Model reduction in mathematical pharmacology

AbstractIn this paper we present a framework for the reduction and linking of physiologically based pharmacokinetic (PBPK) models with models of systems biology to describe the effects of drug administration across multiple scales. To address the issue of model complexity, we propose the reduction of each type of model separately prior to being linked. We highlight the use of balanced truncation in reducing the linear components of PBPK models, whilst proper lumping is shown to be efficient in reducing typically nonlinear systems biology type models. The overall methodology is demonstrated via two example systems; a model of bacterial chemotactic signalling in Escherichia coli and a model of extracellular regulatory kinase activation mediated via the extracellular growth factor and nerve growth factor receptor pathways. Each system is tested under the simulated administration of three hypothetical compounds; a strong base, a weak base, and an acid, mirroring the parameterisation of pindolol, midazolam, and thiopental, respectively. Our method can produce up to an 80% decrease in simulation time, allowing substantial speed-up for computationally intensive applications including parameter fitting or agent based modelling. The approach provides a straightforward means to construct simplified Quantitative Systems Pharmacology models that still provide significant insight into the mechanisms of drug action. Such a framework can potentially bridge pre-clinical and clinical modellin...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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Publication date: July 2020Source: Journal of Food Engineering, Volume 276Author(s): Luís Marangoni Júnior, Léa Mariza de Oliveira, Paula Fernanda Janetti Bócoli, Marcelo Cristianini, Marisa Padula, Carlos Alberto Rodrigues AnjosAbstractThe effect of high-pressure processing on the morphological surface, thermal and mechanical properties of three PA and EVOH based multilayer flexible packaging materials were evaluated. LDPE/PA/LDPE, LDPE/EVOH/LDPE and PET/LDPE/PA/EVOH/PA/LDPE packaging samples were processed under three different conditions (600 MPa/25 °C/10 min, 600 MPa/90 &d...
Source: Journal of Food Engineering - Category: Food Science Source Type: research
Publication date: Available online 22 January 2020Source: Biochimica et Biophysica Acta (BBA) - Proteins and ProteomicsAuthor(s): Esther S. Taxon, Lila P. Halbers, Stanley M. ParsonsAbstractTwo groups of metabolically related enzymes, the Group III family of Fe2+-dependent alcohol dehydrogenases (ADHs) and the separate subfamily of nucleoside diphosphates linked to x (nudix) hydrolases that activate Group III ADHs are under-characterized. Here we report the steady-state initial-velocity forward direction (alcohol → aldehyde) reaction of a Group III ADH, namely gamma-hydroxybutyrate dehydrogenase (GHBDH, UniProt: Q5910...
Source: Biochimica et Biophysica Acta (BBA) Proteins and Proteomics - Category: Biochemistry Source Type: research
Publication date: Available online 22 January 2020Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Feng Xue, Charles D. Cox, Navid Bavi, Paul R. Rohde, Yoshitaka Nakayama, Boris MartinacAbstractMechanosensitive (MS) channels have an intimate relationship with membrane lipids that underlie their mechanosensitivity. Membrane lipids may influence channel activity by directly interacting with MS channels or by influencing the global properties of the membrane such as elastic area expansion modulus or bending rigidity. Previous work has implicated membrane stiffness as a potential determinant of the mechanos...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research
In this study, we aimed at developing an efficient biocatalytic process for bio-production of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). First, adenylate cyclase from Escherichia coli MG1655 (EAC) and Bordetella Pertussis (BAC) were expressed in E. coli BL21(DE3) and comparatively analyzed for their activities. As a result, EAC from E. coli MG1655 exhibited a higher activity. However, amount of EAC were obtained in an insoluble form. Therefore, we expressed the first 446 amino acids of EAC (EAC446) to avoid the inclusion body. The effects of induction temperature, incubation time, and incubati...
Source: Chinese Journal of Chemical Engineering - Category: Chemistry Source Type: research
Publication date: 1 March 2020Source: Materials Chemistry and Physics, Volume 243Author(s): Ahmed gamal El-ShamyAbstractIn this literature, magnesium peroxide (MgO2) nanorods with an average Ddiameter = 166 nm have been successfully synthesized via fast and simple microwave assisted hydrothermal reaction for photocatalysis and antibacterial applications, for the first time. The as synthesized MgO2 nanorods are characterized by various techniques like XRD, FTIR, TEM, FE-SEM and BET. The photocatalytic activity of MgO2 nanorods has been studied for methyl orange (MO) degradation, and it is found that MO dye ha...
Source: Materials Chemistry and Physics - Category: Materials Science Source Type: research
Contributors : Rhea M Derke ; Micheal J GraySeries Type : Expression profiling by high throughput sequencingOrganism : Escherichia coliRNA sequencing of Escherichia coli Nissle 1917 before and after HOCl treatment was perfomed to identify pathways that may be important in responding to oxidative stress caused by reachive chlorine species (RCS).
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Escherichia coli Source Type: research
In this study, composite gels based on konjac and fish gelatin (FG) were prepared by alkali processing and thermal treatment subsequently. The influence of FG contents on the gel fraction, swelling behavior, biodegradation. was researched. Matrine was incorporated into the hydrogel and its effect on the hemocompatibility and antibacterial activity of gels were evaluated. According to the results, all gels presented at least 270% swelling degree and 72.7%∼81.5% equilibrium water content. Pure konjac hydrogel presented 83.9% gel fraction and 96.9% water evaporation rate, while those of the composite gels were 84.8%∼9...
Source: Food Hydrocolloids - Category: Food Science Source Type: research
CONCLUSION: Although the number of cases is small, the clinical and microbiological outcomes showed that most were successfully treated with non-carbapenem antibiotics, with low recurrence of new episodes of urinary tract infections. PMID: 31962058 [PubMed - as supplied by publisher]
Source: Acta Medica Portuguesa - Category: General Medicine Tags: Acta Med Port Source Type: research
Introduction: Gram-negative bacteria are the major cause of urinary tract infections (UTI) in children. There is limited data on UTI systemic response as measured using C-reactive protein (CRP). Here, we report the association of CRP and UTI among children attending the Bugando Medical Centre, Mwanza, Tanzania.Methods: A cross-sectional study was conducted between May and July 2017. Urine and blood were collected and processed within an hour of collection. Data were analyzed using STATA version 13.Results: Of 250 enrolled children, 76(30.4%) had significant bacteriuria with 56(22.4%, 95%CI; 11.5-33.3) having gram-negative ...
Source: African Health Sciences - Category: African Health Source Type: research
This study provides a TtSPase with high thermostability for potential industrial applications, and develops an effective strategy for improving soluble TtSPase production in E. coli.
Source: Protein Expression and Purification - Category: Biochemistry Source Type: research
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