A segregated finite element method for cardiac elastodynamics in a fully coupled human heart model

One key characterstic of the cardiac function is its complexity, i.e., the multitude of different phenomena acting on various temporal and spatial scales interacting with each other. Over the past decades, many models varying in complexity describing these interactions were presented and are used in current research. Despite the incredible progress made in describing and simulating cardiac function, most of the more detailed models are not properly embedded within mathematical theory. This work aims to give a precise and comprehensive mathematical formulation of coupled cardiac elastodynamics, including electrophysiology, elasticity and physiological boundary conditions developed in recent years. Focussing on the analysis of dynamic elasticity, the concept of anisotropy is applied to common cardiac tissue models, such as the models of Guccione et al. and Holzapfel and Ogden. Frequently used modeling approaches, such as incompressibility and the active strain decomposition, are integrated in one overarching framework, allowing for propositions on polyconvexity of the materials and solvability of the elastic system. The equations of elastodynamics are then complemented by the monodomain equations, describing the propagation of the excitation potential in cardiac tissue, and a surrogate model to simulate cardiovascular blood pressure. The full mathematical description of this coupled model allows a detailed formulation of a discretization scheme in space and time for the electro-elastodynamical system. The classification of the coupled model within the context of weak solutions is presented and a time-segregated numerical approximation method for the full system is derived. The formulated numerical method is then examined by application on coupled test cases, providing first convergence results in space for the displacement in coupled cardiac problems

The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion

The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization.Leibniz Graduate School grants: (SFB958, SFB635)

A Large-scale Virtual Patient Cohort to Study ECG Features of Interatrial Conduction Block

Interatrial conduction block refers to a disturbance in the propagation of electrical impulses in the conduction pathways between the right and the left atrium. It is a risk factor for atrial fibrillation, stroke, and premature death. Clinical diagnostic criteria comprise an increased P wave duration and biphasic P waves in lead II, III and aVF due to retrograde activation of the left atrium. Machine learning algorithms could improve the diagnosis but require a large-scale, well-controlled and balanced dataset. In silico electrocardiogram (ECG) signals, optimally obtained from a statistical shape model to cover anatomical variability, carry the potential to produce an extensive database meeting the requirements for successful machine learning application. We generated the first in silico dataset including interatrial conduction block of 9,800 simulated ECG signals based on a bi-atrial statistical shape model. Automated feature analysis was performed to evaluate P wave morphology, duration and P wave terminal force in lead V1. Increased P wave duration and P wave terminal force in lead V1 were found for models with interatrial conduction block compared to healthy models. A wide variability of P wave morphology was detected for models with interatrial conduction block. Contrary to previous assumptions, our results suggest that a biphasic P wave morphology seems to be neither necessary nor sufficient for the diagnosis of interatrial conduction block. The presented dataset is ready for a classification with machine learning algorithms and can be easily extended

A SENTENÇA DE MÉRITO PROLATADA COM A PRETERIÇÃO DO(S) LITISCONSORTE(S) NECESSÁRIO(S) UNITÁRIO(S): UMA ANÁLISE SOB A ÓTICA DOS PLANOS DOS ATOS PROCESSUAIS

RESUMOO presente estudo tem como objetivo geral compreender em qual dos planos dos atos processuais – existência, validade ou eficácia – reside o defeito que acomete a sentença de mérito prolatada com a preterição do(s) litisconsorte(s) necessário(s) unitário(s). A partir dos resultados obtidos com a pesquisa, constatou-se que, para o alcance de uma conclusão satisfatória a seu respeito, é imprescindível a verificação do momento em que é alegada a preterição do(s) litisconsorte(s) necessário(s) unitário(s). Assim, concluiu-se que, na eventualidade de a alegação ocorrer anteriormente ao trânsito em julgado, o defeito estará situado no plano da validade, tratando-se de uma nulidade absoluta. Por outro lado, após o trânsito em julgado, o que remanesce é o vício no plano da eficácia. Dessa forma, observa-se que a atual legislação processual civil não é incorreta, mas incompleta e carente de precisão. Isso porque, apesar da superlativa importância da definição do momento em que se está analisando o vício, o Código de Processo Civil de 2015 é omisso com relação a esse aspecto, potencializando as dúvidas a respeito do tema. Por fim, verificou-se que, devido à gravidade do defeito que acomete essa sentença – oriunda, sobretudo, da ofensa aos princípios constitucionais –, é possível que qualquer interessado o alegue. Além disso, pelos mesmos motivos, as vias processuais admissíveis para combater esse vício são variadas, podendo ser manejada a ação rescisória, a impugnação ao cumprimento de sentença, a querela nullitatis insanabilis ou, ainda, qualquer outro meio idôneo e compatível com a situação concreta.Palavras-chave: Litisconsórcio necessário unitário. Sentença de mérito. Inexistência. Invalidade. Ineficácia. ABSTRACTThe purpose of the present study is to understand in which of the plans of procedural acts – existence, validity or efficacy – is situated the defect that affects the judgment of merit prolated with the pretermission of the necessary unitary collegitimate. From the results obtained with the research, it was verified that, in order to arrive at a satisfactory conclusion about it, it is essential to verify the moment when is alleged the omission of the necessary unitary collegitimate. Thus, it was concluded that, if the claim occurs before it is formed the res judicata, the defect is situated in the validity plan, being an absolute nullity. On the other hand, after the res judicata is formed, what remains is the inefficacy. Therefore, it was verified that the current civil procedural law is not incorrect, but incomplete and lacking precision. This is because, in spite of the superlative importance of defining which moment the defect is being analyzed, the Brazilian Civil Procedure Code of 2015 do not consider this aspect, potentializing doubts about the issue. Finally, it was discovered that, because of the severity of the defect that affects this veredict – originated, principally, from the offense to the constitutional principles – it is possible that any interested subject of the process can claim it. Besides that, for the same reasons, it is admitted the use of several procedural means to combat this decision, like the rescissory action, the enforcement’s impugnment of the judgment, the querela nullitatis insanabilis or any other suitable procedural means and compatible with the specific situation.Keywords: Necessary unitary joinder of parties. Judgment of merit. Inexistence. Invalidity. Inefficacy

Electro-mechanical whole-heart digital twins: A fully coupled multi-physics approach

Mathematical models of the human heart are evolving to become a cornerstone of precision medicine and support clinical decision making by providing a powerful tool to understand the mechanisms underlying pathophysiological conditions. In this study, we present a detailed mathematical description of a fully coupled multi-scale model of the human heart, including electrophysiology, mechanics, and a closed-loop model of circulation. State-of-the-art models based on human physiology are used to describe membrane kinetics, excitation-contraction coupling and active tension generation in the atria and the ventricles. Furthermore, we highlight ways to adapt this framework to patient specific measurements to build digital twins. The validity of the model is demonstrated through simulations on a personalized whole heart geometry based on magnetic resonance imaging data of a healthy volunteer. Additionally, the fully coupled model was employed to evaluate the effects of a typical atrial ablation scar on the cardiovascular system. With this work, we provide an adaptable multi-scale model that allows a comprehensive personalization from ion channels to the organ level enabling digital twin modeling

CENP-C facilitates the recruitment of M18BP1 to centromeric chromatin

Centromeres are important structural constituents of chromosomes that ensure proper chromosome segregation during mitosis by providing defined sites for kinetochore attachment. In higher eukaryotes, centromeres have no specific DNA sequence and thus, they are rather determined through epigenetic mechanisms. A fundamental process in centromere establishment is the incorporation of the histone variant CENP-A into centromeric chromatin, which provides a binding platform for the other centromeric proteins. The Mis18 complex, and, in particular, its member M18BP1 was shown to be essential for both incorporation and maintenance of CENP-A

Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy

The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid adverse side effects from continuous dosing. Here we show that geroprotective effects of chronic rapamycin treatment can be obtained with a brief pulse of the drug in early adulthood in female Drosophila and mice. In Drosophila, a brief, early rapamycin treatment of adults extended lifespan and attenuated age-related decline in the intestine to the same degree as lifelong dosing. Lasting memory of earlier treatment was mediated by elevated autophagy in intestinal enterocytes, accompanied by increased levels of intestinal LManV and lysozyme. Brief elevation of autophagy in early adulthood itself induced a long-term increase in autophagy. In mice, a 3-month, early treatment also induced a memory effect, with maintenance similar to chronic treatment, of lysozyme distribution, Man2B1 level in intestinal crypts, Paneth cell architecture and gut barrier function, even 6 months after rapamycin was withdrawn

A novel subset of CD4+ TH2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma

Memory CD4+ T cells that produce both Th2 and Th17 cytokines are increased in the blood of patients with atopic asthma and in the lungs of asthmatic mice, where they contribute to inflammation

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.