Quantitative whole-body muscle MRI in idiopathic inflammatory myopathies including polymyositis with mitochondrial pathology: indications for a disease spectrum.

Objective: Inflammatory myopathies (IIM) include dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and overlap myositis (OLM)/antisynthetase syndrome (ASyS). There is also a rare variant termed polymyositis with mitochondrial pathology (PM-Mito), which is considered a sIBM precursor. There is no information regarding muscle MRI for this rare entity.

Transdermal and lateral effective diffusivities for drug transport in stratum corneum from a microscopic anisotropic diffusion model.

This paper presents a computational model of molecular diffusion through the interfollicular stratum corneum. Specifically, it extends an earlier two-dimensional microscopic model for the permeability in two ways: (1) a microporous leakage pathway through the intercellular lipid lamellae allows slow permeation of highly hydrophilic permeants through the tissue; and (2) the model yields explicit predictions of both lateral (D‾) and transdermal (D‾) effective (average, homogenized) diffusivities of solutes within the tissue. We present here the mathematical framework for the analysis and a comparison of the predictions with experimental data on desorption of both hydrophilic and lipophilic solutes from human stratum corneum in vitro.

Influence of T-Bar on Calcium Concentration Impacting Release Probability.

The relation of form and function, namely the impact of the synaptic anatomy on calcium dynamics in the presynaptic bouton, is a major challenge of present (computational) neuroscience at a cellular level. The Drosophila larval neuromuscular junction (NMJ) is a simple model system, which allows studying basic effects in a rather simple way. This synapse harbors several special structures.

Development of a New Bead Movement-Based Computational Framework Shows that Bacterial Amyloid Curli Reduces Bead Mobility in Biofilms.

Biofilms exist in complex environments, including the intestinal tract, as a part of the gastrointestinal microbiota. The interaction of planktonic bacteria with biofilms can be influenced by material properties of the biofilm. During previous confocal studies, we observed that amyloid curli-containing serotype Typhimurium and biofilms appeared rigid.

Advanced Hepatitis C Virus Replication PDE Models within a Realistic Intracellular Geometric Environment.

The hepatitis C virus (HCV) RNA replication cycle is a dynamic intracellular process occurring in three-dimensional space (3D), which is difficult both to capture experimentally and to visualize conceptually. HCV-generated replication factories are housed within virus-induced intracellular structures termed membranous webs (MW), which are derived from the Endoplasmatic Reticulum (ER). Recently, we published 3D spatiotemporal resolved diffusion⁻reaction models of the HCV RNA replication cycle by means of surface partial differential equation (sPDE) descriptions.

Spine-to-Dendrite Calcium Modeling Discloses Relevance for Precise Positioning of Ryanodine Receptor-Containing Spine Endoplasmic Reticulum.

The endoplasmic reticulum (ER) forms a complex endomembrane network that reaches into the cellular compartments of a neuron, including dendritic spines. Recent work discloses that the spine ER is a dynamic structure that enters and leaves spines. While evidence exists that ER Ca release is involved in synaptic plasticity, the role of spine ER morphology remains unknown.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles.

3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle.

Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors.

Generating Neuron Geometries for Detailed Three-Dimensional Simulations Using AnaMorph.

Generating realistic and complex computational domains for numerical simulations is often a challenging task. In neuroscientific research, more and more one-dimensional morphology data is becoming publicly available through databases. This data, however, only contains point and diameter information not suitable for detailed three-dimensional simulations.

The role of tight junctions in skin barrier function and dermal absorption.

The skin protects our body from external assaults like pathogens, xenobiotics or UV irradiation. In addition, it prevents the loss of water and solutes. To fulfill these important tasks, a complex barrier system has developed which comprises the stratum corneum, tight junctions, the microbiome, the chemical barrier and the immunological barrier.

Anatomically Detailed and Large-Scale Simulations Studying Synapse Loss and Synchrony Using NeuroBox.

The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function.

Kinetics of biogas production in Anaerobic Filters.

This study investigates methane production kinetics from individual volatile fatty acids (VFA) in an Upflow Anaerobic Filter (AF). 1gCOD in the form of acetic (HAc), propionic (HPr) or butyric acid (HBu) was injected into the AF while operating at an organic loading rate (OLRCOD) of 3.5gL(-1)d(-1).

A three-dimensional mathematical model for the signal propagation on a neuron's membrane.

In order to be able to examine the extracellular potential's influence on network activity and to better understand dipole properties of the extracellular potential, we present and analyze a three-dimensional formulation of the cable equation which facilitates numeric simulations. When the neuron's intra- and extracellular space is assumed to be purely resistive (i.e.

Synaptic bouton properties are tuned to best fit the prevailing firing pattern.

The morphology of presynaptic specializations can vary greatly ranging from classical single-release-site boutons in the central nervous system to boutons of various sizes harboring multiple vesicle release sites. Multi-release-site boutons can be found in several neural contexts, for example at the neuromuscular junction (NMJ) of body wall muscles of Drosophila larvae. These NMJs are built by two motor neurons forming two types of glutamatergic multi-release-site boutons with two typical diameters.

A dynamic model for calculating methane emissions from digestate based on co-digestion of animal manure and biogas crops in full scale German biogas plants.

The focus of this work is the development of a model for the estimation of methane emissions for storage tanks of biogas plants. Those can be estimated depending on (i) hydraulic retention time in the digester, (ii) an arbitrary removal rate of the digestate from the storage tank and (iii) arbitrary temperature conditions in the storage tank. Furthermore, the model is capable of considering an arbitrary mixture of manure and crops in the input material.

1D-3D hybrid modeling-from multi-compartment models to full resolution models in space and time.

Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing the spatial aspect of each cell.

Do two-phase biogas plants separate anaerobic digestion phases? - a mathematical model for the distribution of anaerobic digestion phases among reactor stages.

In this article a mathematical model is introduced, which estimates the distribution of the four anaerobic digestion phases (hydrolysis, acidogenesis, acetogenesis and methanogenesis) that occur among the leach bed reactor and the anaerobic filter of a biogas plant. It is shown that only the hydrolysis takes place in the first stage (leach bed reactor), while all other anaerobic digestion phases take place in both reactor stages. It turns out that, besides the usually measured raw materials of the acetogenesis and the methanogenesis phases (organic acids), it is also necessary to analyze the process liquid for raw materials of the acidogenesis phase, i.

Detailed modeling of skin penetration--an overview.

In recent years, the combination of computational modeling and experiments has become a useful tool that is proving increasingly powerful for explaining biological complexity. As computational power is increasing, scientists are able to explore ever more complex models in finer detail and to explain very complex real world data. This work provides an overview of one-, two- and three-dimensional diffusion models for penetration into mammalian skin.

Employing NeuGen 2.0 to automatically generate realistic morphologies of hippocampal neurons and neural networks in 3D.

Detailed cell and network morphologies are becoming increasingly important in Computational Neuroscience. Great efforts have been undertaken to systematically record and store the anatomical data of cells. This effort is visible in databases, such as NeuroMorpho.

SpineLab: tool for three-dimensional reconstruction of neuronal cell morphology.

SpineLab is a software tool developed for reconstructing neuronal feature skeletons from three-dimensional single- or multi-photon image stacks. These images often suffer from limited resolution and a low signal-to-noise ratio, making the extraction of morphometric information difficult. To overcome this limitation, we have developed a software tool that offers the possibility to create feature skeletons in various modes-automatically as well as with manual interaction.

Mathematical modeling of process liquid flow and acetoclastic methanogenesis under mesophilic conditions in a two-phase biogas reactor.

Acetoclastic methanogenesis in the second stage of a two-phase biogas reactor is investigated. A mathematical model coupling chemical reactions with transport of process liquid and with the variation of population of the microorganisms living on the plastic tower packing of the reactor is proposed. The evolution of the liquid is described by an advection-diffusion-reaction equation, while a monod-type kinetic is used for the reactions.

Computational modeling of the skin barrier.

A simulation environment for the numerical calculation of permeation processes through human skin has been developed. In geometry models that represent the actual cell morphology of stratum corneum (SC) and deeper skin layers, the diffusive transport is simulated by a finite volume method. As reference elements for the corneocyte cells and lipid matrix, both three-dimensional tetrakaidecahedra and cuboids as well as two-dimensional brick-and-mortar models have been investigated.

Structural dynamics of the cell nucleus: basis for morphology modulation of nuclear calcium signaling and gene transcription.

Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions.

A comparison of two- and three-dimensional models for the simulation of the permeability of human stratum corneum.

The stratum corneum is the outermost layer of cells in mammalian epidermis. It is widely believed to play the key role for the barrier function of the skin. This study characterises how the cell geometry influences the permeability of the membrane.