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1.
  • Falk Erhag, Hanna, et al. (författare)
  • A Multidisciplinary Approach to Capability in Age and Ageing
  • 2022
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • This open access book provides insight on how to interpret capability in ageing – one’s individual ability to perform actions in order to reach goals one has reason to value – from a multidisciplinary approach. With for the first time in history there being more people in the world aged 60 years and over than there are children below the age of 5, the book describes this demographic trends as well as the large global challenges and important societal implications this will have such as a worldwide increase in the number of persons affected with dementia, and in the ratio of retired persons to those still in the labor market. Through contributions from many different research areas, it discussed how capability depends on interactions between the individual (e.g. health, genetics, personality, intellectual capacity), environment (e.g. family, friends, home, work place), and society (e.g. political decisions, ageism, historical period). The final chapter by the editors summarizes the differences and similarities in these contributions. As such this book provides an interesting read for students, teachers and researchers at different levels and from different fields interested in capability and multidisciplinary research.
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2.
  • Solinas, Giovanni, et al. (författare)
  • An adipoincretin effect links adipostasis with insulin secretion.
  • 2024
  • Ingår i: Trends in endocrinology and metabolism: TEM. - 1879-3061. ; 35:6, s. 466-477
  • Forskningsöversikt (refereegranskat)abstract
    • The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretins, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect.
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3.
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4.
  • Mamontov, Eugen, 1955 (författare)
  • Homeorhesis and evolutionary properties of living systems: From ordinary differential equations to the active-particle generalized kinetics theory
  • 2006
  • Ingår i: 10th Evolutionary Biology Meeting at Marseilles, 20-22 September 2006, Marseilles, France.
  • Konferensbidrag (refereegranskat)abstract
    • Advanced generalized-kinetic-theory (GKT) models for biological systems are developed for populations of active (or living) particles [1]-[5]. These particles are described with both the stochastic variables common in kinetic theory (such as time, the particle random location and velocity) and the stochastic variables related to the internal states of an active particle. Evolution of these states represents biological, ecological, or social properties of the particle behavior. Paper [6] analyzes a number of the well-known statistical-mechanics approaches and shows that the active-particle GKT (APGKT) is the only treatment capable of modelling living systems. Work [2] summarizes the significance of the notion of an active particle in kinetic models. This notion draws attention to the features distinguishing living matter from nonliving matter. They are discussed by many authors (e.g., [7]-[15], [1]-[3], [6], [16]-[18]). Work [11] considers a lot of differences between living and nonliving matters, and the limitations of the modelling approaches developed for nonliving matter. Work [6] mainly focuses on the comparison of a few theoretical mechanics treatments in terms of the key living-matter properties formulated in [15]. One of the necessary properties of the evolution of living systems is homeorhesis. It is, loosely speaking, a peculiar qualitative and quantitative insensitivity of a living system to the exogenous signals acting on it. The earlier notion, homeostasis, was introduced by W. B. Cannon in 1926 who discussed the phenomenon in detail later [7]. Homeorhesis introduced by C. H. Waddington [8, p. 32] generalizes homeostasis and is well known in biology [8], [9], [12]. It is an inherent part of mathematical models for oncogeny (e.g., [16]-[18], [6, Appendix]). Homeorhesis is also discussed in [3, Section 4] in connection with APGKT. Homeorhesis is documented in ecology (e.g., [11], [13, the left column on p. 675]) where it is one of the key notions of the strong Gaia theory, a version of the Gaia theory (e.g., [14, Chapter 8]). The strong Gaia theory “states that the planet with its life, a single living system, is regulated in certain aspects by that life” [14, p. 124]. The very origin of the name “Gaia” is related to homeorhesis or homeostasis [14, p. 118]. These notions are also used in psychology and sociology. If evolution of a system is not homeorhetic, the system can not be living. Work [6, Appendix] derives a preliminary mathematical formulation of homeorhesis in terms of the simplest dynamical systems, i.e. ordinary differential equations (ODEs). The present work complements, extended, and further specify the approach of [6, Appendix]. The work comprises the two main parts. The first part develops the sufficient conditions for ODE systems to describe homeorhesis, and suggests a fairly general structure of the ODE model. It regards homeorhesis as piecewise homeostasis. The model can be specified in different ways depending on specific systems and specific purposes of the analysis. An example of the specification is also noted (the PhasTraM nonlinear reaction-diffusion model for hyperplastic oncogeny [16]-[18]). The second part of the work discusses implementation of the above homeorhesis ODE model in terms of a special version [3] of APGKT (see above). The key feature of this version is that the components of a living population need not be discrete: the subdivision into the components is described with a general, continuous-discrete probability distribution (see also [6]). This enables certain properties of living matter noted in [15]. Moreover, the corresponding APGKT model presents a system of, firstly, a generalized kinetic equation for the conditional distribution function conditioned by the internal states of the population and, secondly, Ito's stochastic differential equations for these states. This treatement employs the results on nonstationary invariant diffusion stochastic processes [19]. The second part of the work also stresses that APGKT is substantially more important for the living-matter analysis than in the case of nonliving matter. One of the reasons is certain limitations in experimental sampling of the living-system modes presented with stochastic processes. A few directions for future research are suggested as well. REFERENCES: [1] Bellomo, N., Bellouquid, A. and Delitala, M., 2004, Mathematical topics on the modelling complex multicellular systems and tumor immune cells competition, Math. Models Methods Appl. Sci., 14, 1683-1733. [2] Bellomo, N., 2006, New hot Paper Comments, Essential Science Indicators, http://www.esi-topics.com/nhp/2006 /may- 06-NicolaBellomo.html. [3] Willander, M., Mamontov, E. and Chiragwandi, Z., 2004, Modelling living fluids with the subdivision into the components in terms of probability distributions, Math. Models Methods Appl. Sci. 14, 1495-1520. [4] Bellomo, N. and Maini, P.K., 2005, Preface and the Special Issue “Multiscale Cancer Modelling-A New Frontier in Applied Mathematics”, Math. Models Methods Appl. Sci., 15, iii-viii. [5] De Angelis, E. and Delitala, M., 2006, Modelling complex systems in applied sciences: Methods and tools of the mathematical kinetic theory for active particles. Mathl Comput. Modelling, 43, 1310-1328. [6] Mamontov, E., Psiuk-Maksymowicz, K. and Koptioug, A., 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, Article in Press, 13 pp. [7] Cannon, W.B., 1932, The Wisdom of the Body (New York: Norton). [8] Waddington, C.H., 1957, The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology (London, George Allen and Unwin). [9] Waddington, C.H., 1968, Towards a theoretical biology, Nature, 218, 525-527. [10] Cotnoir, P.-A., 1981, La compétence environnementale: Une affaire d’adaptation. Séminaire en écologie behaviorale, Univeristé du Québec, Montralé. Available online at: http://pac.cam.org/culture.doc . [11] O’Neill, R.V., DeAngelis, D.L., Waide, J.B. and Allen, T.F.H., 1986, A Hierarchical Concept of Ecosystems, Princeton: Princeton Univ. Press). [12] Sauvant, D., 1992, La modélisation systémique en nutrition, Reprod. Nutr. Dev., 32, 217-230. [13] Christensen, N.L., Bartuska, A.M., Brown, J.H., Carpenter, S., D'Antonio, C., Francis, R., Franklin, J.F., MacMahon, J.A., Noss, R.F., Parsons, D.J., Peterson, C.H., Turner, M.G. and Woodmansee, R.G., 1996, The Report of the Ecological Society of America Committee on the Scientific Basis for Ecosystem Management, Ecological Applications, 6, 665-691. Available online at: http://www.esa.org/pao/esaPositions/Papers/ReportOfSBEM.php. [14] Margulis, L., 1998, Symbiotic Planet. A New Look at Evolution (Amherst: Sciencewriters). [15] Hartwell, L.H., Hopfield, J.J., Leibler, S. and Murray, A.W., 1999, From molecular to modular cell biology, Nature, 402, C47-C52. [16] Mamontov, E., Koptioug, A.V. and Psiuk-Maksymowicz, K., 2006, The minimal, phase-transition model for the cell- number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54, 44 pp., (no. 2, May-June, accepted). [17] Psiuk-Maksymowicz, K. and Mamontov, E., 2005, The time-slices method for rapid solving the Cauchy problem for nonlinear reaction-diffusion equations in the competition of homeorhesis with genotoxically activated hyperplasia, In: European Conference on Mathematical and Theoretical Biology - ECMTB05 (July 18-22, 2005) Book of Abstracts, Vol.1 (Dresden: Center for Information Services and High Performance Computing, Dresden Univ. Technol.), p. 429 (http://www.ecmtb05.org/). [18] Psiuk-Maksymowicz, K. and Mamontov, E., 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiation therapy, submitted. [19] Mamontov, E., 2005, Nonstationary invariant distributions and the hydrodynamic-style generalization of the Kolmogorov-forward/Fokker-Planck equation, Appl. Math. Lett. 18 (9) 976-982.
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5.
  • Mamontov, Eugen, 1955, et al. (författare)
  • The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
  • 2006
  • Ingår i: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
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6.
  • Mamontov, Eugen, 1955, et al. (författare)
  • Oncogenic hyperplasia caused by combination of various factors: A decision-support software for radionuclide therapy
  • 2007
  • Ingår i: Workshop "Mathematical Modelling and Analysis of Cancer Invasion of Tissues", Mar 26, 2007 - Mar 30, 2007, Dundee, Scotland.
  • Konferensbidrag (refereegranskat)abstract
    • The present work deals with the software based on the PhasTraM model [1] for oncogenic hyperplasia, the first stage of formation of any solid tumor. The work generalizes the related results of [2]-[6] and discusses application of the software for decision support in radionuclide therapy. The software capabilities to allow for combinations of various causes of oncogeny are emphasized. The causes comprise inflammation, immune dysfunction, and chronic psychological stress. The immune dysfunction is represented with hypogammaglobulenimia expressed in terms of the concentration of the immunoglobulin-G molecules. The level of chronic pychological stress is described with the concentration of the interleukin-6 molecules. The work considers how application of the software can support decisions on the specific radionuclide-therapy setting depending on the tissue-, organ-, and patient-specific data. This is illustrated by a number of numerical-simulation results, also the ones which include the effects of common and fractionation-based radionuclide-therapy modalities. A proper attention is paid to how specifically the input data can be prepared by prospective users of the software, i.e. the specialists who apply radionuclide therapy. The work also formulates a few directions for future research in connection with the features of the everyday work of the prospective users. REFERENCES: [1] E. Mamontov, K. Psiuk-Maksymowicz, A. Koptioug, 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, 44(7-8) 595-607. [2] E. Mamontov, A. V. Koptioug, K. Psiuk-Maksymowicz, 2006, The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54(2) 61-101. [3] K. Psiuk-Maksymowicz and E. Mamontov, 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiotherapy, Mathl Comput. Modelling, Special Issue
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7.
  • Norrman, Eva, et al. (författare)
  • Optimization of image process parameters through factorial experiments using a flat panel detector
  • 2007
  • Ingår i: Physics in Medicine and Biology. - Bristol : IOP publishing. - 0031-9155 .- 1361-6560. ; 52:17, s. 5263-5276
  • Tidskriftsartikel (refereegranskat)abstract
    • In the optimization process of lumbar spine examinations, factorial experiments were performed addressing the question of whether the effective dose can be reduced and the image quality maintained by adjusting the image processing parameters. A 2(k)-factorial design was used which is a systematic and effective method of investigating the influence of many parameters on a result variable. Radiographic images of a Contrast Detail phantom were exposed using the default settings of the process parameters for lumbar spine examinations. The image was processed using different settings of the process parameters. The parameters studied were ROI density, gamma, detail contrast enhancement (DCE), noise compensation, unsharp masking and unsharp masking kernel (UMK). The images were computer analysed and an image quality figure (IQF) was calculated and used as a measurement of the image quality. The parameters with the largest influence on image quality were noise compensation, unsharp masking, unsharp masking kernel and detail contrast enhancement. There was an interaction between unsharp masking and kernel indicating that increasing the unsharp masking improved the image quality when combined with a large kernel size. Combined with a small kernel size however the unsharp masking had a deteriorating effect. Performing a factorial experiment gave an overview of how the image quality was influenced by image processing. By adjusting the level of noise compensation, unsharp masking and kernel, the IQF was improved to a 30% lower effective dose.
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8.
  • Brännmark, Cecilia, et al. (författare)
  • Mathematical modeling of white adipocyte exocytosis predicts adiponectin secretion and quantifies the rates of vesicle exo- and endocytosis
  • 2017
  • Ingår i: Journal of Biological Chemistry. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 0021-9258 .- 1083-351X. ; 292:49, s. 20032-20043
  • Tidskriftsartikel (refereegranskat)abstract
    • Adiponectin is a hormone secreted from white adipocytes and takes part in the regulation of several metabolic processes. Although the pathophysiological importance of adiponectin has been thoroughly investigated, the mechanisms controlling its release are only partly understood. We have recently shown that adiponectin is secreted via regulated exocytosis of adiponectin-containing vesicles, that adiponectin exocytosis is stimulated by cAMP-dependent mechanisms, and that Ca2+ and ATP augment the cAMP-triggered secretion. However, much remains to be discovered regarding the molecular and cellular regulation of adiponectin release. Here, we have used mathematical modeling to extract detailed information contained within our previously obtained high-resolution patch-clamp time-resolved capacitance recordings to produce the first model of adiponectin exocytosis/secretion that combines all mechanistic knowledge deduced from electrophysiological experimental series. This model demonstrates that our previous understanding of the role of intracellular ATP in the control of adiponectin exocytosis needs to be revised to include an additional ATP-dependent step. Validation of the model by introduction of data of secreted adiponectin yielded a very close resemblance between the simulations and experimental results. Moreover, we could show that Ca2+-dependent adiponectin endocytosis contributes to the measured capacitance signal, and we were able to predict the contribution of endocytosis to the measured exocytotic rate under different experimental conditions. In conclusion, using mathematical modeling of published and newly generated data, we have obtained estimates of adiponectin exo- and endocytosis rates, and we have predicted adiponectin secretion. We believe that our model should have multiple applications in the study of metabolic processes and hormonal control thereof.
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9.
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10.
  • Ghorbani, Ramin, 1981- (författare)
  • Real-time breath gas analysis of carbon monoxide : laser-based detection and pulmonary gas exchange modeling
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Breath gas analysis is a promising approach for non-invasive medical diagnostics and physiological monitoring. Real-time, breath-cycle resolved biomarker detection facilitates data interpretation and has the potential to improve the diagnostic value of breath tests as exhalation profiles carry spatiotemporal information about biomarker origin and gas exchange in the respiratory tract. This thesis presents and scrutinizes a novel methodology for the analysis of real-time breath data, where single-exhalation profiles are simulated using a pulmonary gas exchange model and least-squares fitted to measured expirograms to extract airway and alveolar contributions and diffusing capacities. The methodology is demonstrated on exhaled breath carbon monoxide (eCO), a candidate biomarker for oxidative stress and respiratory diseases. The thesis mainly covers (1) the construction of a compact optical sensor based on tunable diode laser absorption spectroscopy (TDLAS) in the mid-infrared region (4.7 μm) for selective and precise real-time detection of CO in breath and ambient air (detection limit 9 ± 5 ppb at 0.1 s), (2) the design of an advanced online breath sampling system, (3) the implementation of a trumpet model with axial diffusion (TMAD) to simulate the CO gas exchange, and (4) the application of extended eCO analysis in clinical studies to establish the healthy non-smoker baseline of the eCO parameters and to study the response to CO and wood smoke exposure. It is shown that the TMAD adequately describes the gas exchange during systemic CO elimination for different breathing patterns, and that there is no difference between eCO parameters from mouth- and nose exhalations. Expirogram shape and eCO parameters exhibit a dependence on the exhalation flow rate, but for a given breathing maneuverer, the parameters lie in a narrow range. Airway CO is close to and correlates with ambient air CO, indicating negligible airway production in the healthy population. The alveolar diffusing capacity is independent of endogenous CO, even after exposure to elevated exogenous CO, and could be used to assess lung diffusion abnormalities. Compared to CO exposure, no clear additional effect of exposure to wood smoke particles on eCO is observed. The discrimination between endogenous and exogenous CO sources remains a challenge.
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