Publications
127 results found
Yamakawa Y, Ikeda K, Saiki I, et al., 2017, Diffuse bifurcations engraving diverse shear bands in granular materials, International Journal for Numerical and Analytical Methods in Geomechanics, Vol: 42, Pages: 3-33, ISSN: 1096-9853
Shear bands with characteristic spatial patterns observed in an experiment for a cubic or parallelepipedspecimen of dry dense sand were simulated by numerical bifurcation analysis using the Cam-clay plasticitymodel. By incorporating the subloading surface concept into the plasticity model, the model became capableof reproducing hardening/softening and contractive/dilative behavior observed in the experiment. The modelwas re-formulated to be compatible with the multiplicative hyperelasto-plasticity for nite strains. Thisenhanced constitutive model was implemented into a nite-element code reinforced by a stress updatingalgorithm based on the return-mapping scheme, and by an efficient numerical procedure to compute criticaleigenvectors of elastoplastic tangent stiffness matrix at bifurcation points. The emergence of diamond-likeand column-like diffuse bifurcation modes breaking uniformity of the materials, followed by the evolutionof shear bands through strain localization, was observed in the analysis. In the bifurcation analysis of planestrain compression test, unexpected bifurcation modes, which break out-of-plane uniformity and lead tothree-dimensional diamond-like patterns, were detected. Diffuse bifurcations, which are difficult to observeby experiments, have thus been found as a catalyst creating diverse shear band patterns.
DomÃnguez-Hüttinger E, Christodoulides P, Miyauchi K, et al., 2017, Mathematical modeling of atopic dermatitis reveals "double switch" mechanisms underlying 4 common disease phenotypes, Journal of Allergy and Clinical Immunology, Vol: 139, Pages: 1861-1872.e7, ISSN: 0091-6749
Background: The skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems-biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data.Objective: To develop a multi-scale mathematical model of AD pathogenesis that describes the dynamic interplay between the skin barrier, environmental stress and immune dysregulation, and use it to achieve a coherent mechanistic understanding of onset, progression and prevention of AD. Methods: We mathematically investigated synergistic effects of known genetic and environmental risk factors on the dynamic onset and progression of the AD phenotype, from a mostly asymptomatic mild phenotype to a severe treatment-resistant form. Results: Our model analysis identified a “double switch”, with two concatenated bistable switches, as a key network motif that dictates AD pathogenesis: The first switch is responsible for the reversible onset of inflammation; The second switch is triggered by long-lasting or frequent activation of the first switch, causing the irreversible onset of systemic Th2 sensitization and worsening of AD symptoms. Conclusions: Our mathematical analysis of the bistable switch predicts that genetic risk factors lower the threshold of environmental stressors to trigger systemic Th2 sensitization. This analysis predicts and explains four common clinical AD phenotypes from a mild and reversible phenotype through to severe and recalcitrant disease and provides a mechanistic explanation for clinically-demonstrated preventive effects of emollient treatments against development of AD.
Granados AA, Crane MM, Montano-Gutierrez LF, et al., 2017, Distributing tasks via multiple input pathways increase cellular survival in stress, eLife, Vol: 6, ISSN: 2050-084X
Improving in one aspect of a task can undermine performance in another, but how such opposing demands play out in single cells and impact on fitness is mostly unknown. Here we study budding yeast in dynamic environments of hyperosmotic stress and show how the corresponding signalling network increases cellular survival both by assigning the requirements of high response speed and high response accuracy to two separate input pathways and by having these pathways interact to converge on Hog1, a p38 MAP kinase. Cells with only the less accurate, reflex-like pathway are fitter in sudden stress, whereas cells with only the slow, more accurate pathway are fitter in increasing but fluctuating stress. Our results demonstrate that cellular signalling is vulnerable to trade-offs in performance, but that these trade-offs can be mitigated by assigning the opposing tasks to different signalling subnetworks. Such division of labour could function broadly within cellular signal transduction.
Christodoulides P, Hirata Y, Dominguez-Huttinger E, et al., 2017, Computational design of treatment strategies for proactive therapy on atopic dermatitis using optimal control theory, Royal Society of London. Philosophical Transactions A. Mathematical, Physical and Engineering Sciences, Vol: 375, ISSN: 1364-503X
Atopic dermatitis (AD) is a common chronic skindisease characterised by recurrent skin inflammationand weak skin barrier, and is known to be aprecursor to other allergic diseases such as asthma.AD affects up to 25% of children worldwideand the incidence continues to rise. There is stilluncertainty about the optimal treatment strategyin terms of choice of treatment, potency, durationand frequency. This study aims to develop acomputational method to design optimal treatmentstrategies for the clinically recommended "proactivetherapy" for AD. Proactive therapy aims to preventrecurrent flares once the disease has been broughtunder initial control. Typically this is done by usingan anti-inflammatory treatment such as a potenttopical corticosteroid intensively for a few weeksto "get control", followed by intermittent weeklytreatment to suppress subclinical inflammation to"keep control". Using a hybrid mathematical modelof AD pathogenesis that we recently proposed,we computationally derived the optimal treatmentstrategies for individual virtual patient cohorts, byrecursively solving optimal control problems usinga differential evolution algorithm. Our simulationresults suggest that such an approach can inform thedesign of optimal individualised treatment schedulesthat include application of topical corticosteroidsand emollients, based on the disease status ofpatients observed on their weekly hospital visits.We demonstrate the potential and the gaps of ourapproach to be applied to clinical settings.
Dominguez-Huettinger E, Boon NJ, Clarke TB, et al., 2017, Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment, FRONTIERS IN PHYSIOLOGY, Vol: 8, ISSN: 1664-042X
Streptococcus pneumoniae (Sp) is a commensal bacterium that normally resides on the upper airway epithelium without causing infection. However, factors such as co-infection with influenza virus can impair the complex Sp-host interactions and the subsequent development of many life-threatening infectious and inflammatory diseases, including pneumonia, meningitis or even sepsis. With the increased threat of Sp infection due to the emergence of new antibiotic resistant Sp strains, there is an urgent need for better treatment strategies that effectively prevent progression of disease triggered by Sp infection, minimizing the use of antibiotics. The complexity of the host-pathogen interactions has left the full understanding of underlying mechanisms of Sp-triggered pathogenesis as a challenge, despite its critical importance in the identification of effective treatments. To achieve a systems-level and quantitative understanding of the complex and dynamically-changing host-Sp interactions, here we developed a mechanistic mathematical model describing dynamic interplays between Sp, immune cells, and epithelial tissues, where the host-pathogen interactions initiate. The model serves as a mathematical framework that coherently explains various in vitro and in vitro studies, to which the model parameters were fitted. Our model simulations reproduced the robust homeostatic Sp-host interaction, as well as three qualitatively different pathogenic behaviors: immunological scarring, invasive infection and their combination. Parameter sensitivity and bifurcation analyses of the model identified the processes that are responsible for qualitative transitions from healthy to such pathological behaviors. Our model also predicted that the onset of invasive infection occurs within less than 2 days from transient Sp challenges. This prediction provides arguments in favor of the use of vaccinations, since adaptive immune responses cannot be developed de novo in such a short time. We furthe
Yokouchi M, Atsugi T, van Logtestijn M, et al., 2016, Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape, eLife, Vol: 5, ISSN: 2050-084X
In multicellular organisms, cells adopt various shapes, from flattened sheets of endothelium to dendritic neurons, that allow the cells to function effectively. Here, we elucidated the unique shape of cells in the stratified epithelia of the epidermis that allows them to achieve homeostasis of the tight junction (TJ) barrier. Using intimate in vivo 3D imaging, we found that the basic shape of TJ-bearing cells is a flattened Kelvin’s tetrakaidecahedron(f-TKD), an optimal shape for filling space. In vivo live imaging further elucidated the dynamic replacement of TJs on the edges of f-TKD cells that enables the TJ-bearing cells to translocate across the TJ barrier. We propose a spatiotemporal orchestration model of f-TKD cell turnover, where in the classic context of “form follows function,” cell shape provides a fundamental basis for the barrier homeostasis and physical strength of cornified stratified epithelia.
Lee SY, Boon NJ, Webb AAR, et al., 2016, Synergistic Activation of RD29A via Integration of Salinity Stress and Abscisic Acid in Arabidopsis thaliana, Plant and Cell Physiology, Vol: 57, Pages: 2147-2160, ISSN: 1471-9053
Plants perceive information from the surroundings and elicit appropriate molecular responses. How plants dynamically respond to combinations of external inputs is yet to be revealed, despite the detailed current knowledge of intracellular signalling pathways. We measured dynamics of Response-to-Dehydration 29A (RD29A) expression induced by single or combined NaCl and ABA treatments in Arabidopsis thaliana. RD29A expression in response of combination of NaCl and ABA leads to unique dynamical behaviours that cannot be explained by the sum of responses to individual NaCl and ABA. To explore the potential mechanisms responsible for the observed synergistic response, we developed a mathematical model of the DREB2 and AREB pathways based upon the existing knowledge, where NaCl and ABA act as the cognate inputs, respectively, and examined various system structures with cross-input modulation, where non-cognate input affects expression of the genes involved in adjacent signalling pathways. The results from the analysis of system structures, combined with the insights from microarray expression profiles and model-guided experiments, predicted that synergistic activation of RD29A originates from enhancement of DREB2 activity by ABA. Our analysis of RD29A expression profiles demonstrates that a simple mathematical model can be used to extract information from temporal dynamics induced by combinatorial stimuli and produce experimentally testable hypotheses.
van Logtestijn M, Caspers PJ, Kezic S, et al., 2015, Water resistance profile as a marker of skin barrier damage in atopic dermatitis patients, Journal of Dermatological Science, Vol: 81, Pages: 126-128, ISSN: 1873-569X
Tanaka RJ, Boon NJ, Vrcelj K, et al., 2015, In silico modeling of spore inhalation reveals fungal persistence following low dose exposure, Scientific Reports, Vol: 5, ISSN: 2045-2322
The human lung is constantly exposed to spores of the environmental mould Aspergillus fumigatus, a major opportunistic pathogen. The spectrum of resultant disease is the outcome of complex host-pathogen interactions, an integrated, quantitative understanding of which lies beyond the ethical and technical reach permitted by animal studies. Here we construct a mathematical model of spore inhalation and clearance by concerted actions of macrophages and neutrophils, and use it to derive a mechanistic understanding of pathogen clearance by the healthy, immunocompetent host. In particular, we investigated the impact of inoculum size upon outcomes of single-dose fungal exposure by simulated titrations of inoculation dose, from 106 to 102 spores. Simulated low-dose (102) spore exposure, an everyday occurrence for humans, revealed a counter-intuitive prediction of fungal persistence (>3 days). The model predictions were reflected in the short-term dynamics of experimental murine exposure to fungal spores, thereby highlighting the potential of mathematical modelling for studying relevant behaviours in experimental models of fungal disease. Our model suggests that infectious outcomes can be highly dependent upon short-term dynamics of fungal exposure, which may govern occurrence of cyclic or persistent subclinical fungal colonisation of the lung following low dose spore inhalation in non-neutropenic hosts.
Ono M, Tanaka RJ, 2015, Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective, Immunology and Cell Biology, Vol: 94, Pages: 3-10, ISSN: 1440-1711
Thymus-derived regulatory T cells (Tregs) are considered to be a distinct T-cell lineage that is genetically programmed and specialised for immunosuppression. This perspective is based on the key evidence that CD25+ Tregs emigrate to neonatal spleen a few days later than other T cells and that thymectomy of 3-day-old mice depletes Tregs only, causing autoimmune diseases. Although widely believed, the evidence has never been reproduced as originally reported, and some studies indicate that Tregs exist in neonates. Thus we examine the consequences of the controversial evidence, revisit the fundamental issues of Tregs and thereby reveal the overlooked relationship of T-cell activation and Foxp3-mediated control of the T-cell system. Here we provide a new model of Tregs and Foxp3, a feedback control perspective, which views Tregs as a component of the system that controls T-cell activation, rather than as a distinct genetically programmed lineage. This perspective provides new insights into the roles of self-reactivity, T cell–antigen-presenting cell interaction and T-cell activation in Foxp3-mediated immune regulation.
van Logtestijn MDA, Dominguez Huttinger E, Stamatas GN, et al., 2015, Resistance to Water Diffusion in the Stratum Corneum Is Depth-Dependent, PLOS One, Vol: 10, ISSN: 1932-6203
Huettinger ED, Christodoulides P, Tanaka RJ, 2015, Mathematical modelling approach to elucidate multi-scale regulatory mechanisms for stratum corneum homeostasis, INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Vol: 37, Pages: 143-144, ISSN: 0142-5463
Boon N, Bignell E, Tanaka RJ, 2014, <i>In silico</i> prediction of the temporal effects of anti-fungal treatments, IMMUNOLOGY, Vol: 143, Pages: 58-58, ISSN: 0019-2805
Dominguez-Huttinger E, Clarke TB, Tanaka RJ, 2014, Mathematical modelling of host pathogen interactions at mucosal surfaces reveals the dual role of the epithelial barrier in determining the outcome of infectious processes, IMMUNOLOGY, Vol: 143, Pages: 150-150, ISSN: 0019-2805
Ono M, Tanaka RJ, Kano M, 2014, Visualisation of the T cell differentiation programme by Canonical Correspondence Analysis of transcriptomes, BMC Genomics, Vol: 15, ISSN: 1471-2164
Huettinger ED, Christodoulides P, Tanaka RJ, 2014, Uncovering risk factor-dependent mechanisms for development of atopic dermatitis using a systems biology approach, 8th Georg Rajka Symposium on Atopic Dermatitis (ISAD), Publisher: WILEY-BLACKWELL, Pages: E30-E30, ISSN: 0007-0963
Sabatier Q, Krapp HG, Tanaka RJ, 2014, Dynamic optimisation for fly gaze stabilisation based on noisy and delayed sensor information, 13th European Control Conference (ECC), Publisher: IEEE, Pages: 1783-1788
Tanaka RJ, Ono M, 2013, Skin Disease Modeling from a Mathematical Perspective, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 133, Pages: 1472-1478, ISSN: 0022-202X
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Dominguez-Huettinger E, Ono M, Barahona M, et al., 2013, Risk factor-dependent dynamics of atopic dermatitis: modelling multi-scale regulation of epithelium homeostasis, INTERFACE FOCUS, Vol: 3, ISSN: 2042-8898
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- Citations: 11
Ejaz N, Krapp HG, Tanaka RJ, 2013, Closed-loop response properties of a visual interneuron involved in fly optomotor control, FRONTIERS IN NEURAL CIRCUITS, Vol: 7
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Ono M, Tanaka RJ, Kano M, et al., 2013, Visualising the Cross-Level Relationships between Pathological and Physiological Processes and Gene Expression: Analyses of Haematological Diseases, PLOS ONE, Vol: 8, ISSN: 1932-6203
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Huettinger ED, Ono M, Barahona M, et al., 2012, Mathematical model of the development of Atopic dermatitis, 22nd IUBMB Congress/37th FEBS Congress, Publisher: WILEY-BLACKWELL, Pages: 523-523, ISSN: 1742-464X
Dominguez-Huttinger E, Ono M, Barahona M, et al., 2012, System-level investigation of risk factors for atopic dermatitis by mathematical modelling and analysis, 42nd Annual Meeting of the European-Society-for-Dermatological-Research (ESDR), Publisher: NATURE PUBLISHING GROUP, Pages: S25-S25, ISSN: 0022-202X
Ejaz N, Tanaka RJ, Krapp HG, 2012, Static versus adaptive gain control strategy for visuo-motor stabilization, Pages: 107-119, ISSN: 0302-9743
Biological principles of closed-loop motor control have gained much interest over the last years for their potential applications in robotic system. Although some progress has been made in understanding of how biological systems use sensory signals to control reflex and voluntary behaviour, experimental platforms are still missing which allow us to study sensorimotor integration under closed-loop conditions. We developed a fly-robot interface (FRI) to investigate the dynamics of a 1-DoF image stabilization task. Neural signals recorded from an identified visual interneuron were used to control a two-wheeled robot which compensated for wide-field visual image shifts caused by externally induced rotations. We compared the frequency responses of two different controllers with static and adaptive feedback gains and their performance and found that they offer competing benefits for visual stabilization. In future research will use the FRI to study how different sensor systems contribute towards robust closed-loop motor control. © 2012 Springer-Verlag.
Schley D, Tanaka RJ, Leungchavaphongse K, et al., 2012, Modelling the influence of foot-and-mouth disease vaccine antigen stability and dose on the bovine immune response, PLOS One, Vol: 7, ISSN: 1932-6203
Ejaz N, Tanaka RJ, Krapp HG, 2011, Closed-loop performance of a proportional controller for visual stabilization using a fly-robot interface, Pages: 1509-1515
The blowfly Calliphora is the model of choice for studying sensori-motor control principles common in biological systems. We present a fly-robot interface where the neural activity of an identified visual interneuron is used to control the angular velocity of a rotating robot. By placing the robot on a rotating turn-table in a visual arena, we use the fly-robot interface to quantify the dynamics and performance of a proportional controller in a closed-loop visual stabilization system. The properties of the system were characterized for both step and frequency responses. We analysed the data using a performance index based on the input-output energy dissipated by the controller. Our results suggest that the optimal strategy for the fly to minimize the visual slip speed would be to tune the closed-loop gain to the angular velocity and angular acceleration of the input stimuli. The design principles discovered by reverse-engineering sensori-motor control in to develop the next generation of autonomous robots and smart sensors. © 2011 IEEE.
Tanaka RJ, Ono M, 2011, Mathematical modelling approach for systems-level understanding of skin barrier homeostasis in Atopic dermatitis, 41st Annual Meeting of the European-Society-for-Dermatological-Research, Publisher: NATURE PUBLISHING GROUP, Pages: S11-S11, ISSN: 0022-202X
Satti R, Deakin G, Tanaka RJ, et al., 2011, Genesforadaptationandlearningspanningevolution:computationalcomparisonbetweensynaptictransmissionandchemotacticsignalingproteinnetworks, 20th Annual Computational Neuroscience Meeting
Schwyn DA, Heras FJH, Bolliger G, et al., 2011, Interplay between Feedback and Feedforward Control in Fly Gaze Stabilization, 18th IFAC World Congress
Tanaka RJ, Ono M, Harrington HA, 2011, Skin Barrier Homeostasis in Atopic Dermatitis: Feedback Regulation of Kallikrein Activity, PLoS one, Vol: 5
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