Modelling the spatiotemporal dynamics of senescent cells in wound healing, chronic wounds, and fibrosis.

Cellular senescence is known to drive age-related pathology through the senescence-associated secretory phenotype (SASP). However, it also plays important physiological roles such as cancer suppression, embryogenesis and wound healing. Wound healing is a tightly regulated process which when disrupted results in conditions such as fibrosis and chronic wounds.

MOTHER-DB: A Database for Sharing Nonhuman Ovarian Histology Images.

The goal of the Multispecies Ovary Tissue Histology Electronic Repository (MOTHER) project is to establish a collection of nonhuman ovary histology images for multiple species as a resource for researchers and educators. An important component of sharing scientific data is the inclusion of the contextual metadata that describes the data. MOTHER extends the Ecological Metadata Language (EML) for documenting research data, leveraging its data provenance and usage license with the inclusion of metadata for ovary histology images.

Overview of the Multispecies Ovary Tissue Histology Electronic Repository†.

The Multispecies Ovary Tissue Histology Electronic Repository (MOTHER) is a publicly accessible repository of ovary histology images. MOTHER includes hundreds of images from nonhuman primates, as well as ovary histology images from an expanding range of other species. Along with an image, MOTHER provides metadata about the image, and for selected species, follicle identification annotations.

Morphological basis of the lung adenocarcinoma subtypes.

Lung adenocarcinoma (LUAD), which accounts for a large proportion of lung cancers, is divided into five major subtypes based on histologic characteristics. The clinical characteristics, prognosis, and responses to treatments vary among subtypes. Here, we demonstrate that the variations of cell-cell contact energy result in the LUAD subtype-specific morphogenesis.

Tissue Forge: Interactive biological and biophysics simulation environment.

Tissue Forge is an open-source interactive environment for particle-based physics, chemistry and biology modeling and simulation. Tissue Forge allows users to create, simulate and explore models and virtual experiments based on soft condensed matter physics at multiple scales, from the molecular to the multicellular, using a simple, consistent interface. While Tissue Forge is designed to simplify solving problems in complex subcellular, cellular and tissue biophysics, it supports applications ranging from classic molecular dynamics to agent-based multicellular systems with dynamic populations.

Multiscale Model of Antiviral Timing, Potency, and Heterogeneity Effects on an Epithelial Tissue Patch Infected by SARS-CoV-2.

We extend our established agent-based multiscale computational model of infection of lung tissue by SARS-CoV-2 to include pharmacokinetic and pharmacodynamic models of remdesivir. We model remdesivir treatment for COVID-19; however, our methods are general to other viral infections and antiviral therapies. We investigate the effects of drug potency, drug dosing frequency, treatment initiation delay, antiviral half-life, and variability in cellular uptake and metabolism of remdesivir and its active metabolite on treatment outcomes in a simulated patch of infected epithelial tissue.

Computational modelling of nephron progenitor cell movement and aggregation during kidney organogenesis.

During early kidney organogenesis, nephron progenitor (NP) cells move from the tip to the corner region of the ureteric bud (UB) branches in order to form the pretubular aggregate, the early structure giving rise to nephron formation. NP cells derive from metanephric mesenchymal cells and physically interact with them during the movement. Chemotaxis and cell-cell adhesion differences are believed to drive the cell patterning during this critical period of organogenesis.

Deep Learning Approaches to Surrogates for Solving the Diffusion Equation for Mechanistic Real-World Simulations.

In many mechanistic medical, biological, physical, and engineered spatiotemporal dynamic models the numerical solution of partial differential equations (PDEs), especially for diffusion, fluid flow and mechanical relaxation, can make simulations impractically slow. Biological models of tissues and organs often require the simultaneous calculation of the spatial variation of concentration of dozens of diffusing chemical species. One clinical example where rapid calculation of a diffusing field is of use is the estimation of oxygen gradients in the retina, based on imaging of the retinal vasculature, to guide surgical interventions in diabetic retinopathy.

A computational model of liver tissue damage and repair.

Drug induced liver injury (DILI) and cell death can result from oxidative stress in hepatocytes. An initial pattern of centrilobular damage in the APAP model of DILI is amplified by communication from stressed cells and immune system activation. While hepatocyte proliferation counters cell loss, high doses are still lethal to the tissue.

Mitochondrial depolarization and repolarization in the early stages of acetaminophen hepatotoxicity in mice.

Mitochondrial injury and depolarization are primary events in acetaminophen hepatotoxicity. Previous studies have shown that restoration of mitochondrial function in surviving hepatocytes, which is critical to recovery, is at least partially accomplished via biogenesis of new mitochondria. However, other studies indicate that mitochondria also have the potential to spontaneously repolarize.

Spatial Temporal Analysis of Fieldwise Flow in Microvasculature.

Changes in blood flow velocity and distribution are vital in maintaining tissue and organ perfusion in response to varying cellular needs. Further, appearance of defects in microcirculation can be a primary indicator in the development of multiple pathologies. Advances in optical imaging have made intravital microscopy (IVM) a practical approach, permitting imaging at the cellular and subcellular level in live animals at high-speed over time.

The 2019 mathematical oncology roadmap.

Whether the nom de guerre is Mathematical Oncology, Computational or Systems Biology, Theoretical Biology, Evolutionary Oncology, Bioinformatics, or simply Basic Science, there is no denying that mathematics continues to play an increasingly prominent role in cancer research. Mathematical Oncology-defined here simply as the use of mathematics in cancer research-complements and overlaps with a number of other fields that rely on mathematics as a core methodology. As a result, Mathematical Oncology has a broad scope, ranging from theoretical studies to clinical trials designed with mathematical models.

A simple automated method for continuous fieldwise measurement of microvascular hemodynamics.

Microvascular perfusion dynamics are vital to physiological function and are frequently dysregulated in injury and disease. Typically studies measure microvascular flow in a few selected vascular segments over limited time, failing to capture spatial and temporal variability. To quantify microvascular flow in a more complete and unbiased way we developed STAFF (Spatial Temporal Analysis of Fieldwise Flow), a macro for FIJI open-source image analysis software.

Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models.

Computational models of normal liver function and xenobiotic induced liver damage are increasingly being used to interpret in vitro and in vivo data and as an approach to the de novo prediction of the liver's response to xenobiotics. The microdosimetry (dose at the level of individual cells) of xenobiotics vary spatially within the liver because of both compound-independent and compound-dependent factors. In this paper, we build model liver lobules to investigate the interplay between vascular structure, blood flow and cellular transport that lead to regional variations in microdosimetry.

Formalizing Knowledge in Multi-Scale Agent-Based Simulations.

Multi-scale, agent-based simulations of cellular and tissue biology are increasingly common. These simulations combine and integrate a range of components from different domains. Simulations continuously create, destroy and reorganize constituent elements causing their interactions to dynamically change.

A Liver-Centric Multiscale Modeling Framework for Xenobiotics.

We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level.

Multiscale Modeling in the Clinic: Drug Design and Development.

A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research.

Toxicokinetic Triage for Environmental Chemicals.

Toxicokinetic (TK) models link administered doses to plasma, blood, and tissue concentrations. High-throughput TK (HTTK) performs in vitro to in vivo extrapolation to predict TK from rapid in vitro measurements and chemical structure-based properties. A significant toxicological application of HTTK has been "reverse dosimetry," in which bioactive concentrations from in vitro screening studies are converted into in vivo doses (mg/kg BW/day).

The cell behavior ontology: describing the intrinsic biological behaviors of real and model cells seen as active agents.

Motivation: Currently, there are no ontologies capable of describing both the spatial organization of groups of cells and the behaviors of those cells. The lack of a formalized method for describing the spatiality and intrinsic biological behaviors of cells makes it difficult to adequately describe cells, tissues and organs as spatial objects in living tissues, in vitro assays and in computational models of tissues.

Results: We have developed an OWL-2 ontology to describe the intrinsic physical and biological characteristics of cells and tissues.