Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

Kinematics of the Local Group gas and galaxies in the hestia simulations

We investigate the kinematic properties of gas and galaxies in the Local Group (LG) using high-resolution simulations performed by the hestia (High-resolution Environmental Simulations of The Immediate Area) collaboration. Our simulations include the correct cosmography surrounding LG-like regions consisting of two main spiral galaxies of ∼1012 M⊙, their satellites and minor isolated galaxies, all sharing the same large-scale motion within a volume of a few Mpc. We characterize the gas and galaxy kinematics within the simulated LGs, from the perspective of the Sun, to compare with observed trends from recent HST/COS absorption-line observations and LG galaxy data. To analyse the velocity pattern of LG gas and galaxies seen in the observational data, we build sky maps from the local standard of rest, and the Galactic and LG barycentre frames. Our findings show that the establishment of a radial velocity dipole at low/high latitudes, near the preferred barycentre direction, is a natural outcome of simulation kinematics for material outside the Milky Way virial radius after removing Galaxy rotation when the two main LG galaxies are approaching. Our results favour a scenario where gas and galaxies stream towards the LG barycentre producing a velocity dipole resembling observations. While our study shows in a qualitative way the global matter kinematics in the LG as part of its ongoing assembly, quantitative estimates of gas-flow rates and physical conditions of the LG gas have to await a more detailed modelling of the ionization conditions, which will be presented in a follow-up paper

Linkage study of 14 candidate genes and loci in four large Dutch families with vesico-ureteral reflux

Vesico-ureteral reflux (VUR) is a major contributing factor to end-stage renal disease in paediatric patients. Primary VUR is a familial disorder, but little is known about its genetic causes. To investigate the involvement of 12 functional candidate genes and two reported loci in VUR, we performed a linkage study in four large, Dutch, multi-generational families with multiple affected individuals. We were unable to detect linkage to any of the genes and loci and could exclude the GDNF, RET, SLIT2, SPRY1, PAX2, AGTR2, UPK1A and UPK3A genes and the 1p13 and 20p13 loci from linkage to VUR. Our results provide further evidence that there appears to be genetic heterogeneity in VUR

Anisotropic satellite accretion on to the Local Group with HESTIA

How the cosmic web feeds haloes, and fuels galaxy formation is an open question with wide implications. This study explores the mass assembly in the Local Group (LG) within the context of the local cosmography by employing simulations whose initial conditions have been constrained to reproduce the local environment. The goal of this study is to inspect whether the direction of accretion of satellites on to the Milky Way and Andromeda galaxies is related to the cosmic web. The analysis considers the three high-resolution simulations available in the HESTIA simulation suite, as well as the derived velocity shear and tidal tensors. We notice two eras in the LG accretion history, delimited by an epoch around z ≈ 0.7. We also find that satellites can travel up to ∼4 Mpc, relative to their parent halo before crossing its viral radius R200. Finally, we observe a strong alignment of the infall direction with the axis of slowest collapse boldsymbol e3 of both tidal and shear tensors, implying satellites of the LG originated from one particular region of the cosmic web and were channeled towards us via the process of accretion.This alignment is dominated by the satellites that enter during the early infall era, i.e. z > 0.7

Cold and hot gas distribution around the Milky-Way - M31 system in the HESTIA simulations

Recent observations have revealed remarkable insights into the gas reservoir in the circumgalactic medium (CGM) of galaxy haloes. In this paper, we characterize the gas in the vicinity of Milky Way and Andromeda analogues in the hestia (High resolution Environmental Simulations of The Immediate Area) suite of constrained Local Group (LG) simulations. The hestia suite comprise of a set of three high-resolution arepo-based simulations of the LG, run using the Auriga galaxy formation model. For this paper, we focus only on the z = 0 simulation data sets and generate mock skymaps along with a power spectrum analysis to show that the distributions of ions tracing low-temperature gas (H i and Si iii) are more clumpy in comparison to warmer gas tracers (O vi, O vii, and O viii). We compare to the spectroscopic CGM observations of M31 and low-redshift galaxies. hestia underproduces the column densities of the M31 observations, but the simulations are consistent with the observations of low-redshift galaxies. A possible explanation for these findings is that the spectroscopic observations of M31 are contaminated by gas residing in the CGM of the Milky Way

The stellar halo in Local Group Hestia simulations: I. The in situ component and the effect of mergers

Theory suggests that mergers play an important role in shaping galactic discs and stellar haloes, which was observationally confirmed in the Milky Way (MW) thanks to Gaia data. In this work, aiming to probe the contribution of mergers to the in situ stellar halo formation, we analyse six M 31 and MW analogues from the HESTIA suite of cosmological hydrodynamical zoom-in simulations of the Local Group. We found that all the HESTIA galaxies experience between one to four mergers with stellar mass ratios between 0.2 and 1 relative to the host at the time of the merger. These significant mergers, with a single exception, happened 7-11 Gyr ago. The overall impact of the most massive mergers in HESTIA is clearly seen as a sharp increase in the orbital eccentricity (and a corresponding decrease in the rotational velocity Vφ) of pre-existing disc stars of the main progenitor, thus nicely reproducing the Splash-, Plume-like feature that was discovered in the MW. We do find a correlation between mergers and close pericentric passages of massive satellites and bursts of the star formation in the in situ component. Massive mergers sharply increase the disc velocity dispersion of the in situ stars; however, the latest significant merger often heats up the disc up to the numbers when the contribution of the previous ones is less prominent in the age-velocity dispersion relation. In HESTIA galaxies, the in situ halo is an important component of the inner stellar halo where its fraction is about 30?-40%, while in the outer parts it typically does not exceed-5% beyond 15 kpc from the galactic centre. The simulations suggest that this component of the stellar haloes continues to grow well after mergers conclude; however, the most significant contribution comes from stars that formed recently before the merger. The orbital analysis of the HESTIA galaxies suggests that wedges in Rmax-Zmax (apocentre-maximum height from the mid-plane) space are mainly populated by the stars born in between significant mergers

Linkage study of 14 candidate genes and loci in four large Dutch families with vesico-ureteral reflux

Vesico-ureteral reflux (VUR) is a major contributing factor to end-stage renal disease in paediatric patients. Primary VUR is a familial disorder, but little is known about its genetic causes. To investigate the involvement of 12 functional candidate genes and two reported loci in VUR, we performed a linkage study in four large, Dutch, multi-generational families with multiple affected individuals. We were unable to detect linkage to any of the genes and loci and could exclude the GDNF, RET, SLIT2, SPRY1, PAX2, AGTR2, UPK1A and UPK3A genes and the 1p13 and 20p13 loci from linkage to VUR. Our results provide further evidence that there appears to be genetic heterogeneity in VUR

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO