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Schmidt, Fabian

Publications and source records attributed to Schmidt, Fabian.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations

Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Novel Probes Project: Tests of gravity on astrophysical scales

The Novel Probes Project, an initiative to advance the field of astrophysical tests of the dark sector by creating a forum that connects observers and theorists, is introduced. This review focuses on tests of gravity and is intended to be of use primarily to observers, as well as theorists with an interest in the development of experimental tests. It is twinned with a separate upcoming review on dark matter self-interactions. The review focuses on astrophysical tests of gravity in the weak-field regime, ranging from stars to quasilinear cosmological scales. This regime is complementary to both strong-field tests of gravity and background and linear probes in cosmology. In particular, the nonlinear screening mechanisms that are an integral part of viable modified-gravity models lead to characteristic signatures, specifically on astrophysical scales. The potential of these probes is not limited by cosmic variance but comes with the challenge of building robust theoretical models of the nonlinear dynamics of stars, galaxies, and large-scale structure. The groundwork is laid for a thorough exploration of the weak-field, nonlinear regime, with an eye to using the current and next generation of observations for tests of gravity. The scene is set by showing how gravitational theories beyond general relativity are expected to behave, focusing primarily on screening mechanisms. Analytic and numerical techniques for exploring the relevant astrophysical regime are described, as are the pertinent observational signals. With these in hand a range of astrophysical tests of gravity are presented, and prospects for future measurements and theoretical developments are discussed.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2020

Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/ neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1 A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryoelectron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Response approach to the squeezed-limit bispectrum: application to the correlation of quasar and Lyman-α forest power spectrum

We present the squeezed-limit bispectrum, which is generated by nonlinear gravitational evolution as well as inflationary physics, measures the correlation of three wavenumbers, in the configuration where one wavenumber is much smaller than the other two. Since the squeezed-limit bispectrum encodes the impact of a large-scale fluctuation on the small-scale power spectrum, it can be understood as how the small-scale power spectrum ``responds'' to the large-scale fluctuation. Viewed in this way, the squeezed-limit bispectrum can be calculated using the response approach even in the cases which do not submit to perturbative treatment. To illustrate this point, we apply this approach to the cross-correlation between the large-scale quasar density field and small-scale Lyman-α forest flux power spectrum. In particular, using separate universe simulations which implement changes in the large-scale density, velocity gradient, and primordial power spectrum amplitude, we measure how the Lyman-α forest flux power spectrum responds to the local, long-wavelength quasar overdensity, and equivalently their squeezed-limit bispectrum. We perform a Fisher forecast for the ability of future experiments to constrain local non-Gaussianity using the bispectrum of quasars and the Lyman-α forest. Combining with quasar and Lyman-α forest power spectra to constrain the biases, we find that for DESI the expected 1-σ constraint is err[f NL ]~60. Ability for DESI to measure f NL through this channel is limited primarily by the aliasing and instrumental noise of the Lyman-α forest flux power spectrum. Lastly, the combination of response approach and separate universe simulations provides a novel technique to explore the constraints from the squeezed-limit bispectrum between different observables.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Responses in large-scale structure

We introduce a rigorous definition of general power-spectrum responses as resummed vertices with two hard and n soft momenta in cosmological perturbation theory. These responses measure the impact of long-wavelength perturbations on the local small-scale power spectrum. The kinematic structure of the responses (i.e., their angular dependence) can be decomposed unambiguously through a ''bias'' expansion of the local power spectrum, with a fixed number of physical response coefficients , which are only a function of the hard wavenumber k . Further, the responses up to n -th order completely describe the ( n +2)-point function in the squeezed limit, i.e. with two hard and n soft modes, which one can use to derive the response coefficients. This generalizes previous results, which relate the angle-averaged squeezed limit to isotropic response coefficients. We derive the complete expression of first- and second-order responses at leading order in perturbation theory, and present extrapolations to nonlinear scales based on simulation measurements of the isotropic response coefficients. As an application, we use these results to predict the non-Gaussian part of the angle-averaged matter power spectrum covariance Cov{sup NG}{sub ℓ=0}( k {sub 1}, k {sub 2}), in the limit where one of the modes, say k {sub 2}, is much smaller than the other. Without any free parameters, our model results are in very good agreement with simulations for k {sub 2} ∼< 0.06 h Mpc{sup −1}, and for any k {sub 1} ∼> 2 k {sub 2}. The well-defined kinematic structure of the power spectrum response also permits a quick evaluation of the angular dependence of the covariance matrix. While we focus on the matter density field, the formalism presented here can be generalized to generic tracers such as galaxies.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2017

Testing ΛCDM at the lowest redshifts with SN Ia and galaxy velocities

Peculiar velocities of objects in the nearby universe are correlated due to the gravitational pull of large-scale structure. By measuring these velocities, we have a unique opportunity to test the cosmological model at the lowest redshifts. We perform this test, using current data to constrain the amplitude of the "signal" covariance matrix describing the velocities and their correlations. We consider a new, well-calibrated "Supercal" set of low-redshift SNe Ia as well as a set of distances derived from the fundamental plane relation of 6dFGS galaxies. Here, analyzing the SN and galaxy data separately, both results are consistent with the peculiar velocity signal of our fiducial ΛCDM model, ruling out the noise-only model with zero peculiar velocities at greater than 7σ (SNe) and 8σ (galaxies). When the two data sets are combined appropriately, the precision of the test increases slightly, resulting in a constraint on the signal amplitude of A = 1.05 -0.21 +0.25 where A = 1 corresponds to our fiducial model. Equivalently, we report an 11% measurement of the product of the growth rate and amplitude of mass fluctuations evaluated at z eff = 0.02, f σ 8 = 0.428 -0.045 +0.048 , valid for our fiducial ΛCDM model. Here, we explore the robustness of the results to a number of conceivable variations in the analysis and find that individual variations shift the preferred signal amplitude by less than ~0.5σ. We briefly discuss our Supercal SN Ia results in comparison with our previous results using the JLA compilation.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Large-scale assembly bias of dark matter halos

We present precise measurements of the assembly bias of dark matter halos, i.e. the dependence of halo bias on other properties than the mass, using curved 'separate universe' N-body simulations which effectively incorporate an infinite-wavelength matter overdensity into the background density. This method measures the LIMD (local-in-matter-density) bias parameters b {sub n} in the large-scale limit. We focus on the dependence of the first two Eulerian biases b {sup E} {sup {sub 1}} and b {sup E} {sup {sub 2}} on four halo properties: the concentration, spin, mass accretion rate, and ellipticity. We quantitatively compare our results with previous works in which assembly bias was measured on fairly small scales. Despite this difference, our findings are in good agreement with previous results. We also look at the joint dependence of bias on two halo properties in addition to the mass. Finally, using the excursion set peaks model, we attempt to shed new insights on how assembly bias arises in this analytical model.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2017

Lensing is low: cosmology, galaxy formation or new physics?

Here, we introduce high signal-to-noise galaxy-galaxy lensing measurements of the Baryon Oscillation Spectroscopic Survey constant mass (CMASS) sample using 250 deg 2 of weak-lensing data from Canada-France-Hawaii Telescope Lensing Survey and Canada-France-Hawaii Telescope Stripe 82 Survey. We compare this signal with predictions from mock catalogues trained to match observables including the stellar mass function and the projected and two-dimensional clustering of CMASS. We show that the clustering of CMASS, together with standard models of the galaxy-halo connection, robustly predicts a lensing signal that is 20-40 per cent larger than observed. Detailed tests show that our results are robust to a variety of systematic effects. Lowering the value of S 8 = σ 8 √{Ω m /0.3 compared to Planck Collaboration XIII reconciles the lensing with clustering. However, given the scale of our measurement (r < 10 h -1 Mpc), other effects may also be at play and need to be taken into consideration. We explore the impact of baryon physics, assembly bias, massive neutrinos and modifications to general relativity on ΔΣ and show that several of these effects may be non-negligible given the precision of our measurement. Disentangling cosmological effects from the details of the galaxy-halo connection, the effect of baryons, and massive neutrinos, is the next challenge facing joint lensing and clustering analyses. This is particularly true in the context of large galaxy samples from Baryon Acoustic Oscillation surveys with precise measurements but complex selection functions.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Large-scale tides in general relativity

Density perturbations in cosmology, i.e. spherically symmetric adiabatic perturbations of a Friedmann-Lemaȋtre-Robertson-Walker (FLRW) spacetime, are locally exactly equivalent to a different FLRW solution, as long as their wavelength is much larger than the sound horizon of all fluid components. This fact is known as the 'separate universe' paradigm. However, no such relation is known for anisotropic adiabatic perturbations, which correspond to an FLRW spacetime with large-scale tidal fields. Here, we provide a closed, fully relativistic set of evolutionary equations for the nonlinear evolution of such modes, based on the conformal Fermi (CFC) frame. We show explicitly that the tidal effects are encoded by the Weyl tensor, and are hence entirely different from an anisotropic Bianchi I spacetime, where the anisotropy is sourced by the Ricci tensor. In order to close the system, certain higher derivative terms have to be dropped. We show that this approximation is equivalent to the local tidal approximation of Hui and Bertschinger [1]. We also show that this very simple set of equations matches the exact evolution of the density field at second order, but fails at third and higher order. This provides a useful, easy-to-use framework for computing the fully relativistic growth of structure at second order.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2016

Precision measurement of the local bias of dark matter halos

We present accurate measurements of the linear, quadratic, and cubic local bias of dark matter halos, using curved 'separate universe' N-body simulations which effectively incorporate an infinite-wavelength overdensity. This can be seen as an exact implementation of the peak-background split argument. We compare the results with the linear and quadratic bias measured from the halo-matter power spectrum and bispectrum, and find good agreement. On the other hand, the standard peak-background split applied to the Sheth and Tormen (1999) and Tinker et al. (2008) halo mass functions matches the measured linear bias parameter only at the level of 10%. The prediction from the excursion set-peaks approach performs much better, which can be attributed to the stochastic moving barrier employed in the excursion set-peaks prediction. We also provide convenient fitting formulas for the nonlinear bias parameters b{sub 2}(b{sub 1}) and b{sub 3}(b{sub 1}), which work well over a range of redshifts.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

No evidence for bulk velocity from type Ia supernovae

We revisit the effect of peculiar velocities on low-redshift type Ia supernovae. Velocities introduce an additional guaranteed source of correlations between supernova magnitudes that should be considered in all analyses of nearby supernova samples but has largely been neglected in the past. Applying a likelihood analysis to the latest compilation of nearby supernovae, we find no evidence for the presence of these correlations, although, given the significant noise, the data is also consistent with the correlations predicted for the standard ΛCDM model. We then consider the dipolar component of the velocity correlations—the frequently studied ''bulk velocity''—and explicitly demonstrate that including the velocity correlations in the data covariance matrix is crucial for drawing correct and unambiguous conclusions about the bulk flow. In particular, current supernova data is consistent with no excess bulk flow on top of what is expected in ΛCDM and effectively captured by the covariance. We further clarify the nature of the apparent bulk flow that is inferred when the velocity covariance is ignored. We show that a significant fraction of this quantity is expected to be noise bias due to uncertainties in supernova magnitudes and not any physical peculiar motion.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

Galaxy bias and primordial non-Gaussianity

We present a systematic study of galaxy biasing in the presence of primordial non-Gaussianity. For a large class of non-Gaussian initial conditions, we define a general bias expansion and prove that it is closed under renormalization, thereby showing that the basis of operators in the expansion is complete. We then study the effects of primordial non-Gaussianity on the statistics of galaxies. We show that the equivalence principle enforces a relation between the scale-dependent bias in the galaxy power spectrum and that in the dipolar part of the bispectrum. This provides a powerful consistency check to confirm the primordial origin of any observed scale-dependent bias. Finally, we also discuss the imprints of anisotropic non-Gaussianity as motivated by recent studies of higher-spin fields during inflation.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

Conformal Fermi Coordinates

Fermi Normal Coordinates (FNC) are a useful frame for isolating the locally observable, physical effects of a long-wavelength spacetime perturbation. Their cosmological application, however, is hampered by the fact that they are only valid on scales much smaller than the horizon. We introduce a generalization that we call Conformal Fermi Coordinates (CFC). CFC preserve all the advantages of FNC, but in addition are valid outside the horizon. They allow us to calculate the coupling of long- and short-wavelength modes on all scales larger than the sound horizon of the cosmological fluid, starting from the epoch of inflation until today, by removing the complications of the second order Einstein equations to a large extent, and eliminating all gauge ambiguities. As an application, we present a calculation of the effect of long-wavelength tensor modes on small scale density fluctuations. We recover previous results, but clarify the physical content of the individual contributions in terms of locally measurable effects and ''projection'' terms.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

Imprint of inflation on galaxy shape correlations

We show that intrinsic (not lensing-induced) correlations between galaxy shapes offer a new probe of primordial non-Gaussianity and inflationary physics which is complementary to galaxy number counts. Specifically, intrinsic alignment correlations are sensitive to an anisotropic squeezed limit bispectrum of the primordial perturbations. Such a feature arises in solid inflation, as well as more broadly in the presence of light higher spin fields during inflation (as pointed out recently by Arkani-Hamed and Maldacena). We present a derivation of the all-sky two-point correlations of intrinsic shapes and number counts in the presence of non-Gaussianity with general angular dependence, and show that a quadrupolar (spin-2) anisotropy leads to the analog in galaxy shapes of the well-known scale-dependent bias induced in number counts by isotropic (spin-0) non-Gaussianity. Moreover, in the presence of non-zero anisotropic non-Gaussianity, the quadrupole of galaxy shapes becomes sensitive to far superhorizon modes. These effects come about because long-wavelength modes induce a local anisotropy in the initial power spectrum, with which galaxies will correlate. We forecast that future imaging surveys could provide constraints on the amplitude of anisotropic non-Gaussianity that are comparable to those from the Cosmic Microwave Background (CMB). These are complementary as they probe different physical scales. The constraints, however, depend on the sensitivity of galaxy shapes to the initial conditions which we only roughly estimate from observed tidal alignments.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

Solar system constraints on disformal gravity theories

Disformal theories of gravity are scalar-tensor theories where the scalar couples derivatively to matter via the Jordan frame metric. These models have recently attracted interest in the cosmological context since they admit accelerating solutions. We derive the solution for a static isolated mass in generic disformal gravity theories and transform it into the parameterised post-Newtonian form. This allows us to investigate constraints placed on such theories by local tests of gravity. The tightest constraints come from preferred-frame effects due to the motion of the Solar System with respect to the evolving cosmological background field. The constraints we obtain improve upon the previous solar system constraints by two orders of magnitude, and constrain the scale of the disformal coupling for generic models to ℳ ∼> 100 eV. These constraints render all disformal effects irrelevant for cosmology.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

On separate universes

The separate universe conjecture states that in General Relativity a density perturbation behaves locally (i.e. on scales much smaller than the wavelength of the mode) as a separate universe with different background density and curvature. We prove this conjecture for a spherical compensated tophat density perturbation of arbitrary amplitude and radius in ΛCDM. We then use Conformal Fermi Coordinates to generalize this result to scalar perturbations of arbitrary configuration and scale in a general cosmology with a mixture of fluids, but to linear order in perturbations. In this case, the separate universe conjecture holds for the isotropic part of the perturbations. The anisotropic part on the other hand is exactly captured by a tidal field in the Newtonian form. We show that the separate universe picture is restricted to scales larger than the sound horizons of all fluid components. We then derive an expression for the locally measured matter bispectrum induced by a long-wavelength mode of arbitrary wavelength, a new result which in standard perturbation theory is equivalent to a relativistic second-order calculation. We show that nonlinear gravitational dynamics does not generate observable contributions that scale like local-type non-Gaussianity f{sup loc}{sub NL}, and hence does not contribute to a scale-dependent galaxy bias Δ b ∝ k{sup −2} on large scales; rather, the locally measurable long-short mode coupling assumes a form essentially identical to subhorizon perturbation theory results, once the long-mode density perturbation is replaced by the synchronous-comoving gauge density perturbation. Apparent f{sup loc}{sub NL}-type contributions arise through projection effects on photon propagation, which depend on the specific large-scale structure tracer and observable considered, and are in principle distinguishable from the local mode coupling induced by gravity. We conclude that any observation of f{sup loc}{sub NL} beyond these projection effects signals a departure from standard single-clock inflation.

79 ASTRONOMY AND ASTROPHYSICS↗