Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.     

Automatic analysis of human posture equilibrium using empirical mode decomposition

The present study proposes a new approach for the assessment of the human balance control. This approach is based on the decomposition of the center of pressure displacement using empirical mode decomposition (EMD) that provides an effective time-frequency analysis of non-stationary signals. Twenty-eight healthy subjects performed quiet standing in four conditions—feet apart/together with respect to eyes open/closed—while recording the stabilometric signals in the anteroposterior (AP) and mediolateral (ML) directions. The EMD method decomposes each stabilometric signal into several subsignals called intrinsic mode functions (IMFs). Stabilogram-diffusion analysis technique is applied to generate the diffusion curve of each IMF signal. Each diffusion curve is modeled as a second-order system and provides representative features, such as the gain parameter. Analysis of the gain parameter shows the major effect of visual input and feet conditions on the strategy to control/stabilize the balance. Significant differences were found between young and elderly, and between women and men. In addition, the impact of feet position seems to be higher in ML direction than in AP direction.     

A New Strategy to Preserve and Assess Oxygen Consumption in Murine Tissues

Mitochondrial dysfunctions are implicated in several pathologies, such as metabolic, cardiovascular, respiratory, and neurological diseases, as well as in cancer and aging. These metabolic alterations are usually assessed in human or murine samples by mitochondrial respiratory chain enzymatic assays, by measuring the oxygen consumption of intact mitochondria isolated from tissues, or from cells obtained after physical or enzymatic disruption of the tissues. However, these methodologies do not maintain tissue multicellular organization and cell-cell interactions, known to influence mitochondrial metabolism. Here, we develop an optimal model to measure mitochondrial oxygen consumption in heart and lung tissue samples using the XF24 Extracellular Flux Analyzer (Seahorse) and discuss the advantages and limitations of this technological approach. Our results demonstrate that tissue organization, as well as mitochondrial ultrastructure and respiratory function, are preserved in heart and lung tissues freshly processed or after overnight conservation at 4 °C. Using this method, we confirmed the repeatedly reported obesity-associated mitochondrial dysfunction in the heart and extended it to the lungs. We set up and validated a new strategy to optimally assess mitochondrial function in murine tissues. As such, this method is of great potential interest for monitoring mitochondrial function in cohort samples.     

New huprine derivatives functionalized at position 9 as highly potent acetylcholinesterase inhibitors

A series of 24 huprine derivatives diversely functionalized at position 9 have been synthesized and evaluated for their inhibitory activity against human recombinant acetylcholinesterase (AChE). These derivatives were prepared in one to five steps from huprine 1 bearing an ester function at position 9. Ten analogues ( 1 , 2 , 6 – 9 , 13 – 15 , and 23 ) are active in the low nanomolar range (IC₅₀ <5 nM ), very close to the parent compound huprine X. Compounds 2 , 6 , and 7 show a very good selectivity for AChE, with AChE inhibitory activities 700–1160‐fold higher than those for butyrylcholinesterase (BChE). The inhibitory potency of these compounds decreases with the steric bulk of the substituents at position 9. According to docking simulations, small substituents fit into the acyl‐binding pocket, whereas the larger ones stick out of the active site gorge of AChE. Determination of the kinetic parameters of three of the most potent huprines ( 2 , 6 , and 7 ) showed that most of the difference in K_D is accounted by a decrease in k_on, which is correlated to the increase of the substituent size. A first in vivo evaluation has been performed in mice for the most active compound 2 (IC₅₀=1.1 nM ) and showed a rather weak toxicity (LD₅₀=40 mg kg^?1) and an ability to cross the blood–brain barrier with doses above 15 mg kg^?1.     

Statistical prediction of fracture parameters of concrete and implications for choice of testing standard

This article shows how the fracture energy of concrete, as well as other fracture parameters such as the effective length of the fracture process zone, critical crack-tip opening displacement and the fracture toughness, can be approximately predicted from the standard compression strength, maximum aggregate size, water-cement ratio, and aggregate type (river or crushed). A database, consisting of 238 test data, is extracted from the literature and tabulated, and approximate mean prediction formulae calibrated by this very large data set are developed. A distinction is made between (a) the fracture energy, G_f, corresponding to the area under the initial tangent of the softening stress-separation curve of cohesive crack model, which governs the maximum loads of structures and is obtained by the size effect method (SEM) or related methods (Jenq-Shah two-parameter method and Karihaloo's effective crack model, ECM) and (b) the fracture energy, G_F, corresponding to the area under the complete stress-separation curve, which governs large postpeak deflections of structures and is obtained by the work-of-fracture method (WFM) proposed for concrete by Hillerborg. The coefficients of variation of the errors in the prediction formulae compared to the test data are calculated; they are 17.8% for G_f and 29.9% for G_F, the latter being 1.67 times higher than the former. Although the errors of the prediction formulae taking into account the differences among different concretes doubtless contribute significantly to the high values of these coefficients of variation, there is no reason for a bias of the statistics in favor of G_f or G_F. Thus, the statistics indicate that the fracture energy based on the measurements in the maximum load region is much less uncertain than that based on the measurement of the tail of the postpeak load-deflection curve. While both G_f and G_F are needed for accurate structural analysis, it follows that if the testing standard should measure, for the sake of simplicity, only one of these two fracture energies, then G_f is preferable.     

Carbon–polymer composites with extreme electrical conductivity

The aim of this study was to develop Carbon–polymer composites with extreme electrical conductivity (100 S/cm) combined with good flexural strength. Despite the many optimization methods described in the literature, no comprehensive optimization procedure was to be found because the formulation did not control by itself the final properties. This study showed the major influence of the processing conditions with these peculiar materials. A detailed study of the influence of the processing conditions on the microstructural and macroscopic properties was performed. We, thereby, proposed a comprehensive way to optimize the properties of the final product. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42274.     

Thermochemical stability of the Y2O3–SiO2 system

A thermodynamic study was carried out in order to quantify the stability of yttrium silicates under different atmospheres (argon, air, moisture), and to predict their behaviour as an EBC. For this purpose, the partial pressures of gaseous species formed during the reactive vaporization in equilibrium with yttrium silicates were evaluated and compared to those over each oxide taken separately. The partial pressures of silicon and rare earth hydroxides at the equilibrium over rare earth silicates are lower than those over each single oxide. Thus yttrium silicates appear to be sufficiently stable to be promising materials to be used as environmental barrier coatings.