Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14–39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty^® (Pfizer-BioNTech) (n = 11), Vaxzevria^® (AstraZenica) (n = 2) and Janssen^® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4⁺ and CD8⁺ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4⁺ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.     

Consensus reaching in multi-agent packet-switched networks with non-linear coupling

An important task for multi-agent systems (MAS) is to reach a consensus, e.g. to align their velocity vectors. Recent results propose appropriate consensus protocols to achieve such tasks, but most of them do not consider the effect of communication constraints such as the presence of time-delays in the exchange of information between the agents. In this article, we provide conditions for a non-linear, locally passive MAS of arbitrary size to reach a consensus, when the agents communicate over a packet-switched network that is characterised by a given topology. Both the cases of constant and switching topologies are considered. The nature of the communication channel imposes constraints that are modelled using stochastic delays of arbitrary distribution. We first embed this model in another, distributed but deterministic delay model and provide conditions for the error introduced by this simplification. In our main result, we provide conditions for the locally passive MAS with distributed delays to reach a consensus. In the case of a fixed topology, the underlying directed graph has to contain a spanning tree. In the case of a switching topology, only the union graph of all graphs that persist over time is required to contain a spanning tree. These conditions are independent of the distribution and the size of the packet delays. To show attractivity of the consensus set, we use an invariance principle for systems described by functional differential equations based on an appropriate Lyapunov–Razumikhin function. This methodological approach is the main contribution of this work and can also be applied to other consensus problems with delays. We illustrate our results by numerical simulations showing synchronisation of non-linear Kuramoto oscillators over a digital network.     

Coinduction for Exact Real Number Computation

This paper studies coinductive representations of real numbers by signed digit streams and fast Cauchy sequences. It is shown how the associated coinductive principle can be used to give straightforward and easily implementable proofs of the equivalence of the two representations as well as the correctness of various corecursive exact real number algorithms. The basic framework is the classical theory of coinductive sets as greatest fixed points of monotone operators and hence is different from (though related to) the type theoretic approach by Ciaffaglione and Gianantonio.     

Col4a3-/- Mice on Balb/C Background Have Less Severe Cardiorespiratory Phenotype and SGLT2 Over-Expression Compared to 129x1/SvJ and C57Bl/6 Backgrounds

Alport syndrome (AS) is a hereditary renal disorder with no etiological therapy. In the preclinical Col4a3^-/- model of AS, disease progression and severity vary depending on mouse strain. The sodium-glucose cotransporter 2 (SGLT2) is emerging as an attractive therapeutic target in cardiac/renal pathologies, but its application to AS remains untested. This study investigates cardiorespiratory function and SGLT2 renal expression in Col4a3^-/- mice from three different genetic backgrounds, 129x1/SvJ, C57Bl/6 and Balb/C. male Col4a3^-/- 129x1/SvJ mice displayed alterations consistent with heart failure with preserved ejection fraction (HFpEF). Female, but not male, C57Bl/6 and Balb/C Col4a3^-/- mice exhibited mild changes in systolic and diastolic function of the heart by echocardiography. Male C57Bl/6 Col4a3^-/- mice presented systolic dysfunction by invasive hemodynamic analysis. All strains except Balb/C males demonstrated alterations in respiratory function. SGLT2 expression was significantly increased in AS compared to WT mice from all strains. However, cardiorespiratory abnormalities and SGLT2 over-expression were significantly less in AS Balb/C mice compared to the other two strains. Systolic blood pressure was significantly elevated only in mutant 129x1/SvJ mice. The results provide further evidence for strain-dependent cardiorespiratory and hypertensive phenotype variations in mouse AS models, corroborated by renal SGLT2 expression, and support ongoing initiatives to develop SGLT2 inhibitors for the treatment of AS.     

用于细旦长丝变形的MPS CoolFlex

由于能耗可降低30%,MPS变形机可很容易地将速度提高30%,从而使MPS的构想成为一种用于细旦长丝变形加工的十分经济的方案.     

Mismatch Modeling and Simulation—A Comprehensive Approach

This article describes a comprehensive approach to mismatch simulation and modeling as needed for integrated circuit design. Local device mismatch as well as global process variations and parameter correlations are regarded. A method for mismatch modeling based on spatial frequencies is described, which enables to overcome insufficiencies of the first order models. Measurement results are presented to demonstrate the achieved modeling precision. All models and methods mentioned here are commercially available in the simulation tool GAME (General Analysis of Mismatch Effects) which is used in the semiconductor industry since 1998.     

Reconciling fault-tolerant distributed computing and systems-on-chip

Classic distributed computing abstractions do not match well the reality of digital logic gates, which are the elementary building blocks of Systems-on-Chip (SoCs) and other Very Large Scale Integrated (VLSI) circuits: Massively concurrent, continuous computations undermine the concept of sequential processes executing sequences of atomic zero-time computing steps, and very limited computational resources at gate-level make even simple operations prohibitively costly. In this paper, we introduce a modeling and analysis framework based on continuous computations and zero-bit message channels, and employ this framework for the correctness & performance analysis of a distributed fault-tolerant clocking approach for Systems-on-Chip (SoCs). Starting out from a “classic” distributed Byzantine fault-tolerant tick generation algorithm, we show how to adapt it for direct implementation in clockless digital logic, and rigorously prove its correctness and derive analytic expressions for worst case performance metrics like synchronization precision and clock frequency. Rather than on absolute delay values, both the algorithm’s correctness and the achievable synchronization precision depend solely on the ratio of certain path delays. Since these ratios can be mapped directly to placement & routing constraints, there is typically no need for changing the algorithm when migrating to a faster implementation technology and/or when using a slightly different layout in an SoC.