Molecular definition of severe acute respiratory syndrome coronavirus 2 receptor-binding domain mutations: Receptor affinity versus neutralization of receptor interaction.

BACKGROUND Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor-binding domain (RBD) of the spike protein. It is unclear which mutations affect receptor affinity versus immune recognition. METHODS We produced wild type RBD, RBD with single mutations (E484K, K417N, or N501Y) or with all three mutations combined and tested their binding to ACE2 by biolayer interferometry (BLI). The ability of convalescent sera to recognize RBDs and block their interaction with ACE2 was tested as well. RESULTS We demonstrated that single mutation N501Y increased binding affinity to ACE2 but did not strongly affect its recognition by convalescent sera. In contrast, single mutation E484K had almost no impact on the binding kinetics, but essentially abolished recognition of RBD by convalescent sera. Interestingly, combining mutations E484K, K417N, and N501Y resulted in a RBD with both features: enhanced receptor binding and abolished immune recognition. CONCLUSIONS Our data demonstrate that single mutations either affect receptor affinity or immune recognition while triple mutant RBDs combine both features

What breeding strategy(ies) should be carry up for organic winter wheat? Results and prospects from a long-term comparison with low input variety trials

Breeding varieties adapted to various organic farming conditions is one solution, among others, to increase yields and improve organic winter bread wheat quality. From 2004 to 2011, INRA winter wheat breeders have conducted variety trials in three contrasting agro-climatic regions across north-west France to test the relative response of 25 to 30 diversified genotypes when cultivated in low input (FI) and organic (AB) conditions. The comparison of 17 paired management trials showed the relevance of low input conditions to identify genotypes adapted to organic farming conditions for yield and protein content. Such a selection environment is useful also to screen “GPD+” (positive Grain Protein Deviation) genotypes with better nutrient use efficiency. In contrast, our results highlighted the need to evaluate genotypes baking quality in organic conditions in which bread making ability is frequently lost

Combined coherent x-ray micro-diffraction and local mechanical loading on copper nanocrystals

Coherent x-ray micro-diffraction and local mechanical loading can be combined to investigate the mechanical deformation in crystalline nanostructures. Here we present measurements of plastic deformation in a copper crystal of sub-micron size obtained by loading the sample with an Atomic Force Microscopy tip. The appearance of sharp features in the diffraction pattern, while conserving its global shape, is attributed to crystal defects induced by the tip

Thick surface flows of granular materials: The effect of the velocity profile on the avalanche amplitude

A few years ago, Bouchaud al. introduced a phenomenological model to describe surface flows of granular materials [J. Phys. Fr. I, 4, 1383 (1994)]. According to this model, one can distinguish between a static phase and a rolling phase that are able to exchange grains through an erosion/accretion mechanism. Boutreux et al. [Phys. Rev. E, 58, 4692 (1998)] proposed a modification of the exchange term in order to describe thicker flows where saturation effects are present. However, these approaches assumed that the downhill convection velocity of the grains is constant inside the rolling phase, a hypothesis that is not verified experimentally. In this article, we therefore modify the above models by introducing a velocity profile in the flow, and study the physical consequences of this modification in the simple situation of an avalanche in an open cell. We present a complete analytical description of the avalanche in the case of a linear velocity profile, and generalize the results for a power-law dependency. We show, in particular, that the amplitude of the avalanche is strongly affected by the velocity profile.Comment: 7 figures, accepted for publication in Phys. Rev.

A model for the formation energies of alanates and boranates

We develop a simple model for the formation energies (FEs) of alkali and lkaline earth alanates and boranates, based upon ionic bonding between metal cations and (AlH4)- or (BH4)- anions. The FEs agree well with values obtained from first principles calculations and with experimental FEs. The model shows that details of the crystal structure are relatively unimportant. The small size of the (BH4)- anion causes a strong bonding in the crystal, which makes boranates more stable than alanates. Smaller alkali or alkaline earth cations do not give an increased FE. They involve a larger ionization potential that compensates for the increased crystal bonding.Comment: 3 pages, 2 figure

Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron.

In this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by physio-chemical characterization of this variant in comparison to the wild-type Wuhan and the Delta variant (B.1.617.2). Convalescent sera, as well as sera obtained from participants who received two or three doses of mRNA vaccines (Moderna-mRNA-1273® or Pfizer-BNT162b2®), were used for comparison in this study. Our data demonstrate that both Delta, as well as Omicron variants, exhibit a higher affinity for the receptor ACE2, facilitating infection and causing antibody escape by receptor affinity (affinity escape), due to the reduced ability of antibodies to compete with RBD-receptor interaction and virus neutralization. In contrast, only Omicron but not the Delta variant escaped antibody recognition, most likely because only Omicron exhibits the mutation at E484A, a position associated with reduced recognition, resulting in further reduced neutralization (specificity escape). Nevertheless, the immunizations with RNA-based vaccines resulted in marked viral neutralization in vitro for all strains, compatible with the fact that Omicron is still largely susceptible to vaccination-induced antibodies, despite affinity- and specificity escape

Density Modulations and Addition Spectra of Interacting Electrons in Disordered Quantum Dots

We analyse the ground state of spinless fermions on a lattice in a weakly disordered potential, interacting via a nearest neighbour interaction, by applying the self-consistent Hartree-Fock approximation. We find that charge density modulations emerge progressively when r_s >1, even away from half-filling, with only short-range density correlations. Classical geometry dependent "magic numbers" can show up in the addition spectrum which are remarkably robust against quantum fluctuations and disorder averaging.Comment: 4 pages, 3 eps figure

Profile and professional expectations of medical students in Mozambique: a longitudinal study

<p>Abstract</p> <p>Introduction</p> <p>This paper compares the socioeconomic profile of medical students registered at the Faculty of Medicine of Universidade Eduardo Mondlane (FM-UEM), Maputo, for the years 1998/99 and 2007/08.</p> <p>Case study</p> <p>The objective is to describe the medical students' social and geographical origins, expectations and perceived difficulties regarding their education and professional future. Data were collected through questionnaires administered to all medical students.</p> <p>Discussion and evaluation</p> <p>The response rate in 1998/99 was 51% (227/441) and 50% in 2007/08 (484/968).</p> <p>The main results reflect a doubling of the number of students enrolled for medical studies at the FM-UEM, associated with improved student performance (as reflected by failure rates). Nevertheless, satisfaction with the training received remains low and, now as before, students still identify lack of access to books or learning technology and inadequate teacher preparedness as major problems.</p> <p>Conclusions</p> <p>There is a high level of commitment to public sector service. However, students, as future doctors, have very high salary expectations that will not be met by current public sector salary scales. This is reflected in an increasing degree of orientation to double sector employment after graduation.</p

The Addition Spectrum and Koopmans' Theorem for Disordered Quantum Dots

We investigate the addition spectrum of disordered quantum dots containing spinless interacting fermions using the self-consistent Hartree-Fock approximation. We concentrate on the regime r_s >~1, with finite dimensionless conductance g. We find that in this approximation the peak spacing fluctuations do not scale with the mean single particle level spacing for either Coulomb or nearest neighbour interactions when r_s >~1. We also show that Koopmans' approximation to the addition spectrum can lead to errors that are of order the mean level spacing or larger, both in the mean addition spectrum peak spacings, and in the peak spacing fluctuations.Comment: 35 pages including 22 figures (eps

Dark pair coherent states of the motion of a trapped ion

We propose a scheme for generating vibrational pair coherent states of the motion of an ion in a two-dimensional trap. In our scheme, the trapped ion is excited bichromatically by three laser beams along different directions in the X-Y plane of the ion trap. We show that if the initial vibrational state is given by a two-mode Fock state, the final steady state, indicated by the extinction of the fluorescence emitted by the ion, is a pure state. The motional state of the ion in the equilibrium realizes that of the highly-correlated pair coherent state.Comment: 14 pages, 3 figure