 101F antigen-binding fragment in complex with peptides from the fusion glycoprotein defined both the extent of the linear epitope and the interactions of residues that are mutated in antibody escape variants. The structure allowed for modeling ofmore » 101F in complex with trimers of the fusion glycoprotein, and the resulting models suggested that 101F may contact additional surfaces located outside the linear epitope. This hypothesis was supported by surface plasmon resonance experiments that demonstrated 101F bound the peptide epitope {approx}16,000-fold more weakly than the fusion glycoprotein. The modeling also showed no substantial clashes between 101F and the fusion glycoprotein in either the pre- or postfusion state, and cell-based assays indicated that 101F neutralization was not associated with blocking virus attachment. Collectively, these results provide a structural basis for RSV neutralization by antibodies that target a major antigenic site on the fusion glycoprotein.« less

Identification of conformational neutralization sites on the fusion protein of mumps virus.

PubMed

Šantak, Maja; Örvell, Claes; Gulija, Tanja Košutić

2015-05-01

In spite of the success of the mumps vaccination, recent mumps outbreaks have been reported even among individuals with a history of mumps vaccination. For a better understanding of why the vaccination failed in cases of vaccinees who fell ill during recent mumps outbreaks, the immunological events during infection and/or vaccination should be better defined. In the work presented here we sought to identify new neutralization sites on the mumps virus surface glycoproteins. By using anti-mumps mAbs, three amino acid positions at residues 221, 323 and 373 in the F protein of mumps virus were shown to be located in at least two conformational neutralization epitopes. mAbs that specifically target these sites effectively neutralized mumps virus in vitro. The newly acquired glycosylation site at position 373 or loss of the existing one at position 323 was identified as the mechanism behind the escape from the specific mAbs. Based on the findings of this study, we suggest that the influence of the antigenic structure of the F protein should not be ignored in a thorough investigation of the underlying mechanism of the mumps vaccine failure or when making a strategy for development of a new vaccine. © 2015 The Authors.

A self-consistent view on plasma-neutral interaction near a wall: plasma acceleration by momentum removal and heating by cold walls

NASA Astrophysics Data System (ADS)

van Rooij, Gerard; den Harder, Niek; Minea, Teofil; Shumack, Amy; de Blank, H.; Plasma Physics Team

2014-10-01

In plasma physics, material walls are generally regarded as perfect sinks for charged particles and their energy. A special case arises when the wall efficiently reflects the neutralized plasma particles (with a significant portion of their kinetic energy) and at the same time the upstream plasma is of sufficiently high density to yield strong neutral-ion coupling (i.e. reflected energy and momentum will not escape from the plasma). Under these conditions, plasma-surface interaction will feedback to the upstream plasma and a self-consistent view on the coupling between plasma and neutrals is required for correct prediction of plasma conditions and plasma-surface interaction. Here, an analytical and numerical study of the fluid equations is combined with experiments (in hydrogen and argon) to construct such a self-consistent view. It shows how plasma momentum removal builds up upstream pressure and causes plasma acceleration towards the wall. It also shows how energy reflection causes plasma heating, which recycles part of the reflected power to the wall and induces additional flow acceleration due to local sound speed increase. The findings are relevant as generic textbook example and are at play in the boundary plasma of fusion devices.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Leopold; Giang, Erick; Robbins, Justin B.

Hepatitis C virus (HCV) infects more than 2% of the global population and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and end-stage liver diseases. Circulating HCV is genetically diverse, and therefore a broadly effective vaccine must target conserved T- and B-cell epitopes of the virus. Human mAb HCV1 has broad neutralizing activity against HCV isolates from at least four major genotypes and protects in the chimpanzee model from primary HCV challenge. The antibody targets a conserved antigenic site (residues 412-423) on the virus E2 envelope glycoprotein. Two crystal structures of HCV1 Fab in complex with an epitope peptidemore » at 1.8-{angstrom} resolution reveal that the epitope is a {beta}-hairpin displaying a hydrophilic face and a hydrophobic face on opposing sides of the hairpin. The antibody predominantly interacts with E2 residues Leu{sup 413} and Trp{sup 420} on the hydrophobic face of the epitope, thus providing an explanation for how HCV isolates bearing mutations at Asn{sup 415} on the same binding face escape neutralization by this antibody. The results provide structural information for a neutralizing epitope on the HCV E2 glycoprotein and should help guide rational design of HCV immunogens to elicit similar broadly neutralizing antibodies through vaccination.« less

Does an Intrinsic Magnetic Field Inhibit or Enhance Planetary Ionosphere Outflow and Loss?

NASA Astrophysics Data System (ADS)

Strangeway, R. J.; Russell, C. T.; Luhmann, J. G.; Moore, T. E.; Foster, J. C.; Barabash, S. V.; Nilsson, H.

2017-12-01

A characteristic feature of the planets Earth, Venus and Mars is the observation of the outflow of ionospheric ions, most notably oxygen. The oxygen ion outflow is frequently assumed to be a proxy for the loss of water from the planetary atmosphere. In terms of global outflow rates for the Earth the rate varies from 1025 to 1026 s-1, depending on geomagnetic activity. For both Venus and Mars global rates of the order 5x1024 s-1 have been reported. Venus and Mars do not have a large-scale intrinsic magnetic field, and there are several pathways for atmospheric and ionospheric loss. At Mars, because of its low gravity, neutral oxygen can escape through dissociative recombination. At Venus only processes related to the solar wind interaction with the planet such as sputtering and direct scavenging of the ionosphere by the solar wind can result in oxygen escape. At the Earth the intrinsic magnetic field forms a barrier to the solar wind, but reconnection of the Earth's magnetic field with the Interplanetary Magnetic Field allows solar wind energy and momentum to be transferred into the magnetosphere, resulting in ionospheric outflows. Observations of oxygen ions at the dayside magnetopause suggest that at least some of these ions escape. In terms of the evolution of planetary atmospheres how the solar-wind driven escape rates vary for magnetized versus umagnetized planets is also not clear. An enhanced solar wind dynamic pressure will increase escape from the unmagnetized planets, but it may also result in enhanced reconnection at the Earth, increasing outflow and loss rates for the Earth as well. Continued improvement in our understanding of the different pathways for ionospheric and atmospheric loss will allow us to determine how effective an intrinsic planetary field is in preserving a planetary atmosphere, or if we have to look for other explanations as to why the atmospheres of Venus and Mars have evolved to their desiccated state.

Free Radical-Surface Interactions Using Multiphoton Ionization of Free Radicals

DTIC Science & Technology

1989-01-01

Atoms, Rgf4PI 9 t Free Radl!cals)aj" i Atoms, Cross Section -’r RE)* I of Free Radicals arid Atonn. 𔄃 43S’RACT (Conti n reverse if necessary Ind identi...these surfaces. The basic philosophy of our CF 3I -+- nhv-CF, - t - I . program consists of generating a particular neutral species at A low pressures...constant for the escape of radicals out of the " reactor is shown in Eq. (6): .= k =, 4 .4,., I /V, (6) L !J 7 where t ,,, is the thermal molecular

Survey of heating and current drive for K-DEMO

DOE PAGES

Mikkelsen, D. R.; Kessel, C. E.; Poli, F. M.; ...

2018-01-22

Here, we present calculations of heating and current drive by neutral injection and by electromagnetic waves in the ion cyclotron, helicon, lower hybrid, and electron cyclotron frequency ranges for the steady state burn conditions in a K-DEMO configuration withmore » $$I_{\\rm p}=12.3$$ MA, a = 2.1 m, $$R_{\\rm o}=6.8$$ m, $$B_{\\rm o}=7.4$$ T, $$ \

Survey of heating and current drive for K-DEMO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikkelsen, D. R.; Kessel, C. E.; Poli, F. M.

Here, we present calculations of heating and current drive by neutral injection and by electromagnetic waves in the ion cyclotron, helicon, lower hybrid, and electron cyclotron frequency ranges for the steady state burn conditions in a K-DEMO configuration withmore » $$I_{\\rm p}=12.3$$ MA, a = 2.1 m, $$R_{\\rm o}=6.8$$ m, $$B_{\\rm o}=7.4$$ T, $$ \

Stable Spheromaks Sustained by Neutral Beam Injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, T K; Jayakumar, R; McLean, H S

It is shown that spheromak equilibria, stable at zero-beta but departing from the Taylor state, could be sustained by non-inductive current drive at acceptable power levels. Stability to both ideal MHD and tearing modes is verified using the NIMROD code for linear stability analysis. Non-linear NIMROD calculations with non-inductive current drive and pressure effects could point the way to improved fusion reactors.

Subliminal smells can guide social preferences.

PubMed

Li, Wen; Moallem, Isabel; Paller, Ken A; Gottfried, Jay A

2007-12-01

It is widely accepted that unconscious processes can modulate judgments and behavior, but do such influences affect one's daily interactions with other people? Given that olfactory information has relatively direct access to cortical and subcortical emotional circuits, we tested whether the affective content of subliminal odors alters social preferences. Participants rated the likeability of neutral faces after smelling pleasant, neutral, or unpleasant odors delivered below detection thresholds. Odor affect significantly shifted likeability ratings only for those participants lacking conscious awareness of the smells, as verified by chance-level trial-by-trial performance on an odor-detection task. Across participants, the magnitude of this priming effect decreased as sensitivity for odor detection increased. In contrast, heart rate responses tracked odor valence independently of odor awareness. These results indicate that social preferences are subject to influences from odors that escape awareness, whereas the availability of conscious odor information may disrupt such effects.

Improved Temperature Diagnostic for Non-Neutral Plasmas with Single-Electron Resolution

NASA Astrophysics Data System (ADS)

Shanman, Sabrina; Evans, Lenny; Fajans, Joel; Hunter, Eric; Nelson, Cheyenne; Sierra, Carlos; Wurtele, Jonathan

2016-10-01

Plasma temperature diagnostics in a Penning-Malmberg trap are essential for reliably obtaining cold, non-neutral plasmas. We have developed a setup for detecting the initial electrons that escape from a trapped pure electron plasma as the confining electrode potential is slowly reduced. The setup minimizes external noise by using a silicon photomultiplier to capture light emitted from an MCP-amplified phosphor screen. To take advantage of this enhanced resolution, we have developed a new plasma temperature diagnostic analysis procedure which takes discrete electron arrival times as input. We have run extensive simulations comparing this new discrete algorithm to our existing exponential fitting algorithm. These simulations are used to explore the behavior of these two temperature diagnostic procedures at low N and at high electronic noise. This work was supported by the DOE DE-FG02-06ER54904, and the NSF 1500538-PHY.

Invasive plants may promote predator-mediated feedback that inhibits further invasion

PubMed Central

Smith, Lauren M; Schmitz, Oswald J

2015-01-01

Understanding the impacts of invasive species requires placing invasion within a full community context. Plant invaders are often considered in the context of herbivores that may drive invasion by avoiding invaders while consuming natives (enemy escape), or inhibit invasion by consuming invaders (biotic resistance). However, predators that attack those herbivores are rarely considered as major players in invasion. Invasive plants often promote predators, generally by providing improved habitat. Here, we show that predator-promoting invaders may initiate a negative feedback loop that inhibits invasion. By enabling top-down control of herbivores, predator-promoting invaders lose any advantage gained through enemy escape, indirectly favoring natives. In cases where palatable invaders encounter biotic resistance, predator promotion may allow an invader to persist, but not dominate. Overall, results indicate that placing invaders in a full community context may reveal reduced impacts of invaders compared to expectations based on simple plant–plant or plant–herbivore subsystems. PMID:26120430

Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp

PubMed Central

Erickson, Dana; Miles, John M.; Bowers, Cyril Y.

2011-01-01

To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E2; women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design. By three-way ANCOVA, sex difference, sex hormone treatment, peptide stimulation, and placebo/saline responses (covariate) controlled total (integrated) GH recovery during feedback (each P < 0.001). Both sex steroid milieu (P = 0.019) and dual-peptide stimulation (P < 0.001) determined nadir (maximally feedback-suppressed) GH concentrations. E2/T exposure elevated nadir GH concentrations during saline infusion (P = 0.003), whereas dual-peptide infusion did so independently of T/E2 and sex difference (P = 0.001). All three of sex difference (P = 0.001), sex steroid treatment (P = 0.005), and double-peptide stimulation (P < 0.001) augmented recovery of peak (maximally feedback-escaped) GH concentrations. Peak GH responses to dual-peptidyl agonists were greater in women than in men (P = 0.016). E2/T augmented peak GH recovery during saline infusion (P < 0.001). Approximate entropy analysis corroborated independent effects of sex steroid treatment (P = 0.012) and peptide infusion (P < 0.001) on GH regularity. In summary, sex difference, sex steroid supplementation, and combined peptide drive influence nadir, peak, and entropic measurements of GH release under controlled negative feedback. To the degree that the pharmacological sex steroid, GH, and dual-peptide clamps provide prephysiological regulatory insights, these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain. PMID:21467302

Study of the virulence and cross-neutralization capability of recent porcine parvovirus field isolates and vaccine viruses in experimentally infected pregnant gilts.

PubMed

Zeeuw, E J L; Leinecker, N; Herwig, V; Selbitz, H-J; Truyen, U

2007-02-01

The pathogenicity of two recent German field isolates of Porcine parvovirus (PPV-27a and PPV-143a) and two vaccine viruses [PPV-NADL-2 and PPV-IDT (MSV)], which are used for the production of inactivated vaccines, was investigated by inoculation of pregnant sows at day 40 of gestation. Post-infection sera of these sows as well as antisera prepared in rabbits by immunization with the four above-mentioned PPV isolates and with the virulent strain PPV-Challenge (Engl.) were tested for their homologous and heterologous neutralization activities. All antisera had high neutralization activity against the vaccine viruses, the PPV-Challenge (Engl.) virus and PPV-143a, but much lower activity against PPV-27a. These results suggest that PPV-27a represents a new antigenic variant or type of PPV and vaccines based on the established vaccine viruses may not be fully protective against this field isolate. PPV-27a has been characterized based on the amino acid sequences of the capsid protein as a member of a new and distinct PPV cluster (Zimmermann et al., 2006). Interestingly, the homologous neutralizing antibody titres of the sera of all three pigs and both rabbits inoculated or immunized with PPV-27a were 100- to 1000-fold lower than the heterologous titres against any of the other viruses. The low homologous neutralizing antibody titres suggest a possible, yet undefined, immune escape mechanism of this PPV isolate.

Driving under the influence--a level-I trauma center's experience.

PubMed

Fantus, R J; Zautcke, J L; Hickey, P A; Fantus, P P; Nagorka, F W

1991-11-01

Alcohol-impaired driving is a major issue confronting today's society. New legislation is emerging to help curtail this ongoing problem. To evaluate the legislative effects in terms of outcome pertaining to injured drivers, we analyzed the records of 116 consecutive motor vehicle drivers who were admitted to our trauma center over a 16-month period. Medical reports, police reports, and drivers' abstracts were reviewed. Of the 116 drives, 61 (53%) had blood alcohol concentrations that exceeded the legal limit (blood alcohol level greater than or equal to 100 mg/dL) on arrival at the emergency department. Only four of these patients were ticketed for driving under the influence and received the mandatory suspension of their driver's license. None was convicted of this offense, which carries criminal charges and a revocation of the driver's license. Mechanisms for efficient collection of blood specimens and mandatory occurrence reporting are two recommendations that merit investigation to obviate further escape of injured, intoxicated drivers from the legal net. In addition, alcohol rehabilitation and education cannot be overlooked and should warrant strong societal support.

Theory for planetary exospheres: III. Radiation pressure effect on the Circular Restricted Three Body Problem and its implication on planetary atmospheres

NASA Astrophysics Data System (ADS)

Beth, A.; Garnier, P.; Toublanc, D.; Dandouras, I.; Mazelle, C.

2016-12-01

The planetary exospheres are poorly known in their outer parts, since the neutral densities are low compared with the instruments detection capabilities. The exospheric models are thus often the main source of information at such high altitudes. We present a new way to take into account analytically the additional effect of the stellar radiation pressure on planetary exospheres. In a series of papers, we present with a Hamiltonian approach the effect of the radiation pressure on dynamical trajectories, density profiles and escaping thermal flux. Our work is a generalization of the study by Bishop and Chamberlain [1989] Icarus, 81, 145-163. In this third paper, we investigate the effect of the stellar radiation pressure on the Circular Restricted Three Body Problem (CR3BP), called also the photogravitational CR3BP, and its implication on the escape and the stability of planetary exospheres, especially for hot Jupiters. In particular, we describe the transformation of the equipotentials and the location of the Lagrange points, and we provide a modified equation for the Hill sphere radius that includes the influence of the radiation pressure. Finally, an application to the hot Jupiter HD 209458b and hot Neptune GJ 436b reveals the existence of a blow-off escape regime induced by the stellar radiation pressure.

Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies

PubMed Central

Louie, Raymond H. Y.; Kaczorowski, Kevin J.; Chakraborty, Arup K.; McKay, Matthew R.

2018-01-01

HIV is a highly mutable virus, and over 30 years after its discovery, a vaccine or cure is still not available. The isolation of broadly neutralizing antibodies (bnAbs) from HIV-infected patients has led to renewed hope for a prophylactic vaccine capable of combating the scourge of HIV. A major challenge is the design of immunogens and vaccination protocols that can elicit bnAbs that target regions of the virus’s spike proteins where the likelihood of mutational escape is low due to the high fitness cost of mutations. Related challenges include the choice of combinations of bnAbs for therapy. An accurate representation of viral fitness as a function of its protein sequences (a fitness landscape), with explicit accounting of the effects of coupling between mutations, could help address these challenges. We describe a computational approach that has allowed us to infer a fitness landscape for gp160, the HIV polyprotein that comprises the viral spike that is targeted by antibodies. We validate the inferred landscape through comparisons with experimental fitness measurements, and various other metrics. We show that an effective antibody that prevents immune escape must selectively bind to high escape cost residues that are surrounded by those where mutations incur a low fitness cost, motivating future applications of our landscape for immunogen design. PMID:29311326

Systemic salt loading decreases body temperature and increases heat-escape/cold-seeking behaviour via the central AT1 and V1 receptors in rats.

PubMed

Konishi, Masahiro; Nagashima, Kei; Kanosue, Kazuyuki

2002-11-15

Salt loading decreases body core temperature (T(core)) at neutral ambient temperature (26 degrees C) and increases heat-escape/cold-seeking behaviour in desalivated rats. In this study, we tested the hypothesis that brain angiotensin II (AII) and arginine vasopressin (AVP) are associated with these responses. Surgically desalivated rats (n = 28) were administered an injection (S.C., 10 ml kg(-1)) of either normal saline (154 mM, NS) or hypertonic saline (2500 mM, HS) following an intracerebroventricular injection (10 microl kg(-1)) of an AII AT(1)-receptor antagonist (candesartan, 5 microg microl(-1)), an AVP V(1)-receptor antagonist ((beta-mercapto-beta, beta-cyclopenta-methylene propionyl(1), O-Me-Tyr(2), Arg(8))-vasopressin, 0.5 microg microl(-1)), or normal saline (154 mM). Each rat was placed in a behaviour box, first at 26 degrees C for 1 h to allow the measurement of baseline T(core) and movement. The ambient temperature was then elevated to 40 degrees C for the next 2 h, during which time the rat was able to trigger a 0 degrees C air reward for 30 s by moving into a specific area of the box (operant behaviour). The S.C. HS significantly decreased baseline T(core) at 26 degrees C (36.5 +/- 0.1 degrees C) and increased counts of operant behaviour at 40 degrees C (57 +/- 3) compared with results obtained following S.C. NS injection (37.4 +/- 0.1 degrees C and 42 +/- 1, respectively). These responses to s.c. HS were inhibited by the intracerebroventricular injection of AT(1) (37.3 +/- 0.1 degrees C and 43 +/- 2, respectively; P < 0.05) and V(1) antagonists (37.2 +/- 0.2 degrees C and 42 +/- 2, respectively; P < 0.05), although administration of both antagonists with S.C. NS had no effect. These results suggest that brain AII and AVP are involved in the decrease in T(core) observed at neutral ambient temperature and the increase in heat-escape/cold-seeking behaviour in response to osmotic stimulation, via the central AT(1) and V(1) receptors, respectively

New Measurements of Mars Thermospheric Variability from MAVEN EUVM Solar Occultations

NASA Astrophysics Data System (ADS)

Thiemann, E.; Eparvier, F. G.; Andersson, L.; Pilinski, M.; Chamberlin, P. C.; Fowler, C. M.; Dominique, M.; Bougher, S. W.; Gröller, H.; Girazian, Z.; Lillis, R. J.

2017-12-01

The Mars thermosphere encompasses both the coldest and hottest regions of the Mars neutral atmosphere, where temperatures warm from below 150 K at the well-mixed homopause to 300 K at the collisionless exobase, and change by comparable magnitudes over the diurnal cycle. In this dynamic and highly-structured region, atoms and molecules are accelerated by a number of processes, potentially leading to escape and permanent loss to space. Increasingly, evidence shows that atmospheric escape to space has resulted in the loss of a substantial portion of Mars's atmosphere over the planet's history. Given that the thermosphere is the neutral reservoir for atmospheric escape, understanding how and why it varies is crucial for understanding how Mars's climate has evolved over time. The Mars Atmosphere and Volatile EvolutioN (MAVEN) orbiter's Extreme Ultraviolet (EUV) Monitor (EUVM) has recently demonstrated the capability to measure thermospheric density from 100 to 200 km with solar occultations of its 17-22 nm channel. These measurements are routine, inherently constrained to either 06:00 or 18:00 Local Time, and span all latitudes, a number of which have been revisited multiple times over the past 3 Earth years due to MAVEN's orbital precession. These factors, coupled with uncertainties in retrieved densities below 10%, make MAVEN EUVM occultations ideal for tracking both long-term and latitudinal thermospheric variability. Some notable trends revealed by the EUVM occultation data are variations in poleward warming due to changes in global circulation patterns, planetary-scale waves due to varying gravity wave or tidal forcing, and temperature due to solar EUV variability. In this study, we present these new measurements in detail. We begin by briefly presenting the measurement methods and uncertainties, and show an overview of the measurements made to-date, putting them in the context of observations made by other missions, other instruments onboard MAVEN, and the newly arrived ExoMars Trace Gas Orbiter (TGO). We then show observations of latitudinal and seasonal temperature and density variability made over the MAVEN mission, and discuss the possible underlying causes. We conclude by discussing plans to make these new data publically available as an official MAVEN data product.

No hydrogen exosphere detected around the super-Earth HD 97658 b

NASA Astrophysics Data System (ADS)

Bourrier, V.; Ehrenreich, D.; King, G.; Lecavelier des Etangs, A.; Wheatley, P. J.; Vidal-Madjar, A.; Pepe, F.; Udry, S.

2017-01-01

The exoplanet HD 97658 b provides a rare opportunity to probe the atmospheric composition and evolution of moderately irradiated super-Earths. It transits a bright K star at a moderate orbital distance of 0.08 au. Its low density is compatible with a massive steam envelope that could photodissociate at high altitudes and become observable as escaping neutral hydrogen. Our analysis of three transits with HST/STIS at Lyman-α reveals no such signature, suggesting that the thermosphere of HD 97658 b is not hydrodynamically expanding and is subjected to a low escape of neutral hydrogen (<108 g s-1 at 3σ). Using HST/STIS Lyman-α observations and Chandra/ACIS-S and XMM-Newton/EPIC X-ray observations at different epochs, we find that HD 97658 is in fact a weak and soft X-ray source with signs of chromospheric variability in the Lyman-α line core. We determine an average reference for the intrinsic Lyman-α line and X-EUV (XUV) spectrum of the star, and show that HD 97658 b is in mild conditions of irradiation compared to other known evaporating exoplanets with an XUV irradiation about three times lower than the evaporating warm Neptune GJ436 b. This could be the reason why the thermosphere of HD 97658 b is not expanding: the low XUV irradiation prevents an efficient photodissociation of any putative steam envelope. Alternatively, it could be linked to a low hydrogen content or inefficient conversion of the stellar energy input. The HD 97658 system provides clues for understanding the stability of low-mass planet atmospheres in terms of composition, planetary density, and irradiation. Our study of HD 97658 b can be seen as a control experiment of our methodology, confirming that it does not bias detections of atmospheric escape and underlining its strength and reliability. Our results show that stellar activity can be efficiently discriminated from absorption signatures by a transiting exospheric cloud. They also highlight the potential of observing the upper atmosphere of small transiting planets to probe their physical and chemical properties.

Synthetic C-start maneuver in fish-like swimming

NASA Astrophysics Data System (ADS)

Zenit, R.; Godoy-Diana, R.

2013-11-01

We investigate the mechanics of the unsteady fish-like swimming maneuver using a simplified experimental model in a water tank. A flexible foil (which emulates the fish body) is impulsively actuated by rotating a cylindrical rod that holds the foil. This rod constitutes the head of the swimmer and is mounted through the shaft of the driving motor on an rail with an air bearing. The foil is initially positioned at a start angle and then rapidly rotated to a final angle, which coincides with the free-moving direction of the rail. As the foil rotates, it pushes the surrounding fluid, it deforms and stores elastic energy which drive the recovery of the straight body shape after the motor actuation has stopped; during the rotation, a trust force is induced which accelerates the array. We measure the resulting escape velocity and acceleration as a function of the beam stiffness, size, initial angle, etc. Some measurements of the velocity field during the escape were obtained using a PIV technique. The measurements agree well with a simple mechanical model that quantifies the impulse of the maneuver. The objective of this work is to understand the fundamental mechanisms of thrust generation in unsteady fast-start swimming. We acknowledge support of EADS Foundation through the project ``Fluids and elasticity in biomimetic propulsion'' and of the Chaire Total for RZ as a visiting professor at ESPCI ParisTech.

Protective efficacy of passive immunization with monoclonal antibodies in animal models of H5N1 highly pathogenic avian influenza virus infection.

PubMed

Itoh, Yasushi; Yoshida, Reiko; Shichinohe, Shintaro; Higuchi, Megumi; Ishigaki, Hirohito; Nakayama, Misako; Pham, Van Loi; Ishida, Hideaki; Kitano, Mitsutaka; Arikata, Masahiko; Kitagawa, Naoko; Mitsuishi, Yachiyo; Ogasawara, Kazumasa; Tsuchiya, Hideaki; Hiono, Takahiro; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Ito, Mutsumi; Quynh Mai, Le; Kawaoka, Yoshihiro; Miyamoto, Hiroko; Ishijima, Mari; Igarashi, Manabu; Suzuki, Yasuhiko; Takada, Ayato

2014-06-01

Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.

Spatial calibration of a tokamak neutral beam diagnostic using in situ neutral beam emission

DOE PAGES

Chrystal, Colin; Burrell, Keith H.; Grierson, Brian A.; ...

2015-10-20

Neutral beam injection is used in tokamaks to heat, apply torque, drive non-inductive current, and diagnose plasmas. Neutral beam diagnostics need accurate spatial calibrations to benefit from the measurement localization provided by the neutral beam. A new technique has been developed that uses in-situ measurements of neutral beam emission to determine the spatial location of the beam and the associated diagnostic views. This technique was developed to improve the charge exchange recombination diagnostic (CER) at the DIII-D tokamak and uses measurements of the Doppler shift and Stark splitting of neutral beam emission made by that diagnostic. These measurements contain informationmore » about the geometric relation between the diagnostic views and the neutral beams when they are injecting power. This information is combined with standard spatial calibration measurements to create an integrated spatial calibration that provides a more complete description of the neutral beam-CER system. The integrated spatial calibration results are very similar to the standard calibration results and derived quantities from CER measurements are unchanged within their measurement errors. Lastly, the methods developed to perform the integrated spatial calibration could be useful for tokamaks with limited physical access.« less

Spatial calibration of a tokamak neutral beam diagnostic using in situ neutral beam emission

NASA Astrophysics Data System (ADS)

Chrystal, C.; Burrell, K. H.; Grierson, B. A.; Pace, D. C.

2015-10-01

Neutral beam injection is used in tokamaks to heat, apply torque, drive non-inductive current, and diagnose plasmas. Neutral beam diagnostics need accurate spatial calibrations to benefit from the measurement localization provided by the neutral beam. A new technique has been developed that uses in situ measurements of neutral beam emission to determine the spatial location of the beam and the associated diagnostic views. This technique was developed to improve the charge exchange recombination (CER) diagnostic at the DIII-D tokamak and uses measurements of the Doppler shift and Stark splitting of neutral beam emission made by that diagnostic. These measurements contain information about the geometric relation between the diagnostic views and the neutral beams when they are injecting power. This information is combined with standard spatial calibration measurements to create an integrated spatial calibration that provides a more complete description of the neutral beam-CER system. The integrated spatial calibration results are very similar to the standard calibration results and derived quantities from CER measurements are unchanged within their measurement errors. The methods developed to perform the integrated spatial calibration could be useful for tokamaks with limited physical access.

Landscape-scale distribution and persistence of genetically modified oilseed rape (Brassica napus) in Manitoba, Canada.

PubMed

Knispel, Alexis L; McLachlan, Stéphane M

2010-01-01

Genetically modified herbicide-tolerant (GMHT) oilseed rape (OSR; Brassica napus L.) was approved for commercial cultivation in Canada in 1995 and currently represents over 95% of the OSR grown in western Canada. After a decade of widespread cultivation, GMHT volunteers represent an increasing management problem in cultivated fields and are ubiquitous in adjacent ruderal habitats, where they contribute to the spread of transgenes. However, few studies have considered escaped GMHT OSR populations in North America, and even fewer have been conducted at large spatial scales (i.e. landscape scales). In particular, the contribution of landscape structure and large-scale anthropogenic dispersal processes to the persistence and spread of escaped GMHT OSR remains poorly understood. We conducted a multi-year survey of the landscape-scale distribution of escaped OSR plants adjacent to roads and cultivated fields. Our objective was to examine the long-term dynamics of escaped OSR at large spatial scales and to assess the relative importance of landscape and localised factors to the persistence and spread of these plants outside of cultivation. From 2005 to 2007, we surveyed escaped OSR plants along roadsides and field edges at 12 locations in three agricultural landscapes in southern Manitoba where GMHT OSR is widely grown. Data were analysed to examine temporal changes at large spatial scales and to determine factors affecting the distribution of escaped OSR plants in roadside and field edge habitats within agricultural landscapes. Additionally, we assessed the potential for seed dispersal between escaped populations by comparing the relative spatial distribution of roadside and field edge OSR. Densities of escaped OSR fluctuated over space and time in both roadside and field edge habitats, though the proportion of GMHT plants was high (93-100%). Escaped OSR was positively affected by agricultural landscape (indicative of cropping intensity) and by the presence of an adjacent field planted to OSR. Within roadside habitats, escaped OSR was also strongly associated with large-scale variables, including road surface (indicative of traffic intensity) and distance to the nearest grain elevator. Conversely, within field edges, OSR density was affected by localised crop management practices such as mowing, soil disturbance and herbicide application. Despite the proximity of roadsides and field edges, there was little evidence of spatial aggregation among escaped OSR populations in these two habitats, especially at very fine spatial scales (i.e. <100 m), suggesting that natural propagule exchange is infrequent. Escaped OSR populations were persistent at large spatial and temporal scales, and low density in a given landscape or year was not indicative of overall extinction. As a result of ongoing cultivation and transport of OSR crops, escaped GMHT traits will likely remain predominant in agricultural landscapes. While escaped OSR in field edge habitats generally results from local seeding and management activities occurring at the field-scale, distribution patterns within roadside habitats are determined in large part by seed transport occurring at the landscape scale and at even larger regional scales. Our findings suggest that these large-scale anthropogenic dispersal processes are sufficient to enable persistence despite limited natural seed dispersal. This widespread dispersal is likely to undermine field-scale management practices aimed at eliminating escaped and in-field GMHT OSR populations. Agricultural transport and landscape-scale cropping patterns are important determinants of the distribution of escaped GM crops. At the regional level, these factors ensure ongoing establishment and spread of escaped GMHT OSR despite limited local seed dispersal. Escaped populations thus play an important role in the spread of transgenes and have substantial implications for the coexistence of GM and non-GM production systems. Given the large-scale factors driving the spread of escaped transgenes, localised co-existence measures may be impracticable where they are not commensurate with regional dispersal mechanisms. To be effective, strategies aimed at reducing contamination from GM crops should be multi-scale in approach and be developed and implemented at both farm and landscape levels of organisation. Multiple stakeholders should thus be consulted, including both GM and non-GM farmers, as well as seed developers, processors, transporters and suppliers. Decisions to adopt GM crops require thoughtful and inclusive consideration of the risks and responsibilities inherent in this new technology.

Effects of convincing power and neutrality on minority opinion spreading

NASA Astrophysics Data System (ADS)

Wu, Yue; Xiong, Xi; Zhang, Yi

2017-02-01

The dynamics evolution of the minority opinion in public debates is studied using a convincing power (CP) model with neutrality. In a given group, an agent with a definite standpoint (yes or no) can be persuaded to be a neutral agent, if its capacity of persuasion is lower than the average CP of its opponents. Besides that a neutral agent will change its state and follow a more persuasive opinion. Starting from two opposite opinions with different rates, repeated local discussions are found to drive the minority reversal. It reveals that in addition to the initial minority, the number of neutral agents is also an important factor to the eventual winners. During the process of consensus, there exists a threshold of initial fraction to guarantee one side win. The results have a guiding significance for designing strategies to win a public debate.

Lyman continuum escape fraction of faint galaxies at z 3.3 in the CANDELS/GOODS-North, EGS, and COSMOS fields with LBC

NASA Astrophysics Data System (ADS)

Grazian, A.; Giallongo, E.; Paris, D.; Boutsia, K.; Dickinson, M.; Santini, P.; Windhorst, R. A.; Jansen, R. A.; Cohen, S. H.; Ashcraft, T. A.; Scarlata, C.; Rutkowski, M. J.; Vanzella, E.; Cusano, F.; Cristiani, S.; Giavalisco, M.; Ferguson, H. C.; Koekemoer, A.; Grogin, N. A.; Castellano, M.; Fiore, F.; Fontana, A.; Marchi, F.; Pedichini, F.; Pentericci, L.; Amorín, R.; Barro, G.; Bonchi, A.; Bongiorno, A.; Faber, S. M.; Fumana, M.; Galametz, A.; Guaita, L.; Kocevski, D. D.; Merlin, E.; Nonino, M.; O'Connell, R. W.; Pilo, S.; Ryan, R. E.; Sani, E.; Speziali, R.; Testa, V.; Weiner, B.; Yan, H.

2017-06-01

Context. The reionization of the Universe is one of the most important topics of present-day astrophysical research. The most plausible candidates for the reionization process are star-forming galaxies, which according to the predictions of the majority of the theoretical and semi-analytical models should dominate the H I ionizing background at z ≳ 3. Aims: We measure the Lyman continuum escape fraction, which is one of the key parameters used to compute the contribution of star-forming galaxies to the UV background. It provides the ratio between the photons produced at λ ≤ 912 Å rest-frame and those that are able to reach the inter-galactic medium, I.e. that are not absorbed by the neutral hydrogen or by the dust of the galaxy's inter-stellar medium. Methods: We used ultra-deep U-band imaging (U = 30.2 mag at 1σ) from Large Binocular Camera at the Large Binocular Telescope (LBC/LBT) in the CANDELS/GOODS-North field and deep imaging in the COSMOS and EGS fields in order to estimate the Lyman continuum escape fraction of 69 star-forming galaxies with secure spectroscopic redshifts at 3.27 ≤ z ≤ 3.40 to faint magnitude limits (L = 0.2L∗, or equivalently M1500 - 19). The narrow redshift range implies that the LBC U-band filter exclusively samples the λ ≤ 912 Å rest-frame wavelengths. Results: We measured through stacks a stringent upper limit (<1.7% at 1σ) for the relative escape fraction of H I ionizing photons from bright galaxies (L>L∗), while for the faint population (L = 0.2L∗) the limit to the escape fraction is ≲ 10%. We computed the contribution of star-forming galaxies to the observed UV background at z 3 and find that it is not sufficient to keep the Universe ionized at these redshifts unless their escape fraction increases significantly (≥ 10%) at low luminosities (M1500 ≥ - 19). Conclusions: We compare our results on the Lyman continuum escape fraction of high-z galaxies with recent estimates in the literature, and discuss future prospects to shed light on the end of the Dark Ages. In the future, strong gravitational lensing will be fundamental in order to measure the Lyman continuum escape fraction down to faint magnitudes (M1500 - 16) that are inaccessible with the present instrumentation on blank fields. These results will be important in order to quantify the role of faint galaxies to the reionization budget. Based on observations made at the Large Binocular Telescope (LBT) at Mt. Graham (Arizona, USA).

Examing the Effects of Different IMF, F10.7, and Auroral Inputs on the Thermospheric Neutral Winds

NASA Astrophysics Data System (ADS)

Deng, Y.; Ridley, A. J.

2003-12-01

To obtain a better understanding of how the magnetosphere effects the global thermospheric and ionospheric structure, we conduct some numerical experiments using the University of Michigan's Global Ionosphere-Thermosphere Model (GITM). We have run GITM to roughly steady-state using different strengths of the high-latitude electric potential pattern, F10.7, and auroral inputs to determine how these effect the temporal history and stead-state of the thermospheric neutral winds. Our model reproduces the well known fact that the neutral winds are strongly driven by the ion convection above approximately 300 km, and that the ramp-up time is very dependent upon the altitude. We show quantitative results of the ramp-up times and maximum neutral wind speeds for the different driving conditions.

The escape of Lyman photons from a young starburst: the case of Haro11†

NASA Astrophysics Data System (ADS)

Hayes, Matthew; Östlin, Göran; Atek, Hakim; Kunth, Daniel; Mas-Hesse, J. Miguel; Leitherer, Claus; Jiménez-Bailón, Elena; Adamo, Angela

2007-12-01

Lyman α (Lyα) is one of the dominant tools used to probe the star-forming galaxy population at high redshift (z). However, astrophysical interpretations of data drawn from Lyα alone hinge on the Lyα escape fraction which, due to the complex radiative transport, may vary greatly. Here, we map the Lyα emission from the local luminous blue compact galaxy Haro11, a known emitter of Lyα and the only known candidate for low-z Lyman continuum emission. To aid in the interpretation, we perform a detailed ultraviolet and optical multiwavelength analysis and model the stellar population, dust distribution, ionizing photon budget, and star-cluster population. We use archival X-ray observations to further constrain properties of the starburst and estimate the neutral hydrogen column density. The Lyα morphology is found to be largely symmetric around a single young star-forming knot and is strongly decoupled from other wavelengths. From general surface photometry, only very slight correlation is found between Lyα and Hα, E(B - V), and the age of the stellar population. Only around the central Lyα bright cluster do we find the Lyα/Hα ratio at values predicted by the recombination theory. The total Lyα escape fraction is found to be just 3 per cent. We compute that ~90 per cent of the Lyα photons that escape do so after undergoing multiple resonance scattering events, masking their point of origin. This leads to a largely symmetric distribution and, by increasing the distance that photons must travel to escape, decreases the escape probability significantly. While dust must ultimately be responsible for the destruction of Lyα, it plays a little role in governing the observed morphology, which is regulated more by interstellar medium kinematics and geometry. We find tentative evidence for local Lyα equivalent width in the immediate vicinity of star clusters being a function of cluster age, consistent with hydrodynamic studies. We estimate the intrinsic production of ionizing photons and put further constraints of ~9 per cent on the escaping fraction of photons at 900Å. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Incorporated, under NASA contract NAS 5-26555. These observations are associated with programmes #GO9470 and #GO10575. Based on observations made with ESO Telescopes at the La Silla Observatories under programme ID 073.B-0785. ‡ E-mail: matthew@astro.su.se

Fault-tolerant three-level inverter

DOEpatents

Edwards, John; Xu, Longya; Bhargava, Brij B.

2006-12-05

A method for driving a neutral point clamped three-level inverter is provided. In one exemplary embodiment, DC current is received at a neutral point-clamped three-level inverter. The inverter has a plurality of nodes including first, second and third output nodes. The inverter also has a plurality of switches. Faults are checked for in the inverter and predetermined switches are automatically activated responsive to a detected fault such that three-phase electrical power is provided at the output nodes.

Particle and momentum confinement in tokamak plasmas with unbalanced neutral beam injection and strong rotation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malik, M.A.

1988-01-01

There is a self-consistent theory of the effects of neutral beam injection on impurity transport in tokamak plasmas. The theory predicts that co-injection drives impurities outward and that counter-injection enhances the normally inward flow of impurities. The theory was applied to carry out a detailed analysis of the large experimental database from the PLT and the ISX-B tokamaks. The theory was found to generally model the experimental data quite well. It is, therefore, concluded that neutral beam co-injection can drive impurities outward to achieve clean central plasmas and a cool radiating edge. Theoretical predictions for future thermonuclear reactors such asmore » INTOR, TIBER II, and ITER indicated that neutral beam driven flow reversal might be an effective impurity control method if the rate of beam momentum deposited per plasma ion is adequate. The external momentum drag, which is a pivotal concept in impurity flow reversal theory, is correctly predicted by the gyroviscous theory of momentum confinement. The theory was applied to analyze experimental data from the PLT and the PDX tokamaks with exact experimental conditions. The theory was found to be in excellent agreement with experiment over a wide range of parameters. It is, therefore, possible to formulate the impurity transport theory from first principles, without resort to empiricism.« less

Unraveling the Complexities of the Upper Atmosphere as a System

NASA Astrophysics Data System (ADS)

Fuller-Rowell, T. J.

2016-12-01

The Earth's upper atmosphere responds as a system to external forcing from the Sun, magnetosphere, and lower atmosphere. The underlying system components comprise a highly dynamic, non-linear neutral fluid supporting fast propagating wave fields, advective transport, dissipation, and chemical changes, coupled to an active plasma constrained by all-encompassing magnetic and electric fields. More importantly, the plasma and more massive neutral gas are intimately coupled. Ion-neutral coupling can drive winds ten-times hurricane strength making inertia a dominant force; it can sometimes wipe out 90% of the plasma, and at other times allow plasma content to explode with dangerous consequences. Ion-neutral dissipation can result in intense heating, allowing the atmosphere to expand to double its normal size, dragging Earth orbiting satellites to the ground. The thermospheric dynamo, ultimately driven by the solar and magnetosphere dynamos, redistributes equatorial plasma and can drive structure, steep gradients, and irregularities. A single satellite sampling the medium is suitable for uncovering perhaps one or two of the many interacting processes, in what could be called discovery mode science. Without a three-dimensional imaging capability, a single satellite cannot explore the interaction and balance between the multiple of processes actually present. Unraveling the system-wide or global response requires multi-point in-situ constellation-type measurements, together with available two-dimensional imaging. Modeling the system can create an illusion of understanding, but until we really look we will never know.

Host Immune Response to Influenza A Virus Infection.

PubMed

Chen, Xiaoyong; Liu, Shasha; Goraya, Mohsan Ullah; Maarouf, Mohamed; Huang, Shile; Chen, Ji-Long

2018-01-01

Influenza A viruses (IAVs) are contagious pathogens responsible for severe respiratory infection in humans and animals worldwide. Upon detection of IAV infection, host immune system aims to defend against and clear the viral infection. Innate immune system is comprised of physical barriers (mucus and collectins), various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, which provide first line of defense against IAV infection. The adaptive immunity is mediated by B cells and T cells, characterized with antigen-specific memory cells, capturing and neutralizing the pathogen. The humoral immune response functions through hemagglutinin-specific circulating antibodies to neutralize IAV. In addition, antibodies can bind to the surface of infected cells and induce antibody-dependent cell-mediated cytotoxicity or complement activation. Although there are neutralizing antibodies against the virus, cellular immunity also plays a crucial role in the fight against IAVs. On the other hand, IAVs have developed multiple strategies to escape from host immune surveillance for successful replication. In this review, we discuss how immune system, especially innate immune system and critical molecules are involved in the antiviral defense against IAVs. In addition, we highlight how IAVs antagonize different immune responses to achieve a successful infection.

Global distribution of the Energetic Neutral Atom (ENA) / precipitating ion particulate albedo from Low Altitude Emission (LAE) source regions over the last solar maximum

NASA Astrophysics Data System (ADS)

Mackler, D. A.; Jahn, J.; Mukherjee, J.; Pollock, C. J.

2012-12-01

Charge exchange between ring current ions spiraling into the upper atmosphere and terrestrial neutral constituents produces a non-isotropic distribution of escaping Energetic Neutral Atoms (ENA). These ENA's are no longer tied to the magnetic field, and can therefore be observed remotely from orbiting platforms. Particularly of interest is Low Altitude Emissions (LAE) of ENA's. These ENA emissions occur near the oxygen exobase and constitute the brightest ENA signatures during geomagnetic storms. In this study we build on previous work described in Pollock et al. [2009] in which IMAGE/MENA data was used to compute the Invariant Latitude (IL) and Magnetic Local Time (MLT) distributions of ENA's observed in the 29 October 2003 storm. The algorithms developed in Pollock et al. [2009] are used to compute the IL and MLT of LAE source regions for 76 identified storms at different phases of solar cycle 23. The ENA flux from the source regions are divided by in-situ ion precipitation obtained by DMSP-SSJ4 and NOAA-TED to give a global mapping of the particulate albedo during storm times.

Modeling the Extended Neutral Atmosphere and Plasma Environment near Saturn

NASA Technical Reports Server (NTRS)

Richardson, John D.

2003-01-01

In the three years of this study we have published five papers in refereed journals. We have first examined satellite sources and their contribution to the observed neutral cloud. Based on the total calculated satellite sources and the spatial distribution of sputtered H20, we concluded that they cannot produce observed OH cloud. The E-ring contribution has been also studied in detail.In order to produce observed OH cloud we suggested that the E-ring might be the dominant source in inner Saturnian magnetosphere. We proposed a possible resupply mechanism which is needed to keep both E-ring and OH cloud in the present state: collisions between E-ring grains and remains of a disrupted satellite near Enceladus Lagrangian points. In this scenario a large amount of material, ranging from a few micrometers to hundred of meters, which is optically invisible at present, is likely to exist there. The fourth paper compares the magnetosheaths of the outer planets. A surprising result is that the hot proton component comprises about 40% of the total density, much larger than predicted by shock theory. Gas dynamic models of the boundaries show that the magnetospheres of Jupiter and Saturn are flattened at the poles. The last paper was published in GRL and is the first based of the model of neutrals developed as a main goal of this grant and which is now operational.This Monte Carlo collision code self- consistently determines the neutral distribution. from the rings and satellites until they are lost by ionization, by collisions with rings, moons, or Saturn, or by escape from Saturn. Our model is unique in that it includes the effects of plasma chemistry and both plasma-neutral and neutral neutral collisions to determine the dynamical evolution of the water group neutrals in Saturn's magnetosphere. The lifetimes of the neutrals against loss to photoionization, charge exchange, electron dissociation and electron impact dissociation are based on the model given by (Richardson et al. 1998) and vary with position in the magnetosphere. The dominant neutral dissociation channels H20->OH+H, H20-> O+H2, and OH->O+H2 are considered.

Predation risk modifies behaviour by shaping the response of identified brain neurons.

PubMed

Magani, Fiorella; Luppi, Tomas; Nuñez, Jesus; Tomsic, Daniel

2016-04-15

Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs ITALIC! Neohelice granulatafrom two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome. © 2016. Published by The Company of Biologists Ltd.

Turbulent Dispersion of Pathogenic Spores Within and Above Plant Canopies: Field Experiments and Lagrangian Modeling

NASA Astrophysics Data System (ADS)

Gleicher, S.; Chamecki, M.; Isard, S.; Katul, G. G.

2012-12-01

Plant disease epidemics caused by pathogenic spores are a common and consequential threat to agricultural crops. In most cases, pathogenic spores are produced and released deep inside plant canopies and must be transported out of the canopy region in order to infect other fields and spread the disease. The fraction of spores that "escape" the canopy is crucial in determining how fast and far these plant diseases will spread. The goal of this work is to use a field experiment, coupled with a Lagrangian Stochastic Model (LSM), to investigate how properties of canopy turbulence impact the dispersion of spores inside the canopy and the fraction of spores that escape from the canopy. An extensive field experiment was conducted to study spore dispersion inside and outside a corn canopy. The spores were released from point sources located at various depths inside the canopy. Concentration measurements were obtained inside and above the canopy by a 3-dimensional grid of spore collectors. The experimental measurements of mean spore concentration are used to validate a LSM for spore dispersion. In the LSM, flow field statistics used to drive the particle dispersion are specified by a second-order closure model for turbulence within plant canopies. The dispersion model includes spore deposition on and rebound from canopy elements. The combination of experimental and numerical simulations is used to quantify the fraction of spores that escape the canopy. Effects of release height, friction velocity, and canopy architecture on the escape fraction of spores are explored using the LSM, and implications for disease propagation are discussed.

Numerical exploration of non-axisymmetric divertor closure in the small angle slot (SAS) divertor at DIII-D

DOE PAGES

Frerichs, H.; Schmitz, O.; Covele, B.; ...

2018-02-28

Numerical simulations of toroidal asymmetries in a tightly baffled small angle slot (SAS) divertor on the DIII-D tokamak show that toroidal asymmetries in divertor closure result in (non-axisymmetric) local onset of detachment within a density window of 10-15% on top of the nominal threshold separatrix density. The SAS divertor is explored at DIII-D for improving access to cold, dissipative/detached divertor conditions. The narrow width of the slot divertor coupled with a small magnetic field line-to-target angle facilitates the buildup of neutral density, thereby increasing radiative and neutrals-related (atoms and molecules) losses in the divertor. Therefore, small changes in the strikemore » point location can be expected to have a large impact on diverter conditions. The combination of misaligned slot structure and non-axisymmetric perturbations to the magnetic field configuration causes the strike point to move along the divertor target plate, possibly leaving the diverter slot at some locations. The latter extreme case essentially introduces an opening in the divertor slot from where recycling neutrals can easily escape, and thereby degrade the performance of the slot divertor. Such a strike point dislocation is approximated by a finite gap in the divertor baffle for which three dimensional edge plasma and neutral gas simulations are performed with the EMC3-EIRENE code.« less

Concerning neutral flux shielding in the U-3M torsatron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dreval, N. B., E-mail: mdreval@kipt.kharkov.ua

2015-03-15

The volume of the torsatron U-3M vacuum chamber is about 70 m{sup 3}, whereas the plasma volume is about 0.3 m{sup 3}. The large buffer volume of the chamber serves as a source of a substantial neutral flux into the U-3M plasma. A fraction of this flux falls onto the torsatron helical coils located in front of the plasma, due to which the dynamics of neutral influx into the plasma modifies. The shielding of the molecular flux from the buffer volume into the plasma is estimated using numerical calculations. Only about 10% of the incident flux reaches the plasma volume.more » Estimates show that about 20% of atoms escape beyond the helical coils without colliding with them. Under these conditions, the helical coils substantially affect the neutral flux. A discharge regime with a hot low-density plasma produced by a frame antenna is considered. The spatial distribution of the molecular density produced in this regime by the molecular flux from the chamber buffer volume after it has passed between the helical coils is calculated. The contributions of the fluxes emerging from the side and inner surfaces of the helical coils are considered. The calculations show that the shape of the spatial distribution of the molecular density differs substantially from the shape of the magnetic surfaces.« less

Numerical exploration of non-axisymmetric divertor closure in the small angle slot (SAS) divertor at DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frerichs, H.; Schmitz, O.; Covele, B.

Numerical simulations of toroidal asymmetries in a tightly baffled small angle slot (SAS) divertor on the DIII-D tokamak show that toroidal asymmetries in divertor closure result in (non-axisymmetric) local onset of detachment within a density window of 10-15% on top of the nominal threshold separatrix density. The SAS divertor is explored at DIII-D for improving access to cold, dissipative/detached divertor conditions. The narrow width of the slot divertor coupled with a small magnetic field line-to-target angle facilitates the buildup of neutral density, thereby increasing radiative and neutrals-related (atoms and molecules) losses in the divertor. Therefore, small changes in the strikemore » point location can be expected to have a large impact on diverter conditions. The combination of misaligned slot structure and non-axisymmetric perturbations to the magnetic field configuration causes the strike point to move along the divertor target plate, possibly leaving the diverter slot at some locations. The latter extreme case essentially introduces an opening in the divertor slot from where recycling neutrals can easily escape, and thereby degrade the performance of the slot divertor. Such a strike point dislocation is approximated by a finite gap in the divertor baffle for which three dimensional edge plasma and neutral gas simulations are performed with the EMC3-EIRENE code.« less

Numerical exploration of non-axisymmetric divertor closure in the small angle slot (SAS) divertor at DIII-D

NASA Astrophysics Data System (ADS)

Frerichs, H.; Schmitz, O.; Covele, B.; Feng, Y.; Guo, H. Y.; Hill, D.

2018-05-01

Numerical simulations of toroidal asymmetries in a tightly baffled small angle slot (SAS) divertor on the DIII-D tokamak show that toroidal asymmetries in divertor closure result in (non-axisymmetric) local onset of detachment within a density window of 10-15% on top of the nominal threshold separatrix density. The SAS divertor is explored at DIII-D for improving access to cold, dissipative/detached divertor conditions. The narrow width of the slot divertor coupled with a small magnetic field line-to-target angle facilitates the buildup of neutral density, thereby increasing radiative and neutrals-related (atoms and molecules) losses in the divertor. Small changes in the strike point location can be expected to have a large impact on divertor conditions. The combination of misaligned slot structure and non-axisymmetric perturbations to the magnetic field configuration causes the strike point to move along the divertor target plate, possibly leaving the divertor slot at some locations. The latter extreme case essentially introduces an opening in the divertor slot from where recycling neutrals can easily escape, and thereby degrade the performance of the slot divertor. Such a strike point dislocation is approximated by a finite gap in the divertor baffle for which 3D edge plasma and neutral gas simulations are performed with the EMC3-EIRENE code.

In-situ observation of Martian neutral exosphere: Results from MENCA aboard Indian Mars Orbiter Mission (MOM)

NASA Astrophysics Data System (ADS)

Bhardwaj, Anil; Pratim Das, Tirtha; Dhanya, M. B.; Thampi, Smitha V.

2016-07-01

Till very recently, the only in situ measurements of the Martian upper atmospheric composition was from the mass spectrometer experiments aboard the two Viking landers, which covered the altitude region from 120 to 200 km. Hence, the exploration by the Mars Exospheric Neutral Composition Analyser (MENCA) aboard the Mars Orbiter Mission (MOM) spacecraft of ISRO and the Neutral Gas and Ion Mass Spectrometer (NGIMS) experiment aboard the Mars Atmosphere and Volatile ENvironment (MAVEN) mission of NASA are significant steps to further understand the Martian neutral exosphere and its variability. MENCA is a quadrupole based neutral mass spectrometer which observes the radial distribution of the Martian neutral exosphere. The analysis of the data from MENCA has revealed unambiguous detection of the three major constituents, which are amu 44 (CO2), amu 28 (contributions from CO and N2) and amu 16 (atomic O), as well as a few minor species. Since MOM is in a highly elliptical orbit, the MENCA observations pertain to different local times, in the low-latitude region. Examples of such observations would be presented, and compared with NGIMS results. Emphasis would be given to the observations pertaining to high solar zenith angles and close to perihelion period. During the evening hours, the transition from CO2 to O dominated region is observed near 270 km, which is significantly different from the previous observations corresponding to sub-solar point and SZA of ~45°. The mean evening time exospheric temperature derived using these observations is 271±5 K. These are the first observations corresponding to the Martian evening hours, which would help to provide constraints to the thermal escape models.

O2 and Water Migration Pathways between the Solvent and Heme Pockets of Hemoglobin with Open and Closed Conformations of the Distal HisE7.

PubMed

Shadrina, Maria S; Peslherbe, Gilles H; English, Ann M

2015-09-01

Hemoglobin transports O2 by binding the gas at its four hemes. Hydrogen bonding between the distal histidine (HisE7) and heme-bound O2 significantly increases the affinity of human hemoglobin (HbA) for this ligand. HisE7 is also proposed to regulate the release of O2 to the solvent via a transient E7 channel. To reveal the O2 escape routes controlled by HisE7 and to evaluate its role in gating heme access, we compare simulations of O2 diffusion from the distal heme pockets of the T and R states of HbA performed with HisE7 in its open (protonated) and closed (neutral) conformations. Irrespective of HisE7's conformation, we observe the same four or five escape routes leading directly from the α- or β-distal heme pockets to the solvent. Only 21-53% of O2 escapes occur via these routes, with the remainder escaping through routes that encompass multiple internal cavities in HbA. The conformation of the distal HisE7 controls the escape of O2 from the heme by altering the distal pocket architecture in a pH-dependent manner, not by gating the E7 channel. Removal of the HisE7 side chain in the GlyE7 variant exposes the distal pockets to the solvent, and the percentage of O2 escapes to the solvent directly from the α- or β-distal pockets of the mutant increases to 70-88%. In contrast to O2, the dominant water route from the bulk solvent is gated by HisE7 because protonation and opening of this residue dramatically increase the rate of influx of water into the empty distal heme pockets. The occupancy of the distal heme site by a water molecule, which functions as an additional nonprotein barrier to binding of the ligand to the heme, is also controlled by HisE7. Overall, analysis of gas and water diffusion routes in the subunits of HbA and its GlyE7 variant sheds light on the contribution of distal HisE7 in controlling polar and nonpolar ligand movement between the solvent and the hemes.

An objective assessment of safety to drive in an upper limb cast.

PubMed

Stevenson, H L; Peterson, N; Talbot, C; Dalal, S; Watts, A C; Trail, I A

2013-03-01

Patients managed with upper limb cast immobilization often seek advice about driving. There is very little published data to assist in decision making, and advice given varies between healthcare professionals. There are no specific guidelines available from the UK Drivers and Vehicles Licensing Agency, police, or insurance companies. Evidence-based guidelines would enable clinicians to standardize the advice given to patients. Six individuals (three male, three female; mean age 36 years, range 27-43 years) were assessed by a mobility occupational therapist and driving standards agency examiner while completing a formal driving test in six different types of upper limb casts (above-elbow, below-elbow neutral, and below-elbow cast incorporating the thumb [Bennett's cast]) on both left and right sides. Of the 36 tests, participants passed 31 tests, suggesting that most people were able to safely drive with upper limb cast immobilization. However, driving in a left above-elbow cast was considered unsafe.

Assessment of the Effectiveness of Clay Soil Covers as Engineered Barriers in Waste Disposal Facilities with Emphasis on Modeling Cracking Behavior

DTIC Science & Technology

2008-06-01

escaping the clay and keeping its compacted conditions constant. Other stabilizing additives such as surfactants or cement and applications such as foamed ...not a local phenomenon. Once a crack is formed, increasing the width of the crack at the surface by additional shrinkage will also extend the depth...at the surface, increasing the width of the crack by additional shrinkage will drive the crack deeper into the soil mass, expos- ing new surfaces to

Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin.

PubMed

Wu, Nicholas C; Xie, Jia; Zheng, Tianqing; Nycholat, Corwin M; Grande, Geramie; Paulson, James C; Lerner, Richard A; Wilson, Ian A

2017-06-14

Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has not been fully explored. Here, we performed a large-scale mutational analysis of the RBS of A/WSN/33 (H1N1) and A/Hong Kong/1/1968 (H3N2) HAs. Many replication-competent mutants not yet observed in nature were identified, including some that could escape from an RBS-targeted broadly neutralizing antibody. This functional sequence diversity is made possible by pervasive epistasis in the RBS 220-loop and can be buffered by avidity in viral receptor binding. Overall, our study reveals that the HA RBS can accommodate a much greater range of sequence diversity than previously thought, which has significant implications for the complex evolutionary interrelationships between receptor specificity and immune escape. Copyright © 2017 Elsevier Inc. All rights reserved.

Exponential synchronization of delayed neutral-type neural networks with Lévy noise under non-Lipschitz condition

NASA Astrophysics Data System (ADS)

Ma, Shuo; Kang, Yanmei

2018-04-01

In this paper, the exponential synchronization of stochastic neutral-type neural networks with time-varying delay and Lévy noise under non-Lipschitz condition is investigated for the first time. Using the general Itô's formula and the nonnegative semi-martingale convergence theorem, we derive general sufficient conditions of two kinds of exponential synchronization for the drive system and the response system with adaptive control. Numerical examples are presented to verify the effectiveness of the proposed criteria.

DOUBLE code simulations of emissivities of fast neutrals for different plasma observation view-lines of neutral particle analyzers on the COMPASS tokamak

NASA Astrophysics Data System (ADS)

Mitosinkova, K.; Tomes, M.; Stockel, J.; Varju, J.; Stano, M.

2018-03-01

Neutral particle analyzers (NPA) measure line-integrated energy spectra of fast neutral atoms escaping the tokamak plasma, which are a product of charge-exchange (CX) collisions of plasma ions with background neutrals. They can observe variations in the ion temperature T i of non-thermal fast ions created by additional plasma heating. However, the plasma column which a fast atom has to pass through must be sufficiently short in comparison with the fast atom’s mean-free-path. Tokamak COMPASS is currently equipped with one NPA installed at a tangential mid-plane port. This orientation is optimal for observing non-thermal fast ions. However, in this configuration the signal at energies useful for T i derivation is lost in noise due to the too long fast atoms’ trajectories. Thus, a second NPA is planned to be connected for the purpose of measuring T i. We analyzed different possible view-lines (perpendicular mid-plane, tangential mid-plane, and top view) for the second NPA using the DOUBLE Monte-Carlo code and compared the results with the performance of the present NPA with tangential orientation. The DOUBLE code provides fast-atoms’ emissivity functions along the NPA view-line. The position of the median of these emissivity functions is related to the location from where the measured signal originates. Further, we compared the difference between the real central T i used as a DOUBLE code input and the T iCX derived from the exponential decay of simulated energy spectra. The advantages and disadvantages of each NPA location are discussed.

Progress of long pulse operation with high performance plasma in KSTAR

NASA Astrophysics Data System (ADS)

Bae, Young; Kstar Team

2015-11-01

Recent KSTAR experiments showed the sustained H-mode operation up to the pulse duration of 46 s at the plasma current of 600 kA. The long-pulse H-mode operation has been supported by long-pulse capable neutral beam injection (NBI) system with high NB current drive efficiency attributed by highly tangential injections of three beam sources. In next phase, aiming to demonstrate the long pulse stationary high performance plasma operation, we are attempting the long pulse inductive operation at the higher performance (MA plasma current, high normalized beta, and low q95) for the final goal of demonstration of ITER-like baseline scenario in KSTAR with progressive improvement of the plasma shape control and higher neutral beam injection power. This paper presents the progress of long pulse operation and the analysis of energy confinement time and non-inductive current drive in KSTAR.

Photochemistry of Triton's Atmosphere and Ionosphere

NASA Technical Reports Server (NTRS)

Krasnopolsky, Vladimir A.; Cruikshank, Dale P.

1995-01-01

The photochemistry of 32 neutral and 21 ion species in Triton's atmosphere is considered. Parent species N2, CH4, and CO (with a mixing ratio of 3 x 10(exp -4) in our basic model) sublime from the ice with rates of 40, 208, and 0.3 g/sq cm/b.y., respectively. Chemistry below 50 km is driven mostly by photolysis of methane by the solar and interstellar medium Lyman-alpha photons, producing hydrocarbons C2H4, C2H6, and C2H2 which form haze particles with precipitation rates of 135, 28, and 1.3 g/sq cm/b.y., respectively. Some processes are discussed which increase the production of HCN (by an order of magnitude to a value of 29 g/sq cm/b.y.) and involve indirect photolysis of N2 by neutrals. Reanalysis of the measured methane profiles gives an eddy diffusion coefficient K = 4 x 10(exp 3)sq cm/s above the tropopause and a more accurate methane number density near the surface, (3.1 +/- 0.8)x IO(exp 11)/cu cm. Chemistry above 200 km is driven by the solar EUV radiation (lambda less than 1000 A) and by precipitation of magnetospheric electrons with a total energy input of 10(exp 8) W (based on thermal balance calculations). The most abundant photochemical species are N, H2, H, 0, and C. They escape with the total rates of 7.7 x 10(exp 24)/ s, 4.5 x 10(exp 25)/s, 2.4 x 10(exp 25)/s, 4.4 x 10(exp 22)/s, and 1.1 x 10(exp 24), respectively. Atomic species are transported to a region of 50-200 km and drive the chemistry there. Ionospheric chemistry explains the formation of an E region at 150-240 km with HCO(+) as a major ion, and of an F region above 240 km with a peak at 320 km and C(+) as a major ion. The ionosphere above 500 km consists of almost equal densities of C(+) and N(+) ions. The model profiles agree with the measured atomic nitrogen and electron density profiles. A number of other models with varying rate coefficients of some reactions, differing properties of the haze particles (chemically passive or active), etc., were developed. These models show that there are four basic unknown values which have strong impacts on the composition and structure of the atmosphere and ionosphere. These values and their plausible ranges are the CO mixing ratio f(sub co) = 10(exp -4) - 10(exp -3), the magnetospheric electron energy input (1 +/- 0.5) x 10(exp 8) W, the rate coefficient of charge-exchange reaction N2(+) + C(kappa) = 10(exp -11) - 10(exp -10)cu cm/s, and the ion escape velocity upsilon(sub i) approx. equals 150 cm/s.

Globally fixed-time synchronization of coupled neutral-type neural network with mixed time-varying delays.

PubMed

Zheng, Mingwen; Li, Lixiang; Peng, Haipeng; Xiao, Jinghua; Yang, Yixian; Zhang, Yanping; Zhao, Hui

2018-01-01

This paper mainly studies the globally fixed-time synchronization of a class of coupled neutral-type neural networks with mixed time-varying delays via discontinuous feedback controllers. Compared with the traditional neutral-type neural network model, the model in this paper is more general. A class of general discontinuous feedback controllers are designed. With the help of the definition of fixed-time synchronization, the upper right-hand derivative and a defined simple Lyapunov function, some easily verifiable and extensible synchronization criteria are derived to guarantee the fixed-time synchronization between the drive and response systems. Finally, two numerical simulations are given to verify the correctness of the results.

Globally fixed-time synchronization of coupled neutral-type neural network with mixed time-varying delays

PubMed Central

2018-01-01

This paper mainly studies the globally fixed-time synchronization of a class of coupled neutral-type neural networks with mixed time-varying delays via discontinuous feedback controllers. Compared with the traditional neutral-type neural network model, the model in this paper is more general. A class of general discontinuous feedback controllers are designed. With the help of the definition of fixed-time synchronization, the upper right-hand derivative and a defined simple Lyapunov function, some easily verifiable and extensible synchronization criteria are derived to guarantee the fixed-time synchronization between the drive and response systems. Finally, two numerical simulations are given to verify the correctness of the results. PMID:29370248

XUV-exposed, non-hydrostatic hydrogen-rich upper atmospheres of terrestrial planets. Part II: hydrogen coronae and ion escape.

PubMed

Kislyakova, Kristina G; Lammer, Helmut; Holmström, Mats; Panchenko, Mykhaylo; Odert, Petra; Erkaev, Nikolai V; Leitzinger, Martin; Khodachenko, Maxim L; Kulikov, Yuri N; Güdel, Manuel; Hanslmeier, Arnold

2013-11-01

We studied the interactions between the stellar wind plasma flow of a typical M star, such as GJ 436, and the hydrogen-rich upper atmosphere of an Earth-like planet and a "super-Earth" with a radius of 2 R(Earth) and a mass of 10 M(Earth), located within the habitable zone at ∼0.24 AU. We investigated the formation of extended atomic hydrogen coronae under the influences of the stellar XUV flux (soft X-rays and EUV), stellar wind density and velocity, shape of a planetary obstacle (e.g., magnetosphere, ionopause), and the loss of planetary pickup ions on the evolution of hydrogen-dominated upper atmospheres. Stellar XUV fluxes that are 1, 10, 50, and 100 times higher compared to that of the present-day Sun were considered, and the formation of high-energy neutral hydrogen clouds around the planets due to the charge-exchange reaction under various stellar conditions was modeled. Charge-exchange between stellar wind protons with planetary hydrogen atoms, and photoionization, lead to the production of initially cold ions of planetary origin. We found that the ion production rates for the studied planets can vary over a wide range, from ∼1.0×10²⁵ s⁻¹ to ∼5.3×10³⁰ s⁻¹, depending on the stellar wind conditions and the assumed XUV exposure of the upper atmosphere. Our findings indicate that most likely the majority of these planetary ions are picked up by the stellar wind and lost from the planet. Finally, we estimated the long-time nonthermal ion pickup escape for the studied planets and compared them with the thermal escape. According to our estimates, nonthermal escape of picked-up ionized hydrogen atoms over a planet's lifetime within the habitable zone of an M dwarf varies between ∼0.4 Earth ocean equivalent amounts of hydrogen (EO(H)) to <3 EO(H) and usually is several times smaller in comparison to the thermal atmospheric escape rates.

The neutral wind 'flywheel' as a source of quiet-time, polar-cap currents

NASA Technical Reports Server (NTRS)

Lyons, L. R.; Walterscheid, R. L.; Killeen, T. L.

1985-01-01

The neutral wind pattern over the summer polar cap can be driven by plasma convection to resemble the convection pattern. For a north-south component of the interplanetary magnetic field Bz directed southward, the wind speeds in the conducting E-region can become approximately 25 percent of the electric field drift speeds. If convection ceases, this neutral wind distribution can drive a significant polar cap current system for approximately 6 hours. The currents are reversed from those driven by the electric fields for southward Bz, and the Hall and field-aligned components of the current system resemble those observed during periods of northward Bz. The current magnitudes are similar to those observed during periods of small, northward Bz; however, observations indicate that electric fields often contribute to the currents as much as, or more than, the neutral winds.

Design of a toroidal device with a high temperature superconductor coil for non-neutral plasma trap

NASA Astrophysics Data System (ADS)

Ogawa, Yuichi; Morikawa, Junji; Nihei, Hitoshi; Ozawa, Daisaku; Yoshida, Zensho; Mito, Toshiyuki; Yanagi, Nagato; Iwakuma, Masataka

2002-01-01

The non-neutral plasma confinement device with a floating internal coil is under construction, where the high temperature superconductor (HTS) Ag-sheathed BSCCO-2223 is employed as the floating coil. We have two topics with this device: one is a trap of a non-neutral plasma consisting of one species, and another is an exploration of a high beta plasma based on two-fluid MHD relaxation theory. In the latter case the plasma should be non-neutralized in order to drive the plasma flow in the toroidal direction. The expected plasma parameters are discussed. Key elements of engineering issues have already developed. In addition, we have fabricated a small HTS coil and succeeded in levitating it within an accuracy of 25˜30 μm for 4 min or more.

Kinematics and Optical Depth in the Green Peas: Suppressed Superwinds in Candidate LyC Emitters

NASA Astrophysics Data System (ADS)

Jaskot, Anne E.; Oey, M. S.; Scarlata, Claudia; Dowd, Tara

2017-12-01

By clearing neutral gas away from a young starburst, superwinds may regulate the escape of Lyman continuum (LyC) photons from star-forming galaxies. However, models predict that superwinds may not launch in the most extreme, compact starbursts. We explore the role of outflows in generating low optical depths in the Green Peas (GPs), the only known star-forming population with several confirmed and candidate LyC-leaking galaxies. With Hubble Space Telescope UV spectra of 25 low-redshift GPs, including new observations of 13 of the most highly ionized GPs, we compare the kinematics of UV absorption lines with indirect H I optical depth diagnostics: Lyα escape fraction, Lyα peak separation, or low-ionization absorption line equivalent width. The data suggest that high-ionization kinematics tracing superwind activity may correlate with low optical depth in some objects. However, the most extreme GPs, including many of the best candidate LyC emitters with weak low-ionization absorption and strong, narrow Lyα profiles, show the lowest velocities. These results are consistent with models for suppressed superwinds, which suggests that outflows may not be the only cause of LyC escape from galaxies. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS-5-26555. These observations are associated with programs GO-14080, GO-13293, and GO-12928.

Direct and indirect selection on flowering time, water-use efficiency (WUE, δ 13C), and WUE plasticity to drought in Arabidopsis thaliana

PubMed Central

Kenney, Amanda M; McKay, John K; Richards, James H; Juenger, Thomas E

2014-01-01

Flowering time and water-use efficiency (WUE) are two ecological traits that are important for plant drought response. To understand the evolutionary significance of natural genetic variation in flowering time, WUE, and WUE plasticity to drought in Arabidopsis thaliana, we addressed the following questions: (1) How are ecophysiological traits genetically correlated within and between different soil moisture environments? (2) Does terminal drought select for early flowering and drought escape? (3) Is WUE plasticity to drought adaptive and/or costly? We measured a suite of ecophysiological and reproductive traits on 234 spring flowering accessions of A. thaliana grown in well-watered and season-ending soil drying treatments, and quantified patterns of genetic variation, correlation, and selection within each treatment. WUE and flowering time were consistently positively genetically correlated. WUE was correlated with WUE plasticity, but the direction changed between treatments. Selection generally favored early flowering and low WUE, with drought favoring earlier flowering significantly more than well-watered conditions. Selection for lower WUE was marginally stronger under drought. There were no net fitness costs of WUE plasticity. WUE plasticity (per se) was globally neutral, but locally favored under drought. Strong genetic correlation between WUE and flowering time may facilitate the evolution of drought escape, or constrain independent evolution of these traits. Terminal drought favored drought escape in these spring flowering accessions of A. thaliana. WUE plasticity may be favored over completely fixed development in environments with periodic drought. PMID:25512847

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.

Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates.

PubMed

Prowse, Thomas A A; Cassey, Phillip; Ross, Joshua V; Pfitzner, Chandran; Wittmann, Talia A; Thomas, Paul

2017-08-16

Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial 'silver bullet' for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that are replicated during meiosis via homologous recombination. However, their efficacy for controlling wild populations is threatened by inherent polymorphic resistance and the creation of resistance alleles via non-homologous end-joining (NHEJ)-mediated DNA repair. We used stochastic individual-based models to identify realistic gene-drive strategies capable of eradicating vertebrate pest populations (mice, rats and rabbits) on islands. One popular strategy, a sex-reversing drive that converts heterozygous females into sterile males, failed to spread and required the ongoing deployment of gene-drive carriers to achieve eradication. Under alternative strategies, multiplexed gRNAs could overcome inherent polymorphic resistance and were required for eradication success even when the probability of NHEJ was low. Strategies causing homozygotic embryonic non-viability or homozygotic female sterility produced high probabilities of eradication and were robust to NHEJ-mediated deletion of the DNA sequence between multiplexed endonuclease recognition sites. The latter two strategies also purged the gene drive when eradication failed, therefore posing lower long-term risk should animals escape beyond target islands. Multiplexing gRNAs will be necessary if this technology is to be useful for insular extirpation attempts; however, precise knowledge of homing rates will be required to design low-risk gene drives with high probabilities of eradication success. © 2017 The Author(s).

Potent Neutralization of Vaccinia Virus by Divergent Murine Antibodies Targeting a Common Site of Vulnerability in L1 Protein

PubMed Central

Kaever, Thomas; Meng, Xiangzhi; Matho, Michael H.; Schlossman, Andrew; Li, Sheng; Sela-Culang, Inbal; Ofran, Yanay; Buller, Mark; Crump, Ryan W.; Parker, Scott; Frazier, April; Crotty, Shane; Zajonc, Dirk M.; Peters, Bjoern

2014-01-01

ABSTRACT Vaccinia virus (VACV) L1 is an important target for viral neutralization and has been included in multicomponent DNA or protein vaccines against orthopoxviruses. To further understand the protective mechanism of the anti-L1 antibodies, we generated five murine anti-L1 monoclonal antibodies (MAbs), which clustered into 3 distinct epitope groups. While two groups of anti-L1 failed to neutralize, one group of 3 MAbs potently neutralized VACV in an isotype- and complement-independent manner. This is in contrast to neutralizing antibodies against major VACV envelope proteins, such as H3, D8, or A27, which failed to completely neutralize VACV unless the antibodies are of complement-fixing isotypes and complement is present. Compared to nonneutralizing anti-L1 MAbs, the neutralization antibodies bound to the recombinant L1 protein with a significantly higher affinity and also could bind to virions. By using a variety of techniques, including the isolation of neutralization escape mutants, hydrogen/deuterium exchange mass spectrometry, and X-ray crystallography, the epitope of the neutralizing antibodies was mapped to a conformational epitope with Asp35 as the key residue. This epitope is similar to the epitope of 7D11, a previously described potent VACV neutralizing antibody. The epitope was recognized mainly by CDR1 and CDR2 of the heavy chain, which are highly conserved among antibodies recognizing the epitope. These antibodies, however, had divergent light-chain and heavy-chain CDR3 sequences. Our study demonstrates that the conformational L1 epitope with Asp35 is a common site of vulnerability for potent neutralization by a divergent group of antibodies. IMPORTANCE Vaccinia virus, the live vaccine for smallpox, is one of the most successful vaccines in human history, but it presents a level of risk that has become unacceptable for the current population. Studying the immune protection mechanism of smallpox vaccine is important for understanding the basic principle of successful vaccines and the development of next-generation, safer vaccines for highly pathogenic orthopoxviruses. We studied antibody targets in smallpox vaccine by developing potent neutralizing antibodies against vaccinia virus and comprehensively characterizing their epitopes. We found a site in vaccinia virus L1 protein as the target of a group of highly potent murine neutralizing antibodies. The analysis of antibody-antigen complex structure and the sequences of the antibody genes shed light on how these potent neutralizing antibodies are elicited from immunized mice. PMID:25031354

Optimal combinations of broadly neutralizing antibodies for prevention and treatments of HIV-1 clade C infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn

In this study, the identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and themore » gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP). By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.« less

Optimal combinations of broadly neutralizing antibodies for prevention and treatments of HIV-1 clade C infection

DOE PAGES

Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn; ...

2016-03-30

In this study, the identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and themore » gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP). By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.« less

Neutral Buoyancy Simulator - SADE NBS Test

NASA Technical Reports Server (NTRS)

1983-01-01

One of the main components of the Hubble Space Telescope (HST) is the Solar Array Drive Electronics (SADE) system. This system interfaces with the Support System Module (SSM) for exchange of operational commands and telemetry data. SADE operates and controls the Solar Array Drive Mechanisms (SADM) for the orientation of the Solar Array Drive (SAD). It also monitors the position of the arrays and the temperature of the SADM. During the first HST servicing mission, the astronauts replaced the SADE component because of some malfunctions. This turned out to be a very challenging extravehicular activity (EVA). Two transistors and two diodes had been thermally stressed with the conformal coating discolored and charred. Soldered cornections became molten and reflowed between the two diodes. The failed transistors gave no indication of defective construction. All repairs were made and the HST was redeposited into orbit. Prior to undertaking this challenging mission, the orbiter's crew trained at Marshall Space Flight Center's (MSFC) Neutral Buoyancy Simulator (NBS) to prepare themselves for working in a low gravity environment. They also practiced replacing HST parts and exercised maneuverability and equipment handling. Pictured is an astronaut practicing climbing a space platform that was necessary in making repairs on the HST.

Neutral Buoyancy Simulator-NB50B-SADE Training Exercises

NASA Technical Reports Server (NTRS)

1983-01-01

One of the main components of the Hubble Space Telescope (HST) is the Solar Array Drive Electronics (SADE) system. This system interfaces with the Support System Module (SSM) for exchange of operational commands and telemetry data. SADE operates and controls the Solar Array Drive Mechanisms (SADM) for the orientation of the Solar Array Drive (SAD). It also monitors the position of the arrays and the temperature of the SADM. During the first HST servicing mission, the astronauts replaced the SADE component because of some malfunctions. This turned out to be a very challenging extravehicular activity (EVA). Two transistors and two diodes had been thermally stressed with the conformal coating discolored and charred. Soldered cornections became molten and reflowed between the two diodes. The failed transistors gave no indication of defective construction. All repairs were made and the HST was redeposited into orbit. Prior to undertaking this challenging mission, the orbiter's crew trained at Marshall Space Flight Center's (MSFC) Neutral Buoyancy Simulator (NBS) to prepare themselves for working in a low gravity environment. They also practiced replacing HST parts and exercised maneuverability and equipment handling. Pictured are crew members practicing on a space platform.

Temperature-dependent radiative and non-radiative dynamics of photo-excited carriers in extremely high-density and small InGaN nanodisks fabricated by neutral-beam etching using bio-nano-templates

NASA Astrophysics Data System (ADS)

Chen, Yafeng; Kiba, Takayuki; Takayama, Junichi; Higo, Akio; Tanikawa, Tomoyuki; Chen, Shula; Samukawa, Seiji; Murayama, Akihiro

2018-05-01

Temperature-dependent radiative and non-radiative dynamics of photoexcited carriers were studied in In0.3Ga0.7N nanodisks (NDs) fabricated from quantum wells (QWs) by neutral-beam etching using bio-nano-templates. The NDs had a diameter of 5 nm, a thickness of 2 and 3 nm, and a sheet density of 2 × 1011 cm-2. The radiative decay time, reflecting the displacement between the electron and hole wavefunctions, is about 0.2 ns; this value is almost constant as a function of temperature in the NDs and not dependent on their thickness. We observed non-exponential decay curves of photoluminescence (PL) in the NDs, particularly at temperatures above 150 K. The thermal activation energies of PL quenching in the NDs are revealed to be about 110 meV, corresponding to the barrier heights of the valence bands in the disks. Therefore, hole escape is deemed responsible for the PL quenching, while thermal activation energies of 12 meV due to the trapping of carriers by defects were dominant in the mother QWs. The above-mentioned non-exponential PL decay curves can be attributed to variations in the rate of hole escape in the NDs because of fluctuations in the valence-band barrier height, which, in turn, is possibly due to compositional fluctuations in the QWs. We found that non-radiative trapping, characteristic of the original QW, also exists in about 1% of the NDs in a form that is not masked by other newly formable defects. Therefore, we suggest that additional defect formation is not significant during our ND fabrication process.

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems.

PubMed

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C; Fire, Andrew Z; Sánchez-Amat, Antonio

2017-08-17

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea . One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an 'arms race' in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.

Patterns of variability in supercritical hadronic systems

NASA Astrophysics Data System (ADS)

Petropoulou, M.; Mastichiadis, A.

2018-07-01

A unique and often overlooked property of a source loaded with relativistic protons is that it can become supercritical, i.e. it can undergo an abrupt transition from a radiatively inefficient to a radiatively efficient state once its proton energy density exceeds a certain threshold. In this paper, we investigate the temporal variability of hadronic systems in this hardly explored regime. We show that there exists a range of proton densities that prevent the system from reaching a steady state, but drive it instead in a quasi-periodic mode. The escaping radiation then exhibits limit cycles, even if all physical parameters are held constant in time. We extend our analysis to cases where the proton injection rate varies with time and explore the variability patterns of escaping radiation as the system moves in and out from the supercritical regime. We examine the relevance of our results to the variability of the prompt gamma-ray burst emission and show that, at least on a phenomenological level, some interesting analogies exist.

Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.

PubMed

Wang, Ming; Zuris, John A; Meng, Fantao; Rees, Holly; Sun, Shuo; Deng, Pu; Han, Yong; Gao, Xue; Pouli, Dimitra; Wu, Qi; Georgakoudi, Irene; Liu, David R; Xu, Qiaobing

2016-03-15

A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing.

Secondary antiproton production in relativistic plasmas

NASA Technical Reports Server (NTRS)

Dermer, C. D.; Ramaty, R.

1985-01-01

The possibility is investigated that the reported excess low energy antiproton component of the cosmic radiation results from proton-proton (p-p) interactions in relativistic plasmas. Because of both target and projectile motion in such plasmas, the antiproton production threshold in the frame of the plasma is much lower than the threshold of antiproton production in cosmic ray interactions with ambient matter. The spectrum of the resultant antiprotons therefore extends to much lower energy than in the cosmic ray case. The antiproton spectrum is calculated for relativistic thermal plasmas and the spectrum is estimated for relativistic nonthermal plasmas. As possible production sites, matter accreting onto compact objects located in the galaxy is considered. Possible overproduction of gamma rays from associated neutral pion production can be avoided if the site is optically thick to the photons but not to the antiprotons. A possible scenario involves a sufficiently large photon density that the neutral pion gamma rays are absorbed by photon-photon pair production. Escape of the antiprotons to the interstellar medium can be mediated by antineutron production.

A new upper limit to the field-aligned potential near Titan.

PubMed

Coates, Andrew J; Wellbrock, Anne; Waite, J Hunter; Jones, Geraint H

2015-06-28

Neutral particles dominate regions of the Saturn magnetosphere and locations near several of Saturn's moons. Sunlight ionizes neutrals, producing photoelectrons with characteristic energy spectra. The Cassini plasma spectrometer electron spectrometer has detected photoelectrons throughout these regions, where photoelectrons may be used as tracers of magnetic field morphology. They also enhance plasma escape by setting up an ambipolar electric field, since the relatively energetic electrons move easily along the magnetic field. A similar mechanism is seen in the Earth's polar wind and at Mars and Venus. Here we present a new analysis of Titan photoelectron data, comparing spectra measured in the sunlit ionosphere at ~1.4 Titan radii ( R T ) and at up to 6.8 R T away. This results in an upper limit on the potential of 2.95 V along magnetic field lines associated with Titan at up to 6.8 R T , which is comparable to some similar estimates for photoelectrons seen in Earth's magnetosphere.

Composition/Structure/Dynamics of comet and planetary satellite atmospheres

NASA Technical Reports Server (NTRS)

Combi, Michael R. (Principal Investigator)

1995-01-01

This research program addresses two cases of tenuous planetary atmospheres: comets and Io. The comet atmospheric research seeks to analyze a set of spatial profiles of CN in comet Halley taken in a 7.4-day period in April 1986; to apply a new dust coma model to various observations; and to analyze observations of the inner hydrogen coma, which can be optically thick to the resonance scattering of Lyman-alpha radiation, with the newly developed approach that combines a spherical radiative transfer model with our Monte Carlo H coma model. The Io research seeks to understand the atmospheric escape from Io with a hybrid-kinetic model for neutral gases and plasma given methods and algorithms developed for the study of neutral gas cometary atmospheres and the earth's polar wind and plasmasphere. Progress is reported on cometary Hydrogen Lyman-alpha studies; time-series analysis of cometary spatial profiles; model analysis of the dust comae of comets; and a global kinetic atmospheric model of Io.

A new upper limit to the field‐aligned potential near Titan

PubMed Central

Wellbrock, Anne; Waite, J. Hunter; Jones, Geraint H.

2015-01-01

Abstract Neutral particles dominate regions of the Saturn magnetosphere and locations near several of Saturn's moons. Sunlight ionizes neutrals, producing photoelectrons with characteristic energy spectra. The Cassini plasma spectrometer electron spectrometer has detected photoelectrons throughout these regions, where photoelectrons may be used as tracers of magnetic field morphology. They also enhance plasma escape by setting up an ambipolar electric field, since the relatively energetic electrons move easily along the magnetic field. A similar mechanism is seen in the Earth's polar wind and at Mars and Venus. Here we present a new analysis of Titan photoelectron data, comparing spectra measured in the sunlit ionosphere at ~1.4 Titan radii (R T) and at up to 6.8 R T away. This results in an upper limit on the potential of 2.95 V along magnetic field lines associated with Titan at up to 6.8 R T, which is comparable to some similar estimates for photoelectrons seen in Earth's magnetosphere. PMID:27609997

Non-Conscious Emotional Activation Colors First Impressions: A Regulatory Role for Conscious Awareness

PubMed Central

Lapate, R.C.; Rokers, B.; Li, T.; Davidson, R.J.

2014-01-01

Emotions can color our attitudes toward unrelated objects in the environment. Prior evidence suggests that such emotional coloring is particularly strong when emotion-triggering information escapes conscious awareness. But, is emotional reactivity stronger following non-conscious versus conscious emotional provocation? Or does conscious processing specifically change the association between emotional reactivity and evaluations of unrelated objects? In this study, we independently indexed emotional reactivity and coloring as a function of emotional-stimulus awareness to disentangle these accounts. Specifically, we recorded skin conductance responses (SCRs) to spiders and fearful faces, along with subsequent preferences for novel neutral faces during visually aware and unaware states. Fearful faces increased SCRs comparably in both aware and unaware conditions. Yet, only when visual awareness was precluded did SCRs to fearful faces predict decreased likeability of neutral faces. These findings suggest a regulatory role for conscious awareness in breaking otherwise automatic associations between physiological reactivity and evaluative emotional responses. PMID:24317420

Nonconscious emotional activation colors first impressions: a regulatory role for conscious awareness.

PubMed

Lapate, Regina C; Rokers, Bas; Li, Tianyi; Davidson, Richard J

2014-02-01

Emotions can color people's attitudes toward unrelated objects in the environment. Existing evidence suggests that such emotional coloring is particularly strong when emotion-triggering information escapes conscious awareness. But is emotional reactivity stronger after nonconscious emotional provocation than after conscious emotional provocation, or does conscious processing specifically change the association between emotional reactivity and evaluations of unrelated objects? In this study, we independently indexed emotional reactivity and coloring as a function of emotional-stimulus awareness to disentangle these accounts. Specifically, we recorded skin-conductance responses to spiders and fearful faces, along with subsequent preferences for novel neutral faces during visually aware and unaware states. Fearful faces increased skin-conductance responses comparably in both stimulus-aware and stimulus-unaware conditions. Yet only when visual awareness was precluded did skin-conductance responses to fearful faces predict decreased likability of neutral faces. These findings suggest a regulatory role for conscious awareness in breaking otherwise automatic associations between physiological reactivity and evaluative emotional responses.

The growth and potential of human antiviral monoclonal antibody therapeutics.

PubMed

Marasco, Wayne A; Sui, Jianhua

2007-12-01

Monoclonal antibodies (mAbs) have long provided powerful research tools for virologists to understand the mechanisms of virus entry into host cells and of antiviral immunity. Even so, commercial development of human (or humanized) mAbs for the prophylaxis, preemptive and acute treatment of viral infections has been slow. This is surprising, as new antibody discovery tools have increased the speed and precision with which potent neutralizing human antiviral mAbs can be identified. As longstanding barriers to antiviral mAb development, such as antigenic variability of circulating viral strains and the ability of viruses to undergo neutralization escape, are being overcome, deeper insight into the mechanisms of mAb action and engineering of effector functions are also improving the efficacy of antiviral mAbs. These successes, in both industrial and academic laboratories, coupled with ongoing changes in the biomedical and regulatory environments, herald an era when the commercial development of human antiviral mAb therapies will likely surge.

Clustering and Phase Transitions on a Neutral Landscape

NASA Astrophysics Data System (ADS)

Scott, Adam; King, Dawn; Maric, Nevena; Bahar, Sonya

2012-02-01

The problem of speciation and species aggregation on a neutral landscape, subject to random mutational fluctuations rather than selective drive, has been a focus of research since the seminal work of Kimura on genetic drift. These ideas have received increased attention due to the more recent development of a neutral ecological theory by Hubbell. De Aguiar et al. recently demonstrated, in a computational model, that speciation can occur under neutral conditions; this study bears some comparison with more mathematical studies of clustering on neutral landscapes in the context of branching and annihilating random walks. Here, we show that clustering can occur on a neutral landscape where the dimensions specify the simulated organisms' phenotypes. Unlike the De Aguiar et al. model, we simulate sympatric speciation: the organisms cluster phenotypically, but are not spatially separated. Moreover, we find that clustering occurs not only in the case of assortative mating, but also in the case of asexual fission. Clustering is not observed in a control case where organisms can mate randomly. We find that the population size and the number of clusters undergo phase-transition-like behavior as the maximum mutation size is varied.

Plasma particle sources due to interactions with neutrals in a turbulent scrape-off layer of a toroidally confined plasma

NASA Astrophysics Data System (ADS)

Thrysøe, A. S.; Løiten, M.; Madsen, J.; Naulin, V.; Nielsen, A. H.; Rasmussen, J. Juul

2018-03-01

The conditions in the edge and scrape-off layer (SOL) of magnetically confined plasmas determine the overall performance of the device, and it is of great importance to study and understand the mechanics that drive transport in those regions. If a significant amount of neutral molecules and atoms is present in the edge and SOL regions, those will influence the plasma parameters and thus the plasma confinement. In this paper, it is displayed how neutrals, described by a fluid model, introduce source terms in a plasma drift-fluid model due to inelastic collisions. The resulting source terms are included in a four-field drift-fluid model, and it is shown how an increasing neutral particle density in the edge and SOL regions influences the plasma particle transport across the last-closed-flux-surface. It is found that an appropriate gas puffing rate allows for the edge density in the simulation to be self-consistently maintained due to ionization of neutrals in the confined region.

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

PubMed Central

Brumme, Chanson J.; Martin, Eric; Listgarten, Jennifer; Brockman, Mark A.; Le, Anh Q.; Chui, Celia K. S.; Cotton, Laura A.; Knapp, David J. H. F.; Riddler, Sharon A.; Haubrich, Richard; Nelson, George; Pfeifer, Nico; DeZiel, Charles E.; Heckerman, David; Apps, Richard; Carrington, Mary; Mallal, Simon; Harrigan, P. Richard; John, Mina

2012-01-01

HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues represented the most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responses may be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies. PMID:23055555

Escaping gravity. Movie magic and dreams of flying.

PubMed

Katz, Howard M

2002-01-01

When movie-goers are thrilled by cinematic imagery portraying transcendent motor action, they are drawn into a world of imagination more often inhabited only in dreams of flying or of perfectly executed motion. The drive toward free and expansive movement which such dreams portray doesn't require explanation in terms of symbolic links to other aims, as has been common in the literature. The aim to achieve mastery in the locomotor sphere of action is a basic aim, in itself, integral to ego development. The developing child could not begin to organize perception, intention, and a coherent sense of self without this drive to move. This proposition is supported by emerging views of the ways the developing nervous system integrates systems mediating perception, action, and affect, which complement observations of the bodycentered development of mutual recognition in infants and their caregivers.

Natural selection and neutral evolution jointly drive population divergence between alpine and lowland ecotypes of the allopolyploid plant Anemone multifida (Ranunculaceae).

PubMed

McEwen, Jamie R; Vamosi, Jana C; Rogers, Sean M

2013-01-01

Population differentiation can be driven in large part by natural selection, but selectively neutral evolution can play a prominent role in shaping patters of population divergence. The decomposition of the evolutionary history of populations into the relative effects of natural selection and selectively neutral evolution enables an understanding of the causes of population divergence and adaptation. In this study, we examined heterogeneous genomic divergence between alpine and lowland ecotypes of the allopolyploid plant, Anemone multifida. Using peak height and dominant AFLP data, we quantified population differentiation at non-outlier (neutral) and outlier loci to determine the potential contribution of natural selection and selectively neutral evolution to population divergence. We found 13 candidate loci, corresponding to 2.7% of loci, with signatures of divergent natural selection between alpine and lowland populations and between alpine populations (Fst  = 0.074-0.445 at outlier loci), but neutral population differentiation was also evident between alpine populations (FST  = 0.041-0.095 at neutral loci). By examining population structure at both neutral and outlier loci, we determined that the combined effects of selection and neutral evolution are associated with the divergence of alpine populations, which may be linked to extreme abiotic conditions and isolation between alpine sites. The presence of outlier levels of genetic variation in structured populations underscores the importance of separately analyzing neutral and outlier loci to infer the relative role of divergent natural selection and neutral evolution in population divergence.

Driving Force of Plasma Bullet in Atmospheric-Pressure Plasma

NASA Astrophysics Data System (ADS)

Yambe, Kiyoyuki; Masuda, Seiya; Kondo, Shoma

2018-06-01

When plasma is generated by applying high-voltage alternating current (AC), the driving force of the temporally and spatially varying electric field is applied to the plasma. The strength of the driving force of the plasma at each spatial position is different because the electrons constituting the atmospheric-pressure nonequilibrium (cold) plasma move at a high speed in space. If the force applied to the plasma is accelerated only by the driving force, the plasma will be accelerated infinitely. The equilibrium between the driving force and the restricting force due to the collision between the plasma and neutral particles determines the inertial force and the drift velocity of the plasma. Consequently, the drift velocity depends on the strength of the time-averaged AC electric field. The pressure applied by the AC electric field equilibrates with the plasma pressure. From the law of conservation of energy, the pressure equilibrium is maintained by varying the drift velocity of the plasma.

Extreme Doppler Shifting of Io's Neutral Jets

NASA Astrophysics Data System (ADS)

Schmidt, Carl

2017-08-01

The dynamics and the extension of Jupiter's magnetosphere are determined by the massive internal plasma sources combined with the fast rotation. The vast majority of the plasma originates from the atmosphere of the moon Io, the most volcanically active body in our solar system. Here we propose to characterize the density and velocity of energetic neutral atoms escaping from Io's atmosphere. Exploiting the high resolution and sensitivity of the COS G130M spectral mode, we will measure the Doppler velocities of atomic O, S and Cl streams, which are energized through charge exchange and dissociative recombination of molecular ions. Prior COS observations of Io revealed a large number of emission lines from several ion and neutral species with excellent S/N, obtained over a single HST orbit. Those spectra were obtained surrounding eclipse geometry, where Doppler shifts are minimized and were restricted to Io itself rather than the stream region. Here we will target the extended clouds with only two orbits total when the moon is at eastern and western elongation for maximum Doppler shifts. The observations will provide new constraints on the diffuse large-scale cloud structures in the Jovian system and significantly improve our understanding of the transport of mass and energy within the Io-torus interaction. The absolute brightness, in combination with plasma parameters from line ratios/collision strengths, will allow us to quantify the outflow of energetic neutral atoms from Io's main sulfur-oxygen atmosphere for the first time.

Swarming and pattern formation due to selective attraction and repulsion.

PubMed

Romanczuk, Pawel; Schimansky-Geier, Lutz

2012-12-06

We discuss the collective dynamics of self-propelled particles with selective attraction and repulsion interactions. Each particle, or individual, may respond differently to its neighbours depending on the sign of their relative velocity. Thus, it is able to distinguish approaching (coming closer) and retreating (moving away) individuals. This differentiation of the social response is motivated by the response to looming visual stimuli and may be seen as a generalization of the previously proposed escape and pursuit interactions motivated by empirical evidence for cannibalism as a driving force of collective migration in locusts and Mormon crickets. The model can account for different types of behaviour such as pure attraction, pure repulsion or escape and pursuit, depending on the values (signs) of the different response strengths. It provides, in the light of recent experimental results, an interesting alternative to previously proposed models of collective motion with an explicit velocity-alignment interaction. We discuss the derivation of a coarse-grained description of the system dynamics, which allows us to derive analytically the necessary condition for emergence of collective motion. Furthermore, we analyse systematically the onset of collective motion and clustering in numerical simulations of the model for varying interaction strengths. We show that collective motion arises only in a subregion of the parameter space, which is consistent with the analytical prediction and corresponds to an effective escape and/or pursuit response.

The Solar Wind Ion Analyzer for MAVEN

NASA Astrophysics Data System (ADS)

Halekas, J. S.; Taylor, E. R.; Dalton, G.; Johnson, G.; Curtis, D. W.; McFadden, J. P.; Mitchell, D. L.; Lin, R. P.; Jakosky, B. M.

2015-12-01

The Solar Wind Ion Analyzer (SWIA) on the MAVEN mission will measure the solar wind ion flows around Mars, both in the upstream solar wind and in the magneto-sheath and tail regions inside the bow shock. The solar wind flux provides one of the key energy inputs that can drive atmospheric escape from the Martian system, as well as in part controlling the structure of the magnetosphere through which non-thermal ion escape must take place. SWIA measurements contribute to the top level MAVEN goals of characterizing the upper atmosphere and the processes that operate there, and parameterizing the escape of atmospheric gases to extrapolate the total loss to space throughout Mars' history. To accomplish these goals, SWIA utilizes a toroidal energy analyzer with electrostatic deflectors to provide a broad 360∘×90∘ field of view on a 3-axis spacecraft, with a mechanical attenuator to enable a very high dynamic range. SWIA provides high cadence measurements of ion velocity distributions with high energy resolution (14.5 %) and angular resolution (3.75∘×4.5∘ in the sunward direction, 22.5∘×22.5∘ elsewhere), and a broad energy range of 5 eV to 25 keV. Onboard computation of bulk moments and energy spectra enable measurements of the basic properties of the solar wind at 0.25 Hz.

Solar Wind Interaction with the Martian Upper Atmosphere at Early Mars/Extreme Solar Conditions

NASA Astrophysics Data System (ADS)

Dong, C.; Bougher, S. W.; Ma, Y.; Toth, G.; Lee, Y.; Nagy, A. F.; Tenishev, V.; Pawlowski, D. J.; Combi, M. R.

2014-12-01

The investigation of ion escape fluxes from Mars, resulting from the solar wind interaction with its upper atmosphere/ionosphere, is important due to its potential impact on the long-term evolution of Mars atmosphere (e.g., loss of water) over its history. In the present work, we adopt the 3-D Mars cold neutral atmosphere profiles (0 ~ 300 km) from the newly developed and validated Mars Global Ionosphere Thermosphere Model (M-GITM) and the 3-D hot oxygen profiles (100 km ~ 5 RM) from the exosphere Monte Carlo model Adaptive Mesh Particle Simulator (AMPS). We apply these 3-D model output fields into the 3-D BATS-R-US Mars multi-fluid MHD (MF-MHD) model (100 km ~ 20 RM) that can simulate the interplay between Mars upper atmosphere and solar wind by considering the dynamics of individual ion species. The multi-fluid MHD model solves separate continuity, momentum and energy equations for each ion species (H+, O+, O2+, CO2+). The M-GITM model together with the AMPS exosphere model take into account the effects of solar cycle and seasonal variations on both cold and hot neutral atmospheres. This feature allows us to investigate the corresponding effects on the Mars upper atmosphere ion escape by using a one-way coupling approach, i.e., both the M-GITM and AMPS model output fields are used as the input for the multi-fluid MHD model and the M-GITM is used as input into the AMPS exosphere model. In this study, we present M-GITM, AMPS, and MF-MHD calculations (1-way coupled) for 2.5 GYA conditions and/or extreme solar conditions for present day Mars (high solar wind velocities, high solar wind dynamic pressure, and high solar irradiance conditions, etc.). Present day extreme conditions may result in MF-MHD outputs that are similar to 2.5 GYA cases. The crustal field orientations are also considered in this study. By comparing estimates of past ion escape rates with the current ion loss rates to be returned by the MAVEN spacecraft (2013-2016), we can better constrain the total ion loss to space over Mars history, and thus enhance the science returned from the MAVEN mission.

Energy distribution functions of kilovolt ions in a modified Penning discharge.

NASA Technical Reports Server (NTRS)

Roth, J. R.

1973-01-01

The distribution function of ion energy parallel to the magnetic field of a modified Penning discharge has been measured with a retarding potential energy analyzer. These ions escaped through one of the throats of the magnetic mirror geometry. Simultaneous measurements of the ion energy distribution function perpendicular to the magnetic field have been made with a charge-exchange neutral detector. The ion energy distribution functions are approximately Maxwellian, and the parallel and perpendicular kinetic temperatures are equal within experimental error. These results suggest that turbulent processes previously observed in this discharge Maxwellianize the velocity distribution along a radius in velocity space, and result in an isotropic energy distribution.

Energy distribution functions of kilovolt ions in a modified Penning discharge.

NASA Technical Reports Server (NTRS)

Roth, J. R.

1972-01-01

The distribution function of ion energy parallel to the magnetic field of a modified Penning discharge has been measured with a retarding potential energy analyzer. These ions escaped through one of the throats of the magnetic mirror geometry. Simultaneous measurements of the ion energy distribution function perpendicular to the magnetic field have been made with a charge-exchange neutral detector. The ion energy distribution functions are approximately Maxwellian, and the parallel and perpendicular kinetic temperatures are equal within experimental error. These results suggest that turbulent processes previously observed in this discharge Maxwellianize the velocity distribution along a radius in velocity space, and result in an isotropic energy distribution.

Means of atmospheric air pollution reduction during drilling wells

NASA Astrophysics Data System (ADS)

Shkitsa, L.; Yatsyshyn, T.; Lyakh, M.; Sydorenko, O.

2016-08-01

The process of drilling oil and gas wells is the source of air pollution through drilling mud evaporation containing hazardous chemical substances. The constructive solution for cleaning device of downhole tool that contains elements covering tube and clean the surface from the mud in the process of rising from the well is offered. Inside the device is filled with magnetic fluid containing the substance neutralizing hazardous substances. The use of the equipment proposed will make it possible to avoid penetration of harmful substances into the environment and to escape the harmful effects of aggressive substances for staff health and increase rig's fire safety.

Temporal variations in the evaporating atmosphere of the exoplanet HD 189733b

NASA Astrophysics Data System (ADS)

Bourrier, V.; Lecavelier des Etangs, A.; Wheatley, P. J.; Dupuy, H.; Ehrenreich, D.; Vidal-Madjar, A.; Hébrard, G.; Ballester, G. E.; Désert, J.-M.; Ferlet, R.; Sing, D. K.

2012-12-01

Transit observations of the hydrogen Lyman-α line allowed the detection of atmospheric escape from the exoplanet HD209458b (Vidal-Madjar et al. 2003). Using spectrally resolved Lyman-α transit observations of the exoplanet HD 189733b at two different epochs, Lecavelier des Etangs et al. (2012) detected for the first time temporal variations in the physical conditions of an evaporating planetary atmosphere. Here we summarized the results obtained with the HST/STIS observations as presented in June 2012 at the SF2A 2012 meeting. While atmospheric hydrogen cannot be detected in the STIS observations of April 2010, it is clearly detected in the September 2011 observations. The atomic hydrogen cloud surrounding the transiting planet produces a transit absorption depth of 14.4±3.6% between velocities of -230 to -140 km s^{-1}. These high velocities cannot arise from radiation pressure alone and, contrary to HD 209458b, this requires an additional acceleration mechanism, such as interactions with stellar wind protons. The spectral and temporal signature of the absorption is fitted by an atmospheric escape rate of neutral hydrogen atoms of about 10^9 g s^{-1}, a stellar wind with a velocity of 190 km s^{-1} and a temperature of ˜10^5 K. We also illustrate the power of multi-wavelengths approach with simultaneous observations in the X-rays obtained with Swift/XRT. We detected an X-ray flare about 8 hours before the transit of September 2011. This suggests that the observed changes within the upper part of the escaping atmosphere can be caused by variations in the stellar wind properties, or/and by variations in the stellar energy input to the planet's escaping gas. This multi-wavelengths approach allowed the simultaneous detection of temporal variations both in the stellar X-ray and in the planetary upper atmosphere, providing first observational constraints on the interaction between the exoplanet's atmosphere and the star.

Space weathering on near-Earth objects investigated by neutral-particle detection

NASA Astrophysics Data System (ADS)

Plainaki, C.; Milillo, A.; Orsini, S.; Mura, A.; De Angelis, E.; Di Lellis, A. M.; Dotto, E.; Livi, S.; Mangano, V.; Massetti, S.; Palumbo, M. E.

2009-03-01

The ion-sputtering (IS) process is active in many planetary environments in the solar system where plasma precipitates directly on the surface (for instance, Mercury, Moon and Europa). In particular, solar wind sputtering is one of the most important agents for the surface erosion of a near-Earth object (NEO), acting together with other surface release processes, such as photon stimulated desorption (PSD), thermal desorption (TD) and micrometeoroid impact vaporization (MIV). The energy distribution of the IS-released neutrals peaks at a few eVs and extends up to hundreds of eVs. Since all other release processes produce particles of lower energies, the presence of neutral atoms in the energy range above 10 eV and below a few keVs (sputtered high-energy atoms (SHEA)) identifies the IS process. SHEA easily escape from the NEO, due to NEO's extremely weak gravity. Detection and analysis of SHEA will give important information on surface-loss processes as well as on surface elemental composition. The investigation of the active release processes, as a function of the external conditions and the NEO surface properties, is crucial for obtaining a clear view of the body's present loss rate as well as for getting clues on its evolution, which depends significantly on space weather. In this work, an attempt to analyze processes that take place on the surface of these small airless bodies, as a result of their exposure to the space environment, has been realized. For this reason, a new space weathering model (space weathering on NEO-SPAWN) is presented. Moreover, an instrument concept of a neutral-particle analyzer specifically designed for the measurement of neutral density and the detection of SHEA from a NEO is proposed.

Space weathering on near-Earth objects investigated by neutral-particle detection

NASA Astrophysics Data System (ADS)

Plainaki, C.; Milillo, A.; Orsini, S.; Mura, A.; de Angelis, E.; di Lellis, A. M.; Dotto, E.; Livi, S.; Mangano, V.; Palumbo, M. E.

2009-04-01

The ion-sputtering (IS) process is active in many planetary environments in the solar system where plasma precipitates directly on the surface (for instance, Mercury, Moon and Europa). In particular, solar wind sputtering is one of the most important agents for the surface erosion of a near-Earth object (NEO), acting together with other surface release processes, such as photon stimulated desorption (PSD), thermal desorption (TD) and micrometeoroid impact vaporization (MIV). The energy distribution of the IS-released neutrals peaks at a few eVs and extends up to hundreds of eVs. Since all other release processes produce particles of lower energies, the presence of neutral atoms in the energy range above 10 eV and below a few keVs (sputtered high-energy atoms (SHEA)) identifies the IS process. SHEA easily escape from the NEO, due to NEO's extremely weak gravity. Detection and analysis of SHEA will give important information on surface-loss processes as well as on surface elemental composition. The investigation of the active release processes, as a function of the external conditions and the NEO surface properties, is crucial for obtaining a clear view of the body's present loss rate as well as for getting clues on its evolution, which depends significantly on space weather. In this work, an attempt to analyze processes that take place on the surface of these small airless bodies, as a result of their exposure to the space environment, has been realized. For this reason, a new space weathering model (space weathering on NEO-SPAWN) is presented. Moreover, an instrument concept of a neutral-particle analyzer specifically designed for the measurement of neutral density and the detection of SHEA from a NEO is proposed.

LOCAL INTERSTELLAR MEDIUM: SIX YEARS OF DIRECT SAMPLING BY IBEX

DOE Office of Scientific and Technical Information (OSTI.GOV)

McComas, D. J.; Fuselier, S. A.; Schwadron, N. A., E-mail: dmccomas@swri.edu, E-mail: sfuselier@swri.edu, E-mail: Nathan.schwadron@unh.edu

2015-10-15

The Interstellar Boundary Explorer (IBEX) has been directly observing neutral atoms from the local interstellar medium for the last six years (2009–2014). This paper ties together the 14 studies in this Astrophysical Journal Supplement Series Special Issue, which collectively describe the IBEX interstellar neutral results from this epoch and provide a number of other relevant theoretical and observational results. Interstellar neutrals interact with each other and with the ionized portion of the interstellar population in the “pristine” interstellar medium ahead of the heliosphere. Then, in the heliosphere's close vicinity, the interstellar medium begins to interact with escaping heliospheric neutrals. Inmore » this study, we compare the results from two major analysis approaches led by IBEX groups in New Hampshire and Warsaw. We also directly address the question of the distance upstream to the pristine interstellar medium and adjust both sets of results to a common distance of ∼1000 AU. The two analysis approaches are quite different, but yield fully consistent measurements of the interstellar He flow properties, further validating our findings. While detailed error bars are given for both approaches, we recommend that for most purposes, the community use “working values” of ∼25.4 km s{sup −1}, ∼75.°7 ecliptic inflow longitude, ∼ −5.°1 ecliptic inflow latitude, and ∼7500 K temperature at ∼1000 AU upstream. Finally, we briefly address future opportunities for even better interstellar neutral observations to be provided by the Interstellar Mapping and Acceleration Probe mission, which was recommended as the next major Heliophysics mission by the NRC's 2013 Decadal Survey.« less

Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.

PubMed

El-Diwany, Ramy; Cohen, Valerie J; Mankowski, Madeleine C; Wasilewski, Lisa N; Brady, Jillian K; Snider, Anna E; Osburn, William O; Murrell, Ben; Ray, Stuart C; Bailey, Justin R

2017-02-01

Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 μg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes.

Modeling activities on the negative-ion-based Neutral Beam Injectors of the Large Helical Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agostinetti, P.; Antoni, V.; Chitarin, G.

2011-09-26

At the National Institute for Fusion Science (NIFS) large-scaled negative ion sources have been widely used for the Neutral Beam Injectors (NBIs) mounted on the Large Helical Device (LHD), which is the world-largest superconducting helical system. These injectors have achieved outstanding performances in terms of beam energy, negative-ion current and optics, and represent a reference for the development of heating and current drive NBIs for ITER.In the framework of the support activities for the ITER NBIs, the PRIMA test facility, which includes a RF-drive ion source with 100 keV accelerator (SPIDER) and a complete 1 MeV Neutral Beam system (MITICA)more » is under construction at Consorzio RFX in Padova.An experimental validation of the codes has been undertaken in order to prove the accuracy of the simulations and the soundness of the SPIDER and MITICA design. To this purpose, the whole set of codes have been applied to the LHD NBIs in a joint activity between Consorzio RFX and NIFS, with the goal of comparing and benchmarking the codes with the experimental data. A description of these modeling activities and a discussion of the main results obtained are reported in this paper.« less

Harvesting the Decay Energy of 26-Al to Drive Lightning Discharge and Chondrule Formation

NASA Astrophysics Data System (ADS)

Johansen, A.; Okuzumi, S.

2017-02-01

We demonstrate that positrons released in the decay of 26-Al cause large-scale charging of dense pebble regions. The charge separation is neutralized by lightning discharge and this can lead to the formation of chondrules.

Innovative Escapement-Based Mechanism for Micro-Antenna Boom Deployment

NASA Technical Reports Server (NTRS)

Tokarz, Marta; Grygorczuk, Jerzy; Jarzynka, Stanislaw; Gut, Henryk

2014-01-01

This paper presents the prototype of a tubular boom antenna developed for the Polish BRITE-PL satellite by the Space Research Center of the Polish Academy of Sciences (CBK PAN). What is unique about our work is that we developed an original type of the tubular boom antenna deployment mechanism that can be used widely as a basic solution for compact electrical antennas, booms deploying sensitive instruments, ultra-light planetary manipulators etc. The invented electromagnetic driving unit provides a dual complementary action - it adds extra energy to the driving spring, making the system more reliable, and at the same time it moderates the deployment speed acting as a kind of damper. That distinguishing feature predetermines the mechanism to be applied wherever the dynamic nature of a spring drive introducing dangerous vibrations and inducing severe local stress in the structure needs to be mitigated. Moreover, the paper reveals a product unique in Europe - a miniature beryllium bronze tubular boom free of geometry and strain defects, which is essential for stiffness and fatigue resistance. Both the deployment mechanism and the technology of tubular boom manufacturing are protected by patent rights.

Transport of particles and microorganisms in microfluidic channels using rectified ac electro-osmotic flow

PubMed Central

Wu, Wen-I; Selvaganapathy, P. Ravi; Ching, Chan Y.

2011-01-01

A new method is demonstrated to transport particles, cells, and other microorganisms using rectified ac electro-osmotic flows in open microchannels. The rectified flow is obtained by synchronous zeta potential modulation with the driving potential in the microchannel. Experiments were conducted to transport both neutral, charged particles, and microorganisms of various sizes. A maximum speed of 50 μm∕s was obtained for 8 μm polystyrene beads, without any electrolysis, using a symmetrical square waveform driving electric field of 5 V∕mm at 10 Hz and a 360 V gate potential with its polarity synchronized with the driving potential (phase lag=0°). PMID:21522497

Hostility, driving anger, and dangerous driving: the emerging role of hemispheric preference.

PubMed

Gidron, Yori; Gaygısız, Esma; Lajunen, Timo

2014-12-01

Various studies have implicated psychosocial variables (e.g., hostility) in risk of dangerous driving and traffic accidents. However, whether these variables are related to more basic neurobiological factors, and whether such associations have implications for the modification of psychosocial risk factors in the context of driving, have not been examined in depth. This study examined the relationship between hemispheric preference (HP), hostility and self-reported dangerous driving, and the ability to affect driving anger via hemisphere activating cognitive exercises (HACE). In Study 1, 254 Turkish students completed questionnaires of hostility, HP and driving behavior. In Study 2, we conducted a "proof of concept" experimental study, and tested effects of left, right and neutral HACE on driving anger, by exposing N=650 Turkish students to written scenarios including either logical (left hemisphere), visuo-spatial (right hemisphere) or "mild doses" of both types of contents (control). In Study 1, left-HP was associated with higher hostility and with more dangerous driving, and hostility mediated the relationship between L-HP and reported driving behavior. In Study 2, only right-HACE led to immediate significant reductions in self-reported driving anger. Left-HP is related to hostility and to dangerous driving, and it may be possible to partly reduce driving anger by right-HACE. Future studies must replicate these findings with objective measures, more enduring interventions and longer follow-ups. Copyright © 2014. Published by Elsevier Ltd.

Legionella pneumophila-induced visual learning impairment reversed by anti-interleukin-1 beta.

PubMed

Gibertini, M; Newton, C; Klein, T W; Friedman, H

1995-10-01

Infecting mice with the opportunistic intracellular pathogen Legionella pneumophila markedly inhibited place learning of infected C57BL/6 mice as determined by the Morris water maze test. Mice infected with L. pneumophila evinced much less ability to learn the position of a hidden platform than did normal noninfected mice, which quickly learned the location of the hidden platform and escaped from the cool water of the pool with increasing efficiency. However, infected mice treated with anti-interleukin-1 (anti-IL-1) neutralizing antibody learned the task with about the same efficiency as the controls. When the animals were tested 1 week after learning, control animals remembered the task well and were able to escape with near maximal efficacy. On the other hand, L. pneumophila-infected mice performed as poorly after the 1 week rest as during the training period, indicating that infection blocked learning and not merely performance. Mice infected with L. pneumophila and given the antibody treatment were found to be indistinguishable from controls in that they remembered the task and escaped with good efficiency. Thus, the results of this study suggest that the pro-inflammatory cytokine, IL-1 beta, is involved, at least partly, in the attenuation of spatial navigational learning in mice infected acutely with a sublethal concentration of L. pneumophila. These results, therefore, suggest that cognitive impairment of L. pneumophila-infected mice may be related to the cytokine IL-1 beta and, furthermore, that cytokines may be related to learning and memory changes experienced by individuals suffering acute bacterial infections.

An extended continuum model accounting for the driver's timid and aggressive attributions

NASA Astrophysics Data System (ADS)

Cheng, Rongjun; Ge, Hongxia; Wang, Jufeng

2017-04-01

Considering the driver's timid and aggressive behaviors simultaneously, a new continuum model is put forwarded in this paper. By applying the linear stability theory, we presented the analysis of new model's linear stability. Through nonlinear analysis, the KdV-Burgers equation is derived to describe density wave near the neutral stability line. Numerical results verify that aggressive driving is better than timid act because the aggressive driver will adjust his speed timely according to the leading car's speed. The key improvement of this new model is that the timid driving deteriorates traffic stability while the aggressive driving will enhance traffic stability. The relationship of energy consumption between the aggressive and timid driving is also studied. Numerical results show that aggressive driver behavior can not only suppress the traffic congestion but also reduce the energy consumption.

Natural Selection and Neutral Evolution Jointly Drive Population Divergence between Alpine and Lowland Ecotypes of the Allopolyploid Plant Anemone multifida (Ranunculaceae)

PubMed Central

McEwen, Jamie R.; Vamosi, Jana C.; Rogers, Sean M.

2013-01-01

Population differentiation can be driven in large part by natural selection, but selectively neutral evolution can play a prominent role in shaping patters of population divergence. The decomposition of the evolutionary history of populations into the relative effects of natural selection and selectively neutral evolution enables an understanding of the causes of population divergence and adaptation. In this study, we examined heterogeneous genomic divergence between alpine and lowland ecotypes of the allopolyploid plant, Anemone multifida. Using peak height and dominant AFLP data, we quantified population differentiation at non-outlier (neutral) and outlier loci to determine the potential contribution of natural selection and selectively neutral evolution to population divergence. We found 13 candidate loci, corresponding to 2.7% of loci, with signatures of divergent natural selection between alpine and lowland populations and between alpine populations (Fst  = 0.074–0.445 at outlier loci), but neutral population differentiation was also evident between alpine populations (FST  = 0.041–0.095 at neutral loci). By examining population structure at both neutral and outlier loci, we determined that the combined effects of selection and neutral evolution are associated with the divergence of alpine populations, which may be linked to extreme abiotic conditions and isolation between alpine sites. The presence of outlier levels of genetic variation in structured populations underscores the importance of separately analyzing neutral and outlier loci to infer the relative role of divergent natural selection and neutral evolution in population divergence. PMID:23874801

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petty, C. C., E-mail: petty@fusion.gat.com; Van Zeeland, M. A.; Pace, D. C.

“Steady-state” hybrid plasmas in DIII-D with zero surface loop voltage have been maintained for up to two current relaxation times using 3.4 MW of central electron cyclotron current drive (ECCD). In addition to driving ≈0.2 MA of plasma current, central ECCD leads to significant changes in Alfvén eigenmode (AE) activity and thermal transport. For neutral-beam-only heating, strong AE activity is observed that causes a ∼35% degradation in the neutron rate. With central ECCD this AE activity is suppressed, replaced by a bursty energetic particle mode that appears more benign as the neutron rate is closer to the classical value. Themore » electron thermal diffusivity increases by ≈50% for 2.4 MW of ECCD compared to neutral-beam-only cases. Fortunately, the global thermal confinement factor remains the same (H{sub 98y2}=1.4) as the higher thermal transport for P{sub EC}=2.4 MW hybrids is offset by the decreased fast ion transport resulting from AE suppression.« less

Verification and optimization of the CFETR baseline scenario

NASA Astrophysics Data System (ADS)

Zhao, D.; Lao, L. L.; Meneghini, O.; Staebler, G. M.; Candy, J.; Smith, S. P.; Snyder, P. B.; Prater, R.; Chen, X.; Chan, V. S.; Li, J.; Chen, J.; Shi, N.; Guo, W.; Pan, C.; Jian, X.

2016-10-01

The baseline scenario of China Fusion Engineering Test Reactor (CFETR) was designed starting from 0D calculations. The CFETR baseline scenario satisfies the minimum goal of Fusion Nuclear Science Facility aimed at bridging the gaps between ITER and DEMO. 1.5D calculations are presented to verify the on-going efforts in higher-dimensional modeling of CFETR. Steady-state scenarios are calculated self-consistently by the OMFIT integrated modeling framework that includes EFIT for equilibrium, ONETWO for sources and current, TGYRO for transport. With 68MW of neutral beam power and 8MW of ECH injected to the plasma, the average ion temperature is maintained at 15keV, while 150MW fusion power is produced. The neutral beams also drive 55% of the plasma current. Modest fast ion diffusion will reduce NBCD and affect the profile substantially. Top-launch ECH will increase the current drive and the power absorption rate. EPED model are being included. Work supported by U.S. DOE under DE-FC02-04ER54698 and the USTC CFETR contract.

Emergent neutrality drives phytoplankton species coexistence

PubMed Central

Segura, Angel M.; Calliari, Danilo; Kruk, Carla; Conde, Daniel; Bonilla, Sylvia; Fort, Hugo

2011-01-01

The mechanisms that drive species coexistence and community dynamics have long puzzled ecologists. Here, we explain species coexistence, size structure and diversity patterns in a phytoplankton community using a combination of four fundamental factors: organism traits, size-based constraints, hydrology and species competition. Using a ‘microscopic’ Lotka–Volterra competition (MLVC) model (i.e. with explicit recipes to compute its parameters), we provide a mechanistic explanation of species coexistence along a niche axis (i.e. organismic volume). We based our model on empirically measured quantities, minimal ecological assumptions and stochastic processes. In nature, we found aggregated patterns of species biovolume (i.e. clumps) along the volume axis and a peak in species richness. Both patterns were reproduced by the MLVC model. Observed clumps corresponded to niche zones (volumes) where species fitness was highest, or where fitness was equal among competing species. The latter implies the action of equalizing processes, which would suggest emergent neutrality as a plausible mechanism to explain community patterns. PMID:21177680

Physics-based Control-oriented Modeling of the Current Profile Evolution in NSTX-Upgrade

NASA Astrophysics Data System (ADS)

Ilhan, Zeki; Barton, Justin; Shi, Wenyu; Schuster, Eugenio; Gates, David; Gerhardt, Stefan; Kolemen, Egemen; Menard, Jonathan

2013-10-01

The operational goals for the NSTX-Upgrade device include non-inductive sustainment of high- β plasmas, realization of the high performance equilibrium scenarios with neutral beam heating, and achievement of longer pulse durations. Active feedback control of the current profile is proposed to enable these goals. Motivated by the coupled, nonlinear, multivariable, distributed-parameter plasma dynamics, the first step towards feedback control design is the development of a physics-based, control-oriented model for the current profile evolution in response to non-inductive current drives and heating systems. For this purpose, the nonlinear magnetic-diffusion equation is coupled with empirical models for the electron density, electron temperature, and non-inductive current drives (neutral beams). The resulting first-principles-driven, control-oriented model is tailored for NSTX-U based on the PTRANSP predictions. Main objectives and possible challenges associated with the use of the developed model for control design are discussed. This work was supported by PPPL.

Effects of MHD instabilities on neutral beam current drive

NASA Astrophysics Data System (ADS)

Podestà, M.; Gorelenkova, M.; Darrow, D. S.; Fredrickson, E. D.; Gerhardt, S. P.; White, R. B.

2015-05-01

Neutral beam injection (NBI) is one of the primary tools foreseen for heating, current drive (CD) and q-profile control in future fusion reactors such as ITER and a Fusion Nuclear Science Facility. However, fast ions from NBI may also provide the drive for energetic particle-driven instabilities (e.g. Alfvénic modes (AEs)), which in turn redistribute fast ions in both space and energy, thus hampering the control capabilities and overall efficiency of NB-driven current. Based on experiments on the NSTX tokamak (M. Ono et al 2000 Nucl. Fusion 40 557), the effects of AEs and other low-frequency magneto-hydrodynamic instabilities on NB-CD efficiency are investigated. A new fast ion transport model, which accounts for particle transport in phase space as required for resonant AE perturbations, is utilized to obtain consistent simulations of NB-CD through the tokamak transport code TRANSP. It is found that instabilities do indeed reduce the NB-driven current density over most of the plasma radius by up to ∼50%. Moreover, the details of the current profile evolution are sensitive to the specific model used to mimic the interaction between NB ions and instabilities. Implications for fast ion transport modeling in integrated tokamak simulations are briefly discussed.

Effects of MHD instabilities on neutral beam current drive

DOE PAGES

Podestà, M.; Gorelenkova, M.; Darrow, D. S.; ...

2015-04-17

One of the primary tools foreseen for heating, current drive (CD) and q-profile control in future fusion reactors such as ITER and a Fusion Nuclear Science Facility is the neutral beam injection (NBI). However, fast ions from NBI may also provide the drive for energetic particle-driven instabilities (e.g. Alfvénic modes (AEs)), which in turn redistribute fast ions in both space and energy, thus hampering the control capabilities and overall efficiency of NB-driven current. Based on experiments on the NSTX tokamak (M. Ono et al 2000 Nucl. Fusion 40 557), the effects of AEs and other low-frequency magneto-hydrodynamic instabilities on NB-CDmore » efficiency are investigated. When looking at the new fast ion transport model, which accounts for particle transport in phase space as required for resonant AE perturbations, is utilized to obtain consistent simulations of NB-CD through the tokamak transport code TRANSP. It is found that instabilities do indeed reduce the NB-driven current density over most of the plasma radius by up to ~50%. Moreover, the details of the current profile evolution are sensitive to the specific model used to mimic the interaction between NB ions and instabilities. Finally, implications for fast ion transport modeling in integrated tokamak simulations are briefly discussed.« less

Charge exchange in a planetary corona - Its effect on the distribution and escape of hydrogen

NASA Technical Reports Server (NTRS)

Chamberlain, J. W.

1977-01-01

The theory for a spherical collisionless planetary corona is extended to include charge-exchange collisions between H(+) and H, which are assumed to constitute intermingled gases with different kinetic temperatures. The treatment is based on the conventional concept of a critical level (or exobase) above which the only collisions considered in the Boltzmann equation are those that resonantly exchange charge. Although the geometry treated is an oversimplification for a real planet, numerical examples are given for an idealized earth and Venus. For earth, an ion temperature of 4 times the neutral temperature, an ion density at the exobase of 14,000 per cu cm, and a plasmapause at 1.5 earth radii will raise the escape flux of H by a factor of 6. The total H above the exobase is changed by less than 1%. For Venus, conditions are examined that would account for the peculiar H distribution observed from Mariner 5. The plasma conditions required are not obviously outrageous by terrestrial standards, but the Mariner 5 ionosphere measurements did not show a high plasmapause at, say, 1.25 or 1.5 planetary radii, a fact that might argue against a charge-exchange model.

A model study of the vertical distributions and escape fluxes of the major and minor species in Titan's thermosphere under different conditions

NASA Astrophysics Data System (ADS)

Hsu, Jen-Kai; Liang, Mao-Chang; Ip, Wing-Huen

2017-04-01

From the measurements of the Ion Neutral Mass Spectrometer (INMS) on the Cassini spacecraft at different close encounters with Titan, it is know that the vertical temperature profile and density distributions of N2, CH4, H2 and other species could have large variations which might be driven by environmental effects such as solar radiation and magnetospheric interaction. For example, the atmospheric temperature as determined from the N2 density profiles can vary between 120 K and 175 K. Following the treatment of Li et al. (PSS, 104 (2014) 48-58) by applying a non-monotonic eddy diffusivity profile, we compute the vertical distributions of different species between Titan's surface to 2000 km altitude, for a range of atmospheric temperatures. Intercomparison between the model results and observations leads to better understanding of the production mechanisms of the minor species like C2H2, C2H4, C2H6 and others, all important to the hydrocarbon budgets of Titan's atmosphere and surface, respectively. Furthermore, such detailed photochemical calculations will also yield accurate estimates of the escape fluxes of H, H2 and CH4 into the circum-planetary region.

Seasonal variability of the hydrogen exosphere of Mars

NASA Astrophysics Data System (ADS)

Halekas, J. S.

2017-05-01

The Mars Atmosphere and Volatile EvolutioN (MAVEN) mission measures both the upstream solar wind and collisional products from energetic neutral hydrogen atoms that precipitate into the upper atmosphere after their initial formation by charge exchange with exospheric hydrogen. By computing the ratio between the densities of these populations, we derive a robust measurement of the column density of exospheric hydrogen upstream of the Martian bow shock. By comparing with Chamberlain-type model exospheres, we place new constraints on the structure and escape rates of exospheric hydrogen, derived from observations sensitive to a different and potentially complementary column from most scattered sunlight observations. Our observations provide quantitative estimates of the hydrogen exosphere with nearly complete temporal coverage, revealing order of magnitude seasonal changes in column density and a peak slightly after perihelion, approximately at southern summer solstice. The timing of this peak suggests either a lag in the response of the Martian atmosphere to solar inputs or a seasonal effect driven by lower atmosphere dynamics. The high degree of seasonal variability implied by our observations suggests that the Martian atmosphere and the thermal escape of light elements depend sensitively on solar inputs.

Eight per cent leakage of Lyman continuum photons from a compact, star-forming dwarf galaxy.

PubMed

Izotov, Y I; Orlitová, I; Schaerer, D; Thuan, T X; Verhamme, A; Guseva, N G; Worseck, G

2016-01-14

One of the key questions in observational cosmology is the identification of the sources responsible for ionization of the Universe after the cosmic 'Dark Ages', when the baryonic matter was neutral. The currently identified distant galaxies are insufficient to fully reionize the Universe by redshift z ≈ 6 (refs 1-3), but low-mass, star-forming galaxies are thought to be responsible for the bulk of the ionizing radiation. As direct observations at high redshift are difficult for a variety of reasons, one solution is to identify local proxies of this galaxy population. Starburst galaxies at low redshifts, however, generally are opaque to Lyman continuum photons. Small escape fractions of about 1 to 3 per cent, insufficient to ionize much surrounding gas, have been detected only in three low-redshift galaxies. Here we report far-ultraviolet observations of the nearby low-mass star-forming galaxy J0925+1403. The galaxy is leaking ionizing radiation with an escape fraction of about 8 per cent. The total number of photons emitted during the starburst phase is sufficient to ionize intergalactic medium material that is about 40 times as massive as the stellar mass of the galaxy.

HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC.

PubMed

Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F; McMichael, Andrew; Shaw, George M; Hahn, Beatrice H; Korber, Bette; Seoighe, Cathal

2009-05-01

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections.

HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC

PubMed Central

Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F.; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F.; McMichael, Andrew; Shaw, George M.; Hahn, Beatrice H.; Korber, Bette; Seoighe, Cathal

2009-01-01

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections. PMID:19424423

The BepiColombo SERENA/ELENA unit development: a new technique to detect sputtered neutral atoms escaping from Mercury surface.

NASA Astrophysics Data System (ADS)

di Lellis, Andrea Maria; Selci, Stefano; de Angelis, Elisabetta; Leoni, Roberto; Milillo, Anna; Orsini, Stefano; Dandouras, Iannis

2010-05-01

ELENA (Emitted Low-Energy Neutral Atoms) is one of the four units of the SERENA experiment for the ESA cornerstone BepiColombo mission to Mercury. It is primarily devoted to understanding of Ion Sputtering processes and emission from planetary surfaces, particle back-scattering and Charge Exchange via neutral atoms detections in the energy range ~20 eV - 5 keV ELENA instrument is the first attempt of a new design techniques approached for the neutral particles identification in the low energy range. It is a Time-of-Flight system based on a peculiar Start section: an oscillating shutter (operated at frequencies up to a 100 kHz) and mechanical grating (two self-standing silicon nitride (Si3N4) membranes, patterned with arrays of long and narrow openings) that allows to identify the start time of the particles entering in the Time-of-Flight chamber. The Stop section at the end of the pattern is a 1-dimensional array composed by MCPs detector with discrete anodes corresponding to a Field of View of 4,5°x76°. This system allows having the determination of velocity and direction of the incoming particles. The instrument has a good capability to reject UV photons with the start section and to reject charged particle with a deflector system. In this paper the crucial parts of the instrument and test results will be described: the nano-structure membranes manufacturing, the shuttering system, the position encoder, the optical propriety of the membranes, the photon and particle test, the electronic box.

Mapping the neutralizing epitopes on the glycoprotein of infectious haematopoietic necrosis virus, a fish rhabdovirus

USGS Publications Warehouse

Huang, C.; Chien, M.S.; Landolt, M.L.; Batts, W.; Winton, J.

1996-01-01

Twelve neutralizing monoclonal antibodies (MAbs) against the fish rhabdovirus, infectious haematopoietic necrosis virus (IHNV), were used to select 20 MAb escape mutants. The nucleotide sequence of the entire glycoprotein (G) gene was determined for six mutants representing differing cross-neutralization patterns and each had a single nucleotide change leading to a single amino acid substitution within one of three regions of the protein. These data were used to design nested PCR primers to amplify portions of the G gene of the 14 remaining mutants. When the PCR products from these mutants were sequenced, they also had single nucleotide substitutions coding for amino acid substitutions at the same, or nearby, locations. Of the 20 mutants for which all or part of the glycoprotein gene was sequenced, two MAbs selected mutants with substitutions at amino acids 230-231 (antigenic site I) and the remaining MAbs selected mutants with substitutions at amino acids 272-276 (antigenic site II). Two MAbs that selected mutants mapping to amino acids 272-276, selected other mutants that mapped to amino acids 78-81, raising the possibility that this portion of the N terminus of the protein was part of a discontinuous epitope defining antigenic site II. CLUSTAL alignment of the glycoproteins of rabies virus, vesicular stomatitis virus and IHNV revealed similarities in the location of the neutralizing epitopes and a high degree of conservation among cysteine residues, indicating that the glycoproteins of three different genera of animal rhabdoviruses may share a similar three-dimensional structure in spite of extensive sequence divergence.

Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic Poliovirus Excretors and Emergency Postexposure Prophylaxis▿‡

PubMed Central

Chen, Zhaochun; Chumakov, Konstantin; Dragunsky, Eugenia; Kouiavskaia, Diana; Makiya, Michelle; Neverov, Alexander; Rezapkin, Gennady; Sebrell, Andrew; Purcell, Robert

2011-01-01

Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2, thereby covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 μg/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection. The MAbs described here could be tested in clinical trials to determine whether they might be useful for treatment of immunocompromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case. PMID:21345966

The cold driver: Cold stress while driving results in dangerous behavior.

PubMed

Morris, Drew M; Pilcher, June J

2016-10-01

Cool vehicle cabin temperatures can induce short-term non-hypothermic cold stress. The current study created a cold condition to examine the impact of cold stress on driving behavior. Forty-four participants drove a high-fidelity driving simulator during a thermal neutral or local torso cooled condition. Participants performed additional tasks to assess attention, psychomotor vigilance, and manual dexterity. Skin temperature was significantly lower in the cold condition while internal temperature was unaffected. Participants who had higher subjective ratings of cold followed lead vehicles closer and started to brake later. Participants in the cold condition followed the lead car 22% (0.82s) closer and started braking 20% (2.35s) later when approaching a stop sign during the car-following task. No change in attention, psychomotor vigilance, or dexterity was observed. The current results suggest that cold environmental conditions can contribute to dangerous driving behaviors. Measures of cold perception were also shown to predict changes in driving behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship between needs driving eating occasions and eating behavior in midlife women.

PubMed

Sudo, Noriko; Degeneffe, Dennis; Vue, Houa; Ghosh, Koel; Reicks, Marla

2009-02-01

The purpose of this cross-sectional study was to determine the relationship between type of eating occasion based on need state segments experienced by 200 midlife women (46+/-6 years) and food group, nutrient, and energy intake. Women completed an Eating Occasion Questionnaire for 3 eating occasions over a 3-day period for which they maintained diet records. Cluster analysis segmented 559 eating occasions into six need states. Energy, total fat, and cholesterol consumption per occasion were highest in "routine family meal" occasions of which more than 60% were dinner and eaten at home with their children. The percentage of eating occasions in which fruits/vegetables were eaten was also highest in "routine family meal," followed by "healthy regimen." More than half of "indulgent escape" eating occasions occurred away from home and about one-third were experienced as a snack. Saturated fat and sweets intakes were the highest in the "indulgent escapes" occasions. Eating occasions experienced by women according to needs surrounding the occasion should be considered when developing tailored interventions to improve intake.

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems

PubMed Central

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C

2017-01-01

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea. One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an ‘arms race’ in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems. PMID:28826484

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine.

PubMed

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K; New, Roger; Vanham, Guido; Roitt, Ivan

2016-12-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations.

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

NASA Astrophysics Data System (ADS)

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

2016-07-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations.

Quantitative analyses reveal distinct sensitivities of the capture of HIV-1 primary viruses and pseudoviruses to broadly neutralizing antibodies.

PubMed

Kim, Jiae; Jobe, Ousman; Peachman, Kristina K; Michael, Nelson L; Robb, Merlin L; Rao, Mangala; Rao, Venigalla B

2017-08-01

Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

VizieR Online Data Catalog: Effects of preionization in radiative shocks (Sutherland+, 2017)

NASA Astrophysics Data System (ADS)

Sutherland, R. S.; Dopita, M. A.

2017-06-01

In this paper we treat the preionization problem in shocks over the velocity range 10

Diffuse gamma-ray emission from self-confined cosmic rays around Galactic sources

NASA Astrophysics Data System (ADS)

D'Angelo, Marta; Morlino, Giovanni; Amato, Elena; Blasi, Pasquale

2018-02-01

The propagation of particles accelerated at supernova remnant shocks and escaping the parent remnants is likely to proceed in a strongly non-linear regime, due to the efficient self-generation of Alfvén waves excited through streaming instability near the sources. Depending on the amount of neutral hydrogen present in the regions around the sites of supernova explosions, cosmic rays may accumulate an appreciable grammage in the same regions and get self-confined for non-negligible times, which in turn results in an enhanced rate of production of secondaries. Here we calculate the contribution to the diffuse gamma-ray background due to the overlap along lines of sight of several of these extended haloes as due to pion production induced by self-confined cosmic rays. We find that if the density of neutrals is low, the haloes can account for a substantial fraction of the diffuse emission observed by Fermi-Large Area Telescope (LAT), depending on the orientation of the line of sight with respect to the direction of the Galactic Centre.

The unbearable whiteness of being (in nursing).

PubMed

Puzan, Elayne

2003-09-01

My purpose in writing this paper is to uncover some of the ways in which nursing participates in, reproduces, and resists the detrimental practices associated with white cultural privilege and to share some instances of its personal and social costs. It draws upon the body of scholarship which interrogates racism as it is enacted through whiteness in North America. Whiteness is depicted not as a preordained biological property, but as a socially constructed category of race, wherein non-white people are racially designated, while whites escape such designation and occupy positions which allow them to carry on as if what they say is neutral, rather than historically and ideologically situated. While the concept of whiteness may not have much resonance in nursing, it offers another way to talk about racism, one that does not stop with the scrutiny of the racialized Other. The presumed neutrality of whiteness has been institutionalized so that its authority to define knowledge, membership, and language, as well as its ability to stipulate and enforce the rules and regulations of everyday concourse and discourse within nursing is concealed.

Chemical characteristics of the major thermal springs of Montana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mariner, R.H.; Presser, T.S.; Evans, W.C.

1976-07-01

Twenty-one thermal springs in western Montana were sampled for chemical, isotope, and gas compositions. Most of the springs issue dilute to slightly saline sodium-bicarbonate waters of neutral to slightly alkaline pH. A few of the springs issue sodium-mixed anion waters of near neutral pH. Fluoride concentrations are high in most of the thermal waters, up to 18 miligrams per litre, while F/Cl ratios range from 3/1 in the dilute waters to 1/10 in the slightly saline waters. Most of the springs are theoretically in thermodynamic equilibrium with respect to calcite and fluorite. Nitrogen is the major gas escaping from mostmore » of the hot springs; however, Hunters Hot Springs issue principally methane. The deuterium content of the hot spring waters is typical of meteoric water in western Montana. Geothermal calculations based on silica concentrations and Na-K-Ca ratios indicate that most of the springs are associated with low temperature aquifers (less than 100/sup 0/C). Chalcedony may be controlling the silica concentrations in these low temperature aquifers even in ''granitic'' terranes.« less

Recall dynamics reveal the retrieval of emotional context.

PubMed

Long, Nicole M; Danoff, Michelle S; Kahana, Michael J

2015-10-01

Memory is often better for emotional rather than neutral stimuli. The benefit for emotional items could be the result of an associative mechanism whereby items are associated to a slowly updating context. Through this process, emotional features are integrated with context during study, and are reactivated during test. The presence of emotion in context would both provide a stronger retrieval cue, enhancing memory of emotional items, as well as lead to emotional clustering, whereby emotionally similar items are recalled consecutively. To measure whether associative mechanisms can explain the enhancement for emotional items, we conducted a free recall study in which most items were emotionally neutral to minimize effects of mood induction and to more closely reflect naturalistic settings. We found that emotional items were significantly more likely to be recalled than neutral items and that participants were more likely to transition between emotional items rather than between emotional and neutral items. Together, these results suggest that contextual encoding and retrieval mechanisms may drive the benefit for emotional items both within and outside the laboratory.

Generation of Currents in Weakly Ionized Plasmas through a Collisional Dynamo

NASA Astrophysics Data System (ADS)

Dimant, Yakov; Oppenheim, Meers; Fletcher, Alex

2016-10-01

Intense electric currents called electrojets occur in weakly ionized magnetized plasmas. An example occurs in the Earth's ionosphere near the magnetic equator where neutral winds drive the plasma across the geomagnetic field. Similar processes take place in the Solar chromosphere and MHD generators. We argue that not all convective neutral flows generate electrojets and it introduces the corresponding universal criterion for the current formation, ∇ × (U-> × B->) ≠ ∂ B-> / ∂ t , where U-> is the neutral flow velocity, B-> is the magnetic field, and t is time. This criterion does not depend on the conductivity tensor, σ̂ . For many systems, the displacement current, ∂ B-> / ∂ t , is negligible, making the criterion even simpler. This theory also shows that the neutral-dynamo driver that generates electrojets plays the same role as the DC electric current plays for the generation of the magnetic field in the Biot-Savart law. Work supported by NSF/DOE Grant PHY-1500439.

Io's Sodium Corona and Spatially Extended Cloud: A Consistent Flux Speed Distribution

NASA Technical Reports Server (NTRS)

Smyth, William H.; Combi, Michael R.

1997-01-01

For Io neutral cloud calculations, an SO2 source strength of approximately 4x10(exp 27) molecules/sec was determined by successfully matching the SO2(+) density profile near the satellite deduced from magnetometer data acquired by the Galileo spacecraft during its close flyby on December 7, 1995. The incomplete collision source velocity distribution for SO2 is the same as recently determined for the trace species atomic sodium by Smyth and Combi (1997). Estimates for the total energy loss rate (i.e. power) of O and S atoms escaping Io were also determined and imply a significant pickup current and a significant reduction in the local planetary magnetic field near Io.

The effects of social interactions with in-vehicle agents on a driver's anger level, driving performance, situation awareness, and perceived workload.

PubMed

Jeon, Myounghoon; Walker, Bruce N; Gable, Thomas M

2015-09-01

Research has suggested that interaction with an in-vehicle software agent can improve a driver's psychological state and increase road safety. The present study explored the possibility of using an in-vehicle software agent to mitigate effects of driver anger on driving behavior. After either anger or neutral mood induction, 60 undergraduates drove in a simulator with two types of agent intervention. Results showed that both speech-based agents not only enhance driver situation awareness and driving performance, but also reduce their anger level and perceived workload. Regression models show that a driver's anger influences driving performance measures, mediated by situation awareness. The practical implications include design guidelines for the design of social interaction with in-vehicle software agents. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Novel Covariance-Based Neutrality Test of Time-Series Data Reveals Asymmetries in Ecological and Economic Systems

PubMed Central

Burby, Joshua W.; Lacker, Daniel

2016-01-01

Systems as diverse as the interacting species in a community, alleles at a genetic locus, and companies in a market are characterized by competition (over resources, space, capital, etc) and adaptation. Neutral theory, built around the hypothesis that individual performance is independent of group membership, has found utility across the disciplines of ecology, population genetics, and economics, both because of the success of the neutral hypothesis in predicting system properties and because deviations from these predictions provide information about the underlying dynamics. However, most tests of neutrality are weak, based on static system properties such as species-abundance distributions or the number of singletons in a sample. Time-series data provide a window onto a system’s dynamics, and should furnish tests of the neutral hypothesis that are more powerful to detect deviations from neutrality and more informative about to the type of competitive asymmetry that drives the deviation. Here, we present a neutrality test for time-series data. We apply this test to several microbial time-series and financial time-series and find that most of these systems are not neutral. Our test isolates the covariance structure of neutral competition, thus facilitating further exploration of the nature of asymmetry in the covariance structure of competitive systems. Much like neutrality tests from population genetics that use relative abundance distributions have enabled researchers to scan entire genomes for genes under selection, we anticipate our time-series test will be useful for quick significance tests of neutrality across a range of ecological, economic, and sociological systems for which time-series data are available. Future work can use our test to categorize and compare the dynamic fingerprints of particular competitive asymmetries (frequency dependence, volatility smiles, etc) to improve forecasting and management of complex adaptive systems. PMID:27689714

A Novel Sphingomyelinase-Like Enzyme in Ixodes scapularis Tick Saliva Drives Host CD4+ T cells to Express IL-4

PubMed Central

Alarcon-Chaidez, F. J.; Boppana, V. D.; Hagymasi, A.T.; Adler, A. J.; Wikel, S. K.

2009-01-01

Tick feeding modulates host immune responses. Tick-induced skewing of host CD4+ T cells towards a Th2 cytokine profile facilitates transmission of tick-borne pathogens that would otherwise be neutralized by Th1 cytokines. Tick-derived factors that drive this Th2 response have not previously been characterized. In the current study, we examined an I. scapularis cDNA library prepared at 18-24 hours of feeding and identified and expressed a tick gene with homology to Loxosceles spider venom proteins with sphingomyelinase activity. This I. scapularis sphingomyelinase-like (IsSMase) protein is a Mg+2-dependent, neutral (pH 7.4) form of sphingomyelinase. Significantly, in an in vivo TCR transgenic adoptive transfer assay IsSMase programmed host CD4+ T cells to express the hallmark Th2 effector cytokine IL-4. IsSMase appears to directly program host CD4 T cell IL-4 expression (as opposed to its metabolic by-products) because induced IL-4 expression was not altered when enzymatic activity was neutralized. TCR transgenic CD4 T cell proliferation (CFSE-dilution) was also significantly increased by IsSMase. Furthermore, a Th2 response is superimposed onto a virally-primed Th1 response by IsSMase. Thus, IsSMase is the first identified tick molecule capable of programming host CD4+ T cells to express IL-4. PMID:19292772

Five challenges in evolution and infectious diseases.

PubMed

Metcalf, C J E; Birger, R B; Funk, S; Kouyos, R D; Lloyd-Smith, J O; Jansen, V A A

2015-03-01

Evolution is a key aspect of the biology of many pathogens, driving processes ranging from immune escape to changes in virulence. Because evolution is inherently subject to feedbacks, and because pathogen evolution plays out at scales ranging from within-host to between-host and beyond, evolutionary questions provide special challenges to the modelling community. In this article, we provide an overview of five challenges in modelling the evolution of pathogens and their hosts, and point to areas for development, focussing in particular on the issue of linking theory and data. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Plasma density enhancements created by the ionization of the Earth's upper atmosphere by artificial electron beams

NASA Technical Reports Server (NTRS)

Neubert, Torsten; Banks, Peter M.

1990-01-01

Analytical calculations and experimental observations relating to the interaction with the Earth's upper atmosphere of electron beams emitted from low altitude spacecraft are presented. The problem is described by two coupled nonlinear differential equations in the up-going (along a magnetic field line) and down-going differential energy flux. The equations are solved numerically, using the MSIS atmospheric model and the IRI ionospheric model. The results form the model compare well with recent observations from the CHARGE 2 sounding rocket experiment. Two aspects of the beam-neutral atmosphere interaction are discussed. First, the limits on the electron beam current that can be emitted from a spacecraft without substantial spacecraft charging are investigated. This is important because the charging of the spacecraft to positive potentials limits the current and the escape energy of the beam electrons and thereby limits the ionization of the neutral atmosphere. As an example, we find from CHARGE 2 observations and from the model calculations that below about 180 km, secondary electrons generated through the ionization of the neutral atmosphere by 1 to 10 keV electron beams from sounding rockets, completely balance the beam current, thereby allowing the emission of very high beam currents. Second, the amount of plasma production in the beam-streak is discussed. Results are shown for selected values of the beam energy, spacecraft velocity, and spacecraft altitude.

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

DOE PAGES

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela; ...

2017-03-15

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

Clinical and laboratory studies of the antacid and raft-forming properties of Rennie alginate suspension.

PubMed

Tytgat, G N; Simoneau, G

2006-03-15

Acid pockets at the gastro-oesophageal junction escape buffering from meals in the stomach. Combining high-dose antacid with alginate may therefore be of benefit in gastro-oesophageal reflux disease. To characterize the antacid and raft-forming properties of Rennie alginate suspension (containing high-dose antacid and alginate; Bayer Consumer Care, Bladel, the Netherlands). The in vitro acid-neutralizing capacity of Rennie algniate was compared with Gaviscon (Reckitt Benckiser, Slough, UK) by pH-recorded HCl titration. Alginate raft weight formed in vitro at different pH was used to evaluate the pH dependency of raft formation with each product. A double-blind, placebo-controlled, randomized crossover study also compared the antacid activity of Rennie alginate vs. placebo in vivo using continuous intragastric pH monitoring in 12 healthy fasting volunteers. Compared with Gaviscon, Rennie alginate had a higher acid-neutralizing capacity, greater maximum pH and longer duration of antacid activity in vitro. However, the two products produced comparable alginate rafts at each pH evaluated. In vivo, Rennie alginate provided rapid, effective and long-lasting acid neutralization, with an onset of action of <5 min, and duration of action of almost 90 min. The dual mode of action of Rennie alginate offers an effective treatment option for mild symptomatic gastro-oesophageal reflux disease particularly considering recent findings regarding 'acid pockets'.

Ion Neutral Mass Spectrometer Measurements from Titan

NASA Technical Reports Server (NTRS)

Waite, J. H., Jr.; Niemann, H.; Yelle, R. V.; Kasprzak, W.; Cravens, T.; Luhmann, J.; McNutt, R.; Ip, W.-H.; Gell, D.; Muller-Wordag, I. C. F.

2005-01-01

Introduction: The Ion Neutral Mass Spectrometer (INMS) aboard the Cassini orbiter has obtained the first in situ composition measurements of the neutral densities of molecular nitrogen, methane, argon, and a host of stable carbon-nitrile compounds in its first flyby of Titan. The bulk composition and thermal structure of the moon s upper atmosphere do not appear to be changed since the Voyager flyby in 1979. However, the more sensitive techniques provided by modern in-situ mass spectrometry also give evidence for large-spatial-scale large-amplitude atmospheric waves in the upper atmosphere and for a plethora of stable carbon-nitrile compounds above 1174 km. Furthermore, they allow the first direct measurements of isotopes of nitrogen, carbon, and argon, which provide interesting clues about the evolution of the atmosphere. The atmosphere was first accreted as ammonia and ammonia ices from the Saturn sub-nebula. Subsequent photochemistry likely converted the atmosphere into molecular nitrogen. The early atmosphere was 1.5 to 5 times more substantial and was lost via escape over the intervening 4.5 billion years due to the reduced gravity associated with the relatively small mass of Titan. Carbon in the form of methane has continued to outgas over time from the interior with much of it being deposited in the form of complex hydrocarbons on the surface and some of it also being lost to space.

Epoch of reionization 21 cm forecasting from MCMC-constrained semi-numerical models

NASA Astrophysics Data System (ADS)

Hassan, Sultan; Davé, Romeel; Finlator, Kristian; Santos, Mario G.

2017-06-01

The recent low value of Planck Collaboration XLVII integrated optical depth to Thomson scattering suggests that the reionization occurred fairly suddenly, disfavouring extended reionization scenarios. This will have a significant impact on the 21 cm power spectrum. Using a semi-numerical framework, we improve our model from instantaneous to include time-integrated ionization and recombination effects, and find that this leads to more sudden reionization. It also yields larger H II bubbles that lead to an order of magnitude more 21 cm power on large scales, while suppressing the small-scale ionization power. Local fluctuations in the neutral hydrogen density play the dominant role in boosting the 21 cm power spectrum on large scales, while recombinations are subdominant. We use a Monte Carlo Markov chain approach to constrain our model to observations of the star formation rate functions at z = 6, 7, 8 from Bouwens et al., the Planck Collaboration XLVII optical depth measurements and the Becker & Bolton ionizing emissivity data at z ˜ 5. We then use this constrained model to perform 21 cm forecasting for Low Frequency Array, Hydrogen Epoch of Reionization Array and Square Kilometre Array in order to determine how well such data can characterize the sources driving reionization. We find that the Mock 21 cm power spectrum alone can somewhat constrain the halo mass dependence of ionizing sources, the photon escape fraction and ionizing amplitude, but combining the Mock 21 cm data with other current observations enables us to separately constrain all these parameters. Our framework illustrates how the future 21 cm data can play a key role in understanding the sources and topology of reionization as observations improve.

The Triggering Mechanism of Quiet-Region Coronal Jet Eruptions: Flux Cancelation

NASA Technical Reports Server (NTRS)

Panesar, Navdeep K.; Sterling, Alphonse C.; Moore, Ronald L.

2017-01-01

Coronal jets are frequent transient features on the Sun, observed in EUV and X-ray emissions. They occur in active regions, quiet Sun and coronal holes, and appear as a bright spire with base brightenings. Recent studies show that many coronal jets are driven by the eruption of a minifilament. Here we investigate the magnetic cause of jet-driving minifilament eruptions. We study ten randomly-found on-disk quiet-region coronal jets using SDO/AIA intensity images and SDO/HMI magnetograms. For all ten events, we track the evolution of photospheric magnetic flux in the jet-base region in EUV images and find that (a) a cool (transition-region temperature) minifilament is present prior to each jet eruption; (b) the pre-eruption minifilament resides above the polarity-inversion line between majority-polarity and minority-polarity magnetic flux patches; (c) the opposite-polarity flux patches converge and cancel with each other; (d) the cancelation between the majority-polarity and minority-polarity flux patches eventually destabilizes the field holding the minifilament to erupt outwards; (e) the envelope of the erupting field barges into ambient oppositely-directed far-reaching field and undergoes external reconnection (interchange reconnection); (f) the external reconnection opens the envelope field and the minifilament field inside, allowing reconnected-heated hot material and cool minifilament material to escape along the far-reaching field, producing the jet spire. In summary, we found that each of our ten jets resulted from a minifilament eruption following flux cancelation at the magnetic neutral line under the pre-eruption minifilament. These observations show that flux cancelation is usually the trigger of quiet-region coronal jet eruptions.

Long-range attraction of an ultrarelativistic electron beam by a column of neutral plasma

NASA Astrophysics Data System (ADS)

Adli, E.; Lindstrøm, C. A.; Allen, J.; Clarke, C. I.; Frederico, J.; Gessner, S. J.; Green, S. Z.; Hogan, M. J.; Litos, M. D.; O'Shea, B.; Yakimenko, V.; An, W.; Clayton, C. E.; Marsh, K. A.; Mori, W. B.; Joshi, C.; Vafaei-Najafabadi, N.; Corde, S.; Lu, W.

2016-10-01

We report on the experimental observation of the attraction of a beam of ultrarelativistic electrons towards a column of neutral plasma. In experiments performed at the FACET test facility at SLAC we observe that an electron beam moving parallel to a neutral plasma column, at an initial distance of many plasma column radii, is attracted into the column. Once the beam enters the plasma it drives a plasma wake similar to that of an electron beam entering the plasma column head-on. A simple analytical model is developed in order to capture the essential physics of the attractive force. The attraction is further studied by 3D particle-in-cell numerical simulations. The results are an important step towards better understanding of particle beam-plasma interactions in general and plasma wakefield accelerator technology in particular.

Radial and azimuthal distribution of Io's oxygen neutral cloud observed by Hisaki/EXCEED

NASA Astrophysics Data System (ADS)

Koga, R.; Tsuchiya, F.; Kagitani, M.; Sakanoi, T.; Yoneda, M.; Yoshikawa, I.; Yoshioka, K.; Murakami, G.; Yamazaki, A.; Kimura, T.; Smith, H. T.

2017-12-01

We report the spatial distributions of oxygen neural cloud surrounding Jupiter's moon Io and along Io's orbit observed by the HISAKI satellite. Atomic oxygen and sulfur in Io's atmosphere escape from the exobase and move to corona (< 5.8 Io radii, the boundary where Jupiter's gravity begins to dominate) and neutral clouds (> 5.8 Io radii) mainly due to atmospheric sputtering. Io plasma torus is formed by ionization of these atoms by electron impact and charge exchange processes. It is essential to examine the dominant source of Io plasma torus, particularly in the vicinity of Io (<5.8 Io radii; atmosphere and corona) or the region away from Io (>5.8 Io radii; extended neutral clouds). The spatial distribution of oxygen and sulfur neutral clouds is important to understand the source. The extreme ultraviolet spectrometer called EXCEED (Extreme Ultraviolet Spectroscope for Exospheric Dynamics) installed on the Hisaki satellite observed Io plasma torus continuously in 2014-2015, and we carried out the monitoring of the distribution of atomic oxygen emission at 130.4 nm. The emission averaged over the distance range of 4.5-6.5 Jovian radii on the dawn and dusk sides strongly depends on the Io phase angle (IPA), and has a emission peak between IPA of 60-90 degrees on the dawn side, and between 240-270 degrees on the dusk side, respectively. It also shows the asymmetry with respect to Io's position: the intensity averaged for IPA 60-90 degrees (13.3 Rayleighs (R)) is 1.2 times greater than that for IPA 90-120 degrees (11.1 R) on the dawn side. The similar tendency is found on the dusk side. Weak atomic oxygen emission (4 R) uniformly distributes in every IPA. We also examined the radial distribution of the oxygen neutral cloud during the same period and found the emission peak near Io's orbit with decreasing the intensity toward 8.0 Jupiter radii. The results show the high density component of the oxygen neutral cloud is concentrated around Io and extends mainly toward leading side of Io. In addition, the low density neutrals uniformly exist along Io's orbit. Both components extend radially outward up to 8 Jovian radii with decreasing the density. In the presentation, we give the estimation of spatial distribution of oxygen neutral density and the oxygen ion source rate in the Io plasma torus.

Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs.

PubMed

Li, Hongru; Zony, Chati; Chen, Ping; Chen, Benjamin K

2017-05-01

Broadly neutralizing antibodies (bNAbs) have been isolated from HIV-1 patients and can potently block infection of a wide spectrum of HIV-1 subtypes. These antibodies define common epitopes shared by many viral isolates. While bNAbs potently antagonize infection with cell-free virus, inhibition of HIV-1 transmission from infected to uninfected CD4 + T cells through virological synapses (VS) has been found to require greater amounts of antibody. In this study, we examined two well-studied molecular clones and two transmitted/founder (T/F) clones for their sensitivities to a panel of bNAbs in cell-free and cell-to-cell infection assays. We observed resistance of cell-to-cell transmission to antibody neutralization that was reflected not only by reductions of antibody potency but also by decreases in maximum neutralization capacity relative to the levels seen with cell-free infections. BNAbs targeting different epitopes exhibited incomplete neutralization against cell-associated virus with T/F Envs, which was not observed with the cell-free form of the same virus. We further identified the membrane-proximal internal tyrosine-based sorting motif as a determinant that can affect the incomplete neutralization of these T/F clones in cell-to-cell infection. These findings indicate that the signal that affects surface expression and/or internalization of Env from the plasma membrane can modulate the presentation of neutralizing epitopes on infected cells. These results highlight that a fraction of virus can escape from high concentrations of antibody through cell-to-cell infection while remaining sensitive to neutralization in cell-free infection. The ability to fully inhibit cell-to-cell transmission may represent an important consideration in the development of antibodies for treatment or prophylaxis. IMPORTANCE In recent years, isolation of new-generation HIV-1 bNAbs has invigorated HIV vaccine research. These bNAbs display remarkable potency and breadth of coverage against cell-free virus; however, they exhibit a diminished ability to block HIV-1 cell-to-cell transmission. The mechanism(s) by which HIV-1 resists neutralization when transmitting through VS remains uncertain. We examined a panel of bNAbs for their ability to neutralize HIV-1 T/F viruses in cell-to-cell infection assays. We found that some antibodies exhibit not only reduced potency but also decreased maximum neutralization capacity or in vitro efficacy against cell-to-cell infection of HIV-1 with T/F Envs compared to cell-free infection of the same virus. We further identified the membrane-proximal internal tyrosine-based sorting motif YXXL as a determinant that can affect the incomplete neutralization phenotype of these T/F clones. When the maximum neutralization capacity falls short of 100%, this can have a major impact on the ability of antibodies to halt viral replication. Copyright © 2017 American Society for Microbiology.

Photochemistry of Pluto's Atmosphere

NASA Technical Reports Server (NTRS)

Krasnopolsky, Vladimir A.

1999-01-01

This work include studies of two problems: (1) Modeling thermal balance, structure. and escape processes in Pluto's upper atmosphere. This study has been completed in full. A new method, of analytic solution for the equation of hydrodynamic flow from in atmosphere been developed. It was found that the ultraviolet absorption by methane which was previously ignored is even more important in Pluto's thermal balance than the extreme ultraviolet absorption by nitrogen. Two basic models of the lower atmosphere have been suggested, with a tropopause and a planetary surface at the bottom of the stellar occultation lightcurve, respectively, Vertical profiles, of temperature, density, gas velocity, and the CH4 mixing ratio have been calculated for these two models at low, mean, and high solar activity (six models). We prove that Pluto' " s atmosphere is restricted to 3060-4500 km, which makes possible a close flyby of future spacecraft. Implication for Pluto's evolution have also been discussed. and (2) Modeling of Pluto's photochemistry. Based on the results of (1), we have made some changes in the basic continuity equation and in the boundary conditions which reflect a unique can of hydrodynamic escape and therefore have not been used in modeling of other planetary atmospheres. We model photochemistry of 44 neutral and 23 ion species. This work required solution of a set of 67 second-order nonlinear ordinary differential equations. Two models have been developed. Each model consists of the vertical profiles for 67 species, their escape and precipitation rates. These models predict the chemical structure and basic chemical processes in the current atmosphere and possible implication of these processes for evolution. This study has also been completed in full.

Solar Wind Ablation of Terrestrial Planet Atmospheres

NASA Technical Reports Server (NTRS)

Moore, Thomas Earle; Fok, Mei-Ching H.; Delcourt, Dominique C.

2009-01-01

Internal plasma sources usually arise in planetary magnetospheres as a product of stellar ablation processes. With the ignition of a new star and the onset of its ultraviolet and stellar wind emissions, much of the volatiles in the stellar system undergo a phase transition from gas to plasma. Condensation and accretion into a disk is replaced by radiation and stellar wind ablation of volatile materials from the system- Planets or smaller bodies that harbor intrinsic magnetic fields develop an apparent shield against direct stellar wind impact, but UV radiation still ionizes their gas phases, and the resulting internal plasmas serve to conduct currents to and from the central body along reconnected magnetic field linkages. Photoionization and thermalization of electrons warms the ionospheric topside, enhancing Jeans' escape of super-thermal particles, with ambipolar diffusion and acceleration. Moreover, observations and simulations of auroral processes at Earth indicate that solar wind energy dissipation is concentrated by the geomagnetic field by a factor of 10-100, enhancing heavy species plasma and gas escape from gravity, and providing more current carrying capacity. Thus internal plasmas enable coupling with the plasma, neutral gas and by extension, the entire body. The stellar wind is locally loaded and slowed to develop the required power. The internal source plasma is accelerated and heated, inflating the magnetosphere as it seeks escape, and is ultimately blown away in the stellar wind. Bodies with little sensible atmosphere may still produce an exosphere of sputtered matter when exposed to direct solar wind impact. Bodies with a magnetosphere and internal sources of plasma interact more strongly with the stellar wind owing to the magnetic linkage between the two created by reconnection.

Complexation-induced supramolecular assembly drives metal-ion extraction.

PubMed

Ellis, Ross J; Meridiano, Yannick; Muller, Julie; Berthon, Laurence; Guilbaud, Philippe; Zorz, Nicole; Antonio, Mark R; Demars, Thomas; Zemb, Thomas

2014-09-26

Combining experiment with theory reveals the role of self-assembly and complexation in metal-ion transfer through the water-oil interface. The coordinating metal salt Eu(NO3)3 was extracted from water into oil by a lipophilic neutral amphiphile. Molecular dynamics simulations were coupled to experimental spectroscopic and X-ray scattering techniques to investigate how local coordination interactions between the metal ion and ligands in the organic phase combine with long-range interactions to produce spontaneous changes in the solvent microstructure. Extraction of the Eu(3+)-3(NO3(-)) ion pairs involves incorporation of the "hard" metal complex into the core of "soft" aggregates. This seeds the formation of reverse micelles that draw the water and "free" amphiphile into nanoscale hydrophilic domains. The reverse micelles interact through attractive van der Waals interactions and coalesce into rod-shaped polynuclear Eu(III) -containing aggregates with metal centers bridged by nitrate. These preorganized hydrophilic domains, containing high densities of O-donor ligands and anions, provide improved Eu(III) solvation environments that help drive interfacial transfer, as is reflected by the increasing Eu(III) partitioning ratios (oil/aqueous) despite the organic phase approaching saturation. For the first time, this multiscale approach links metal-ion coordination with nanoscale structure to reveal the free-energy balance that drives the phase transfer of neutral metal salts. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sawtooth control in fusion plasmas

NASA Astrophysics Data System (ADS)

Graves, J. P.; Angioni, C.; Budny, R. V.; Buttery, R. J.; Coda, S.; Eriksson, L.-G.; Gimblett, C. G.; Goodman, T. P.; Hastie, R. J.; Henderson, M. A.; Koslowski, H. R.; Mantsinen, M. J.; Martynov, An; Mayoral, M.-L.; Mück, A.; Nave, M. F. F.; Sauter, O.; Westerhof, E.; Contributors, JET–EFDA

2005-12-01

Clear observations of early triggering of neo-classical tearing modes by sawteeth with long quiescent periods have motivated recent efforts to control, and in particular destabilize, sawteeth. One successful approach explored in TCV utilizes electron cyclotron heating in order to locally increase the current penetration time in the core. The latter is also achieved in various machines by depositing electron cyclotron current drive or ion cyclotron current drive close to the q = 1 rational surface. Crucially, localized current drive also succeeds in destabilizing sawteeth which are otherwise stabilized by a co-existing population of energetic trapped ions in the core. In addition, a recent reversed toroidal field campaign at JET demonstrates that counter-neutral beam injection (NBI) results in shorter sawtooth periods than in the Ohmic regime. The clear dependence of the sawtooth period on the NBI heating power and the direction of injection also manifests itself in terms of the toroidal plasma rotation, which consequently requires consideration in the theoretical interpretation of the experiments. Another feature of NBI, expected to be especially evident in the negative ion based neutral beam injection (NNBI) heating planned for ITER, is the parallel velocity asymmetry of the fast ion population. It is predicted that a finite orbit effect of asymmetrically distributed circulating ions could strongly modify sawtooth stability. Furthermore, NNBI driven current with non-monotonic profile could significantly slow down the evolution of the safety factor in the core, thereby delaying sawteeth.

Destabilization of counter-propagating TAEs by off-axis, co-current Neutral Beam Injection

NASA Astrophysics Data System (ADS)

Podesta', M.; Fredrickson, E.; Gorelenkova, M.

2017-10-01

Neutral Beam injection (NBI) is a common tool to heat the plasma and drive current non-inductively in fusion devices. Energetic particles (EP) resulting from NBI can drive instabilities that are detrimental for the performance and the predictability of plasma discharges. A broad NBI deposition profile, e.g. by off-axis injection aiming near the plasma mid-radius, is often assumed to limit those undesired effects by reducing the radial gradient of the EP density, thus reducing the ``universal'' drive for instabilities. However, this work presents new evidence that off-axis NBI can also lead to undesired effects such as the destabilization of Alfvénic instabilities, as observed in NSTX-U plasmas. Experimental observations indicate that counter propagating toroidal AEs are destabilized as the radial EP density profile becomes hollow as a result of off-axis NBI. Time-dependent analysis with the TRANSP code, augmented by a reduced fast ion transport model (known as kick model), indicates that instabilities are driven by a combination of radial and energy gradients in the EP distribution. Understanding the mechanisms for wave-particle interaction, revealed by the phase space resolved analysis, is the basis to identify strategies to mitigate or suppress the observed instabilities. Work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Contract Number DE-AC02-09CH11466.

Duplicate retention in signalling proteins and constraints from network dynamics.

PubMed

Soyer, O S; Creevey, C J

2010-11-01

Duplications are a major driving force behind evolution. Most duplicates are believed to fix through genetic drift, but it is not clear whether this process affects all duplications equally or whether there are certain gene families that are expected to show neutral expansions under certain circumstances. Here, we analyse the neutrality of duplications in different functional classes of signalling proteins based on their effects on response dynamics. We find that duplications involving intermediary proteins in a signalling network are neutral more often than those involving receptors. Although the fraction of neutral duplications in all functional classes increase with decreasing population size and selective pressure on dynamics, this effect is most pronounced for receptors, indicating a possible expansion of receptors in species with small population size. In line with such an expectation, we found a statistically significant increase in the number of receptors as a fraction of genome size in eukaryotes compared with prokaryotes. Although not confirmative, these results indicate that neutral processes can be a significant factor in shaping signalling networks and affect proteins from different functional classes differently. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

Generation of Werner states via collective decay of coherently driven atoms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Girish S.; Kapale, Kishore T.

2006-02-15

We show deterministic generation of Werner states as a steady state of the collective decay dynamics of a pair of neutral atoms coupled to a leaky cavity and strong coherent drive. We also show how the scheme can be extended to generate a 2N-particle analogue of the bipartite Werner states.

The rhizosphere: a playground and battlefield for soilborne pathogens and beneficial microorganisms

USDA-ARS?s Scientific Manuscript database

The rhizosphere is a hot spot of microbial interactions as exudates released by plant roots are a main food source for microorganisms and a driving force of their population density and activities. The rhizosphere harbors many organisms that have a neutral effect on the plant, but also attracts orga...

Lightning driven EMP in the upper atmosphere

NASA Technical Reports Server (NTRS)

Rowland, H. L.; Fernsler, R. F.; Huba, J. D.; Bernhardt, P. A.

1995-01-01

Large lightning discharges can drive electromagnetic pulses (EMP) that cause breakdown of the neutral atmosphere between 80 and 95 km leading to order of magnitude increases in the plasma density. The increase in the plasma density leads to increased reflection and absorption, and limits the pulse strength that propagates higher into the ionosphere.

Design and Comparison of Cascaded H-Bridge, Modular Multilevel Converter, and 5-L Active Neutral Point Clamped Topologies for Motor Drive Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marzoughi, Alinaghi; Burgos, Rolando; Boroyevich, Dushan

This paper presents the design procedure and comparison of converters currently used in medium-voltage high-power motor drive applications. For this purpose, the cascaded H-bridge (CHB), modular multilevel converter (MMC), and five-level active neutral point clamped (5-L ANPC) topologies are targeted. The design is performed using 1.7-kV insulated gate bipolar transistors (IGBTs) for CHB and MMC converters, and utilizing 3.3- and 4.5-kV IGBTs for 5-L ANPC topology as normally done in industry. The comparison is done between the designed converter topologies at three different voltage levels (4.16, 6.9, and 13.8 kV, with only the first two voltage levels in case ofmore » the 5-L ANPC) and two different power levels (3 and 5 MVA), in order to elucidate the dependence of different parameters on voltage and power rating. Finally, the comparison is done from several points of view such as efficiency, capacitive energy storage, semiconductor utilization, parts count (for measure of reliability), and power density.« less

Numerical simulation of the environmental impact of hydraulic fracturing of tight/shale gas reservoirs on near-surface groundwater: Background, base cases, shallow reservoirs, short-term gas, and water transport.

PubMed

Reagan, Matthew T; Moridis, George J; Keen, Noel D; Johnson, Jeffrey N

2015-04-01

Hydrocarbon production from unconventional resources and the use of reservoir stimulation techniques, such as hydraulic fracturing, has grown explosively over the last decade. However, concerns have arisen that reservoir stimulation creates significant environmental threats through the creation of permeable pathways connecting the stimulated reservoir with shallower freshwater aquifers, thus resulting in the contamination of potable groundwater by escaping hydrocarbons or other reservoir fluids. This study investigates, by numerical simulation, gas and water transport between a shallow tight-gas reservoir and a shallower overlying freshwater aquifer following hydraulic fracturing operations, if such a connecting pathway has been created. We focus on two general failure scenarios: (1) communication between the reservoir and aquifer via a connecting fracture or fault and (2) communication via a deteriorated, preexisting nearby well. We conclude that the key factors driving short-term transport of gas include high permeability for the connecting pathway and the overall volume of the connecting feature. Production from the reservoir is likely to mitigate release through reduction of available free gas and lowering of reservoir pressure, and not producing may increase the potential for release. We also find that hydrostatic tight-gas reservoirs are unlikely to act as a continuing source of migrating gas, as gas contained within the newly formed hydraulic fracture is the primary source for potential contamination. Such incidents of gas escape are likely to be limited in duration and scope for hydrostatic reservoirs. Reliable field and laboratory data must be acquired to constrain the factors and determine the likelihood of these outcomes. Short-term leakage fractured reservoirs requires high-permeability pathways Production strategy affects the likelihood and magnitude of gas release Gas release is likely short-term, without additional driving forces.

Numerical simulations of continuum-driven winds of super-Eddington stars

NASA Astrophysics Data System (ADS)

van Marle, A. J.; Owocki, S. P.; Shaviv, N. J.

2008-09-01

We present the results of numerical simulations of continuum-driven winds of stars that exceed the Eddington limit and compare these against predictions from earlier analytical solutions. Our models are based on the assumption that the stellar atmosphere consists of clumped matter, where the individual clumps have a much larger optical thickness than the matter between the clumps. This `porosity' of the stellar atmosphere reduces the coupling between radiation and matter, since photons tend to escape through the more tenuous gas between the clumps. This allows a star that formally exceeds the Eddington limit to remain stable, yet produce a steady outflow from the region where the clumps become optically thin. We have made a parameter study of wind models for a variety of input conditions in order to explore the properties of continuum-driven winds. The results show that the numerical simulations reproduce quite closely the analytical scalings. The mass-loss rates produced in our models are much larger than can be achieved by line driving. This makes continuum driving a good mechanism to explain the large mass-loss and flow speeds of giant outbursts, as observed in η Carinae and other luminous blue variable stars. Continuum driving may also be important in population III stars, since line driving becomes ineffective at low metallicities. We also explore the effect of photon tiring and the limits it places on the wind parameters.

Deciphering the Intracellular Fate of Propionibacterium acnes in Macrophages

PubMed Central

Fischer, Natalie; Mak, Tim N.; Shinohara, Debika Biswal; Sfanos, Karen S.; Meyer, Thomas F.

2013-01-01

Propionibacterium acnes is a Gram-positive bacterium that colonizes various niches of the human body, particularly the sebaceous follicles of the skin. Over the last years a role of this common skin bacterium as an opportunistic pathogen has been explored. Persistence of P. acnes in host tissue has been associated with chronic inflammation and disease development, for example, in prostate pathologies. This study investigated the intracellular fate of P. acnes in macrophages after phagocytosis. In a mouse model of P. acnes-induced chronic prostatic inflammation, the bacterium could be detected in prostate-infiltrating macrophages at 2 weeks postinfection. Further studies performed in the human macrophage cell line THP-1 revealed intracellular survival and persistence of P. acnes but no intracellular replication or escape from the host cell. Confocal analyses of phagosome acidification and maturation were performed. Acidification of P. acnes-containing phagosomes was observed at 6 h postinfection but then lost again, indicative of cytosolic escape of P. acnes or intraphagosomal pH neutralization. No colocalization with the lysosomal markers LAMP1 and cathepsin D was observed, implying that the P. acnes-containing phagosome does not fuse with lysosomes. Our findings give first insights into the intracellular fate of P. acnes; its persistency is likely to be important for the development of P. acnes-associated inflammatory diseases. PMID:23862148

HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G

PubMed Central

Ikeda, Terumasa; Albin, John S.; Li, Ming; Thali, Markus

2018-01-01

HIV-1 replication normally requires Vif-mediated neutralization of APOBEC3 antiviral enzymes. Viruses lacking Vif succumb to deamination-dependent and -independent restriction processes. Here, HIV-1 adaptation studies were leveraged to ask whether viruses with an irreparable vif deletion could develop resistance to restrictive levels of APOBEC3G. Several resistant viruses were recovered with multiple amino acid substitutions in Env, and these changes alone are sufficient to protect Vif-null viruses from APOBEC3G-dependent restriction in T cell lines. Env adaptations cause decreased fusogenicity, which results in higher levels of Gag-Pol packaging. Increased concentrations of packaged Pol in turn enable faster virus DNA replication and protection from APOBEC3G-mediated hypermutation of viral replication intermediates. Taken together, these studies reveal that a moderate decrease in one essential viral activity, namely Env-mediated fusogenicity, enables the virus to change other activities, here, Gag-Pol packaging during particle production, and thereby escape restriction by the antiviral factor APOBEC3G. We propose a new paradigm in which alterations in viral homeostasis, through compensatory small changes, constitute a general mechanism used by HIV-1 and other viral pathogens to escape innate antiviral responses and other inhibitions including antiviral drugs. PMID:29677220

A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease.

PubMed

Calvert, Amanda E; Dixon, Kandice L; Piper, Joseph; Bennett, Susan L; Thibodeaux, Brett A; Barrett, Alan D T; Roehrig, John T; Blair, Carol D

2016-07-01

The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone. Copyright © 2016 Elsevier B.V. All rights reserved.

A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease

PubMed Central

Calvert, Amanda E.; Dixon, Kandice L.; Piper, Joseph; Bennett, Susan L.; Thibodeaux, Brett A.; Barrett, Alan D.T.; Roehrig, John T.; Blair, Carol D.

2016-01-01

The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone. PMID:27126613

Alanine scanning of the rabies virus glycoprotein antigenic site III using recombinant rabies virus: implication for post-exposure treatment.

PubMed

Papaneri, Amy B; Wirblich, Christoph; Marissen, Wilfred E; Schnell, Matthias J

2013-12-02

The safety and availability of the human polyclonal sera that is currently utilized for post-exposure treatment (PET) of rabies virus (RABV) infection remain a concern. Recombinant monoclonal antibodies have been postulated as suitable alternatives by WHO. To this extent, CL184, the RABV human antibody combination comprising monoclonal antibodies (mAbs) CR57 and CR4098, has been developed and has delivered promising clinical data to support its use for RABV PET. For this fully human IgG1 cocktail, mAbs CR57 and CR4098 are produced in the PER.C6 human cell line and combined in equal amounts in the final product. During preclinical evaluation, CR57 was shown to bind to antigenic site I whereas CR4098 neutralization was influenced by a mutation of position 336 (N336) located within antigenic site III. Here, alanine scanning was used to analyze the influence of mutations within the potential binding site for CR4098, antigenic site III, in order to evaluate the possibility of mutated rabies viruses escaping neutralization. For this approach, twenty flanking amino acids (10 upstream and 10 downstream) of the RABV glycoprotein (G) asparagine (N336) were exchanged to alanine (or serine, if already alanine) by site-directed mutagenesis. Analysis of G expression revealed four of the twenty mutant Gs to be non-functional, as shown by their lack of cell surface expression, which is a requirement for the production of infectious RABV. Therefore, these mutants were excluded from further study. The remaining sixteen mutants were introduced in an infectious clone of RABV, and recombinant RABVs (rRABVs) were recovered and utilized for in vitro neutralization assays. All of the viruses were effectively neutralized by CR4098 as well as by CR57, indicating that single amino acid exchanges in this region does not affect the broad neutralizing capability of the CL184 mAb combination. Copyright © 2013 Elsevier Ltd. All rights reserved.

Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010

PubMed Central

Drexler, Jan Felix; Grard, Gilda; Lukashev, Alexander N.; Kozlovskaya, Liubov I.; Böttcher, Sindy; Uslu, Gökhan; Reimerink, Johan; Gmyl, Anatoly P.; Taty-Taty, Raphaël; Lekana-Douki, Sonia Etenna; Nkoghe, Dieudonné; Eis-Hübinger, Anna M.; Diedrich, Sabine; Koopmans, Marion; Leroy, Eric M.; Drosten, Christian

2014-01-01

In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL→221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15–29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary. PMID:25136105

Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010.

PubMed

Drexler, Jan Felix; Grard, Gilda; Lukashev, Alexander N; Kozlovskaya, Liubov I; Böttcher, Sindy; Uslu, Gökhan; Reimerink, Johan; Gmyl, Anatoly P; Taty-Taty, Raphaël; Lekana-Douki, Sonia Etenna; Nkoghe, Dieudonné; Eis-Hübinger, Anna M; Diedrich, Sabine; Koopmans, Marion; Leroy, Eric M; Drosten, Christian

2014-09-02

In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL → 221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary.

R2d2 Drives Selfish Sweeps in the House Mouse.

PubMed

Didion, John P; Morgan, Andrew P; Yadgary, Liran; Bell, Timothy A; McMullan, Rachel C; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J; Campbell, Karl J; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J; Crowley, James J; Chesler, Elissa J; Förster, Daniel W; French, John E; Gabriel, Sofia I; Gatti, Daniel M; Garland, Theodore; Giagia-Athanasopoulou, Eva B; Giménez, Mabel D; Grize, Sofia A; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C; Herman, Jeremy S; Holt, James M; Hua, Kunjie; Jolley, Wesley J; Lindholm, Anna K; López-Fuster, María J; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P; Searle, Jeremy B; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L; Thomas-Laemont, Patricia; Threadgill, David W; Ventura, Jacint; Weinstock, George M; Pomp, Daniel; Churchill, Gary A; Pardo-Manuel de Villena, Fernando

2016-06-01

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

R2d2 Drives Selfish Sweeps in the House Mouse

PubMed Central

Didion, John P.; Morgan, Andrew P.; Yadgary, Liran; Bell, Timothy A.; McMullan, Rachel C.; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J.; Campbell, Karl J.; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J.; Crowley, James J.; Chesler, Elissa J.; Förster, Daniel W.; French, John E.; Gabriel, Sofia I.; Gatti, Daniel M.; Garland, Theodore; Giagia-Athanasopoulou, Eva B.; Giménez, Mabel D.; Grize, Sofia A.; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C.; Herman, Jeremy S.; Holt, James M.; Hua, Kunjie; Jolley, Wesley J.; Lindholm, Anna K.; López-Fuster, María J.; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P.; Searle, Jeremy B.; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L.; Thomas-Laemont, Patricia; Threadgill, David W.; Ventura, Jacint; Weinstock, George M.; Pomp, Daniel; Churchill, Gary A.; Pardo-Manuel de Villena, Fernando

2016-01-01

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. PMID:26882987

Capacitive Neutralization Dialysis for Direct Energy Generation.

PubMed

Liu, Yue; Zhang, Yi; Ou-Yang, Wei; Bastos Sales, Bruno; Sun, Zhuo; Liu, Fei; Zhao, Ran

2017-08-15

Capacitive neutralization dialysis energy (CNDE) is proposed as a novel energy-harvesting technique that is able to utilize waste acid and alkaline solutions to produce electrical energy. CNDE is a modification based on neutralization dialysis. It was found that a higher NaCl concentration led to a higher open-circuit potential when the concentrations of acid and alkaline solutions were fixed. Upon closing of the circuit, the membrane potential was used as a driving force to move counter ions into the electrical double layers at the electrode-liquid interface, thereby creating an ionic current. Correspondingly, in the external circuit, electrons flow through an external resistor from one electrode to the other, thereby generating electrical energy directly. The influence of external resistances was studied to achieve greater energy extraction, with the maximum output of 110 mW/m 2 obtained by employing an external resistance of 5 Ω together with the AC-coated electrode.

Parametric scaling of neutral and ion excited state densities in an argon helicon source

NASA Astrophysics Data System (ADS)

McCarren, D.; Scime, E.

2016-04-01

We report measurements of the absolute density and temperature of ion and neutral excited states in an argon helicon source. The excited ion state density, which depends on ion density, electron density, and electron temperature, increases sharply with increasing magnetic field in the source. The neutral argon metastable density measurements are consistent with an increasing ionization fraction with increasing magnetic field strength. The ion temperature shows no evidence of increased heating with increasing magnetic field strength (which has only been observed in helicon sources operating at driving frequencies close to the lower hybrid frequency). The measurements were obtained through cavity ring down spectroscopy, a measurement technique that does not require the target excited state to be metastable or part of a fluorescence scheme; and is therefore applicable to any laser accessible atomic or ionic transition in a plasma.

Long-range attraction of an ultrarelativistic electron beam by a column of neutral plasma

DOE PAGES

Adli, Erik; Lindstrom, C. A.; Allen, J.; ...

2016-10-12

Here, we report on the experimental observation of the attraction of a beam of ultrarelativistic electrons towards a column of neutral plasma. In experiments performed at the FACET test facility at SLAC we observe that an electron beam moving parallel to a neutral plasma column, at an initial distance of many plasma column radii, is attracted into the column. Once the beam enters the plasma it drives a plasma wake similar to that of an electron beam entering the plasma column head-on. A simple analytical model is developed in order to capture the essential physics of the attractive force. Themore » attraction is further studied by 3D particle-in-cell numerical simulations. The results are an important step towards better understanding of particle beam–plasma interactions in general and plasma wakefield accelerator technology in particular.« less

Long-range attraction of an ultrarelativistic electron beam by a column of neutral plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adli, Erik; Lindstrom, C. A.; Allen, J.

Here, we report on the experimental observation of the attraction of a beam of ultrarelativistic electrons towards a column of neutral plasma. In experiments performed at the FACET test facility at SLAC we observe that an electron beam moving parallel to a neutral plasma column, at an initial distance of many plasma column radii, is attracted into the column. Once the beam enters the plasma it drives a plasma wake similar to that of an electron beam entering the plasma column head-on. A simple analytical model is developed in order to capture the essential physics of the attractive force. Themore » attraction is further studied by 3D particle-in-cell numerical simulations. The results are an important step towards better understanding of particle beam–plasma interactions in general and plasma wakefield accelerator technology in particular.« less

The role of ecology, neutral processes and antagonistic coevolution in an apparent sexual arms race.

PubMed

Perry, Jennifer C; Garroway, Colin J; Rowe, Locke

2017-09-01

Some of the strongest examples of a sexual 'arms race' come from observations of correlated evolution in sexually antagonistic traits among populations. However, it remains unclear whether these cases truly represent sexually antagonistic coevolution; alternatively, ecological or neutral processes might also drive correlated evolution. To investigate these alternatives, we evaluated the contributions of intersex genetic correlations, ecological context, neutral genetic divergence and sexual coevolution in the correlated evolution of antagonistic traits among populations of Gerris incognitus water striders. We could not detect intersex genetic correlations for these sexually antagonistic traits. Ecological variation was related to population variation in the key female antagonistic trait (spine length, a defence against males), as well as body size. Nevertheless, population covariation between sexually antagonistic traits remained substantial and significant even after accounting for all of these processes. Our results therefore provide strong evidence for a contemporary sexual arms race. © 2017 John Wiley & Sons Ltd/CNRS.

Phenotypic Mismatches Reveal Escape from Arms-Race Coevolution

PubMed Central

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

2008-01-01

Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight into these features of coevolution by sampling across a diverse set of conditions and histories. We used measures of prey traits (tetrodotoxin toxicity in newts) and predator traits (tetrodotoxin resistance of snakes) to assess the degree of phenotypic mismatch across the range of their coevolutionary interaction. Geographic patterns of phenotypic exaggeration were similar in prey and predators, with most phenotypically elevated localities occurring along the central Oregon coast and central California. Contrary to expectations, however, these areas of elevated traits did not coincide with the most intense coevolutionary selection. Measures of functional trait mismatch revealed that over one-third of sampled localities were so mismatched that reciprocal selection could not occur given current trait distributions. Estimates of current locality-specific interaction selection gradients confirmed this interpretation. In every case of mismatch, predators were “ahead” of prey in the arms race; the converse escape of prey was never observed. The emergent pattern suggests a dynamic in which interacting species experience reciprocal selection that drives arms-race escalation of both prey and predator phenotypes at a subset of localities across the interaction. This coadaptation proceeds until the evolution of extreme phenotypes by predators, through genes of large effect, allows snakes to, at least temporarily, escape the arms race. PMID:18336073

Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection.

PubMed

Senba, Masachika; Mori, Naoki

2012-10-02

Human papillomavirus (HPV) has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC) class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-κB in cervical and penile cancers suggests that NF-κB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-κB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

Magnetar giant flares in multipolar magnetic fields. II. Flux rope eruptions with current sheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Lei; Yu, Cong, E-mail: muduri@shao.ac.cn, E-mail: cyu@ynao.ac.cn

2014-11-20

We propose a physical mechanism to explain giant flares and radio afterglows in terms of a magnetospheric model containing both a helically twisted flux rope and a current sheet (CS). With the appearance of a CS, we solve a mixed boundary value problem to get the magnetospheric field based on a domain decomposition method. We investigate properties of the equilibrium curve of the flux rope when the CS is present in background multipolar fields. In response to the variations at the magnetar surface, it quasi-statically evolves in stable equilibrium states. The loss of equilibrium occurs at a critical point and,more » beyond that point, it erupts catastrophically. New features show up when the CS is considered. In particular, we find two kinds of physical behaviors, i.e., catastrophic state transition and catastrophic escape. Magnetic energy would be released during state transitions. This released magnetic energy is sufficient to drive giant flares, and the flux rope would, therefore, go away from the magnetar quasi-statically, which is inconsistent with the radio afterglow. Fortunately, in the latter case, i.e., the catastrophic escape, the flux rope could escape the magnetar and go to infinity in a dynamical way. This is more consistent with radio afterglow observations of giant flares. We find that the minor radius of the flux rope has important implications for its eruption. Flux ropes with larger minor radii are more prone to erupt. We stress that the CS provides an ideal place for magnetic reconnection, which would further enhance the energy release during eruptions.« less

Feedback in low-mass galaxies in the early Universe.

PubMed

Erb, Dawn K

2015-07-09

The formation, evolution and death of massive stars release large quantities of energy and momentum into the gas surrounding the sites of star formation. This process, generically termed 'feedback', inhibits further star formation either by removing gas from the galaxy, or by heating it to temperatures that are too high to form new stars. Observations reveal feedback in the form of galactic-scale outflows of gas in galaxies with high rates of star formation, especially in the early Universe. Feedback in faint, low-mass galaxies probably facilitated the escape of ionizing radiation from galaxies when the Universe was about 500 million years old, so that the hydrogen between galaxies changed from neutral to ionized-the last major phase transition in the Universe.

Senator John Glenn during water survival training at the NBL

NASA Image and Video Library

1998-04-06

S98-04610 (6 April 1998) --- U.S. Sen. John H. Glenn Jr. (D.-Ohio), attired in a training version of the Space Shuttle partial pressure launch and entry suit, surveys the scene of a bailout training exercise. The giant pool in the Neutral Buoyancy Laboratory (NBL)at the Sonny Carter Training Facility allows the STS-95 crewmembers the opportunity to simulate ejection from an aircraft over water. A number of SCUBA-equipped divers assist in the training exercises. The nearby structure contains a simulated version of the escape pole which is located in the middeck on each of four NASA Space Shuttle vehicles. Parachute drops, raft deployment, water bailing, flare signaling and other survival techniques are also covered in the session.

Implications of Voyager data for energetic ion erosion of the icy satellites of Saturn

NASA Technical Reports Server (NTRS)

Lanzerotti, L. J.; Maclennan, C. G.; Brown, W. L.; Johnson, R. E.; Barton, L. A.; Reimann, C. T.; Garrett, J. W.; Boring, J. W.

1983-01-01

The possible production of a neutral-particle torus by magnetosphere-particle sputtering of the icy satellites (Enceladus, Tethys, Dione, Rhea) of Saturn is discussed. Particle spectra from the Voyager low-energy-charged-particle experiment are used together with laboratory-derived erosion rates and velocity distributions for the ejected species. An extended torus region in the inner magnetosphere of Saturn is expected, with H2O escape fluxes in the vicinities of the satellites varying from about 2 to 7 x 10 to the 7th mol/sq cm sec for incident protons and from about 6 to 14 x 10 to the 9th mol/sq cm sec if the incident ions are all oxygen.

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.

PubMed

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H; Beltran, Himisha; Fox, Archa H; Elemento, Olivier; Rubin, Mark A

2014-11-21

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription.

Tomographic Location of Potential Melt-Bearing Phenocrysts in Lunar Glass Spherules

NASA Technical Reports Server (NTRS)

Ebel, D. S.; Fogel, R. A.; Rivers, M. L.

2005-01-01

In 1971, Apollo 17 astronauts collected a 10 cm soil sample (74220) comprised almost entirely of orange glass spherules. Below this, a double drive-tube core sampled a 68 cm thick horizon comprised of orange glass and black beads (crystallized equivalents of orange glass). Primitive lunar glass spherules (e.g.-A17 orange glasses) are thought to represent ejecta from lunar mare fire fountains [1, 2]. The fire-fountains were apparently driven by a combination of C-O gas ex-solution from orange glass melt and the oxidation of graphite [3, 4]. Upon eruption, magmas lost their volatiles (e.g., S, CO, CO2) to space. Evidence for volatile escape remains as volatile-rich coatings on the exteriors of many spherules [e.g., 5,6]. Moreover, [7] showed that Type I and II Fe-Ni-rich metal particles found within orange glass olivine phenocrysts, or free-floating in the glass itself, are powerful evidence for the volatile driving force for lunar fire fountains.

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

PubMed Central

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S.; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y.; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A.; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B.; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H.; Beltran, Himisha; Fox, Archa H.; Elemento, Olivier; Rubin, Mark A.

2014-01-01

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription. PMID:25415230

The effects of positive emotion priming on self-reported reckless driving.

PubMed

Taubman-Ben-Ari, Orit

2012-03-01

Five studies examined the effects of positive emotion priming on the willingness to drive recklessly. In all five, young drivers were exposed to one of the following primes of positive affect: a positive mood story; happy memories; an exciting film; a relaxing film; or thoughts on the meaning in life. Following the prime, the participants were asked to report on their willingness to drive recklessly. The responses were compared to those of groups exposed either to neutral affect, another kind of positive affect, or negative affect priming. In two of the studies, participants were also asked to report on their driving styles (risky, anxious, angry, or careful) as a second dependent variable. Positive affect, especially in the form of arousal, was found to be related to higher willingness to drive recklessly. Although men tended to report higher intentions to drive recklessly, men and women did not react differently to the emotional induction. Most interestingly, positive emotions of a relaxing nature, as well as thinking about the meaning in life, lowered the willingness to engage in risky driving. The discussion emphasizes the importance of looking for new ways to use positive emotions effectively in road safety interventions, and considers the practical implications of the studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Heterogeneity of envelope molecules expressed on primary human immunodeficiency virus type 1 particles as probed by the binding of neutralizing and nonneutralizing antibodies.

PubMed

Poignard, Pascal; Moulard, Maxime; Golez, Edwin; Vivona, Veronique; Franti, Michael; Venturini, Sara; Wang, Meng; Parren, Paul W H I; Burton, Dennis R

2003-01-01

Virion capture assays, in which immobilized antibodies (Abs) capture virus particles, have been used to suggest that nonneutralizing Abs bind effectively to human immunodeficiency virus type 1 (HIV-1) primary viruses. Here, we show that virion capture assays, under conditions commonly reported in the literature, give a poor indication of epitope expression on the surface of infectious primary HIV-1. First, estimation of primary HIV-1 capture by p24 measurements shows a very poor correlation with an estimation based on infectivity measurements. Second, virion capture appears to require relatively low Ab affinity for the virion, as shown by the ability of a monoclonal Ab to capture a wild-type and a neutralization escape variant virus equally well. Nevertheless, in a more interpretable competition format, it is shown that nonneutralizing anti-CD4 binding site (CD4bs) Abs compete with a neutralizing anti-CD4bs Ab (b12) for virus capture, suggesting that the nonneutralizing anti-CD4bs Abs are able to bind to the envelope species that is involved in virion capture in these experiments. However, the nonneutralizing anti-CD4bs Abs do not inhibit neutralization by b12 even at considerable excess. This suggests that the nonneutralizing Abs are unable to bind effectively to the envelope species required for virus infectivity. The results were obtained for three different primary virus envelopes. The explanation that we favor is that infectious HIV-1 primary virions can express two forms of gp120, an accessible nonfunctional form and a functional form with limited access. Binding to the nonfunctional form, which needs only to be present at relatively low density on the virion, permits capture but does not lead to neutralization. The expression of a nonfunctional but accessible form of gp120 on virions may contribute to the general failure of HIV-1 infection to elicit cross-neutralizing Abs and may represent a significant problem for vaccines based on viruses or virus-like particles.

Recall dynamics reveal the retrieval of emotional context

PubMed Central

Long, Nicole M.; Danoff, Michelle S.

2015-01-01

Memory is often better for emotional rather than neutral stimuli. The benefit for emotional items could be the result of an associative mechanism whereby items are associated to a slowly updating context. Through this process, emotional features are integrated with context during study, and are reactivated during test. The presence of emotion in context would both provide a stronger retrieval cue, enhancing memory of emotional items, as well as lead to emotional clustering, whereby emotionally similar items are recalled consecutively. To measure whether associative mechanisms can explain the enhancement for emotional items, we conducted a free recall study in which most items were emotionally neutral to minimize effects of mood induction and to more closely reflect naturalistic settings. We found that emotional items were significantly more likely to be recalled than neutral items and that participants were more likely to transition between emotional items rather than between emotional and neutral items. Together, these results suggest that contextual encoding and retrieval mechanisms may drive the benefit for emotional items both within and outside the laboratory. PMID:25604771

Regulatory neutrality is essential to establishing a level playing field for accountable care organizations.

PubMed

Bacher, Gary E; Chernew, Michael E; Kessler, Daniel P; Weiner, Stephen M

2013-08-01

Accountable care organizations (ACOs) are among the most widely discussed models for encouraging movement away from fee-for-service payment arrangements. Although ACOs have the potential to slow health spending growth and improve quality of care, regulating them poses special challenges. Regulations, particularly those that affect both ACOs and Medicare Advantage plans, could inadvertently favor or disfavor certain kinds of providers or payers. Such favoritism could drive efficient organizations from the market and thus increase costs or reduce quality of and access to care. To avoid this type of outcome, we propose a general principle: Regulation of ACOs should strive to preserve a level playing field among different kinds of organizations seeking the same cost, quality, and access objectives. This is known as regulatory neutrality. We describe the implications of regulatory neutrality in four key areas: antitrust, financial solvency regulation, Medicare governance requirements, and Medicare payment models. We also discuss issues relating to short-term versus long-term perspectives--to promote the goal of regulatory neutrality and allow the most efficient organizations to prevail in the marketplace.

The PEGASUS Drive: A nuclear electric propulsion system for the space exploration initiative

NASA Astrophysics Data System (ADS)

Coomes, Edmund P.; Dagle, Jeffery E.

1991-01-01

The advantages of using electric propulsion for propulsion are well-known in the aerospace community. The high specific impulse, lower propellant requirements, and lower system mass make it a very attractive propulsion option for the Space Exploration Initiative (SEI), especially for the transport of cargo. One such propulsion system is the PEGASUS Drive (Coomes et al. 1987). In its original configuration, the PEGASUS Drive consisted of a 10-MWe power source coupled to a 6-MW magnetoplasmadynamic (MPD) thruster system. The PEGASUS Drive propelled a manned vechicle to Mars and back in 601 days. By removing the crew and their associated support systems from the space craft and by incorporating technology advances in reactor design and heat rejection systems, a second generation PEGASUS Drive can be developed with an alpha less than two. Utilizing this propulsion system, a 400-MT cargo vechicle, assembled and loaded in low Earth orbit (LEO), could deliver 262 MT of supplies and hardware to MARS 282 days after escaping Earth orbit. Upon arrival at Mars the transport vehicle would place its cargo in the desired parking orbit around Mars and then proceed to synchronous orbit above the desired landing sight. Using a laser transmitter, PEGASUS could provide 2-MW on the surface to operate automated systems deployed earlier and then provide surface power to support crew activities after their arrival. The additional supplies and hardware, coupled with the availability of megawatt levels of electric power on the Mars surface, would greatly enhance and even expand the mission options being considered under SEI.

Progress towards a more predictive model for hohlraum radiation drive and symmetry

NASA Astrophysics Data System (ADS)

Jones, O. S.; Suter, L. J.; Scott, H. A.; Barrios, M. A.; Farmer, W. A.; Hansen, S. B.; Liedahl, D. A.; Mauche, C. W.; Moore, A. S.; Rosen, M. D.; Salmonson, J. D.; Strozzi, D. J.; Thomas, C. A.; Turnbull, D. P.

2017-05-01

For several years, we have been calculating the radiation drive in laser-heated gold hohlraums using flux-limited heat transport with a limiter of 0.15, tabulated values of local thermodynamic equilibrium gold opacity, and an approximate model for not in a local thermodynamic equilibrium (NLTE) gold emissivity (DCA_2010). This model has been successful in predicting the radiation drive in vacuum hohlraums, but for gas-filled hohlraums used to drive capsule implosions, the model consistently predicts too much drive and capsule bang times earlier than measured. In this work, we introduce a new model that brings the calculated bang time into better agreement with the measured bang time. The new model employs (1) a numerical grid that is fully converged in space, energy, and time, (2) a modified approximate NLTE model that includes more physics and is in better agreement with more detailed offline emissivity models, and (3) a reduced flux limiter value of 0.03. We applied this model to gas-filled hohlraum experiments using high density carbon and plastic ablator capsules that had hohlraum He fill gas densities ranging from 0.06 to 1.6 mg/cc and hohlraum diameters of 5.75 or 6.72 mm. The new model predicts bang times to within ±100 ps for most experiments with low to intermediate fill densities (up to 0.85 mg/cc). This model predicts higher temperatures in the plasma than the old model and also predicts that at higher gas fill densities, a significant amount of inner beam laser energy escapes the hohlraum through the opposite laser entrance hole.

KSC-01pp0777

NASA Image and Video Library

2001-04-08

STS-100 Commander Kent V. Rominger is ready to take the wheel on the M-113 armored carrier that could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. Driving the tracked vehicle is part of Terminal Countdown Demonstration Test activities, which include emergency escape training, payload walkdown and a simulated launch countdown. The primary payload on mission STS-100 comprises the Canadian robotic arm, SSRMS, and Multi-Purpose Logistics Module, Raffaello. Launch of Space Shuttle Endeavour on mission STS-100 is targeted for April 19 at 2:41 p.m. EDT from Launch Pad 39A

KSC-01pp0779

NASA Image and Video Library

2001-04-08

STS-100 Mission Specialist Chris A. Hadfield is ready to take the wheel on the M-113 armored carrier that could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. Driving the tracked vehicle is part of Terminal Countdown Demonstration Test activities, which include emergency escape training, payload walkdown and a simulated launch countdown. The primary payload on mission STS-100 comprises the Canadian robotic arm, SSRMS, and Multi-Purpose Logistics Module, Raffaello. Launch of Space Shuttle Endeavour on mission STS-100 is targeted for April 19 at 2:41 p.m. EDT from Launch Pad 39A

Encoding quantum information in a stabilized manifold of a superconducting cavity

NASA Astrophysics Data System (ADS)

Touzard, S.; Leghtas, Z.; Mundhada, S. O.; Axline, C.; Reagor, M.; Chou, K.; Blumoff, J.; Sliwa, K. M.; Shankar, S.; Frunzio, L.; Schoelkopf, R. J.; Mirrahimi, M.; Devoret, M. H.

In a superconducting Josephson circuit architecture, we activate a multi-photon process between two modes by applying microwave drives at specific frequencies. This creates a pairwise exchange of photons between a high-Q cavity and the environment. The resulting open dynamical system develops a two-dimensional quasi-energy ground state manifold. Can we encode, protect and manipulate quantum information in this manifold? We experimentally investigate the convergence and escape rates in and out of this confined subspace. Finally, using quantum Zeno dynamics, we aim to perform gates which maintain the state in the protected manifold at all times. Work supported by: ARO, ONR, AFOSR and YINQE.

In the eye of the beholder: individual differences in reward-drive modulate early frontocentral ERPs to angry faces.

PubMed

Bediou, Benoit; Eimer, Martin; d'Amato, Thierry; Hauk, Olaf; Calder, Andrew J

2009-02-01

Individual differences in reward-drive have been associated with increased attention toward facial signals of aggression, heightened experience of anger and vulnerability to display aggressive behaviour. Recent fMRI research suggests that these effects rely on reduced ventromedial prefrontal (and increased amygdala) response to aggressive facial displays compared with neutral and sad expressions in subjects scoring high on reward-drive. However, nothing is known about the timing of this modulation. Using event-related potentials (ERPs), we provide the first evidence that greater proneness to display hostile and aggressive behaviour (measured by high scores on the reward-drive) is associated with a reduced midline frontocentral response to aggressive faces within 200-300ms. In addition to confirming a particular interaction between anger processing and aggression related personality traits in ventromedial prefrontal brain regions, our study brings a first indication of when their interaction occurs in the brain, strengthening results from previous classical as well as functional connectivity fMRI studies.

Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1

PubMed Central

Rousou, Xanthoula; Kalthoff, Donata; Beer, Martin

2016-01-01

Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds. PMID:26763336

On the exhaust of electromagnetic drive

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grahn, Patrick, E-mail: patrick.grahn@comsol.fi; Annila, Arto, E-mail: arto.annila@helsinki.fi; Department of Biosciences, FI-00014 University of Helsinki, Helsinki

2016-06-15

Recent reports about propulsion without reaction mass have been met on one hand with enthusiasm and on the other hand with some doubts. Namely, closed metal cavities, when fueled with microwaves, have delivered thrust that could eventually maintain satellites on orbits using solar power. However, the measured thrust appears to be without any apparent exhaust. Thus the Law of Action-Reaction seems to have been violated. We consider the possibility that the exhaust is in a form that has so far escaped both experimental detection and theoretical attention. In the thruster’s cavity microwaves interfere with each other and invariably some photonsmore » will also end up co-propagating with opposite phases. At the destructive interference electromagnetic fields cancel. However, the photons themselves do not vanish for nothing but continue in propagation. These photon pairs without net electromagnetic field do not reflect back from the metal walls but escape from the resonator. By this action momentum is lost from the cavity which, according to the conservation of momentum, gives rise to an equal and opposite reaction. We examine theoretical corollaries and practical concerns that follow from the paired-photon conclusion.« less

Novel covariance-based neutrality test of time-series data reveals asymmetries in ecological and economic systems

DOE PAGES

Washburne, Alex D.; Burby, Joshua W.; Lacker, Daniel; ...

2016-09-30

Systems as diverse as the interacting species in a community, alleles at a genetic locus, and companies in a market are characterized by competition (over resources, space, capital, etc) and adaptation. Neutral theory, built around the hypothesis that individual performance is independent of group membership, has found utility across the disciplines of ecology, population genetics, and economics, both because of the success of the neutral hypothesis in predicting system properties and because deviations from these predictions provide information about the underlying dynamics. However, most tests of neutrality are weak, based on static system properties such as species-abundance distributions or themore » number of singletons in a sample. Time-series data provide a window onto a system’s dynamics, and should furnish tests of the neutral hypothesis that are more powerful to detect deviations from neutrality and more informative about to the type of competitive asymmetry that drives the deviation. Here, we present a neutrality test for time-series data. We apply this test to several microbial time-series and financial time-series and find that most of these systems are not neutral. Our test isolates the covariance structure of neutral competition, thus facilitating further exploration of the nature of asymmetry in the covariance structure of competitive systems. Much like neutrality tests from population genetics that use relative abundance distributions have enabled researchers to scan entire genomes for genes under selection, we anticipate our time-series test will be useful for quick significance tests of neutrality across a range of ecological, economic, and sociological systems for which time-series data are available. Here, future work can use our test to categorize and compare the dynamic fingerprints of particular competitive asymmetries (frequency dependence, volatility smiles, etc) to improve forecasting and management of complex adaptive systems.« less

Novel covariance-based neutrality test of time-series data reveals asymmetries in ecological and economic systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Washburne, Alex D.; Burby, Joshua W.; Lacker, Daniel

Systems as diverse as the interacting species in a community, alleles at a genetic locus, and companies in a market are characterized by competition (over resources, space, capital, etc) and adaptation. Neutral theory, built around the hypothesis that individual performance is independent of group membership, has found utility across the disciplines of ecology, population genetics, and economics, both because of the success of the neutral hypothesis in predicting system properties and because deviations from these predictions provide information about the underlying dynamics. However, most tests of neutrality are weak, based on static system properties such as species-abundance distributions or themore » number of singletons in a sample. Time-series data provide a window onto a system’s dynamics, and should furnish tests of the neutral hypothesis that are more powerful to detect deviations from neutrality and more informative about to the type of competitive asymmetry that drives the deviation. Here, we present a neutrality test for time-series data. We apply this test to several microbial time-series and financial time-series and find that most of these systems are not neutral. Our test isolates the covariance structure of neutral competition, thus facilitating further exploration of the nature of asymmetry in the covariance structure of competitive systems. Much like neutrality tests from population genetics that use relative abundance distributions have enabled researchers to scan entire genomes for genes under selection, we anticipate our time-series test will be useful for quick significance tests of neutrality across a range of ecological, economic, and sociological systems for which time-series data are available. Here, future work can use our test to categorize and compare the dynamic fingerprints of particular competitive asymmetries (frequency dependence, volatility smiles, etc) to improve forecasting and management of complex adaptive systems.« less

Instability of the heliopause driven by charge exchange interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avinash, K.; Zank, G. P.; Dasgupta, B.

2014-08-20

The stability of the heliopause that separates the tenuous hot magnetized heliosheath plasma from the dense cool local interstellar magnetized plasma is examined using a fully general model that includes all the essential physical processes. Charge exchange coupling between plasma protons and primary interstellar neutral atoms provides an effective gravity that drives Rayleigh-Taylor (RT)-like instabilities. The velocity difference or shear between the heliosheath and interstellar flows, when coupled to energetic neutral atoms (ENAs), drives a Kelvin-Helmholtz (KH)-like instability on the heliopause. The shoulder region of the heliopause is unstable to a new instability that has characteristics of a mixed RT-KH-likemore » mode. The instabilities are not stabilized by typical values of the magnetic fields in the inner and outer heliosheath (OHS). ENAs play an essential role in driving the KH-like instability, which is fully stabilized in their absence by magnetic fields. The nonlinear phase of these instabilities is briefly discussed. We also discuss the possibility that RT-like or mixed KH-RT-like instabilities drag outer heliosheath/very local interstellar medium (OHS/VLISM) magnetic field lines into the inner heliosheath (IHS) with the VLISM flow, and the possibility that IHS and VLISM magnetic field lines experience reconnection. Such reconnection may (1) greatly enhance the mixing of plasmas across the heliopause and (2) provide open magnetic field lines that allow easy ingress of galactic cosmic rays into the heliosphere and corresponding easy loss of anomalous cosmic rays from the heliosphere.« less

Investigation of beam- and wave-plasma interactions in spherical tokamak Globus-M

NASA Astrophysics Data System (ADS)

Gusev, V. K.; Aminov, R. M.; Berezutskiy, A. A.; Bulanin, V. V.; Chernyshev, F. V.; Chugunov, I. N.; Dech, A. V.; Dyachenko, V. V.; Ivanov, A. E.; Khitrov, S. A.; Khromov, N. A.; Kurskiev, G. S.; Larionov, M. M.; Melnik, A. D.; Minaev, V. B.; Mineev, A. B.; Mironov, M. I.; Miroshnikov, I. V.; Mukhin, E. E.; Novokhatsky, A. N.; Panasenkov, A. A.; Patrov, M. I.; Petrov, A. V.; Petrov, Yu. V.; Podushnikova, K. A.; Rozhansky, V. A.; Rozhdestvensky, V. V.; Sakharov, N. V.; Shevelev, A. E.; Senichenkov, I. Yu.; Shcherbinin, O. N.; Stepanov, A. Yu.; Tolstyakov, S. Yu.; Varfolomeev, V. I.; Voronin, A. V.; Yagnov, V. A.; Yashin, A. Yu.; Zhilin, E. G.

2011-10-01

The experimental and theoretical results obtained in the last two years on the interaction of neutral particle beams and high-frequency waves with a plasma using the spherical tokamak Globus-M are discussed. The experiments on the injection of low-energy proton beam of ~300 eV directed particle energy are performed with a plasma gun that produces a hydrogen plasma jet of density up to 3 × 1022 m-3 and a high velocity up to 250 km s-1. A moderate density rise (up to 30%) is achieved in the central plasma region without plasma disruption. Experiments on high-energy (up to 30 keV) neutral beam injection into the D-plasma are analysed. Modelling results on confinement of fast particles inside the plasma column that follows the neutral beam injection are discussed. The influence of the magnetic field on the fast particle losses is argued. A neutral beam injection regime with primary ion heating is obtained and discussed. The new regime with fast current ramp-up and early neutral beam injection shows electron temperature rise and formation of broad Te profiles until the q = 1 flux surface enters the plasma column. An energetic particle mode in the range of frequencies 5-30 kHz and toroidal Alfvén eigenmodes in the range 50-300 kHz are recorded in that regime simultaneously with the Te rise. The energetic particle mode and toroidal Alfvén eigenmodes behaviour are discussed. The toroidal Alfvén eigenmode spectrum appears in Globus-M as a narrow band corresponding to n = 1. The first experimental results on plasma start-up and noninductive current drive generation are presented. The experiments are carried out with antennae providing mostly poloidal slowing down of waves with a frequency of 920 MHz, which is higher than a lower hybrid one existing under the experimental conditions. The high current drive efficiency is shown to be high (of about 0.25 A W-1), and its mechanism is proposed. Some near future plans of the experiments are also discussed.

Superthermal over 36-eV ions observed in the near-tail region of Venus by the Pioneer Venus Orbiter neutral mass spectrometer

NASA Technical Reports Server (NTRS)

Kasprzak, W. T.; Grebowsky, J. M.; Niemann, H. B.; Brace, L. H.

1991-01-01

The PVO neutral mass spectrometer has measured the over 36-eV ions in the 1300-3700 km altitude range for solar zenith angles greater than 120 deg. The composition is mainly O(+), but He(+), N(+), NO(+), and O2(+) have been identified. The average O(+) flux is about 100,000/sq cm/s, but higher fluxes from 10 to the 6th to 10 to the 8th/sq cm/s are observed about 10 percent of the time. The directions of the apparent O(+) flow in the ecliptic plane show predominantly tailward components with a smaller number of nontailward components. The over 36-eV O(+) escape flux in the ionotail is estimated to be about 100,000/sq cm/s. The O(+) flux data show a factor of 2.5 increase from solar minimum to maximum, implying a photoionization source for these ions. The composition of the superthermal ions in the ionotail suggests that their source is most likely the high-altitude nightside ionosphere. Transport of superthermal O(+) across the terminator to the nightside has been observed.

Design and operation of the pellet charge exchange diagnostic for measurement of energetic confined alphas and tritons on TFTR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medley, S.S.; Duong, H.H.; Fisher, R.K.

1996-05-01

Radially-resolved energy and density distributions of the energetic confined alpha particles in D-T experiments on TFTR are being measured by active neutral particle analysis using low-Z impurity pellet injection. When injected into a high temperature plasma, an impurity pellet (e.g. Lithium or Boron) rapidly ablates forming an elongated cloud which is aligned with the magnetic field and moves with the pellet. This ablation cloud provides a dense target with which the alpha particles produced in D-T fusion reactions can charge exchange. A small fraction of the alpha particles incident on the pellet ablation cloud will be converted to helium neutralsmore » whose energy is essentially unchanged by the charge transfer process. By measuring the resultant helium neutrals escaping from the plasma using a mass and energy resolving charge exchange analyzer, this technique offers a direct measurement of the energy distribution of the incident high-energy alpha particles. Other energetic ion species can be detected as well, such as tritons generated in D-D plasmas and H or He{sup 3} RF-driven minority ion tails. The diagnostic technique and its application on TFTR are described in detail.« less

Receptor-binding domain as a target for developing SARS vaccines.

PubMed

Zhu, Xiaojie; Liu, Qi; Du, Lanying; Lu, Lu; Jiang, Shibo

2013-08-01

A decade ago, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a global pandemic with a mortality rate of 10%. Reports of recent outbreaks of a SARS-like disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) have raised serious concerns of a possible reemergence of SARS-CoV, either by laboratory escape or the presence of a natural reservoir. Therefore, the development of effective and safe SARS vaccines is still needed. Based on our previous studies, we believe that the receptor-binding domain (RBD) in the S1 subunit of the SARS-CoV spike (S) protein is the most important target for developing a SARS vaccine. In particular, RBD of S protein contains the critical neutralizing domain (CND), which is able to induce highly potent neutralizing antibody response and cross-protection against divergent SARS-CoV strains. Furthermore, a RBD-based subunit vaccine is expected to be safer than other vaccines that may induce Th2-type immunopathology. This review will discuss key advances in the development of RBD-based SARS vaccines and the possibility of using a similar strategy to develop vaccines against MERS-CoV.

Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A.

PubMed

Wang, Jianfeng; Liu, Bowen; Teng, Zihao; Zhou, Xuan; Wang, Xiyan; Zhang, Bing; Lu, Gejin; Niu, Xiaodi; Yang, Yongjun; Deng, Xuming

2017-01-01

The critical roles of sortase A (SrtA) and listeriolysin O (LLO) in Listeria monocytogenes pathogenicity render these two virulence factors as ideal targets for the development of anti-virulence agents against L. monocytogenes infection. Additionally, the structures of SrtA and LLO are highly conserved among the members of sortase enzyme family and cholesterol dependent toxin family. Here, phloretin, a natural polyphenolic compound derived from apples and pears that has little anti- L. monocytogenes activity, was identified to simultaneously inhibit LLO expression and neutralize SrtA catalytic activity. Phloretin neutralized SrtA activity by causing a conformational change in the protein's active pocket, which prevented engagement with its substrate. Treatment with phloretin simultaneously reduced L. monocytogenes invasion into host cells and blocked the escape of vacuole-entrapped L. monocytogenes into cytoplasm. Further, L. monocytogenes -infected mice that received phloretin showed lower mortality, decreased bacterial burden and reduced pathological injury. Our results demonstrate that phloretin is a promising anti-infective therapeutic for infections caused by L. monocytogenes due to its simultaneous targeting of SrtA and LLO, which may result in fewer side effects than those caused by other antibiotics.

Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A

PubMed Central

Wang, Jianfeng; Liu, Bowen; Teng, Zihao; Zhou, Xuan; Wang, Xiyan; Zhang, Bing; Lu, Gejin; Niu, Xiaodi; Yang, Yongjun; Deng, Xuming

2017-01-01

The critical roles of sortase A (SrtA) and listeriolysin O (LLO) in Listeria monocytogenes pathogenicity render these two virulence factors as ideal targets for the development of anti-virulence agents against L. monocytogenes infection. Additionally, the structures of SrtA and LLO are highly conserved among the members of sortase enzyme family and cholesterol dependent toxin family. Here, phloretin, a natural polyphenolic compound derived from apples and pears that has little anti-L. monocytogenes activity, was identified to simultaneously inhibit LLO expression and neutralize SrtA catalytic activity. Phloretin neutralized SrtA activity by causing a conformational change in the protein's active pocket, which prevented engagement with its substrate. Treatment with phloretin simultaneously reduced L. monocytogenes invasion into host cells and blocked the escape of vacuole-entrapped L. monocytogenes into cytoplasm. Further, L. monocytogenes-infected mice that received phloretin showed lower mortality, decreased bacterial burden and reduced pathological injury. Our results demonstrate that phloretin is a promising anti-infective therapeutic for infections caused by L. monocytogenes due to its simultaneous targeting of SrtA and LLO, which may result in fewer side effects than those caused by other antibiotics. PMID:28154809

Effects of convection electric field on upwelling and escape of ionospheric O(+)

NASA Technical Reports Server (NTRS)

Cladis, J. B.; Chiu, Yam T.; Peterson, William K.

1992-01-01

A Monte Carlo code is used to explore the full effects of the convection electric field on distributions of upflowing O(+) ions from the cusp/cleft ionosphere. Trajectories of individual ions/neutrals are computed as they undergo multiple charge-exchange collisions. In the ion state, the trajectories are computed in realistic models of the magnetic field and the convection, corotation, and ambipolar electric fields. The effects of ion-ion collisions are included, and the trajectories are computed with and without simultaneous stochastic heating perpendicular to the magnetic field by a realistic model of broadband, low frequency waves. In the neutral state, ballistic trajectories in the gravitational field are computed. The initial conditions of the ions, in addition to ambipolar electric field and the number densities and temperatures of O(+), H(+), and electrons as a function of height in the cusp/cleft region were obtained from the results of Gombosi and Killeen (1987), who used a hydrodynamic code to simulate the time-dependent frictional-heating effects in a magnetic tube during its motion though the convection throat. The distribution of the ion fluxes as a function of height are constructed from the case histories.

Control of power, torque, and instability drive using in-shot variable neutral beam energy in tokamaks

DOE PAGES

Pace, D. C.; Collins, C. S.; Crowley, B.; ...

2016-09-28

A first-ever demonstration of controlling power and torque injection through time evolution of neutral beam energy has been achieved in recent experiments at the DIII-D tokamak. Pre-programmed waveforms for the neutral beam energy produce power and torque inputs that can be separately and continuously controlled. Previously, these inputs were tailored using on/off modulation of neutral beams resulting in large perturbations (e.g. power swings of over 1 MW). The new method includes, importantly for experiments, the ability to maintain a fixed injected power while varying the torque. In another case, different beam energy waveforms (in the same plasma conditions) produce significantmore » changes in the observed spectrum of beam ion-driven instabilities. Measurements of beam ion loss show that one energy waveform results in the complete avoidance of coherent losses due to Alfvénic instabilities. This new method of neutral beam operation is intended for further application in a variety of DIII-D experiments including those concerned with high-performance steady state scenarios, fast particle effects, and transport in the low torque regime. As a result, developing this capability would provide similar benefits and improved plasma control for other magnetic confinement fusion facilities.« less

Ferroelectric Plasma Sources for Ion Beam Neutralization

NASA Astrophysics Data System (ADS)

Stepanov, A.; Gilson, E. P.; Grisham, L. R.; Davidson, R. C.

2014-10-01

A 40 keV Ar+ beam with a dimensionless perveance of 4 ×10-4 is propagated through a Ferroelectric Plasma Source (FEPS) to determine the effects of charge neutralization on the transverse beam profile. Neutralization is established 5 μs after the FEPS is triggered, and lasts between 10 and 35 μs. When the beam is fully neutralized, the profile has a Gaussian shape with a half-angle divergence of 0.87°, which is attributed to ion optics. The effects of the resistance and capacitance in the pulser circuit on the FEPS discharge are studied. The electron current emitted by the FEPS is calculated from measurements of the forward and return currents in the circuit. Electron emission typically begins 0.5 μs after the driving pulse, lasting for tens of μs, which is similar to the duration of ion beam neutralization. The total emitted charge does not depend significantly on the resistance, but depends strongly on the storage capacitance. Lowering the capacitance from 141 nF to 47 nF results in a near-complete shut-off of charge emission, although the amplitude of the applied voltage pulse is as high as when high-density plasma is produced. Overall, the data suggest that ferroelectric effects are significant in the physics of the FEPS discharge.

Control of power, torque, and instability drive using in-shot variable neutral beam energy in tokamaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pace, D. C.; Collins, C. S.; Crowley, B.

A first-ever demonstration of controlling power and torque injection through time evolution of neutral beam energy has been achieved in recent experiments at the DIII-D tokamak. Pre-programmed waveforms for the neutral beam energy produce power and torque inputs that can be separately and continuously controlled. Previously, these inputs were tailored using on/off modulation of neutral beams resulting in large perturbations (e.g. power swings of over 1 MW). The new method includes, importantly for experiments, the ability to maintain a fixed injected power while varying the torque. In another case, different beam energy waveforms (in the same plasma conditions) produce significantmore » changes in the observed spectrum of beam ion-driven instabilities. Measurements of beam ion loss show that one energy waveform results in the complete avoidance of coherent losses due to Alfvénic instabilities. This new method of neutral beam operation is intended for further application in a variety of DIII-D experiments including those concerned with high-performance steady state scenarios, fast particle effects, and transport in the low torque regime. As a result, developing this capability would provide similar benefits and improved plasma control for other magnetic confinement fusion facilities.« less

Control of power, torque, and instability drive using in-shot variable neutral beam energy in tokamaks

NASA Astrophysics Data System (ADS)

Pace, D. C.; Collins, C. S.; Crowley, B.; Grierson, B. A.; Heidbrink, W. W.; Pawley, C.; Rauch, J.; Scoville, J. T.; Van Zeeland, M. A.; Zhu, Y. B.; The DIII-D Team

2017-01-01

A first-ever demonstration of controlling power and torque injection through time evolution of neutral beam energy has been achieved in recent experiments at the DIII-D tokamak (Luxon 2002 Nucl. Fusion 42 614). Pre-programmed waveforms for the neutral beam energy produce power and torque inputs that can be separately and continuously controlled. Previously, these inputs were tailored using on/off modulation of neutral beams resulting in large perturbations (e.g. power swings of over 1 MW). The new method includes, importantly for experiments, the ability to maintain a fixed injected power while varying the torque. In another case, different beam energy waveforms (in the same plasma conditions) produce significant changes in the observed spectrum of beam ion-driven instabilities. Measurements of beam ion loss show that one energy waveform results in the complete avoidance of coherent losses due to Alfvénic instabilities. This new method of neutral beam operation is intended for further application in a variety of DIII-D experiments including those concerned with high-performance steady state scenarios, fast particle effects, and transport in the low torque regime. Developing this capability would provide similar benefits and improved plasma control for other magnetic confinement fusion facilities.

Post-concussion driving behaviors and opinions: A survey of collegiate student-athletes.

PubMed

Schmidt, Julianne D; Lynall, Robert C; Lempke, Landon Bryce; Weber, Michelle L; Devos, Hannes

2018-05-08

Post-concussion driving restrictions are eminent, but we lack understanding of current behaviors and opinions about driving following concussion among populations at risk of concussion. We aimed to describe post-concussion driving behaviors and opinions among collegiate student-athletes. Student-athletes completed a survey (response rate=45.3%, 223/492) regarding their post-concussion driving behaviors and opinions. Response frequencies and percentages are presented. Student-athletes self-reported a total of 169 lifetime concussions (0.76±1.02 each). Of the 169 concussions, 52.1% (88/169) were diagnosed and 52.7% (89/169) occurred while the student-athlete possessed a valid driver's license. Student-athletes refrained from driving following 43.8% (39/89) of the concussive events. Student-athletes that refrained most commonly did so for only 24-48 hours (20.5%, 8/39) and because a health care provider advised them to (33.3%: 13/39). Student-athletes most commonly reported that they would feel "very unsafe" driving a car immediately following injury (38.4%, 84/219). When asked whether driving restrictions would influence your decision to report the injury to a health care provider, 7.9% reported that it "definitely would" (17/214), 26.6% "probably would" (57/214), 17.8% "neutral" (38/214), 24.8% "probably would not" (53/214), and 22.9% "definitely would not" (49/214). Despite generally believing that driving immediately following a concussion is unsafe, a majority of student-athletes did not refrain from driving at any point following their previous concussions. Post-concussion driving restrictions may have some influence on student-athletes' decisions to report the injury to a health care provider. Health care providers play a critical role in post-concussion driving restriction, but lack standardized recommendations to guide their care.

Where do winds come from? A new theory on how water vapor condensation influences atmospheric pressure and dynamics

NASA Astrophysics Data System (ADS)

Makarieva, A. M.; Gorshkov, V. G.; Sheil, D.; Nobre, A. D.; Li, B.-L.

2013-01-01

Phase transitions of atmospheric water play a ubiquitous role in the Earth's climate system, but their direct impact on atmospheric dynamics has escaped wide attention. Here we examine and advance a theory as to how condensation influences atmospheric pressure through the mass removal of water from the gas phase with a simultaneous account of the latent heat release. Building from fundamental physical principles we show that condensation is associated with a decline in air pressure in the lower atmosphere. This decline occurs up to a certain height, which ranges from 3 to 4 km for surface temperatures from 10 to 30 °C. We then estimate the horizontal pressure differences associated with water vapor condensation and find that these are comparable in magnitude with the pressure differences driving observed circulation patterns. The water vapor delivered to the atmosphere via evaporation represents a store of potential energy available to accelerate air and thus drive winds. Our estimates suggest that the global mean power at which this potential energy is released by condensation is around one per cent of the global solar power - this is similar to the known stationary dissipative power of general atmospheric circulation. We conclude that condensation and evaporation merit attention as major, if previously overlooked, factors in driving atmospheric dynamics.

Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors ▿ †

PubMed Central

Bonsignori, Mattia; Hwang, Kwan-Ki; Chen, Xi; Tsao, Chun-Yen; Morris, Lynn; Gray, Elin; Marshall, Dawn J.; Crump, John A.; Kapiga, Saidi H.; Sam, Noel E.; Sinangil, Faruk; Pancera, Marie; Yongping, Yang; Zhang, Baoshan; Zhu, Jiang; Kwong, Peter D.; O'Dell, Sijy; Mascola, John R.; Wu, Lan; Nabel, Gary J.; Phogat, Sanjay; Seaman, Michael S.; Whitesides, John F.; Moody, M. Anthony; Kelsoe, Garnett; Yang, Xinzhen; Sodroski, Joseph; Shaw, George M.; Montefiori, David C.; Kepler, Thomas B.; Tomaras, Georgia D.; Alam, S. Munir; Liao, Hua-Xin; Haynes, Barton F.

2011-01-01

V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B.9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies. PMID:21795340

Foundational errors in the Neutral and Nearly-Neutral theories of evolution in relation to the Synthetic Theory: is a new evolutionary paradigm necessary?

PubMed

Valenzuela, Carlos Y

2013-01-01

The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift as the most important evolutionary factors. The most conspicuous feature of evolution is the genomic stability during paleontological eras and lack of variation among taxa; 98% or more of nucleotide sites are monomorphic within a species. NTE explains this homology by random fixation of neutral bases and negative selection (purifying selection) that does not contribute either to evolution or polymorphisms. Purifying selection is insufficient to account for this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE) included negative selection with coefficients as low as mutation rate. These NTE and N-NTE propositions are thermodynamically (tendency to random distributions, second law), biotically (recurrent mutation), logically and mathematically (resilient equilibria instead of fixation by drift) untenable. Recurrent forward and backward mutation and random fluctuations of base frequencies alone in a site make life organization and fixations impossible. Drift is not a directional evolutionary factor, but a directional tendency of matter-energy processes (second law) which threatens the biotic organization. Drift cannot drive evolution. In a site, the mutation rates among bases and selection coefficients determine the resilient equilibrium frequency of bases that genetic drift cannot change. The expected neutral random interaction among nucleotides is zero; however, huge interactions and periodicities were found between bases of dinucleotides separated by 1, 2... and more than 1,000 sites. Every base is co-adapted with the whole genome. Neutralists found that neutral evolution is independent of population size (N); thus neutral evolution should be independent of drift, because drift effect is dependent upon N. Also, chromosome size and shape as well as protein size are far from random.

Martian Ionospheric Observation and Modeling

NASA Astrophysics Data System (ADS)

González-Galindo, Francisco

2018-02-01

The Martian ionosphere is a plasma embedded within the neutral upper atmosphere of the planet. Its main source is the ionization of the CO2-dominated Martian mesosphere and thermosphere by the energetic EUV solar radiation. The ionosphere of Mars is subject to an important variability induced by changes in its forcing mechanisms (e.g., the UV solar flux) and by variations in the neutral atmosphere (e.g., the presence of global dust storms, atmospheric waves and tides, changes in atmospheric composition, etc.). Its vertical structure is dominated by a maximum in the electron concentration placed at about 120–140 km of altitude, coincident with the peak of the ionization rate. Below, a secondary peak produced by solar X-rays and photoelectron-impact ionization is observed. A sporadic third layer, possibly of meteoric origin, has been also detected below. The most abundant ion in the Martian ionosphere is O2+, although O+ can become more abundant in the upper ionospheric layers. While below about 180–200 km the Martian ionosphere is dominated by photochemical processes, above those altitudes the dynamics of the plasma become more important. The ionosphere is also an important source of escaping particles via processes such as dissociative recombination of ions or ion pickup. So, characterization of the ionosphere provides or can provide information about such disparate systems and processes as the solar radiation getting to the planet, the neutral atmosphere, the meteoric influx, the atmospheric escape to space, or the interaction of the planet with the solar wind. It is thus not surprising that the interest about this region dates from the beginning of the space era. From the first measurements provided by the Mariner 4 mission in the 1960s to the contemporaneous observations, still ongoing, by the Mars Express and MAVEN orbiters, our current knowledge of this atmospheric region is the consequence of the accumulation of more than 50 years of discontinuous measurements by different space missions. Numerical simulations by computational models able to simulate the processes that shape the ionosphere have also been commonly employed to obtain information about this region, to provide an interpretation of the observations and to fill their gaps. As a result, the Martian ionosphere is today the best known one after that of the Earth. However, there are still areas for which our knowledge is far from being complete. Examples are the details and balance of the mechanisms populating the nightside ionosphere, or a good understanding of the meteoric ionospheric layer and its variability.

Modern Display Technologies for Airborne Applications.

DTIC Science & Technology

1983-04-01

the case of LED head-down direct view displays, this requires that special attention be paid to the optical filtering , the electrical drive/address...effectively attenuates the LED specular reflectance component, the colour and neutral density filtering attentuate the diffuse component and the... filter techniques are planned for use with video, multi- colour and advanced versions of numeric, alphanumeric and graphic displays; this technique

Impact of Type II Spicules into the Corona

NASA Astrophysics Data System (ADS)

Martinez-Sykora, Juan; De Pontieu, Bart; Carlsson, Mats; Hansteen, Viggo H.; Pereira, Tiago M. D.

2017-08-01

In the lower solar atmosphere, the chromosphere is permeated by jets, in which plasma is propelled at speeds of 50-150 km/s into the Sun’s atmosphere or corona. Although these spicules may play a role in heating the million-degree corona and are associated with Alfvén waves that help drive the solar wind, their generation remains mysterious. We implemented in the radiative MHD Bifrost code the effects of partial ionization using the generalized Ohm’s law. This code also solves the full MHD equations with non-grey and non-LTE radiative transfer and thermal conduction along magnetic field lines. The ion-neutral collision frequency is computed using recent studies that improved the estimation of the cross sections under chromospheric conditions (Vranjes & Krstic 2013). Self-consistently driven jets (spicules type II) in magnetohydrodynamic simulations occur ubiquitously when magnetic tension is confined and transported upwards through interactions between ions and neutrals, and impulsively released to drive flows, heat plasma, generate Alfvén waves, and may play an important role in maintaining the substructure of loop fans. This mechanism explains how spicular plasma can be heated to millions of degrees and how Alfvén waves are generated in the chromosphere.

The influence of image valence on visual attention and perception of risk in drivers.

PubMed

Jones, M P; Chapman, P; Bailey, K

2014-12-01

Currently there is little research into the relationship between emotion and driving in the context of advertising and distraction. Research that has looked into this also has methodological limitations that could be affecting the results rather than emotional processing (Trick et al., 2012). The current study investigated the relationship between image valence and risk perception, eye movements and physiological reactions. Participants watched hazard perception clips which had emotional images from the international affective picture system overlaid onto them. They rated how hazardous or safe they felt, whilst eye movements, galvanic skin response and heart rate were recorded. Results suggested that participants were more aware of potential hazards when a neutral image had been shown, in comparison to positive and negative valenced images; that is, participants showed higher subjective ratings of risk, larger physiological responses and marginally longer fixation durations when viewing a hazard after a neutral image, but this effect was attenuated after emotional images. It appears that emotional images reduce sensitivity to potential hazards, and we suggest that future studies could apply these findings to higher fidelity paradigms such as driving simulators. Copyright © 2014 Elsevier Ltd. All rights reserved.

The impact of Stereotype Threat on the simulated driving performance of older drivers.

PubMed

Joanisse, Mélanie; Gagnon, Sylvain; Voloaca, Mihnea

2013-01-01

Older drivers are perceived as being dangerous and overly cautious by other drivers. We tested the hypothesis that this negative stereotype has a direct influence on the performance of older drivers. Based on the Stereotype Threat literature, we predicted that older driving performance would be altered after exposure to a Stereotype Threat. Sixty-one older drivers aged 65 and above completed a simulated driving assessment course. Prior to testing, half of the participants were told that the objective of the study was to investigate why older adults aged 65 and above were more implicated in on-road accidents (Stereotype Threat condition) and half were showed a neutral statement. Results confirmed that exposure to the threat significantly altered driving performance. Older adults in the Stereotype Threat condition made more driving mistakes than those in the control group. Interestingly, under a Stereotype Threat condition, older adults tended to commit more speeding infractions. We also observed that domain identification (whether driving is deemed important or not) moderated the impact of the threat. Taken together, these results support recent older drivers' performance models suggesting that the interaction between individual and social factors need to be considered when examining older drivers' performance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Stabilization of dynamics of oscillatory systems by nonautonomous perturbation.

PubMed

Lucas, Maxime; Newman, Julian; Stefanovska, Aneta

2018-04-01

Synchronization and stability under periodic oscillatory driving are well understood, but little is known about the effects of aperiodic driving, despite its abundance in nature. Here, we consider oscillators subject to driving with slowly varying frequency, and investigate both short-term and long-term stability properties. For a phase oscillator, we find that, counterintuitively, such variation is guaranteed to enlarge the Arnold tongue in parameter space. Using analytical and numerical methods that provide information on time-variable dynamical properties, we find that the growth of the Arnold tongue is specifically due to the growth of a region of intermittent synchronization where trajectories alternate between short-term stability and short-term neutral stability, giving rise to stability on average. We also present examples of higher-dimensional nonlinear oscillators where a similar stabilization phenomenon is numerically observed. Our findings help support the case that in general, deterministic nonautonomous perturbation is a very good candidate for stabilizing complex dynamics.

Stabilization of dynamics of oscillatory systems by nonautonomous perturbation

NASA Astrophysics Data System (ADS)

Lucas, Maxime; Newman, Julian; Stefanovska, Aneta

2018-04-01

Synchronization and stability under periodic oscillatory driving are well understood, but little is known about the effects of aperiodic driving, despite its abundance in nature. Here, we consider oscillators subject to driving with slowly varying frequency, and investigate both short-term and long-term stability properties. For a phase oscillator, we find that, counterintuitively, such variation is guaranteed to enlarge the Arnold tongue in parameter space. Using analytical and numerical methods that provide information on time-variable dynamical properties, we find that the growth of the Arnold tongue is specifically due to the growth of a region of intermittent synchronization where trajectories alternate between short-term stability and short-term neutral stability, giving rise to stability on average. We also present examples of higher-dimensional nonlinear oscillators where a similar stabilization phenomenon is numerically observed. Our findings help support the case that in general, deterministic nonautonomous perturbation is a very good candidate for stabilizing complex dynamics.

Media influence on drive for thinness, body satisfaction, and eating attitudes among young women in Hong Kong and China.

PubMed

Rochelle, Tina L; Hu, W Y

2017-03-01

The present study examined the impact of thin-ideal media exposure on Chinese women's drive for thinness, attitudes towards body shape, and eating attitude. Women were assigned to one of two video conditions, which portrayed the thin-ideal (experimental) or was neutral (control group), in terms of content. A total of 83 young women from Hong Kong (N = 38) and Shanghai (N = 45), aged between 18 and 25 years (M age  = 22.7) participated in the study. A significant interaction was observed between the experimental video condition and location. Hong Kong women in the experimental group experienced greater levels of body dissatisfaction than Shanghai women exposed to the same condition. Exposure to thin-ideal media produced an increase in drive for thinness, body dissatisfaction and problematic eating attitudes regardless of location, with a greater immediate impact shown in Hong Kong women.

Does the Magnetosphere go to Sleep?

NASA Astrophysics Data System (ADS)

Hesse, M.; Moretto, T.; Friis-Christensen, E. A.; Kuznetsova, M.; Østgaard, N.; Tenfjord, P.; Opgenoorth, H. J.

2017-12-01

An interesting question in magnetospheric research is related to the transition between magnetospheric configurations under substantial solar wind driving, and a putative relaxed state after the driving ceases. While it is conceivable that the latter state may be unique and only dependent on residual solar wind driving, a more likely scenario has magnetospheric memory playing a key role. Memory processes may be manifold: constraints from conservation of flux tube entropy to neutral wind inertia in the upper atmosphere may all contribute. In this presentation, we use high-resolution, global, MHD simulations to begin to shed light on this transition, as well as on the concept of a quiet state of the magnetosphere. We will discuss key elements of magnetospheric memory, and demonstrate their influence, as well as the actual memory time scale, through simulations and analytical estimates. Finally, we will point out processes with the potential to effect magnetospheric memory loss.

Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

PubMed Central

Poon, Art F. Y; Kosakovsky Pond, Sergei L.; Bennett, Phil; Richman, Douglas D; Leigh Brown, Andrew J.; Frost, Simon D. W

2007-01-01

CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design. PMID:17397261

P2X7 Receptors Drive Spine Synapse Plasticity in the Learned Helplessness Model of Depression

PubMed Central

Otrokocsi, Lilla; Sperlágh, Beáta

2017-01-01

Abstract Background Major depressive disorder is characterized by structural and functional abnormalities of cortical and limbic brain areas, including a decrease in spine synapse number in the dentate gyrus of the hippocampus. Recent studies highlighted that both genetic and pharmacological invalidation of the purinergic P2X7 receptor (P2rx7) leads to antidepressant-like phenotype in animal experiments; however, the impact of P2rx7 on depression-related structural changes in the hippocampus is not clarified yet. Methods Effects of genetic deletion of P2rx7s on depressive-like behavior and spine synapse density in the dentate gyrus were investigated using the learned helplessness mouse model of depression. Results We demonstrate that in wild-type animals, inescapable footshocks lead to learned helplessness behavior reflected in increased latency and number of escape failures to subsequent escapable footshocks. This behavior is accompanied with downregulation of mRNA encoding P2rx7 and decrease of spine synapse density in the dentate gyrus as determined by electron microscopic stereology. In addition, a decrease in synaptopodin but not in PSD95 and NR2B/GluN2B protein level was also observed under these conditions. Whereas the absence of P2rx7 was characterized by escape deficit, no learned helpless behavior is observed in these animals. Likewise, no decrease in spine synapse number and synaptopodin protein levels was detected in response to inescapable footshocks in P2rx7-deficient animals. Conclusion Our findings suggest the endogenous activation of P2rx7s in the learned helplessness model of depression and decreased plasticity of spine synapses in P2rx7-deficient mice might explain the resistance of these animals to repeated stressful stimuli. PMID:28633291

Modeling the gain of inner-shell X-ray laser transitions in neon, argon, and copper driven by X-ray free electron laser radiation using photo-ionization and photo-excitation processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nilsen, Joseph

2015-12-16

Using an X-ray free electron laser (XFEL) at 960 eV to photo-ionize the 1s electron in neutral neon followed by lasing on the 2p-1s transition in singly-ionized neon, an inner-shell X-ray laser was demonstrated at 849 eV in singly-ionized neon gas several years ago. It took decades to demonstrate this scheme, because it required a very strong X-ray source that could photo-ionize the 1s (K shell) electron in neon on a timescale comparable to the intrinsic Auger lifetime in neon of 2 fs. In this paper, we model the neon inner shell X-ray laser under similar conditions to those usedmore » in the XFEL experiments at the SLAC Linac Coherent Light Source (LCLS), and show how we can improve the efficiency of the neon laser and reduce the drive requirements by tuning the XFEL to the 1s-3p transition in neutral neon in order to create gain on the 2p-1s line in neutral neon. We also show how the XFEL could be used to photo-ionize L-shell electrons to drive gain on n = 3–2 transitions in singly-ionized Ar and Cu plasmas. Furthermore, these bright, coherent, and monochromatic X-ray lasers may prove very useful for doing high-resolution spectroscopy and for studying non-linear process in the X-ray regime.« less

Landscape genomics in Atlantic salmon (Salmo salar): searching for gene-environment interactions driving local adaptation.

PubMed

Vincent, Bourret; Dionne, Mélanie; Kent, Matthew P; Lien, Sigbjørn; Bernatchez, Louis

2013-12-01

A growing number of studies are examining the factors driving historical and contemporary evolution in wild populations. By combining surveys of genomic variation with a comprehensive assessment of environmental parameters, such studies can increase our understanding of the genomic and geographical extent of local adaptation in wild populations. We used a large-scale landscape genomics approach to examine adaptive and neutral differentiation across 54 North American populations of Atlantic salmon representing seven previously defined genetically distinct regional groups. Over 5500 genome-wide single nucleotide polymorphisms were genotyped in 641 individuals and 28 bulk assays of 25 pooled individuals each. Genome scans, linkage map, and 49 environmental variables were combined to conduct an innovative landscape genomic analysis. Our results provide valuable insight into the links between environmental variation and both neutral and potentially adaptive genetic divergence. In particular, we identified markers potentially under divergent selection, as well as associated selective environmental factors and biological functions with the observed adaptive divergence. Multivariate landscape genetic analysis revealed strong associations of both genetic and environmental structures. We found an enrichment of growth-related functions among outlier markers. Climate (temperature-precipitation) and geological characteristics were significantly associated with both potentially adaptive and neutral genetic divergence and should be considered as candidate loci involved in adaptation at the regional scale in Atlantic salmon. Hence, this study significantly contributes to the improvement of tools used in modern conservation and management schemes of Atlantic salmon wild populations. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Biomechanical investigation of prolonged driving in an ergonomically designed truck seat prototype.

PubMed

Cardoso, Michelle; McKinnon, Colin; Viggiani, Dan; Johnson, Michel J; Callaghan, Jack P; Albert, Wayne J

2018-03-01

A postural evaluation during a prolonged driving task was conducted to determine the ergonomic validity of a new freely adjustable truck seat prototype. Twenty participants were recruited to perform two 2-h simulated driving sessions. Postures were assessed using motion capture, accelerometers and pressure pads. Subjective discomfort was also monitored in 15-min increments using ratings of perceived discomfort (RPD) and the Automotive Seating Discomfort Questionnaire. Participants had a more neutral spine posture during the first hour of the drive and reported lower RPDs while sitting in the prototype. Pairing the gluteal backrest panel with the adjustable seat pan helped reduce the average sitting pressure. The industry-standard truck seat may lead to the development of poor whole body posture, and the proposed ergonomic redesign of a new truck seat helped improve sitting posture and reduce perceived discomfort. Practitioner Summary: A new freely adjustable truck seat prototype was compared to an Industry standard seat to assess hypothesised improvements to sitting posture and discomfort for long haul driving. It was found that the adjustable panels in the prototype helped promote spine posture, reduce sitting pressure and improved discomfort ratings.

Energy distribution functions of kilovolt ions parallel and perpendicular to the magnetic field of a modified Penning discharge

NASA Technical Reports Server (NTRS)

Roth, R. J.

1973-01-01

The distribution function of ion energy parallel to the magnetic field of a modified Penning discharge has been measured with a retarding potential energy analyzer. These ions escaped through one of the throats of the magnetic mirror geometry. Simultaneous measurements of the ion energy distribution function perpendicular to the magnetic field have been made with a charge exchange neutral detector. The ion energy distribution functions are approximately Maxwellian, and the parallel and perpendicular kinetic temperatures are equal within experimental error. These results suggest that turbulent processes previously observed in this discharge Maxwellianize the velocity distribution along a radius in velocity space and cause an isotropic energy distribution. When the distributions depart from Maxwellian, they are enhanced above the Maxwellian tail.

Scintillator-based fast ion loss measurements in the EAST.

PubMed

Chang, J F; Isobe, M; Ogawa, K; Huang, J; Wu, C R; Xu, Z; Jin, Z; Lin, S Y; Hu, L Q

2016-11-01

A new scintillator-based fast ion loss detector (FILD) has been installed on Experimental Advanced Superconducting Tokamak (EAST) to investigate the fast ion loss behavior in high performance plasma with neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH). A two dimensional 40 mm × 40 mm scintillator-coated (ZnS:Ag) stainless plate is mounted in the front of the detector, capturing the escaping fast ions. Photons from the scintillator plate are imaged with a Phantom V2010 CCD camera. The lost fast ions can be measured with the pitch angle from 60° to 120° and the gyroradius from 10 mm to 180 mm. This paper will describe the details of FILD diagnostic on EAST and describe preliminary measurements during NBI and ICRH heating.

Molecular characterization of the monoclonal antibodies composing ZMAb: a protective cocktail against Ebola virus.

PubMed

Audet, Jonathan; Wong, Gary; Wang, Han; Lu, Guangwen; Gao, George F; Kobinger, Gary; Qiu, Xiangguo

2014-11-06

Ebola virus (EBOV) causes severe viral hemorrhagic fever in humans and non-human primates, with a case fatality rate of up to 88% in human outbreaks. Over the past 3 years, monoclonal antibody (mAb) cocktails have demonstrated high efficacy as treatments against EBOV infection. One such cocktail is ZMAb, which consists of three mouse antibodies, 1H3, 2G4, and 4G7. Here, we present the epitope binding properties of mAbs 1H3, 2G4, and 4G7. We showed that these antibodies have different variable region sequences, suggesting that the individual mAbs are not clonally related. All three antibodies were found to neutralize EBOV variant Mayinga. Additionally, 2G4 and 4G7 were shown to cross-inhibit each other in vitro and select for an escape mutation at the same position on the EBOV glycoprotein (GP), at amino acid 508. 1H3 selects an escape mutant at amino acid 273 on EBOV GP. Surface plasmon resonance studies showed that all three antibodies have dissociation constants on the order of 10(-7). In combination with previous studies evaluating the binding sites of other protective antibodies, our results suggest that antibodies targeting the GP1-GP2 interface and the glycan cap are often selected as efficacious antibodies for post-exposure interventions against EBOV.

A SEARCH FOR Hα ABSORPTION AROUND KELT-3 b AND GJ 436 b

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cauley, P. Wilson; Redfield, Seth; Jensen, Adam G., E-mail: pcauley@wesleyan.edu

2017-02-01

Observations of extended atmospheres around hot planets have generated exciting results concerning the dynamics of escaping planetary material. The configuration of the escaping planetary gas can result in asymmetric transit features, producing both pre- and post-transit absorption in specific atomic transitions. Measuring the velocity and strength of the absorption can provide constraints on the mass loss mechanism, and potentially clues to the interactions between the planet and the host star. Here we present a search for H α absorption in the circumplanetary environments of the hot planets KELT-3 b and GJ 436 b. We find no evidence for absorption aroundmore » either planet at any point during the two separate transit epochs for which each system was observed. We provide upper limits on the radial extent and density of the excited hydrogen atmospheres around both planets. The null detection for GJ 436 b contrasts with the strong Ly α absorption measured for the same system, suggesting that the large cloud of neutral hydrogen is almost entirely in the ground state. The only confirmed exoplanetary H α absorption to date has been made around the active star HD 189733 b. KELT-3 and GJ 436 are less active than HD 189733, hinting that exoplanet atmospheres exposed to EUV photons from active stars are better suited for detection of H α absorption.« less

pH Alkalinization by Chloroquine Suppresses Pathogenic Burkholderia Type 6 Secretion System 1 and Multinucleated Giant Cells

PubMed Central

Senft, Jeffrey L.; Lockett, Stephen J.; Brett, Paul J.; Burtnick, Mary N.; DeShazer, David

2016-01-01

ABSTRACT Burkholderia mallei and B. pseudomallei cause glanders and melioidosis, respectively, in humans and animals. A hallmark of pathogenesis is the formation of granulomas containing multinucleated giant cells (MNGCs) and cell death. These processes depend on type 6 secretion system 1 (T6SS-1), which is required for virulence in animals. We examined the cell biology of MNGC formation and cell death. We found that chloroquine diphosphate (CLQ), an antimalarial drug, inhibits Burkholderia growth, phagosomal escape, and subsequent MNGC formation. This depends on CLQ's ability to neutralize the acid pH because other alkalinizing compounds similarly inhibit escape and MNGC formation. CLQ inhibits bacterial virulence protein expression because T6SS-1 and some effectors of type 3 secretion system 3 (T3SS-3), which is also required for virulence, are expressed at acid pH. We show that acid pH upregulates the expression of Hcp1 of T6SS-1 and TssM, a protein coregulated with T6SS-1. Finally, we demonstrate that CLQ treatment of Burkholderia-infected Madagascar hissing cockroaches (HCs) increases their survival. This study highlights the multiple mechanisms by which CLQ inhibits growth and virulence and suggests that CLQ be further tested and considered, in conjunction with antibiotic use, for the treatment of diseases caused by Burkholderia. PMID:27799332

pH Alkalinization by Chloroquine Suppresses Pathogenic Burkholderia Type 6 Secretion System 1 and Multinucleated Giant Cells.

PubMed

Chua, Jennifer; Senft, Jeffrey L; Lockett, Stephen J; Brett, Paul J; Burtnick, Mary N; DeShazer, David; Friedlander, Arthur M

2017-01-01

Burkholderia mallei and B. pseudomallei cause glanders and melioidosis, respectively, in humans and animals. A hallmark of pathogenesis is the formation of granulomas containing multinucleated giant cells (MNGCs) and cell death. These processes depend on type 6 secretion system 1 (T6SS-1), which is required for virulence in animals. We examined the cell biology of MNGC formation and cell death. We found that chloroquine diphosphate (CLQ), an antimalarial drug, inhibits Burkholderia growth, phagosomal escape, and subsequent MNGC formation. This depends on CLQ's ability to neutralize the acid pH because other alkalinizing compounds similarly inhibit escape and MNGC formation. CLQ inhibits bacterial virulence protein expression because T6SS-1 and some effectors of type 3 secretion system 3 (T3SS-3), which is also required for virulence, are expressed at acid pH. We show that acid pH upregulates the expression of Hcp1 of T6SS-1 and TssM, a protein coregulated with T6SS-1. Finally, we demonstrate that CLQ treatment of Burkholderia-infected Madagascar hissing cockroaches (HCs) increases their survival. This study highlights the multiple mechanisms by which CLQ inhibits growth and virulence and suggests that CLQ be further tested and considered, in conjunction with antibiotic use, for the treatment of diseases caused by Burkholderia. Copyright © 2016 American Society for Microbiology.

Simulated orbits of heavy planetary ions at Mars for different IMF configurations

NASA Astrophysics Data System (ADS)

Curry, Shannon; Luhmann, Janet; Livi, Roberto; Hara, Takuya; Dong, Chuanfei; Ma, Yingjuan; McFadden, James; Bougher, Stephen

2014-11-01

We present simulated detections of O+, O2+ and CO2+ ions at Mars along a virtual orbit in the Mars space environment. Planetary pick-up ions are formed through the direct interaction of the solar wind with the neutral upper atmosphere, causing the newly created ions to be picked up and accelerated by the background convective electric field. Because previous missions such as Mars Global Surveyor (MGS) and Mars Express (MEX) have not been able to measure the interplanetary magnetic field (IMF) components simultaneously with plasma measurements, the response of heavy planetary pick-up ions to changes in the IMF has not been well characterized. Using a steady-state multi-species MHD model to provide the background electric and magnetic fields, the Mars Test Particle (MTP) simulation can trace each of these particles along field lines in near-Mars space and construct virtual ion detections from a spacecraft orbit. Specifically, we will present energy-time spectrograms and velocity space distributions (VSDs) for a selection of orbits during different IMF configurations and solar cycle conditions. These simulated orbits have broader implications for how to measure ion escape. Using individual particle traces, the origin and trajectories of different ion populations can be analyzed in order to assess how and where they contribute to the total atmospheric escape rate, which is a major objective of the upcoming MAVEN mission.

Mars-solar wind interaction: LatHyS, an improved parallel 3-D multispecies hybrid model

NASA Astrophysics Data System (ADS)

Modolo, Ronan; Hess, Sebastien; Mancini, Marco; Leblanc, Francois; Chaufray, Jean-Yves; Brain, David; Leclercq, Ludivine; Esteban-Hernández, Rosa; Chanteur, Gerard; Weill, Philippe; González-Galindo, Francisco; Forget, Francois; Yagi, Manabu; Mazelle, Christian

2016-07-01

In order to better represent Mars-solar wind interaction, we present an unprecedented model achieving spatial resolution down to 50 km, a so far unexplored resolution for global kinetic models of the Martian ionized environment. Such resolution approaches the ionospheric plasma scale height. In practice, the model is derived from a first version described in Modolo et al. (2005). An important effort of parallelization has been conducted and is presented here. A better description of the ionosphere was also implemented including ionospheric chemistry, electrical conductivities, and a drag force modeling the ion-neutral collisions in the ionosphere. This new version of the code, named LatHyS (Latmos Hybrid Simulation), is here used to characterize the impact of various spatial resolutions on simulation results. In addition, and following a global model challenge effort, we present the results of simulation run for three cases which allow addressing the effect of the suprathermal corona and of the solar EUV activity on the magnetospheric plasma boundaries and on the global escape. Simulation results showed that global patterns are relatively similar for the different spatial resolution runs, but finest grid runs provide a better representation of the ionosphere and display more details of the planetary plasma dynamic. Simulation results suggest that a significant fraction of escaping O+ ions is originated from below 1200 km altitude.

Relativistic neutrons in active galactic nuclei

NASA Technical Reports Server (NTRS)

Sikora, Marek; Begelman, Mitchell C.; Rudak, Bronislaw

1989-01-01

The acceleration of protons to relativistic energies in active galactic nuclei leads to the creation of relativistic neutrons which escape from the central engine. The neutrons decay at distances of up to 1-100 pc, depositing their energies and momenta in situ. Energy deposition by decaying neutrons may inhibit spherical accretion and drive a wind, which could be responsible for the velocity fields in emission-line regions and the outflow of broad absorption line systems. Enhanced pressure in the neutron decay region may also help to confine emission line clouds. A fraction of the relativistic proton energy is radiated in gamma-rays with energies which may be as large as about 100,000 GeV.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Siyao; Lazarian, A.; Yan, Huirong, E-mail: hryan@pku.edu.cn

We address the problem of the different line widths of coexistent neutrals and ions observed in molecular clouds and explore whether this difference can arise from the effects of magnetohydrodynamic (MHD) turbulence acting on partially ionized gas. Among the three fundamental modes of MHD turbulence, we find that fast and slow modes do not contribute to line width differences. We focus on the Alfvénic component, and consider the damping of Alfvén modes by taking into account both neutral-ion collisions and neutral viscosity. We confirm that the line width difference can be explained by the differential damping of the Alfvénic turbulencemore » in ions and the hydrodynamic turbulence in neutrals, and find it strongly depends on the properties of MHD turbulence. We consider various regimes of turbulence corresponding to different media magnetizations and turbulent drivings. In the case of super-Alfvénic turbulence, when the damping scale of Alfvénic turbulence is below the Alfvénic scale l{sub A}, the line width difference does not depend on magnetic field strength. In other turbulence regimes, however, the dependence is present and evaluation of magnetic field from the observed line width difference is possible.« less

Gas flows in the circumgalactic medium around simulated high-redshift galaxies

NASA Astrophysics Data System (ADS)

Mitchell, Peter D.; Blaizot, Jérémy; Devriendt, Julien; Kimm, Taysun; Michel-Dansac, Léo; Rosdahl, Joakim; Slyz, Adrianne

2018-03-01

We analyse the properties of circumgalactic gas around simulated galaxies in the redshift range z ≥ 3, utilizing a new sample of cosmological zoom simulations. These simulations are intended to be representative of the observed samples of Lyman α (Ly α) emitters recently obtained with the multi unit spectroscopic explorer (MUSE) instrument (halo masses ˜1010-1011 M⊙). We show that supernova feedback has a significant impact on both the inflowing and outflowing circumgalactic medium (CGM) by driving outflows, reducing diffuse inflow rates, and by increasing the neutral fraction of inflowing gas. By temporally stacking simulation outputs, we find that significant net mass exchange occurs between inflowing and outflowing phases: none of the phases are mass-conserving. In particular, we find that the mass in neutral outflowing hydrogen declines exponentially with radius as gas flows outwards from the halo centre. This is likely caused by a combination of both fountain-like cycling processes and gradual photoionization/collisional ionization of outflowing gas. Our simulations do not predict the presence of fast-moving neutral outflows in the CGM. Neutral outflows instead move with modest radial velocities (˜50 km s-1), and the majority of the kinetic energy is associated with tangential rather than radial motion.

Subauroral Ion-neutral Coupling During the March 2015 Superstorm

NASA Astrophysics Data System (ADS)

Zhang, S.; Erickson, P. J.; Foster, J. C.; Holt, J. M.; Coster, A. J.; Makela, J. J.; Noto, J.; Meriwether, J. W.; Otsuka, Y.; Nicolls, M. J.; McCready, M. A.

2015-12-01

The arrival of solar Coronal Mass Ejection materials overlapping a high-speed solar wind stream originated from a nearby coronal hole caused huge magnetic disturbances during March 17-18, 2015. We have coordinated an international campaign to monitor their geospace effects using ground-based facilities, including incoherent scatter radars and Fabry-Perot Interferometers in the America sectors and other instruments in East Asia sectors, forming an observational network along approximately the 60W/120E meridional circle. The presentation will provide highlights of these observations, with a focus on the ion-neutral coupling processes at subauroral and mid-latitudes. One of the most stiking findings is the northward neutral wind surge, observed in multiple sites, accompanying strong westward winds developed at earlier times. We ascribe this unexpected wind disturbances to Subauroal Polarization Stream (SAPS) asscoated strong plasma flows driving ion-neutral coupling. SAPS and strong ion flow were observed by Millstone Hill ISR and DMSP in situ measurements. We will also report the Millstone Hill ISR observations of a significant enhancement in the storm-time molecular ion composition in the F1-region height. This enhancement appears to be caused by strong vertical ion drift due to penetration electric fields.