Heterologous prime-boost immunization strategies have the potential to augment COVID-19 vaccine efficacy. We longitudinally profiled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ...(S)-specific serological and memory B cell (MBC) responses in individuals who received either homologous (ChAdOx1:ChAdOx1) or heterologous (ChAdOx1:mRNA-1273) prime-boost vaccination. Heterologous messenger RNA (mRNA) booster immunization induced higher serum neutralizing antibody and MBC responses against SARS-CoV-2 variants of concern (VOCs) compared with that of homologous ChAdOx1 boosting. Specificity mapping of circulating B cells revealed that mRNA-1273 boost immunofocused ChAdOx1-primed responses onto epitopes expressed on prefusion-stabilized S. Monoclonal antibodies isolated from mRNA-1273-boosted participants displayed overall higher binding affinities and increased breadth of reactivity against VOCs relative to those isolated from ChAdOx1-boosted individuals. Overall, the results provide molecular insight into the enhanced quality of the B cell response induced after heterologous mRNA booster vaccination.
We present the first detailed elemental abundances in the ultra-faint Magellanic satellite galaxies Carina II (Car II) and Carina III (Car III). With high-resolution Magellan/MIKE spectroscopy, we ...determined the abundances of nine stars in Car II, including the first abundances of an RR Lyrae star in an ultra-faint dwarf galaxy (UFD), and two stars in Car III. The chemical abundances demonstrate that both systems are clearly galaxies and not globular clusters. The stars in these galaxies mostly display abundance trends matching those of other similarly faint dwarf galaxies: enhanced but declining /Fe ratios, iron-peak elements matching the stellar halo, and unusually low neutron-capture element abundances. One star displays a low outlying Sc/Fe = −1.0. We detect a large Ba scatter in Car II, likely due to inhomogeneous enrichment by low-mass asymptotic giant branch star winds. The most striking abundance trend is for Mg/Ca in Car II, which decreases from +0.4 to −0.4 and indicates clear variation in the initial progenitor masses of enriching core-collapse supernovae. So far, the only UFDs displaying a similar Mg/Ca trend are likely satellites of the Large Magellanic Cloud. We find two stars with Fe/H ≤ −3.5 whose abundances likely trace the first generation of metal-free Population III stars and are well fit by Population III core-collapse supernova yields. An appendix describes our new abundance uncertainty analysis that propagates line-by-line stellar parameter uncertainties.
Abstract
We report the discovery of a new ultra-faint stellar system found near the Magellanic Clouds in the DECam Local Volume Exploration Survey. This new system, DELVE J0155−6815 (DELVE 2), is ...located at a heliocentric distance of
D
⊙
= 71 ± 4 kpc, which places it at a 3D physical separation of 12 ± 3 kpc from the center of the Small Magellanic Cloud and
from the center of the Large Magellanic Cloud (LMC). DELVE 2 is identified as a resolved overdensity of old (
τ
> 13.3 Gyr) and metal-poor (
dex) stars with a projected half-light radius of
and an absolute magnitude of
. The size and luminosity of DELVE 2 are consistent with both the population of recently discovered ultra-faint globular clusters and the smallest ultra-faint dwarf galaxies. However, its photometrically derived age and metallicity would place it among the oldest and most metal-poor globular clusters in the Magellanic system. In the absence of spectroscopic measurements of the system’s metallicity dispersion and internal kinematics, we are unable to conclusively classify this system at this time. DELVE 2 is detected in
Gaia
DR2 with a clear proper-motion signal, with multiple blue horizontal-branch stars near the centroid of the system with proper motions consistent with the systemic mean. We measure the system proper motion to be
=
mas yr
−1
. We compare the spatial position and proper motion of DELVE 2 with simulations of the accreted satellite population of the LMC and find that it is very likely to be associated with the LMC.
Abstract
We report the discovery of two ultra-faint satellites in the vicinity of the Large Magellanic Cloud (LMC) in data from the Magellanic Satellites Survey (MagLiteS ). Situated 18 deg (∼20 kpc) ...from the LMC and separated from each other by only 18 arcmin, Carina II and III form an intriguing pair. By simultaneously modelling the spatial and the colour–magnitude stellar distributions, we find that both Carina II and Carina III are likely dwarf galaxies, although this is less clear for Carina III. There are in fact several obvious differences between the two satellites. While both are well described by an old and metal poor population, Carina II is located at ∼36 kpc from the Sun, with MV ∼ −4.5 and rh ∼ 90 pc, and it is further confirmed by the discovery of 3 RR Lyrae at the right distance. In contrast, Carina III is much more elongated, measured to be fainter (MV ∼ −2.4), significantly more compact (rh ∼ 30 pc), and closer to the Sun, at ∼28 kpc, placing it only 8 kpc away from Car II. Together with several other systems detected by the Dark Energy Camera, Carina II and III form a strongly anisotropic cloud of satellites in the vicinity of the Magellanic Clouds.
This survey covers rollback-recovery techniques that do not require special language constructs. In the first part of the survey we classify rollback-recovery protocols into
checkpoint-based
and
...log-based.
Checkpoint-based
protocols rely solely on checkpointing for system state restoration. Checkpointing can be coordinated, uncoordinated, or communication-induced.
Log-based
protocols combine checkpointing with logging of nondeterministic events, encoded in tuples called
determinants
. Depending on how determinants are logged, log-based protocols can be pessimistic, optimistic, or causal. Throughout the survey, we highlight the research issues that are at the core of rollback-recovery and present the solutions that currently address them. We also compare the performance of different rollback-recovery protocols with respect to a series of desirable properties and discuss the issues that arise in the practical implementations of these protocols.
Reactive metals are known to electrodeposit with irregular morphological features on planar substrates. A growing body of work suggest that multiple variables: composition, mechanics, structure, ion ...transport properties, reductive stability, and interfacial energy of interphases, formed either spontaneously or by design on the metal electrode play important but differentiated roles in regulating these morphologies. We examine the effect of fluorinated thermoset polymer coatings on Li deposition by means of experiment and theoretical linear stability analysis. By tuning the chemistry of the polymer backbone and side chains, we investigate how physical and mechanical properties of polymeric interphases influence Li electrodeposit morphology. It is found that an interplay between elasticity and diffusivity leads to an optimum interphase thickness and that higher interfacial energy augments elastic stresses at a metal electrode to prevent out-of-plane deposition. These findings are explained using linear stability analysis of electrodeposition and provide guidelines for designing polymer interphases to stabilize metal anodes in rechargeable batteries.
Although intratumor heterogeneity has been inferred in multiple myeloma (MM), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with MM, we ...perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 (IRF4) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγ(null) xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.
Uranium groundwater contamination due to U mining and processing affects numerous sites globally. Bioreduction of soluble, mobile U(VI) to U(IV)-bearing solids is potentially a very effective ...remediation strategy. Uranium isotopes (238U/235U) have been utilized to track the progress of microbial reduction, with laboratory and field studies finding a ∼1‰ isotopic fractionation, with the U(IV) product enriched in 238U. However, the isotopic fractionation produced by adsorption may complicate the use of 238U/235U to trace microbial reduction. A previous study found that adsorption of U(VI) onto Mn oxides produced a −0.2‰ fractionation with the adsorbed U(VI) depleted in 238U. In this study, adsorption to quartz, goethite, birnessite, illite, and aquifer sediments induced an average isotopic fractionation of −0.15‰ with the adsorbed U(VI) isotopically lighter than coexisting aqueous U(VI). In bicarbonate-bearing matrices, the fractionation depended little on the nature of the sorbent, with only birnessite producing an atypically large fractionation. In the case of solutions with ionic strengths much lower than those of typical groundwater, less isotopic fractionation was produced than U(VI) solutions with greater ionic strength. Studies using U isotope data to assess U(VI) reduction must consider adsorption as a lesser, but significant isotope fractionation process.
Summary
Background Peanuts are often consumed after roasting, a process that alters the three‐dimensional structure of allergens and leads to Maillard modification. Such changes are likely to affect ...their allergenicity.
Objective We aimed to establish the effect of thermal treatment mimicking the roasting process on the allergenicity of Ara h 1 and a mix of 2S albumins from peanut (Ara h 2/6).
Methods Ara h 1 and Ara h 2/6 were purified from raw peanuts and heated in a dry form for 20 min at 145 °C in the presence (R+g) or absence (R−g) of glucose, and soluble proteins were then extracted. Sera obtained from 12 well‐characterized peanut‐allergic patients were used to assess the IgE binding and degranulation capacities of the allergens.
Results Extensive heating at low moisture resulted in the hydrolysis of both Ara h 1 and Ara h 2/6. However, in contrast to Ara h 2/6, soluble R+g Ara h 1 formed large aggregates. Although the IgE‐binding capacity of R+g and R−g Ara h 1 was decreased 9000‐ and 3.6‐fold, respectively, compared with native Ara h 1, their capacity to elicit mediator release was increased. Conversely, both the IgE‐binding capacity and the degranulation capacity of R−g Ara h 2/6 were 600–700‐fold lower compared with the native form, although the presence of glucose during heating significantly moderated these losses.
Conclusions and Clinical Relevance Extensive heating reduced the degranulation capacity of Ara h 2/6 but significantly increased the degranulation capacity of Ara h 1. This observation can have important ramifications for component‐resolved approaches for diagnosis and demonstrates the importance of investigating the degranulation capacity in addition to IgE reactivity when assessing the effects of food processing on the allergenicity of proteins.
Cite this as: Y. M. Vissers, M. Iwan, K. Adel‐Patient, P. Stahl Skov, N. M. Rigby, P. E. Johnson, P. Mandrup Müller, L. Przybylski‐Nicaise, M. Schaap, J. Ruinemans‐Koerts, A. P. H. Jansen, E. N. C. Mills, H. F. J. Savelkoul and H. J. Wichers, Clinical & Experimental Allergy, 2011 (41) 1631–1642.
Herpes zoster and postherpetic neuralgia occur more often with increasing age. In this controlled trial among 38,546 adults 60 years of age or older, vaccination with a live attenuated ...varicella–zoster vaccine reduced the incidence of postherpetic neuralgia by 66.5 percent (as compared with placebo) and the incidence of herpes zoster by 51.3 percent.
In adults 60 years of age or older, vaccination with a live attenuated varicella–zoster vaccine reduced the incidence of postherpetic neuralgia by 66.5 percent (as compared with placebo) and the incidence of herpes zoster by 51.3 percent.
Herpes zoster, or shingles, is characterized by unilateral radicular pain and a vesicular rash that is generally limited to a single dermatome.
1
,
2
Herpes zoster results from reactivation of latent varicella–zoster virus (VZV) within the sensory ganglia.
3
,
4
The incidence and severity of herpes zoster increase with advancing age; more than half of all persons in whom herpes zoster develops are older than 60 years. Complications occur in almost 50 percent of older persons with herpes zoster.
3
–
5
The most frequent debilitating complication is postherpetic neuralgia, a neuropathic pain syndrome that persists or develops after the dermatomal rash has healed. . . .
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