Well-posedness of the fully coupled quasi-static thermo-poro-elastic equations with nonlinear convective transport

This paper is concerned with the analysis of the quasi-static thermo-poroelastic model. This model is nonlinear and includes thermal effects compared to the classical quasi-static poroelastic model (also known as Biot's model). It consists of a momentum balance equation, a mass balance equation, and an energy balance equation, fully coupled and nonlinear due to a convective transport term in the energy balance equation. The aim of this article is to investigate, in the context of mixed formulations, the existence and uniqueness of a weak solution to this model problem. The primary variables in these formulations are the fluid pressure, temperature and elastic displacement as well as the Darcy flux, heat flux and total stress. The well-posedness of a linearized formulation is addressed first through the use of a Galerkin method and suitable a priori estimates. This is used next to study the well-posedness of an iterative solution procedure for the full nonlinear problem. A convergence proof for this algorithm is then inferred by a contraction of successive difference functions of the iterates using suitable norms.Comment: 22 page

Targeting the ubiquitin proteasome pathway for the treatment of septic shock in patients

Endotoxic shock is a serious systemic inflammatory response to an external biological stressor. The responsiveness of NF-κB is built upon rapid protein modification and degradation involving the ubiquitin proteasome pathway. Using transgenic mice, we have obtained in vivo evidence that interference with this pathway can alleviate the symptoms of toxic shock. We posit that administration of proteasome inhibitors may enhance the survival of patients with septic shock

Modeling the Process of Speciation Using a Multiscale Framework Including A Posteriori Error Estimates

This paper concerns the modeling and numerical simulation of the process of speciation. In particular, given conditions for which one or more speciation events within an ecosystem occur, our aim is to develop the necessary modeling and simulation tools. Care is also taken to establish a solid mathematical foundation on which our modeling framework is built. This is the subject of the first half of the paper. The second half is devoted to developing a multiscale framework for eco-evolutionary modeling, where the relevant scales are that of species and individual/population, respectively. The species level model we employ can be considered as an extension of the classical Lotka--Volterra model, where in addition to the species abundance, the model also governs the evolution of the species mean traits and species trait covariances and in this sense generalizes the purely ecological Lotka--Volterra model to an eco-evolutionary model. Although the model thus allows for evolving species, it does not (by construction) allow for the branching of species, i.e., speciation events. The reason for this is related to that of separate scales; the unit of species is too coarse to capture the fine-scale dynamics of a speciation event. Instead, the branching species should be regarded as a population of individuals moving along a selection of trait axes (i.e., trait-space). For this, we employ a trait-specific population density model governing the dynamics of the population density as a function of evolutionary traits. At this scale there is no a priori definition of species, but both species and speciation may be defined a posteriori as, e.g., local maxima and saddle points of the population density, respectively. Hence, a system of interacting species can be described at the species level, while for branching species a population level description is necessary. Our multiscale framework thus consists of coupling the species and population level models where speciation events are detected in advance and then resolved at the population scale until the branching is complete. Moreover, since the population level model is formulated as a PDE, we first establish the well-posedness in the time-discrete setting and then derive the a posteriori error estimates, which provides a fully computable upper bound on an energy-type error, including also for the case of general smooth distributions (which will be useful for the detection of speciation events). Several numerical tests validate our framework in practice.publishedVersio

Upscaling of the Coupling of Hydromechanical and Thermal Processes in a Quasi-static Poroelastic Medium

We undertake a formal derivation of a linear poro-thermo-elastic system within the framework of quasi-static deformation. This work is based upon the well-known derivation of the quasi-static poroelastic equations (also known as the Biot consolidation model) by homogenization of the fluid-structure interaction at the microscale. We now include energy, which is coupled to the fluid-structure model by using linear thermoelasticity, with the full system transformed to a Lagrangian coordinate system. The resulting upscaled system is similar to the linear poroelastic equations, but with an added conservation of energy equation, fully coupled to the momentum and mass conservation equations. In the end, we obtain a system of equations on the macroscale accounting for the effects of mechanical deformation, heat transfer, and fluid flow within a fully saturated porous material, wherein the coefficients can be explicitly defined in terms of the microstructure of the material. For the heat transfer we consider two different scaling regimes, one where the Péclet number is small, and another where it is unity.We also establish the symmetry and positivity for the homogenized coefficients.publishedVersio

Regulation of PCNA polyubiquitination in human cells

<p>Abstract</p> <p>Background</p> <p>The ubiquitin-based molecular switch dictating error free versus error prone repair has been conserved throughout eukaryotic evolution. A central component of this switch is the homotrimeric clamp PCNA, which is ubiquitinated in response to genotoxic stress allowing recovery of replication forks blocked at sites of DNA damage. The particulars of PCNA ubiquitination have been elucidated in yeast and to a further extent recently in human cells. However, gaps in the detailed mechanism and regulation of PCNA polyubiquitination still persist in human cells.</p> <p>Findings</p> <p>We expand upon several studies and show that PCNA is polyubiquitnated in normal skin fibroblasts, and that this ubiquitination is dependant on RAD18. Furthermore we define the types of DNA damage that induce ubiquitination on PCNA. Cisplatin, methylmethane sulphonate and benzo(a)pyrene-diol-epoxide induce the polyubiquitination of PCNA to the same extent as UV while polyubiquitination is not detected after X-ray treatment. Moreover, we show that ubiquitination of PCNA is not regulated by cell cycle checkpoint kinases ATM-Chk2 or ATR-Chk1. Significantly, we report that PCNA polyubiquitination is negatively regulated by USP1.</p> <p>Conclusions</p> <p>Our results demonstrate the importance of PCNA polyubiquitination in human cells and define the key regulator of this ubiquitination.</p

Upscaling of the Coupling of Hydromechanical and Thermal Processes in a Quasi-static Poroelastic Medium

We undertake a formal derivation of a linear poro-thermo-elastic system within the framework of quasi-static deformation. This work is based upon the well-known derivation of the quasi-static poroelastic equations (also known as the Biot consolidation model) by homogenization of the fluid-structure interaction at the microscale. We now include energy, which is coupled to the fluid-structure model by using linear thermoelasticity, with the full system transformed to a Lagrangian coordinate system. The resulting upscaled system is similar to the linear poroelastic equations, but with an added conservation of energy equation, fully coupled to the momentum and mass conservation equations. In the end, we obtain a system of equations on the macroscale accounting for the effects of mechanical deformation, heat transfer, and fluid flow within a fully saturated porous material, wherein the coefficients can be explicitly defined in terms of the microstructure of the material. For the heat transfer we consider two different scaling regimes, one where the Péclet number is small, and another where it is unity.We also establish the symmetry and positivity for the homogenized coefficients.publishedVersio

Upscaling of the Coupling of Hydromechanical and Thermal Processes in a Quasi-static Poroelastic Medium

We undertake a formal derivation of a linear poro-thermo-elastic system within the framework of quasi-static deformation. This work is based upon the well-known derivation of the quasi-static poroelastic equations (also known as the Biot consolidation model) by homogenization of the fluid-structure interaction at the microscale. We now include energy, which is coupled to the fluid-structure model by using linear thermoelasticity, with the full system transformed to a Lagrangian coordinate system. The resulting upscaled system is similar to the linear poroelastic equations, but with an added conservation of energy equation, fully coupled to the momentum and mass conservation equations. In the end, we obtain a system of equations on the macroscale accounting for the effects of mechanical deformation, heat transfer, and fluid flow within a fully saturated porous material, wherein the coefficients can be explicitly defined in terms of the microstructure of the material. For the heat transfer we consider two different scaling regimes, one where the Péclet number is small, and another where it is unity.We also establish the symmetry and positivity for the homogenized coefficients.publishedVersio

Separating Agent-Functioning and Inter-Agent Coordination by Activated Modules: The DECOMAS Architecture

The embedding of self-organizing inter-agent processes in distributed software applications enables the decentralized coordination system elements, solely based on concerted, localized interactions. The separation and encapsulation of the activities that are conceptually related to the coordination, is a crucial concern for systematic development practices in order to prepare the reuse and systematic integration of coordination processes in software systems. Here, we discuss a programming model that is based on the externalization of processes prescriptions and their embedding in Multi-Agent Systems (MAS). One fundamental design concern for a corresponding execution middleware is the minimal-invasive augmentation of the activities that affect coordination. This design challenge is approached by the activation of agent modules. Modules are converted to software elements that reason about and modify their host agent. We discuss and formalize this extension within the context of a generic coordination architecture and exemplify the proposed programming model with the decentralized management of (web) service infrastructures