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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on} with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Growth differentiation factor-15 promotes immune escape of ovarian cancer via targeting CD44 in dendritic cells

Immune escape is the main cause of the low response rate to immunotherapy for cancer, including ovarian cancer. Growth differentiation factor-15 (GDF-15) inhibits immune cell function. However, only few reports described the mechanism. Therefore, the aim of this study was to investigate the mechanism of immune escape regulated by GDF-15 in ovarian cancer. Ovarian cancer patients and healthy women were enrolled in this study. Immunohistochemistry and ELISA were performed to measure GDF-15 expression. Immunoprecipitation combined with mass spectrometry, surface plasmon resonance, and co-immunoprecipitation assay were used to evaluate the interaction between GDF-15 and the surface molecules of DCs. Immunofluorescence analysis, flow cytometry and transwell assay were used to evaluate additional effects of GDF-15 on DCs. The results showed that GDF-15 expression was higher in the ovarian cancer patients compared to that in the healthy women. The TIMER algorithm revealed that highly GDF-15 expression is associated with immune DC infiltration in immunoreactive high-grade serous carcinoma. A further study showed that GDF-15 suppressed DCs maturation, as well as IL-12p40 and TNF-α secretion, the length and number of protrusions and the migration. More importantly, CD44 in the surface of DCs interacted with GDF-15. The overexpression of CD44 in DCs resulted in the suppression of the inhibitory effect of GDF-15 on the length and number of DC synapses. In DCs overexpressing CD44 the inhibition of GDF-15 on the expression of CD11c, CD83 and CD86 was decreased, while in DCs with a knockdown of CD44 the inhibition was further enhanced. Knockdown of CD44 in DCs enhanced the inhibitory effect of GDF-15 on DC migration, while the overexpression of CD44 inhibited the inhibitory effect of GDF-15 on DC migration. In conclusion, the present study suggested that GDF-15 might facilitate ovarian cancer immune escape by interacting with CD44 in DCs to inhibit their function.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Structure of a TCR with High Affinity for Self-antigen Reveals Basis for Escape from Negative Selection

The failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3 conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Fusion and fission events regulate endosome maturation and viral escape

Endosomes are intracellular vesicles that mediate the communication of the cell with its extracellular environment. They are an essential part of the cell’s machinery regulating intracellular trafficking via the endocytic pathway. Many viruses, which in order to replicate require a host cell, attach themselves to the cellular membrane; an event which usually initiates uptake of a viral particle through the endocytic pathway. In this way viruses hijack endosomes for their journey towards intracellular sites of replication and avoid degradation without host detection by escaping the endosomal compartment. Recent experimental techniques have defined the role of endosomal maturation in the ability of enveloped viruses to release their genetic material into the cytoplasm. Endosome maturation depends on a family of small hydrolase enzymes (or GTPases) called Rab proteins, arranged on the cytoplasmic surface of its membrane. Here, we model endosomes as intracellular compartments described by two variables (its levels of active Rab5 and Rab7 proteins) and which can undergo coagulation (or fusion) and fragmentation (or fission). The key element in our approach is the “per-cell endosomal distribution” and its dynamical (Boltzmann) equation. The Boltzmann equation allows us to derive the dynamics of the total number of endosomes in a cell, as well as the mean and the standard deviation of its active Rab5 and Rab7 levels. We compare our mathematical results with experiments of Dengue viral escape from endosomes. The relationship between endosomal active Rab levels and pH suggests a mechanism that can account for the observed variability in viral escape times, which in turn regulate the viability of a viral intracellular infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Effect of band alignment on photoluminescence and carrier escape from InP surface quantum dots grown by metalorganic chemical vapor deposition on Si

A detailed analysis of photoluminescence (PL) from InP quantum dots (QDs) grown on Si has been carried out to understand the effect of substrate/host material in the luminescence and carrier escape process from the surface quantum dots. Such studies are required for the development of monolithically integrated next generation III-V QD based optoelectronics with fully developed Si microelectronics. The samples were grown by atmospheric pressure metalorganic chemical vapor deposition technique, and the PL measurements were made in the temperature range 10–80 K. The distribution of the dot diameter as well as the dot height has been investigated from atomic force microscopy. The origin of the photoluminescence has been explained theoretically. The band alignment of InP/Si heterostructure has been determined, and it is found be type II in nature. The positions of the conduction band minimum of Si and the 1st excited state in the conduction band of InP QDs have been estimated to understand the carrier escape phenomenon. A blue shift with a temperature co-efficient of 0.19 meV/K of the PL emission peak has been found as a result of competitive effect of different physical processes like quantum confinement, strain, and surface states. The corresponding effect of blue shift by quantum confinement and strain as well as the red shift by the surface states in the PL peaks has been studied. The origin of the luminescence in this heterojunction is found to be due to the recombination of free excitons, bound excitons, and a transition from the 1st electron excited state in the conduction band (e{sub 1}) to the heavy hole band (hh{sub 1}). Monotonic decrease in the PL intensity due to increase of thermally escaped carriers with temperature has been observed. The change in barrier height by the photogenerated electric-field enhanced the capture of the carriers by the surface states rather than their accumulation in the QD excited state. From an analysis of the dependence of the PL intensity, peak position, and line width with temperature and excitation source, the existence of free and bound excitonic recombination together with e{sub 1} → hh{sub 1} transitions in the QDs is established.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2012

RUNAWAY STARS AND THE ESCAPE OF IONIZING RADIATION FROM HIGH-REDSHIFT GALAXIES

Approximately 30% of all massive stars in the Galaxy are runaways with velocities exceeding 30 km s{sup -1}. Their high speeds allow them to travel {approx}0.1-1 kpc away from their birthplace before they explode at the end of their several Myr lifetimes. At high redshift, when galaxies were much smaller than in the local universe, runaways could venture far from the dense inner regions of their host galaxies. From these large radii, and therefore low column densities, much of their ionizing radiation is able to escape into the intergalactic medium. Runaways may therefore significantly enhance the overall escape fraction of ionizing radiation, f{sub esc}, from small galaxies at high redshift. We present simple models of the high-redshift runaway population and its impact on f{sub esc} as a function of halo mass, size, and redshift. We find that the inclusion of runaways enhances f{sub esc} by factors of Almost-Equal-To 1.1-8, depending on halo mass, galaxy geometry, and the mechanism of runaway production, implying that runaways may contribute 50%-90% of the total ionizing radiation escaping from high-redshift galaxies. Runaways may therefore play an important role in reionizing the universe.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

A NOVEL APPROACH TO CONSTRAIN THE ESCAPE FRACTION AND DUST CONTENT AT HIGH REDSHIFT USING THE COSMIC INFRARED BACKGROUND FRACTIONAL ANISOTROPY

The Cosmic Infrared Background (CIB) provides an opportunity to constrain many properties of the high-redshift (z > 6) stellar population as a whole. This background, specifically from 1 to 200 {mu}m, should contain information about the era of reionization and the stars that are responsible for these ionizing photons. In this paper, we look at the fractional anisotropy ({delta}I/I) of this high-redshift population, where {delta}I is the ratio of the magnitude of the fluctuations and I is the mean intensity. We show that this can be used to constrain the escape fraction of the population as a whole, because the magnitude of the fluctuations of the CIB depends on the escape fraction, while the mean intensity does not. This results in lower values of the escape fraction producing higher values of the fractional anisotropy. This difference is predicted to be larger at longer wavelength bands (above 10 {mu}m), albeit it is also much harder to observe in that range. We show that the fractional anisotropy can also be used to separate a dusty from a dust-free population. Finally, we discuss the constraints provided by current observations on the CIB fractional anisotropy.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

ESCAPING PARTICLE FLUXES IN THE ATMOSPHERES OF CLOSE-IN EXOPLANETS. II. REDUCED MASS-LOSS RATES AND ANISOTROPIC WINDS

In Paper I, we presented a one-dimensional hydrodynamic model for the winds of close-in exoplanets. However, close-in exoplanets are tidally locked and irradiated only on the day sides by their host stars. This requires two-dimensional hydrodynamic models with self-consistent radiative transfer calculations. In this paper, for the tidal-locking (two-dimensional radiative transfer) and non-tidal-locking cases (one-dimensional radiative transfer), we constructed a multi-fluid two-dimensional hydrodynamic model with detailed radiative transfer to depict the escape of particles. We found that the tidal forces (the sum of tidal gravity of the star and centrifugal force due to the planetary rotation) supply significant accelerations and result in anisotropic winds. An important effect of the tidal forces is that it severely depresses the outflow of particles near the polar regions where the density and the radial velocity are a factor of a few (ten) smaller than those of the low-latitude regions. As a consequence, most particles escape the surface of the planet from the regions of low latitude. Comparing the tidal-locking and non-tidal-locking cases, we found that their optical depths are very different so that the flows also emerge with a different pattern. In the case of non-tidal locking, the radial velocities at the base of the wind are higher than the meridional velocities. However, in the case of tidal locking, the meridional velocities dominate the flow at the base of the wind, and they can effectively transfer mass and energy from the day sides to the night sides. Further, we also found that the differences of the winds show a middle extent at large radii. This means that the structure of the wind at the base can be changed by the two-dimensional radiative transfer due to large optical depths, but the extent is reduced with an increase in radius. Because the escape is depressed in the polar regions, the mass-loss rate predicted by the non-tidal-locking model, in the order of magnitude of 10{sup 10} g s{sup -1}, is a factor of two lower than that predicted by the one-dimensional hydrodynamic model. The results of tidal locking show that the mass-loss rate is decreased an order of magnitude, only 4.3 Multiplication-Sign 10{sup 9} g s{sup -1}, due to large optical depths on the night side. We also found that the distributions of hydrogen atoms show clear variations from the day side to the night side, thus the origin of the excess absorption in Ly{alpha} should be reexamined using multi-dimensional hydrodynamic models.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

THE HYADES CLUSTER: IDENTIFICATION OF A PLANETARY SYSTEM AND ESCAPING WHITE DWARFS

Recently, some hot DA-type white dwarfs have been proposed to plausibly be escaping members of the Hyades. We used hydrogen Balmer lines to measure the radial velocities of seven such stars and confirm that three, and perhaps two others, are/were indeed cluster members and one is not. The other candidate Hyad is strongly magnetic and its membership status remains uncertain. The photospheres of at least one quarter of field white dwarf stars are ''polluted'' by elements heavier than helium that have been accreted. These stars are orbited by extended planetary systems that contain both debris belts and major planets. We surveyed the seven classical single Hyades white dwarfs and the newly identified (escaping) Hyades white dwarfs and found calcium in the photosphere of LP 475-242 of type DBA (now DBAZ), thus implying the presence of an orbiting planetary system. The spectrum of white dwarf GD 31, which may be, but probably is not, an escaping member of the Hyades, displays calcium absorption lines; these originate either from the interstellar medium or, less likely, from a gaseous circumstellar disk. If GD 31 was once a Hyades member, then it would be the first identified white dwarf Hyad with a cooling age >340 Myr.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

WARM IONIZED GAS REVEALED IN THE MAGELLANIC BRIDGE TIDAL REMNANT: CONSTRAINING THE BARYON CONTENT AND THE ESCAPING IONIZING PHOTONS AROUND DWARF GALAXIES

The Magellanic System includes some of the nearest examples of galaxies disturbed by galaxy interactions. These interactions have redistributed much of their gas into the halos of the Milky Way (MW) and the Magellanic Clouds. We present Wisconsin H{alpha} Mapper kinematically resolved observations of the warm ionized gas in the Magellanic Bridge over the velocity range of +100 to +300 km s{sup -1} in the local standard of rest reference frame. These observations include the first full H{alpha} intensity map and the corresponding intensity-weighted mean velocity map of the Magellanic Bridge across (l, b) = (281 Degree-Sign .5, -30 Degree-Sign .0) to (302. Degree-Sign 5, -46. Degree-Sign 7). Using the H{alpha} emission from the Small Magellanic Cloud (SMC)-Tail and the Bridge, we estimate that the mass of the ionized material is between (0.7-1.7) Multiplication-Sign 10{sup 8} M{sub Sun }, compared to 3.3 Multiplication-Sign 10{sup 8} M{sub Sun} for the neutral mass over the same region. The diffuse Bridge is significantly more ionized than the SMC-Tail, with an ionization fraction of 36%-52% compared to 5%-24% for the Tail. The H{alpha} emission has a complex multiple-component structure with a velocity distribution that could trace the sources of ionization or distinct ionized structures. We find that incident radiation from the extragalactic background and the MW alone are insufficient to produced the observed ionization in the Magellanic Bridge and present a model for the escape fraction of the ionizing photons from both the SMC and Large Magellanic Cloud (LMC). With this model, we place an upper limit of 4.0% for the average escape fraction of ionizing photons from the LMC and an upper limit of 5.5% for the SMC. These results, combined with the findings of a half a dozen other studies for dwarf galaxies in different environments, provide compelling evidence that only a small percentage of the ionizing photons escape from dwarf galaxies in the present epoch to influence their surroundings.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

Keck spectroscopy of gravitationally lensed z ≅ 4 galaxies: Improved constraints on the escape fraction of ionizing photons

The fraction of ionizing photons that escape from young star-forming galaxies is one of the largest uncertainties in determining the role of galaxies in cosmic reionization. Yet traditional techniques for measuring this fraction are inapplicable at the redshifts of interest due to foreground screening by the Lyα forest. In an earlier study, we demonstrated a reduction in the equivalent width of low-ionization absorption lines in composite spectra of Lyman break galaxies at z ≅ 4 compared to similar measures at z ≅ 3. This might imply a lower covering fraction of neutral gas and hence an increase with redshift in the escape fraction of ionizing photons. However, our spectral resolution was inadequate to differentiate between several alternative explanations, including changes with redshift in the outflow kinematics. Here we present higher quality spectra of three gravitationally lensed Lyman break galaxies at z ≅ 4 with a spectral resolution sufficient to break this degeneracy of interpretation. We present a method for deriving the covering fraction of low-ionization gas as a function of outflow velocity and compare the results with similar quality data taken for galaxies at lower redshift. We find an interesting but tentative trend of lower covering fractions of low-ionization gas for galaxies with strong Lyα emission. In combination with the demographic trends of Lyα emission with redshift from our earlier work, our results provide new evidence for a reduction in the average H I covering fraction, and hence an increase in the escape fraction of ionizing radiation from Lyman break galaxies, with redshift.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2014

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

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

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2014

Atmosphere expansion and mass loss of close-orbit giant exoplanets heated by stellar XUV. I. Modeling of hydrodynamic escape of upper atmospheric material

In the present series of papers we propose a consistent description of the mass loss process. To study in a comprehensive way the effects of the intrinsic magnetic field of a close-orbit giant exoplanet (a so-called hot Jupiter) on atmospheric material escape and the formation of a planetary inner magnetosphere, we start with a hydrodynamic model of an upper atmosphere expansion in this paper. While considering a simple hydrogen atmosphere model, we focus on the self-consistent inclusion of the effects of radiative heating and ionization of the atmospheric gas with its consequent expansion in the outer space. Primary attention is paid to an investigation of the role of the specific conditions at the inner and outer boundaries of the simulation domain, under which different regimes of material escape (free and restricted flow) are formed. A comparative study is performed of different processes, such as X-ray and ultraviolet (XUV) heating, material ionization and recombination, H{sub 3}{sup +} cooling, adiabatic and Lyα cooling, and Lyα reabsorption. We confirm the basic consistency of the outcomes of our modeling with the results of other hydrodynamic models of expanding planetary atmospheres. In particular, we determine that, under the typical conditions of an orbital distance of 0.05 AU around a Sun-type star, a hot Jupiter plasma envelope may reach maximum temperatures up to ∼9000 K with a hydrodynamic escape speed of ∼9 km s{sup –1}, resulting in mass loss rates of ∼(4-7) · 10{sup 10} g s{sup –1}. In the range of the considered stellar-planetary parameters and XUV fluxes, that is close to the mass loss in the energy-limited case. The inclusion of planetary intrinsic magnetic fields in the model is a subject of the follow-up paper (Paper II).

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2014

Hubble space telescope emission line galaxies at z ∼ 2: the Lyα escape fraction

We compare the Hβ line strengths of 1.90 < z < 2.35 star-forming galaxies observed with the near-IR grism of the Hubble Space Telescope with ground-based measurements of Lyα from the HETDEX Pilot Survey and narrow-band imaging. By examining the line ratios of 73 galaxies, we show that most star-forming systems at this epoch have a Lyα escape fraction below ∼6%. We confirm this result by using stellar reddening to estimate the effective logarithmic extinction of the Hβ emission line (c {sub Hβ} = 0.5) and measuring both the Hβ and Lyα luminosity functions in a ∼100, 000 Mpc{sup 3} volume of space. We show that in our redshift window, the volumetric Lyα escape fraction is at most 4.4{sub −1.2}{sup +2.1}%, with an additional systematic ∼25% uncertainty associated with our estimate of extinction. Finally, we demonstrate that the bulk of the epoch's star-forming galaxies have Lyα emission line optical depths that are significantly greater than that for the underlying UV continuum. In our predominantly [O III] λ5007-selected sample of galaxies, resonant scattering must be important for the escape of Lyα photons.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

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

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{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.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

MOLECULAR-KINETIC SIMULATIONS OF ESCAPE FROM THE EX-PLANET AND EXOPLANETS: CRITERION FOR TRANSONIC FLOW

The equations of gas dynamics are extensively used to describe atmospheric loss from solar system bodies and exoplanets even though the boundary conditions at infinity are not uniquely defined. Using molecular-kinetic simulations that correctly treat the transition from the continuum to the rarefied region, we confirm that the energy-limited escape approximation is valid when adiabatic expansion is the dominant cooling process. However, this does not imply that the outflow goes sonic. Rather large escape rates and concomitant adiabatic cooling can produce atmospheres with subsonic flow that are highly extended. Since this affects the heating rate of the upper atmosphere and the interaction with external fields and plasmas, we give a criterion for estimating when the outflow goes transonic in the continuum region. This is applied to early terrestrial atmospheres, exoplanet atmospheres, and the atmosphere of the ex-planet, Pluto, all of which have large escape rates.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2011

Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection

In the present study, we analyzed the functional profile of CD 8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD 8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1b-producing CD 8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Escaping Events at the NOvA Far Detector

aThe NuMI Off-axis $\nu_e$ Appearance (NOvA) experiment studies neutrino oscillations in the NuMI (Neutrinos at the Main Injector) beam. The goal of the experiment is to determine the mass hierarchy and measure $\delta_{CP}$, however it is also sensitive to $\sin\theta_{23}$, and $\Delta m^2_{32}$. The present work tries to improve experimental sensitivity to the oscillation parameters by considering neutrino events which are discarded by the previous analysis - escaping events. The biggest issues with the escaping sample are significant cosmic background and correct energy estimation. Both issues were addressed and inclusion of escaping sample to the final fit led to an effective increase of statistics by 4% with best- fit measurements of $\sin\theta^2_{23} = 0.504$ and $\Delta m^2_{32} = 2.45 \times 10^{-3}$ eV$^2$.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗