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.     

Quadrature ���� Modulators for Cognitive Radio��I/Q Imbalance Analysis and Complex Multiband Principle

This article discusses the applicability of quadrature ΣΔ modulator (QΣΔM) based analog-to-digital (A/D) conversion in cognitive radio (CR) receivers. First, unavoidable in-phase/quadrature (I/Q) mismatch effects, limiting the dynamic range, are analyzed in closed-form in the case of a first-order modulator. In addition, using the derived analytical converter model, it is shown that notching the signal transfer function (STF) of the modulator at the mirror frequencies of the desired signals will effectively cancel the I/Q imbalance induced mirror-frequency interference in case of the modulator feedback mismatch. In practice, such STF design is easy to implement within the existing converter circuitry, as will be demonstrated in this article. The latter part of the article proposes a novel complex multiband QΣΔM scheme, particularly aimed for the CR receivers. This multiband scheme allows parallel reception of scattered frequency chunks in the CR context and is stemming from the additional degrees of freedom in noise transfer function (NTF) design, provided by the QΣΔM principle. Here multiple noise shaping notches on distinct frequencies are effectively realized through proper design of complex NTF. The modulator structure also allows flexible reconfigurability of the notches with straightforward parameterization of the modulator transfer functions. When combined with the above mirror-frequency rejecting STF design, the concept is demonstrated and proved effective and robust against I/Q imbalances using practical radio signal simulations in realistic received signal conditions.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea

We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fruiting bodies. Cocaprins are small proteins (15 kDa) with acidic isoelectric points that form dimers. The three-dimensional structure of cocaprin 1 showed similarity to fungal β-trefoil lectins. Cocaprins inhibit plant C1 family cysteine proteases with K_i in the micromolar range, but do not inhibit the C13 family protease legumain, which distinguishes them from mycocypins. Cocaprins also inhibit the aspartic protease pepsin with K_i in the low micromolar range. Mutagenesis revealed that the β2-β3 loop is involved in the inhibition of cysteine proteases and that the inhibitory reactive sites for aspartic and cysteine proteases are located at different positions on the protein. Their biological function is thought to be the regulation of endogenous proteolytic activities or in defense against fungal antagonists. Cocaprins are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, and demonstrate the incredible plasticity of loop functionalization in fungal proteins with β-trefoil fold.     

Entanglement energetics in the ground state

Abstract

We show how many-body ground state entanglement information may be extracted from sub-system energy measurements at zero temperature. A precise relation between entanglement and energy fluctuations is demonstrated in the weak coupling limit. Examples are given with the two-state system and the harmonic oscillator, and energy probability distributions are calculated. Comparisons made with recent qubit experiments show this type of measurement provides another method to quantify entanglement with the environment.     

Effect of Inclusion Size and Distribution on the Corrosion Behavior of Medical-Device Grade Nitinol Tubing

Nonmetallic inclusions in Nitinol, such as carbides (TiC) and intermetallic oxides (Ti₄Ni₂O _x ), are known to be triggers for fatigue failure of Nitinol medical devices. These mechanically brittle inclusions are introduced during the melting process. As a result of hot and cold working in the production of Nitinol tubing inclusions are fractionalized due to the mechanical deformation imposed. While the role of inclusions regarding Nitinol fatigue performance has been studied extensively in the past, their effect on Nitinol corrosion behavior was investigated in only a limited number of studies. The focus of the present work was to understand the effect of inclusion size and distribution on the corrosion behavior of medical-device grade Nitinol tubing made from three different ingot sources during different manufacturing stages: (i) for the initial stage (hollow: round bar with centric hole), (ii) after hot drawing, and (iii) after the final drawing step (final tubing dimensions: outer diameter 0.3 mm, wall thickness 0.1 mm). For one ingot source, two different material qualities were investigated. Potentiodynamic polarization tests were performed for electropolished samples of the above-mentioned stages. Results indicate that inclusion size rather than inclusion quantity affects the susceptibility of electropolished Nitinol to pitting corrosion.     

Integrating toxin gene expression,growth and fumonisin B1 and B2 production by a strain of Fusarium verticillioides under different environmental factors

The objective of this study was to integrate data on the effect of water activity (a_w; 0.995–0.93) and temperature (20–35°C) on activation of the biosynthetic FUM genes, growth and the mycotoxins fumonisin (FB₁, FB₂) by Fusarium verticillioides in vitro. The relative expression of nine biosynthetic cluster genes (FUM1, FUM7, FUM10, FUM11, FUM12, FUM13, FUM14, FUM16 and FUM19) in relation to the environmental factors was determined using a microarray analysis. The expression was related to growth and phenotypic FB₁ and FB₂ production. These data were used to develop a mixed-growth-associated product formation model and link this to a linear combination of the expression data for the nine genes. The model was then validated by examining datasets outside the model fitting conditions used (35°C). The relationship between the key gene (FUM1) and other genes in the cluster (FUM11, FUM13, FUM9, FUM14) were examined in relation to a_w, temperature, FB₁ and FB₂ production by developing ternary diagrams of relative expression. This model is important in developing an integrated systems approach to develop prevention strategies to control fumonisin biosynthesis in staple food commodities and could also be used to predict the potential impact that climate change factors may have on toxin production.     

Analysis of New Nitinol Ingot Qualities

New ingot qualities, processed by optimized vacuum arc remelting (VAR), optimized vacuum induction melting followed by VAR and VAR followed by electron beam remelting, were compared with standard quality. Finished components as well as diamond-shaped samples representing a typical dimension of self-expanding stents were produced using Nitinol tubing drawn from the new ingot qualities. Metallographic longitudinal sections were prepared and analyzed to determine inclusion size and distributions of the various ingot qualities. Radial force and uniaxial tensile tests were used to determine the mechanical properties of fully processed material and tubing, respectively. Transformation temperatures of tubing as delivered from supplier and processed stents were measured by differential scanning calorimetry and deformation-and-free-recovery testing. Finally, fatigue tests were performed on diamond-shaped samples to evaluate the strain-life characteristics of the new ingot qualities. Results of this study are compared to ADMEDES historical data from standard Nitinol materials to gain an assessment of the new improved ingot qualities with regard to the production of Nitinol vascular implants. The latest developments in Nitinol ingot quality are highlighted and the results of the comparison from technical point of view are shown.     

The influence of the degree of heterogeneity on the elastic properties of random sphere packings

The macroscopic mechanical properties of colloidal particle gels strongly depend on the local arrangement of the powder particles. Experiments have shown that more heterogeneous microstructures exhibit up to one order of magnitude higher elastic properties than their more homogeneous counterparts at equal volume fraction. In this paper, packings of spherical particles are used as model structures to computationally investigate the elastic properties of coagulated particle gels as a function of their degree of heterogeneity. The discrete element model comprises a linear elastic contact law, particle bonding and damping. The simulation parameters were calibrated using a homogeneous and a heterogeneous microstructure originating from earlier Brownian dynamics simulations. A systematic study of the elastic properties as a function of the degree of heterogeneity was performed using two sets of microstructures obtained from Brownian dynamics simulation and from the void expansion method. Both sets cover a broad and to a large extent overlapping range of degrees of heterogeneity. The simulations have shown that the elastic properties as a function of the degree of heterogeneity are independent of the structure generation algorithm and that the relation between the shear modulus and the degree of heterogeneity can be well described by a power law. This suggests the presence of a critical degree of heterogeneity and, therefore, a phase transition between a phase with finite and one with zero elastic properties.