Browsing by Subject "DYNAMICS"

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  • Guenther, Carla; Faisal, Imrul; Uotila, Liisa; Llort Asens, Marc; Harjunpää, Heidi; Savinko, Terhi; Öhman, Tiina; Yao, Sean; Moser, Markus; Morris, Stephan W.; Tojkander, Sari; Fagerholm, Susanna (2019)
    beta2-integrins are essential for immune system function because they mediate immune cell adhesion and signaling. Consequently, a loss of beta2-integrin expression or function causes the immunodeficiency disorders, Leukocyte Adhesion Deficiency (LAD) type I and III. LAD-III is caused by mutations in an important integrin regulator, kindlin-3, but exactly how kindlin-3 regulates leukocyte adhesion has remained incompletely understood. Here we demonstrate that mutation of the kindlin-3 binding site in the b2-integrin (TTT/AAA-b2-integrin knock-in mouse/KI) abolishes activation of the actin-regulated myocardin related transcription factor A/serum response factor (MRTF-A/SRF) signaling pathway in dendritic cells and MRTF-A/SRF-dependent gene expression. We show that Ras homolog gene family, member A (RhoA) activation and filamentous-actin (F-actin) polymerization is abolished in murine TTT/AAA-b2-integrin KI dendritic cells, which leads to a failure ofMRTF-A to localize to the cell nucleus to coactivate genes together with SRF. In addition, we show that dendritic cell gene expression, adhesion and integrin-mediated traction forces on ligand coated surfaces is dependent on the MRTF-A/SRF signaling pathway. The participation of b2-integrin and kindlin-3-mediated cell adhesion in the regulation of the ubiquitous MRTF-A/SRF signaling pathway in immune cells may help explain the role of b2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function.
  • Pallares, Jordi; Senan, Oriol; Guimera, Roger; Vernet, Anton; Aguilar-Mogas, Antoni; Vilahur, Gemma; Badimon, Lina; Sales-Pardo, Marta; Cito, Salvatore (2015)
    Thrombus formation is a multiscale phenomenon triggered by platelet deposition over a protrombotic surface (eg. a ruptured atherosclerotic plaque). Despite the medical urgency for computational tools that aid in the early diagnosis of thrombotic events, the integration of computational models of thrombus formation at different scales requires a comprehensive understanding of the role and limitation of each modelling approach. We propose three different modelling approaches to predict platelet deposition. Specifically, we consider measurements of platelet deposition under blood flow conditions in a perfusion chamber for different time periods (3, 5, 10, 20 and 30 minutes) at shear rates of 212 s(-1), 1390 s(-1) and 1690 s(-1). Our modelling approaches are: i) a model based on the mass-transfer boundary layer theory; ii) a machine-learning approach; and iii) a phenomenological model. The results indicate that the three approaches on average have median errors of 21%, 20.7% and 14.2%, respectively. Our study demonstrates the feasibility of using an empirical data set as a proxy for a real-patient scenario in which practitioners have accumulated data on a given number of patients and want to obtain a diagnosis for a new patient about whom they only have the current observation of a certain number of variables.
  • Pekkanen, Jami Joonas Olavi; Lappi, Otto; Rinkkala, Paavo; Tuhkanen, Niko Samuel; Frantsi, Roosa; Summala, Kari Heikki Ilmari (2018)
    We present a computational model of intermittent visual sampling and locomotor control in a simple yet representative task of a car driver following another vehicle. The model has a number of features that take it beyond the current state of the art in modelling natural tasks, and driving in particular. First, unlike most control theoretical models in vision science and engineering—where control is directly based on observable (optical) variables—actions are based on a temporally enduring internal representation. Second, unlike the more sophisticated engineering driver models based on internal representations, our model explicitly aims to be psychologically plausible, in particular in modelling perceptual processes and their limitations. Third, unlike most psychological models, it is implemented as an actual simulation model capable of full task performance (visual sampling and longitudinal control). The model is developed and validated using a dataset from a simplified car-following experiment (N = 40, in both three-dimensional virtual reality and a real instrumented vehicle). The results replicate our previously reported connection between time headway and visual attention. The model reproduces this connection and predicts that it emerges from control of action uncertainty. Implications for traffic psychological models and future developments for psychologically plausible yet computationally rigorous models of full natural task performance are discussed.
  • Lumby, Casper K.; Zhao, Lei; Breuer, Judith; Illingworth, Christopher J. R. (2020)
    Strains of the influenza virus form coherent global populations, yet exist at the level of single infections in individual hosts. The relationship between these scales is a critical topic for understanding viral evolution. Here we investigate the within-host relationship between selection and the stochastic effects of genetic drift, estimating an effective population size of infection N-e for influenza infection. Examining whole-genome sequence data describing a chronic case of influenza B in a severely immunocompromised child we infer an N-e of 2.5 x 10(7) (95% confidence range 1.0 x 10(7) to 9.0 x 10(7)) suggesting that genetic drift is of minimal importance during an established influenza infection. Our result, supported by data from influenza A infection, suggests that positive selection during within-host infection is primarily limited by the typically short period of infection. Atypically long infections may have a disproportionate influence upon global patterns of viral evolution.
  • Kupiainen-Määttä, Oona (2016)
    Evaporation rates of small negatively charged sulfuric acid-ammonia clusters are determined by combining detailed cluster formation simulations with cluster distributions measured in the CLOUD experiment at CERN. The analysis is performed by varying the evaporation rates with Markov chain Monte Carlo (MCMC), running cluster formation simulations with each new set of evaporation rates and comparing the obtained cluster distributions to the measurements. In a second set of simulations, the fragmentation of clusters in the mass spectrometer due to energetic collisions is studied by treating also the fragmentation probabilities as unknown parameters and varying them with MCMC. This second set of simulations results in a better fit to the experimental data, suggesting that a large fraction of the observed HSO4- and HSO4-center dot H2SO4 signals may result from fragmentation of larger clusters, most importantly the HSO4-center dot(H2SO4)(2) trimer.
  • Gyllenberg, Mats; Jiang, Jifa; Niu, Lei (2019)
    In the recent paper [E. C. Balreira, S. Elaydi, and R. Luis, J. Differ. Equ. Appl. 23 (2017), pp. 2037-2071], Balreira, Elaydi and Luis established a good criterion for competitive mappings to have a globally asymptotically stable interior fixed point by a geometric approach. This criterion can be applied to three dimensional Kolmogorov competitive mappings on a monotone region with a carrying simplex whose planar fixed points are saddles but globally asymptotically stable on their positive coordinate planes. For three dimensional Ricker models, they found mild conditions on parameters such that the criterion can be applied to. Observing that Balreira, Elaydi and Luis' discussion is still valid for the monotone region with piecewise smooth boundary, we prove in this note that the interior fixed point of three dimensional Kolmogorov competitive mappings is globally asymptotically stable if they admit a carrying simplex and three planar fixed points which are saddles but globally asymptotically stable on their positive coordinate planes. This result is much easier to apply in the application.
  • Fritsch, Coralie; Campillo, Fabien; Ovaskainen, Otso (2017)
    We propose a numerical approach to study the invasion fitness of a mutant and to determine evolutionary singular strategies in evolutionary structured models in which the competitive exclusion principle holds. Our approach is based on a dual representation, which consists of the modeling of the small size mutant population by a stochastic model and the computation of its corresponding deterministic model. The use of the deterministic model greatly facilitates the numerical determination of the feasibility of invasion as well as the convergence-stability of the evolutionary singular strategy. Our approach combines standard adaptive dynamics with the link between the mutant survival criterion in the stochastic model and the sign of the eigenvalue in the corresponding deterministic model. We present our method in the context of a mass-structured individual-based chemostat model. We exploit a previously derived mathematical relationship between stochastic and deterministic representations of the mutant population in the chemostat model to derive a general numerical method for analyzing the invasion fitness in the stochastic models. Our method can be applied to the broad class of evolutionary models for which a link between the stochastic and deterministic invasion fitnesses can be established. (C) 2017 Elsevier Inc. All rights reserved.
  • Purhonen, Janne; Grigorjev, Vladislav; Ekiert, Robert; Aho, Noora; Rajendran, Jayasimman; Pietras, Rafal; Truve, Katarina; Wikström, Mårten; Sharma, Vivek; Osyczka, Artur; Fellman, Vineta; Kallijärvi, Jukka (2020)
    We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1/(p.S78G) mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cyb(p.D254N)), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1/(p.S78G) tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc(1) complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes.
  • Cornell, Stephen J.; Suprunenko, Yevhen F.; Finkelshtein, Dmitri; Somervuo, Panu; Ovaskainen, Otso (2019)
    Individual-based models, 'IBMs', describe naturally the dynamics of interacting organisms or social or financial agents. They are considered too complex for mathematical analysis, but computer simulations of them cannot give the general insights required. Here, we resolve this problem with a general mathematical framework for IBMs containing interactions of an unlimited level of complexity, and derive equations that reliably approximate the effects of space and stochasticity. We provide software, specified in an accessible and intuitive graphical way, so any researcher can obtain analytical and simulation results for any particular IBM without algebraic manipulation. We illustrate the framework with examples from movement ecology, conservation biology, and evolutionary ecology. This framework will provide unprecedented insights into a hitherto intractable panoply of complex models across many scientific fields.
  • Baumeister, Dorothea; Järvisalo, Matti; Neugebauer, Daniel; Niskanen, Andreas; Rothe, Jörg (2021)
    A Abstract argumentation frameworks (AFs), originally proposed by Dung, constitute a central formal model for the study of computational aspects of argumentation in AI. Credulous and skeptical acceptance of arguments in a given AF are well-studied problems both in terms of theoretical analysis-especially computational complexity-and the development of practical decision procedures for the problems. However, AFs make the assumption that all attacks between arguments are certain (i.e., present attacks are known to exist, and missing attacks are known to not exist), which can in various settings be a restrictive assumption. A generalization of AFs to incomplete AFs was recently proposed as a formalism that allows the representation of both uncertain attacks and uncertain arguments in AFs. In this article, we explore the impact of allowing for modeling such uncertainties in AFs on the computational complexity of natural generalizations of acceptance problems to incomplete AFs under various central AF semantics. Complementing the complexity-theoretic analysis, we also develop the first practical decision procedures for all of the NP-hard variants of acceptance in incomplete AFs. In terms of complexity analysis, we establish a full complexity landscape, showing that depending on the variant of acceptance and property/semantics, the complexity of acceptance in incomplete AFs ranges from polynomial-time decidable to completeness for Sigma(p)(3). In terms of algorithms, we show through an extensive empirical evaluation that an implementation of the proposed decision procedures, based on boolean satisfiability (SAT) solving, is effective in deciding variants of acceptance under uncertainties. We also establish conditions for what type of atomic changes are guaranteed to be redundant from the perspective of preserving extensions of completions of incomplete AFs, and show that the results allow for considerably improving the empirical efficiency of the proposed SAT-based counterexample-guided abstraction refinement algorithms for acceptance in incomplete AFs for problem variants with complexity beyond NP. (C) 2021 The Authors. Published by Elsevier B.V.
  • Korhonen, Jaana; Giurca, Alexandru; Brockhaus, Maria; Toppinen, Anne (2018)
    To foster innovativeness for supporting (forest-based) bioeconomy development, participation in decision-making and interaction between diverse actors become a necessary precondition for designing and implementing transition policies. However, who forms the emerging policy networks, and which policy beliefs are promoted? Based on data from a national online survey, we performed a quantitative social network analysis to investigate emerging social structures and policy beliefs in the context of the Finnish forest-based bioeconomy. Our explorative analysis shows that research, governmental, and industrial organizations mainly constitute the Finnish forest-based bioeconomy network. Actors primarily exchange information, and most key organizations report high levels of trust among each other. However, the network structure is rather closed. This raises concerns about equal benefit sharing and the inclusiveness of concerned actors. We discuss the implication of this network structure for enabling new innovations. Finally, we present the key aspects and drivers of business as usual, and suggest an option for or a more transformative change in the Finnish forest-based bioeconomy.
  • Flamant, Cyrille; Deroubaix, Adrien; Chazette, Patrick; Brito, Joel; Gaetani, Marco; Knippertz, Peter; Fink, Andreas H.; de Coetlogon, Gaelle; Menut, Laurent; Colomb, Aurelie; Denjean, Cyrielle; Meynadier, Remi; Rosenberg, Philip; Dupuy, Regis; Dominutti, Pamela; Duplissy, Jonathan; Bourrianne, Thierry; Schwarzenboeck, Alfons; Ramonet, Michel; Totems, Julien (2018)
    The complex vertical distribution of aerosols over coastal southernWest Africa (SWA) is investigated using airborne observations and numerical simulations. Observations were gathered on 2 July 2016 offshore of Ghana and Togo, during the field phase of the Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa project. This was the only flight conducted over the ocean during which a downward-looking lidar was operational. The aerosol loading in the lower troposphere includes emissions from coastal cities (Accra, Lome, Cotonou, and Lagos) as well as biomass burning aerosol and dust associated with long-range transport from central Africa and the Sahara, respectively. Our results indicate that the aerosol distribution on this day is impacted by subsidence associated with zonal and meridional regional-scale overturning circulations associated with the land-sea surface temperature contrast and orography over Ghana and Togo, as typically observed on hot, cloud-free summer days such as 2 July 2016. Furthermore, we show that the zonal circulation evidenced on 2 July is a persistent feature over the Gulf of Guinea during July 2016. Numerical tracer re-lease experiments highlight the dominance of aged emissions from Accra on the observed pollution plume loadings over the ocean, in the area of aircraft operation. The contribution of aged emission from Lome and Cotonou is also evident above the marine boundary layer. Given the general direction of the monsoon flow, the tracer experiments indicate no contribution from Lagos emissions to the atmospheric composition of the area west of Cotonou, where our airborne observations were gathered. The tracer plume does not extend very far south over the ocean (i.e. less than 100 km from Accra), mostly because emissions are transported northeastward near the surface over land and westward above the marine atmospheric boundary layer. The latter is possible due to interactions between the monsoon flow, complex terrain, and land-sea breeze systems, which support the vertical mixing of the urban pollution. This work sheds light on the complex - and to date undocumented - mechanisms by which coastal shallow circulations can distribute atmospheric pollutants over the densely populated SWA region.
  • Georgiadou, Maria; Lilja, Johanna; Jacquemet, Guillaume; Guzman, Camilo; Rafaeva, Maria; Alibert, Charlotte; Yan, Yan; Sahgal, Pranshu; Lerche, Martina; Manneville, Jean-Baptiste; Makela, Tomi P.; Ivaska, Johanna (2017)
    Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the metabolic sensor AMP-activated protein kinase (AMPK) as a beta 1-integrin inhibitor in fibroblasts. Loss of AMPK promotes beta 1-integrin activity, the formation of centrally located active beta 1-integrin- and tensin-rich mature fibrillar adhesions, and cell spreading. Moreover, in the absence of AMPK, cells generate more mechanical stress and increase fibronectin fibrillogenesis. Mechanistically, we show that AMPK negatively regulates the expression of the integrin-binding proteins tensin1 and tensin3. Transient expression of tensins increases beta 1-integrin activity, whereas tensin silencing reduces integrin activity in fibroblasts lacking AMPK. Accordingly, tensin silencing in AMPK-depleted fibroblasts impedes enhanced cell spreading, traction stress, and fibronectin fiber formation. Collectively, we show that the loss of AMPK up-regulates tensins, which bind beta 1-integrins, supporting their activity and promoting fibrillar adhesion formation and integrin-dependent processes.
  • Fang, Keyan; Makkonen, Risto; Guo, Zhengtang; Zhao, Yan; Seppä, Heikki (2015)
    A significant wetting trend since the early 1980s in Tibetan Plateau (TP) is most conspicuous in central and eastern Asia as shown in the instrumental data and the long-term moisture sensitive tree rings. We found that anomalies in the large-scale oceanic and atmospheric circulations do not play a significant role on the wetting trend in TP. Meanwhile, the weak correlation between local temperature and precipitation suggests that the temperature-induced enhancement of the local water cycle cannot fully explain the wetting trend either. This may indicate the presence of nonlinear processes between local temperature and precipitation. We hypothesize that the current warming may enhance the emissions of the biogenic volatile organic compounds (BVOC) that can increase the secondary organic aerosols (SOA), contributing to the precipitation increase. The wetting trend can increase the vegetation cover and cause a positive feedback on the BVOC emissions. Our simulations indicate a significant contribution of increased BVOC emissions to the regional organic aerosol mass and the simulated increase in BVOC emissions is significantly correlated with the wetting trend in TP.
  • Katainen, Anu; Heikkilä, Riie (2020)
    Critical discussions on the focus group method have highlighted the importance of considering the forms of interaction generated in groups. In this empirical paper we argue that these forms of interaction are intimately linked to the ways participants interpret the study setting, and these interpretations are likely to differ significantly depending on participants' social backgrounds. In the light of our data consisting of 18 focus groups with 15-year-old school pupils from both affluent and deprived neighbourhoods of Helsinki discussing film clips about young people drinking alcohol, we ask what kinds of modes of participation are mobilised in focus group discussions in order to mark the social position of participants. We further analyse these modes in relation to situated identity performances, arguing that contextual factors of the study setting become especially important to consider when researching vulnerable groups and heterogeneous populations. The analysis yields three modes of participation: these are active/engaged, resistant/passive and dominant/transformative. We argue that these modes can be viewed as actively taken positions that reveal what kinds of identities and competences participants are able and willing to mobilise in the study setting, and that recognising these modes is important in all interview settings.
  • Skaugen, Audun; Murray, Peyton; Laurson, Lasse (2019)
    Due to its nonlocal nature, calculating the demagnetizing field remains the biggest challenge in understanding domain structures in ferromagnetic materials. Analytical descriptions of demagnetizing effects typically approximate domain walls as uniformly magnetized ellipsoids, neglecting both the smooth rotation of magnetization from one domain to the other and the interaction between the two domains. Here, instead of the demagnetizing field, we compute analytically the demagnetizing energy of a straight domain wall described by the classical tanh magnetization profile in a thin film with perpendicular magnetic anisotropy. We then use our expression for the demagnetizing energy to derive an improved version of the 1D model of field-driven domain wall motion, resulting in accurate expressions for important properties of the domain wall such as the domain wall width and the Walker breakdown field. We verify the accuracy of our analytical results by micromagnetic simulations.
  • Hiltunen, Teppo; Virta, Marko; Laine, Anna-Liisa (2017)
    The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently. This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'.
  • Seppala, Otto; Karvonen, Anssi; Kuosa, Marja; Haataja, Maarit; Jokela, Jukka (2013)
  • Sakha, Prasanna; Vesikansa, Aino; Orav, Ester; Heikkinen, Joonas; Kukko-Lukjanov, Tiina-Kaisa; Shintyapina, Alexandra; Franssila, Sami; Jokinen, Ville; Huttunen, Henri J.; Lauri, Sari E. (2016)
    Kainate type of glutamate receptors (KARs) are highly expressed during early brain development and may influence refinement of the circuitry, via modulating synaptic transmission and plasticity. KARs are also localized to axons, however, their exact roles in regulating presynaptic processes remain controversial. Here, we have used a microfluidic chamber system allowing specific manipulation of KARs in presynaptic neurons to study their functions in synaptic development and function in vitro. Silencing expression of endogenous KARs resulted in lower density of synaptophysin immunopositive puncta in microfluidically isolated axons. Various recombinant KAR subunits and pharmacological compounds were used to dissect the mechanisms behind this effect. The calcium permeable (Q) variants of the low-affinity (GluK1-3) subunits robustly increased synaptophysin puncta in axons in a manner that was dependent on receptor activity and PKA and PKC dependent signaling. Further, an associated increase in the mean active zone length was observed in electron micrographs. Selective presynaptic expression of these subunits resulted in higher success rate of evoked EPSCs consistent with higher probability of glutamate release. In contrast, the calcium-impermeable (R) variant of GluK1 or the high-affinity subunits (GluK4,5) had no effect on synaptic density or transmission efficacy. These data suggest that calcium permeable axonal KARs promote efferent connectivity by increasing the density of functional presynaptic release sites.