A5088817993- 3D Printing in Biomedical Research
- Peer-to-Peer Network Technologies
- Mathematical Biology Tumor Growth
- Liver physiology and pathology
- Computational Drug Discovery Methods
- Cancer, Hypoxia, and Metabolism
- Pharmacogenetics and Drug Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Cellular Mechanics and Interactions
- Caching and Content Delivery
- Access Control and Trust
- ATP Synthase and ATPases Research
- Gambling Behavior and Treatments
- Pancreatic function and diabetes
- Evolution and Genetic Dynamics
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- Gene Regulatory Network Analysis
- Drug Transport and Resistance Mechanisms
- Animal testing and alternatives
- Mathematical and Theoretical Epidemiology and Ecology Models
- Effects and risks of endocrine disrupting chemicals
- Pesticide Exposure and Toxicity
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Image Analysis Techniques
Syngenta (United Kingdom)
2020-2024
Syngenta (Switzerland)
2023
Liverpool John Moores University
2016-2021
University of Liverpool
2012-2020
Engineering and Physical Sciences Research Council
2018-2020
Medical Research Council
2014-2019
Webb Institute
2018
Liverpool Hospital
2016
Oak Ridge National Laboratory
2015
University of Strathclyde
2007-2012
The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. most frequently described acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines data, which pseudopods are made a self-generated cycle. If chemoattractants present, they modulate the cycle rather than directly polymerization. aim this work is test explanatory predictive powers such...
We have developed a method for creating C3A liver spheroids and demonstrated cellular polarisation, zonation as well increased liver-specific functionality more predictive toxicological response compared to standard 2D models.
Abstract Redox cycling is an understated mechanism of toxicity associated with a plethora xenobiotics, responsible for preventing the effective treatment serious conditions such as malaria and cardiomyopathy. Quinone compounds are notorious redox cyclers, present in drugs doxorubicin, which used to treat host human cancers. However, therapeutic index doxorubicin undermined by dose-dependent cardiotoxicity, may be function futile cycling. In this study, doxorubicin-specific silico quinone...
A computational framework is presented for the simulation of eukaryotic cell migration and chemotaxis. An empirical pattern formation model, based on a system nonlinear reaction-diffusion equations, approximated an evolving boundary using arbitrary Lagrangian Eulerian surface finite element method (ALE-SFEM). The solution state used to drive mechanical model protrusive retractive forces exerted boundary. Movement achieved level set method. Results are with without simulated behavior compared...
The increasing popularity of Massively Multiplayer Online Games (MMOG) -- games involving thousands players participating simultaneously in a single virtual world - has highlighted the scalability bottlenecks present centralised Client/Server (C/S) architectures. Researchers are proposing Peer-to-Peer (P2P) architectures as scalable alternative to C/S; however, P2P is more vulnerable cheating it decentralises game state and logic un-trusted peer machines, rather than using trusted servers....
In early preclinical drug development, potential candidates are tested in the laboratory using isolated cells. These vitro experiments traditionally involve cells cultured a two-dimensional monolayer environment. However, three-dimensional spheroid systems have been shown to more closely resemble functionality and morphology of vivo . While increasing usage hepatic cultures allows for relevant experimentation realistic biological environment, underlying physical processes transport, uptake...
Abstract Acetaminophen overdose is the leading cause of acute liver failure. One dose 10–15 g causes severe damage in humans, whereas repeated exposure to acetaminophen humans and animal models results autoprotection. Insight this process limited select proteins implicated toxicity cellular defence. Here we investigate hepatic adaptation from a whole proteome perspective, using quantitative mass spectrometry. In rat model, show response involves expression 30% all detected liver. Genetic...
Many in vitro liver cell models, such as 2D systems, that are used to assess the hepatotoxic potential of xenobiotics suffer major limitations arising from a lack preservation physiological phenotype and metabolic competence. To circumvent some these there has been increased focus on producing more representative 3D models. Here we have novel approach construct size-controllable hepatic spheroid model using freshly isolated primary rat hepatocytes (PRH) utilising liquid-overlay technique...
The ability of the liver to simultaneously carry out multiple functions is dependent on metabolic heterogeneity hepatocytes spatially located within a lobule spanning from portal triad central vein. This complex zonal architecture liver, however, makes accurate in vitro modeling challenge and often standard culture systems assume homogenous model which may lead inaccurate translatability results. Here, we use combination mathematical experimental data demonstrate readily constructible flow...
The Mirrored Server (MS) architecture uses multiple mirrored servers across locations to alleviate the bandwidth bottleneck in Client/Server (C/S) architecture. Each mirror receives and multicasts player updates others, simulates game, disseminates new game state players. However, keeping consistent between mirrors presence of network delay, maintaining responsiveness requires each server MS simulate times for update, additional event costly rollbacks. In this paper we propose Enhanced (EMS)...
Acetaminophen is a widespread and commonly used painkiller all over the world. However, it can cause liver damage when taken in large doses or at repeated chronic doses. Current models of acetaminophen metabolism are complex, limited to numerical investigation though provide results that represent clinical well. We derive mathematical model based on mass action laws aimed capturing main dynamics metabolism, particular contrast between normal overdose cases, whilst remaining simple enough for...
Tissue culture has been used for over 100 years to study cells and responses ex vivo. The convention of this technique is the growth anchorage dependent on 2-dimensional surface tissue plastic. More recently, there a growing body data demonstrating more in vivo-like behaviors grown 3-dimensional systems. This manuscript describes detail set-up operation hollow fiber bioreactor system mammalian cells. delivers media manner akin delivery blood through capillary networks designed fit onto shelf...
Branching networks are ubiquitous in nature and their growth often responds to environmental cues dynamically. Using the antibiotic-producing soil bacterium Streptomyces as a model we have developed flexible mathematical platform for study of branched biological networks. form large aggregates liquid culture that can impair industrial antibiotic fermentations. Understanding features these could aid improvement such processes. The requires relatively few experimental values parameterisation,...
Dose-dependent cardiotoxicity is the leading adverse reaction seen in cancer patients treated with doxorubicin. Currently, dexrazoxane only approved drug that can partially protect against this toxicity patients, however, its administration restricted to those receiving a high cumulative dose of anthracyclines. Investigations into mechanisms and efforts improve cardioprotective strategies have been hindered by limited availability phenotypically relevant vitro adult human cardiac model...