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Sample records for cell population model

  1. A Structured Population Model of Cell Differentiation

    CERN Document Server

    Doumic, Marie; Perthame, Benoit; Zubelli, Jorge P

    2010-01-01

    We introduce and analyze several aspects of a new model for cell differentiation. It assumes that differentiation of progenitor cells is a continuous process. From the mathematical point of view, it is based on partial differential equations of transport type. Specifically, it consists of a structured population equation with a nonlinear feedback loop. This models the signaling process due to cytokines, which regulate the differentiation and proliferation process. We compare the continuous model to its discrete counterpart, a multi-compartmental model of a discrete collection of cell subpopulations recently proposed by Marciniak-Czochra et al. in 2009 to investigate the dynamics of the hematopoietic system. We obtain uniform bounds for the solutions, characterize steady state solutions, and analyze their linearized stability. We show how persistence or extinction might occur according to values of parameters that characterize the stem cells self-renewal. We also perform numerical simulations and discuss the q...

  2. Modelling Spread of Oncolytic Viruses in Heterogeneous Cell Populations

    Science.gov (United States)

    Ellis, Michael; Dobrovolny, Hana

    2014-03-01

    One of the most promising areas in current cancer research and treatment is the use of viruses to attack cancer cells. A number of oncolytic viruses have been identified to date that possess the ability to destroy or neutralize cancer cells while inflicting minimal damage upon healthy cells. Formulation of predictive models that correctly describe the evolution of infected tumor systems is critical to the successful application of oncolytic virus therapy. A number of different models have been proposed for analysis of the oncolytic virus-infected tumor system, with approaches ranging from traditional coupled differential equations such as the Lotka-Volterra predator-prey models, to contemporary modeling frameworks based on neural networks and cellular automata. Existing models are focused on tumor cells and the effects of virus infection, and offer the potential for improvement by including effects upon normal cells. We have recently extended the traditional framework to a 2-cell model addressing the full cellular system including tumor cells, normal cells, and the impacts of viral infection upon both populations. Analysis of the new framework reveals complex interaction between the populations and potential inability to simultaneously eliminate the virus and tumor populations.

  3. Synergistic interaction between selective drugs in cell populations models.

    Directory of Open Access Journals (Sweden)

    Victoria Doldán-Martelli

    Full Text Available The design of selective drugs and combinatorial drug treatments are two of the main focuses in modern pharmacology. In this study we use a mathematical model of chimeric ligand-receptor interaction to show that the combination of selective drugs is synergistic in nature, providing a way to gain optimal selective potential at reduced doses compared to the same drugs when applied individually. We use a cell population model of proliferating cells expressing two different amounts of a target protein to show that both selectivity and synergism are robust against variability and heritability in the cell population. The reduction in the total drug administered due to the synergistic performance of the selective drugs can potentially result in reduced toxicity and off-target interactions, providing a mechanism to improve the treatment of cell-based diseases caused by aberrant gene overexpression, such as cancer and diabetes.

  4. A sub-cellular viscoelastic model for cell population mechanics.

    Directory of Open Access Journals (Sweden)

    Yousef Jamali

    Full Text Available Understanding the biomechanical properties and the effect of biomechanical force on epithelial cells is key to understanding how epithelial cells form uniquely shaped structures in two or three-dimensional space. Nevertheless, with the limitations and challenges posed by biological experiments at this scale, it becomes advantageous to use mathematical and 'in silico' (computational models as an alternate solution. This paper introduces a single-cell-based model representing the cross section of a typical tissue. Each cell in this model is an individual unit containing several sub-cellular elements, such as the elastic plasma membrane, enclosed viscoelastic elements that play the role of cytoskeleton, and the viscoelastic elements of the cell nucleus. The cell membrane is divided into segments where each segment (or point incorporates the cell's interaction and communication with other cells and its environment. The model is capable of simulating how cells cooperate and contribute to the overall structure and function of a particular tissue; it mimics many aspects of cellular behavior such as cell growth, division, apoptosis and polarization. The model allows for investigation of the biomechanical properties of cells, cell-cell interactions, effect of environment on cellular clusters, and how individual cells work together and contribute to the structure and function of a particular tissue. To evaluate the current approach in modeling different topologies of growing tissues in distinct biochemical conditions of the surrounding media, we model several key cellular phenomena, namely monolayer cell culture, effects of adhesion intensity, growth of epithelial cell through interaction with extra-cellular matrix (ECM, effects of a gap in the ECM, tensegrity and tissue morphogenesis and formation of hollow epithelial acini. The proposed computational model enables one to isolate the effects of biomechanical properties of individual cells and the

  5. Preface of the "Symposium on Mathematical Models and Methods to investigate Heterogeneity in Cell and Cell Population Biology"

    Science.gov (United States)

    Clairambault, Jean

    2016-06-01

    This session investigates hot topics related to mathematical representations of cell and cell population dynamics in biology and medicine, in particular, but not only, with applications to cancer. Methods in mathematical modelling and analysis, and in statistical inference using single-cell and cell population data, should contribute to focus this session on heterogeneity in cell populations. Among other methods are proposed: a) Intracellular protein dynamics and gene regulatory networks using ordinary/partial/delay differential equations (ODEs, PDEs, DDEs); b) Representation of cell population dynamics using agent-based models (ABMs) and/or PDEs; c) Hybrid models and multiscale models to integrate single-cell dynamics into cell population behaviour; d) Structured cell population dynamics and asymptotic evolution w.r.t. relevant traits; e) Heterogeneity in cancer cell populations: origin, evolution, phylogeny and methods of reconstruction; f) Drug resistance as an evolutionary phenotype: predicting and overcoming it in therapeutics; g) Theoretical therapeutic optimisation of combined drug treatments in cancer cell populations and in populations of other organisms, such as bacteria.

  6. A host-parasite model for a two-type cell population

    CERN Document Server

    Alsmeyer, Gerold

    2012-01-01

    A host-parasite model is considered for a population of cells that can be of two types, A or B, and exhibits unilateral reproduction: while a B-cell always splits into two cells of the same type, the two daughter cells of an A-cell can be of any type. The random mechanism that describes how parasites within a cell multiply and are then shared into the daughter cells is allowed to depend on the hosting mother cell as well as its daughter cells. Focusing on the subpopulation of A-cells and its parasites, the model differs from the single-type model recently studied by Bansaye (2008) in that the sharing mechanism may be biased towards one of the two types. Main results are concerned with the nonextinctive case and provide information on the behavior, as $n\\to\\infty$, of the number A-parasites in generation n and the relative proportion of A- and B-cells in this generation which host a given number of parasites. As in (Bansaye,2008), proofs will make use of a so-called random cell line which, when conditioned to ...

  7. Population based model of human embryonic stem cell (hESC differentiation during endoderm induction.

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    Keith Task

    Full Text Available The mechanisms by which human embryonic stem cells (hESC differentiate to endodermal lineage have not been extensively studied. Mathematical models can aid in the identification of mechanistic information. In this work we use a population-based modeling approach to understand the mechanism of endoderm induction in hESC, performed experimentally with exposure to Activin A and Activin A supplemented with growth factors (basic fibroblast growth factor (FGF2 and bone morphogenetic protein 4 (BMP4. The differentiating cell population is analyzed daily for cellular growth, cell death, and expression of the endoderm proteins Sox17 and CXCR4. The stochastic model starts with a population of undifferentiated cells, wherefrom it evolves in time by assigning each cell a propensity to proliferate, die and differentiate using certain user defined rules. Twelve alternate mechanisms which might describe the observed dynamics were simulated, and an ensemble parameter estimation was performed on each mechanism. A comparison of the quality of agreement of experimental data with simulations for several competing mechanisms led to the identification of one which adequately describes the observed dynamics under both induction conditions. The results indicate that hESC commitment to endoderm occurs through an intermediate mesendoderm germ layer which further differentiates into mesoderm and endoderm, and that during induction proliferation of the endoderm germ layer is promoted. Furthermore, our model suggests that CXCR4 is expressed in mesendoderm and endoderm, but is not expressed in mesoderm. Comparison between the two induction conditions indicates that supplementing FGF2 and BMP4 to Activin A enhances the kinetics of differentiation than Activin A alone. This mechanistic information can aid in the derivation of functional, mature cells from their progenitors. While applied to initial endoderm commitment of hESC, the model is general enough to be applicable

  8. Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells

    DEFF Research Database (Denmark)

    Hald, Bjørn Olav; Hendriksen, Morten; Sørensen, Preben Graae

    2013-01-01

    Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredict...... unpredictable. In heterogeneous populations, synchronization of events becomes a cardinal problem-particularly for phase coherence in oscillating systems....

  9. Programmable models of growth and mutation of cancer-cell populations

    CERN Document Server

    Bortolussi, Luca; 10.4204/EPTCS.67.4

    2011-01-01

    In this paper we propose a systematic approach to construct mathematical models describing populations of cancer-cells at different stages of disease development. The methodology we propose is based on stochastic Concurrent Constraint Programming, a flexible stochastic modelling language. The methodology is tested on (and partially motivated by) the study of prostate cancer. In particular, we prove how our method is suitable to systematically reconstruct different mathematical models of prostate cancer growth - together with interactions with different kinds of hormone therapy - at different levels of refinement.

  10. A mathematical model of radiation-induced responses in a cellular population including cell-to-cell communications

    International Nuclear Information System (INIS)

    Cell-to-cell communication is an important factor for understanding the mechanisms of radiation-induced responses such as bystander effects. In this study, a new mathematical model of intercellular signalling between individual cells in a cellular population is proposed. The authors considered two types of transmission of signals: via culture medium and via gap junction. They focus on the effects that radiation and intercellular signalling have on cell-cycle modification. The cell cycle is represented as a virtual clock that includes several checkpoint pathways within a cyclic process. They also develop a grid model and set up diffusion equations to model the propagation of signals to and from spatially located cells. The authors have also considered the role that DNA damage plays in the cycle of cells which can progress through the cell cycle or stop at the G1, S, G2 or M-phase checkpoints. Results of testing show that the proposed model can simulate intercellular signalling and cell-cycle progression in individual cells during and after irradiation. (authors)

  11. Modelling the anabolic response of bone using a cell population model

    OpenAIRE

    Buenzli, Pascal R.; Pivonka, Peter; Gardiner, Bruce S.; Smith, David W.

    2011-01-01

    To maintain bone mass during bone remodelling, coupling is required between bone resorption and bone formation. This coordination is achieved by a network of autocrine and paracrine signalling molecules between cells of the osteoclast lineage and cells of the osteoblastic lineage. Mathematical modelling of signalling between cells of both lineages can assist in the interpretation of experimental data, clarify signalling interactions and help develop a deeper understanding of complex bone dise...

  12. Explicit kinetic heterogeneity: mathematical models for interpretation of deuterium labeling of heterogeneous cell populations.

    Directory of Open Access Journals (Sweden)

    Vitaly V Ganusov

    2010-02-01

    Full Text Available Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system. Deuterium, in the form of deuterated glucose or heavy water, can be used to measure rates of proliferation and death of lymphocytes in vivo. Inferring these rates from labeling and delabeling curves has been subject to considerable debate with different groups suggesting different mathematical models for that purpose. We show that the three most common models, which are based on quite different biological assumptions, actually predict mathematically identical labeling curves with one parameter for the exponential up and down slope, and one parameter defining the maximum labeling level. By extending these previous models, we here propose a novel approach for the analysis of data from deuterium labeling experiments. We construct a model of "kinetic heterogeneity" in which the total cell population consists of many sub-populations with different rates of cell turnover. In this model, for a given distribution of the rates of turnover, the predicted fraction of labeled DNA accumulated and lost can be calculated. Our model reproduces several previously made experimental observations, such as a negative correlation between the length of the labeling period and the rate at which labeled DNA is lost after label cessation. We demonstrate the reliability of the new explicit kinetic heterogeneity model by applying it to artificially generated datasets, and illustrate its usefulness by fitting experimental data. In contrast to previous models, the explicit kinetic heterogeneity model 1 provides a novel way of interpreting labeling data; 2 allows for a non-exponential loss of labeled cells during delabeling, and 3 can be used to describe data with variable labeling length.

  13. A population balance equation model of aggregation dynamics in Taxus suspension cell cultures.

    Science.gov (United States)

    Kolewe, Martin E; Roberts, Susan C; Henson, Michael A

    2012-02-01

    The nature of plant cells to grow as multicellular aggregates in suspension culture has profound effects on bioprocess performance. Recent advances in the measurement of plant cell aggregate size allow for routine process monitoring of this property. We have exploited this capability to develop a conceptual model to describe changes in the aggregate size distribution that are observed over the course of a Taxus cell suspension batch culture. We utilized the population balance equation framework to describe plant cell aggregates as a particulate system, accounting for the relevant phenomenological processes underlying aggregation, such as growth and breakage. We compared model predictions to experimental data to select appropriate kernel functions, and found that larger aggregates had a higher breakage rate, biomass was partitioned asymmetrically following a breakage event, and aggregates grew exponentially. Our model was then validated against several datasets with different initial aggregate size distributions and was able to quantitatively predict changes in total biomass and mean aggregate size, as well as actual size distributions. We proposed a breakage mechanism where a fraction of biomass was lost upon each breakage event, and demonstrated that even though smaller aggregates have been shown to produce more paclitaxel, an optimum breakage rate was predicted for maximum paclitaxel accumulation. We believe this is the first model to use a segregated, corpuscular approach to describe changes in the size distribution of plant cell aggregates, and represents an important first step in the design of rational strategies to control aggregation and optimize process performance. PMID:21910121

  14. Distinct population of highly malignant cells in a head and neck squamous cell carcinoma cell line established by xenograft model

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    Jan Chia-Ing

    2009-11-01

    Full Text Available Abstract The progression and metastasis of solid tumors, including head and neck squamous cell carcinoma (HNSCC, have been related to the behavior of a small subpopulation of cancer stem cells. Here, we have established a highly malignant HNSCC cell line, SASVO3, from primary tumors using three sequential rounds of xenotransplantation. SASVO3 possesses enhanced tumorigenic ability both in vitro and in vivo. Moreover, SASVO3 exhibits properties of cancer stem cells, including that increased the abilities of sphere-forming, the number of side population cells, the potential of transplanted tumor growth and elevated expression of the stem cell marker Bmi1. Injection of SASVO3 into the tail vein of nude mice resulted in lung metastases. These results are consistent with the postulate that the malignant and/or metastasis potential of HNSCC cells may reside in a stem-like subpopulation.

  15. A model combining cell physiology and population genetics to explain Escherichia coli laboratory evolution

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    Acerenza Luis

    2001-12-01

    Full Text Available Abstract Background Laboratory experiments under controlled conditions during thousands of generations are useful tools to assess the processes underlying bacterial evolution. As a result of these experiments, the way in which the traits change in time is obtained. Under these conditions, the bacteria E. coli shows a parallel increase in cell volume and fitness. Results To explain this pattern it is required to consider organismic and population contributions. For this purpose we incorporate relevant information concerning bacterial structure, composition and transformations in a minimal modular model. In the short time scale, the model reproduces the physiological responses of the traits to changes in nutrient concentration. The decay of unused catabolic functions, found experimentally, is introduced in the model using simple population genetics. The resulting curves representing the evolution of volume and fitness in time are in good agreement with those obtained experimentally. Conclusions This study draws attention on physiology when studying evolution. Moreover, minimal modular models appear to be an adequate strategy to unite these barely related disciplines of biology.

  16. A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.

    Directory of Open Access Journals (Sweden)

    Roman Bauer

    Full Text Available Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

  17. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  18. Kinetics of Infection and Effects on Placental Cell Populations in a Murine Model of Chlamydia psittaci-Induced Abortion

    OpenAIRE

    Buendía, Antonio J.; Sánchez, Joaquín; Martínez, María C.; Cámara, Paulina; Navarro, Jose A.; Rodolakis, Annie; Salinas, Jesus

    1998-01-01

    The anatomical progression of chlamydial infection was studied in different areas of the placenta, using a mouse model and two inoculation times: early pregnancy (day 7, group A) and midpregnancy (day 11, group B). The first population cells affected were decidual cells and neutrophils located just at the limits of the maternal and fetal placenta. The following invaded area was the layer of giant cells. Complete colonization of the maternal placenta occurred after day 15 of pregnancy independ...

  19. A novel quantitative model of cell cycle progression based on cyclin-dependent kinases activity and population balances.

    Science.gov (United States)

    Pisu, Massimo; Concas, Alessandro; Cao, Giacomo

    2015-04-01

    Cell cycle regulates proliferative cell capacity under normal or pathologic conditions, and in general it governs all in vivo/in vitro cell growth and proliferation processes. Mathematical simulation by means of reliable and predictive models represents an important tool to interpret experiment results, to facilitate the definition of the optimal operating conditions for in vitro cultivation, or to predict the effect of a specific drug in normal/pathologic mammalian cells. Along these lines, a novel model of cell cycle progression is proposed in this work. Specifically, it is based on a population balance (PB) approach that allows one to quantitatively describe cell cycle progression through the different phases experienced by each cell of the entire population during its own life. The transition between two consecutive cell cycle phases is simulated by taking advantage of the biochemical kinetic model developed by Gérard and Goldbeter (2009) which involves cyclin-dependent kinases (CDKs) whose regulation is achieved through a variety of mechanisms that include association with cyclins and protein inhibitors, phosphorylation-dephosphorylation, and cyclin synthesis or degradation. This biochemical model properly describes the entire cell cycle of mammalian cells by maintaining a sufficient level of detail useful to identify check point for transition and to estimate phase duration required by PB. Specific examples are discussed to illustrate the ability of the proposed model to simulate the effect of drugs for in vitro trials of interest in oncology, regenerative medicine and tissue engineering. PMID:25601491

  20. Physiologically structured cell population dynamic models with applications to combined drug delivery optimisation in oncology

    OpenAIRE

    Clairambault, Jean; Fercoq, Olivier

    2016-01-01

    In this paper, we introduce a model for drug delivery optimisation in a chronotherapeu-tics framework. We present a pharmacokinetics and pharmacodynamics model for oxaliplatin and 5-Fluorouracil, a classic therapeutic association in the treatment of colorectal cancer. We derive the phar-macokinetics model using law of mass action and enzyme kinetics. We design an age-structured cell cycle PDE model with drug damage and repair phases to account for the effect of the drugs on proliferating cell...

  1. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  2. Development of a population of cancer cells: Observation and modeling by a Mixed Spatial Evolutionary Games approach.

    Science.gov (United States)

    Świerniak, Andrzej; Krześlak, Michał; Student, Sebastian; Rzeszowska-Wolny, Joanna

    2016-09-21

    Living cells, like whole living organisms during evolution, communicate with their neighbors, interact with the environment, divide, change their phenotypes, and eventually die. The development of specific ways of communication (through signaling molecules and receptors) allows some cellular subpopulations to survive better, to coordinate their physiological status, and during embryonal development to create tissues and organs or in some conditions to become tumors. Populations of cells cultured in vitro interact similarly, also competing for space and nutrients and stimulating each other to better survive or to die. The results of these intercellular interactions of different types seem to be good examples of biological evolutionary games, and have been the subjects of simulations by the methods of evolutionary game theory where individual cells are treated as players. Here we present examples of intercellular contacts in a population of living human cancer HeLa cells cultured in vitro and propose an evolutionary game theory approach to model the development of such populations. We propose a new technique termed Mixed Spatial Evolutionary Games (MSEG) which are played on multiple lattices corresponding to the possible cellular phenotypes which gives the possibility of simulating and investigating the effects of heterogeneity at the cellular level in addition to the population level. Analyses performed with MSEG suggested different ways in which cellular populations develop in the case of cells communicating directly and through factors released to the environment. PMID:27216640

  3. Kinetics of Infection and Effects on Placental Cell Populations in a Murine Model of Chlamydia psittaci-Induced Abortion

    Science.gov (United States)

    Buendía, Antonio J.; Sánchez, Joaquín; Martínez, María C.; Cámara, Paulina; Navarro, Jose A.; Rodolakis, Annie; Salinas, Jesus

    1998-01-01

    The anatomical progression of chlamydial infection was studied in different areas of the placenta, using a mouse model and two inoculation times: early pregnancy (day 7, group A) and midpregnancy (day 11, group B). The first population cells affected were decidual cells and neutrophils located just at the limits of the maternal and fetal placenta. The following invaded area was the layer of giant cells. Complete colonization of the maternal placenta occurred after day 15 of pregnancy independently of the inoculation time, the metrial gland being the last area to be invaded; numerous granulated metrial gland (GMG) cells were infected. Finally, chlamydial inclusions were observed in labyrinthine trophoblastic cells from day 18 of pregnancy onward. Since no fetal damage was observed, it seems that an indirect mechanism involving the lysis of GMG cells and neutrophil infiltration of the decidua and metrial gland may be the pathogenic mechanism that leads to abortion. PMID:9573099

  4. Synchronisation and control of proliferation in cycling cell population models with age structure

    OpenAIRE

    Billy, Frédérique; Clairambault, Jean; Fercoq, Olivier; Gaubert, Stéphane; Lepoutre, Thomas; Ouillon, Thomas; Saito, Shoko

    2014-01-01

    International audience We present and analyse in this article a mathematical question with a biological origin, the theoretical treatment of which may have far-reaching implications in the practical treatment of cancers. Starting from biological and clinical observations on cancer cells, tumourbearing laboratory rodents, and patients with cancer, we ask from a theoretical biology viewpoint questions that may be transcribed, using physiologically based modelling of cell proliferation dynami...

  5. Composite Waves for a Cell Population System Modeling Tumor Growth and Invasion

    Institute of Scientific and Technical Information of China (English)

    Min TANG; Nicolas VAUCHELET; Ibrahim CHEDDADI; Irene VIGNON-CLEMENTEL; Dirk DRASDO; Beno(i)t PERTHAME

    2013-01-01

    In the recent biomechanical theory of cancer growth,solid tumors are considered as liquid-like materials comprising elastic components.In this fluid mechanical view,the expansion ability of a solid tumor into a host tissue is mainly driven by either the cell diffusion constant or the cell division rate,with the latter depending on the local cell density (contact inhibition) or/and on the mechanical stress in the tumor.For the two by two degenerate parabolic/elliptic reaction-diffusion system that results from this modeling,the authors prove that there are always traveling waves above a minimal speed,and analyse their shapes.They appear to be complex with composite shapes and discontinuities.Several small parameters allow for analytical solutions,and in particular,the incompressible cells limit is very singular and related to the Hele-Shaw equation.These singular traveling waves are recovered numerically.

  6. Model animal experiments on UV-c irradiation of blood and isolated cell populations

    International Nuclear Information System (INIS)

    The cellular and molecular basis of the therapeutically used effect of reinjected ultraviolet (UVC) irradiated blood is unknown. First approaches to that problem were made in this study by aid of model experiments. Neither the spontaneous degranulation nor the antigen-induced histamine release from rat connective tissue mast cells (in vivo) was influenced by the injection (i.v.) of UV-irradiated blood or blood lymphocytes. By comparison of the effect of UV light on blood lymphocytes (number of dead cells, strength of chemoluminescence) after irradiation of the isolated cells and the unfractionated blood, respectively, it was shown that the strong light absorption within the blood sample prevents damage or functional alterations of the blood lymphocytes. The compound 48/80 - induced histamine release from rat peritoneal mast cells can be completely inhibited by UV irradiation (0.6 mJ/cm2) without increasing the spontaneous histamine release. (author)

  7. Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza

    Science.gov (United States)

    Zarnitsyna, Veronika I.; Handel, Andreas; McMaster, Sean R.; Hayward, Sarah L.; Kohlmeier, Jacob E.; Antia, Rustom

    2016-01-01

    The current influenza vaccine provides narrow protection against the strains included in the vaccine, and needs to be reformulated every few years in response to the constantly evolving new strains. Novel approaches are directed toward developing vaccines that provide broader protection by targeting B and T cell epitopes that are conserved between different strains of the virus. In this paper, we focus on developing mathematical models to explore the CD8 T cell responses to influenza, how they can be boosted, and the conditions under which they contribute to protection. Our models suggest that the interplay between spatial heterogeneity (with the virus infecting the respiratory tract and the immune response being generated in the secondary lymphoid organs) and T cell differentiation (with proliferation occurring in the lymphoid organs giving rise to a subpopulation of resident T cells in the respiratory tract) is the key to understand the dynamics of protection afforded by the CD8 T cell response to influenza. Our results suggest that the time lag for the generation of resident T cells in the respiratory tract and their rate of decay following infection are the key factors that limit the efficacy of CD8 T cell responses. The models predict that an increase in the level of central memory T cells leads to a gradual decrease in the viral load, and, in contrast, there is a sharper protection threshold for the relationship between the size of the population of resident T cells and protection. The models also suggest that repeated natural influenza infections cause the number of central memory CD8 T cells and the peak number of resident memory CD8 T cells to reach their plateaus, and while the former is maintained, the latter decays with time since the most recent infection.

  8. Modeling Honey Bee Populations.

    Directory of Open Access Journals (Sweden)

    David J Torres

    Full Text Available Eusocial honey bee populations (Apis mellifera employ an age stratification organization of egg, larvae, pupae, hive bees and foraging bees. Understanding the recent decline in honey bee colonies hinges on understanding the factors that impact each of these different age castes. We first perform an analysis of steady state bee populations given mortality rates within each bee caste and find that the honey bee colony is highly susceptible to hive and pupae mortality rates. Subsequently, we study transient bee population dynamics by building upon the modeling foundation established by Schmickl and Crailsheim and Khoury et al. Our transient model based on differential equations accounts for the effects of pheromones in slowing the maturation of hive bees to foraging bees, the increased mortality of larvae in the absence of sufficient hive bees, and the effects of food scarcity. We also conduct sensitivity studies and show the effects of parameter variations on the colony population.

  9. Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, P; Vaz, P [Technological and Nuclear Institute, Estrada Nacional No 10, 2686-953 Sacavem (Portugal); Zankl, M; Schlattl, H, E-mail: pedro.nogueira@helmholtz-muenchen.de [Helmholtz Zentrum Muenchen-German Research Center for Environmental Health, Research Unit Medical Radiation Physics and Diagnostics, Ingolstaedter Landstrasse 1, D-85764 Neuherberg (Germany)

    2011-11-07

    The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation-the germinative cells-absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV.

  10. Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations

    International Nuclear Information System (INIS)

    The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation-the germinative cells-absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV.

  11. Modeling the dynamics and migratory pathways of virus-specific antibody-secreting cell populations in primary influenza infection.

    Directory of Open Access Journals (Sweden)

    Hongyu Miao

    Full Text Available The B cell response to influenza infection of the respiratory tract contributes to viral clearance and establishes profound resistance to reinfection by related viruses. Numerous studies have measured virus-specific antibody-secreting cell (ASC frequencies in different anatomical compartments after influenza infection and provided a general picture of the kinetics of ASC formation and dispersion. However, the dynamics of ASC populations are difficult to determine experimentally and have received little attention. Here, we applied mathematical modeling to investigate the dynamics of ASC growth, death, and migration over the 2-week period following primary influenza infection in mice. Experimental data for model fitting came from high frequency measurements of virus-specific IgM, IgG, and IgA ASCs in the mediastinal lymph node (MLN, spleen, and lung. Model construction was based on a set of assumptions about ASC gain and loss from the sampled sites, and also on the directionality of ASC trafficking pathways. Most notably, modeling results suggest that differences in ASC fate and trafficking patterns reflect the site of formation and the expressed antibody class. Essentially all early IgA ASCs in the MLN migrated to spleen or lung, whereas cell death was likely the major reason for IgM and IgG ASC loss from the MLN. In contrast, the spleen contributed most of the IgM and IgG ASCs that migrated to the lung, but essentially none of the IgA ASCs. This finding points to a critical role for regional lymph nodes such as the MLN in the rapid generation of IgA ASCs that seed the lung. Results for the MLN also suggest that ASC death is a significant early feature of the B cell response. Overall, our analysis is consistent with accepted concepts in many regards, but it also indicates novel features of the B cell response to influenza that warrant further investigation.

  12. Biased swimming cells do not disperse in pipes as tracers: a population model based on microscale behaviour

    CERN Document Server

    Bearon, R N; Croze, O A

    2012-01-01

    There is much current interest in modelling suspensions of algae and other micro-organisms for biotechnological exploitation, and many bioreactors are of tubular design. Using generalized Taylor dispersion theory, we develop a population-level swimming-advection-diffusion model for suspensions of micro-organisms in a vertical pipe flow. In particular, a combination of gravitational and viscous torques acting on individual cells can affect their swimming behaviour, which is termed gyrotaxis. This typically leads to local cell drift and diffusion in a suspension of cells. In a flow in a pipe, small amounts of radial drift across streamlines can have a major impact on the effective axial drift and diffusion of the cells. We present a Galerkin method to calculate the local mean swimming velocity and diffusion tensor based on local shear for arbitrary flow rates. This method is validated with asymptotic results obtained in the limits of weak and strong shear. We solve the resultant swimming-advection-diffusion equ...

  13. Experimental methods and modeling techniques for description of cell population heterogeneity

    DEFF Research Database (Denmark)

    Lencastre Fernandes, Rita; Nierychlo, M.; Lundin, L.;

    2011-01-01

    is acknowledged but seldom accounted for. In order to include population heterogeneity mechanisms in the development of novel bioprocess control strategies, a reliable mathematical description of such phenomena has to be developed. With this review, we search to summarize the potential of currently...

  14. Modeling Exponential Population Growth

    Science.gov (United States)

    McCormick, Bonnie

    2009-01-01

    The concept of population growth patterns is a key component of understanding evolution by natural selection and population dynamics in ecosystems. The National Science Education Standards (NSES) include standards related to population growth in sections on biological evolution, interdependence of organisms, and science in personal and social…

  15. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  16. Population-expression models of immune response

    International Nuclear Information System (INIS)

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable. (paper)

  17. Population-expression models of immune response

    Science.gov (United States)

    Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

    2013-06-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

  18. Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

    OpenAIRE

    Hyejin Choi; Jianting Sheng; Dingcheng Gao; Fuhai Li; Anna Durrans; Seongho Ryu; Sharrell B. Lee; Navneet Narula; Shahin Rafii; Olivier Elemento; Nasser K. Altorki; Stephen T.C. Wong; Vivek Mittal

    2015-01-01

    Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial c...

  19. Endometrial Stromal Cells and Immune Cell Populations Within Lymph Nodes in a Nonhuman Primate Model of Endometriosis

    OpenAIRE

    Hey-Cunningham, A. J.; Fazleabas, A.T.; Braundmeier, A. G.; Markham, R; Fraser, I S; Berbic, M.

    2011-01-01

    Mounting evidence suggests that immunological responses may be altered in endometriosis. The baboon (Papio anubis) is generally considered the best model of endometriosis pathogenesis. The objective of the current study was to investigate for the first time immunological changes within uterine and peritoneal draining lymph nodes in a nonhuman primate baboon model of endometriosis. Paraffin-embedded femoral lymph nodes were obtained from 22 normally cycling female baboons (induced endometriosi...

  20. Modeling Approaches for Describing Microbial Population Heterogeneity

    DEFF Research Database (Denmark)

    Lencastre Fernandes, Rita

    Although microbial populations are typically described by averaged properties, individual cells present a certain degree of variability. Indeed, initially clonal microbial populations develop into heterogeneous populations, even when growing in a homogeneous environment. A heterogeneous microbial...... an extension of the proposed model framework (PBM coupled to an unstructured model) to a continuous cultivation. A compartment model approach was applied for addressing situations where two zones (compartments) are formed due to non-ideal mixing in the bioreactor. In particular, this approach was used in order...

  1. High prevalence of side population in human cancer cell lines

    OpenAIRE

    Boesch, Maximilian; Zeimet, Alain G; Fiegl, Heidi; Wolf, Barbara; Huber, Julia; Klocker, Helmut; Gastl, Guenther; Sopper, Sieghart; Wolf, Dominik

    2016-01-01

    Cancer cell lines are essential platforms for performing cancer research on human cells. We here demonstrate that, across tumor entities, human cancer cell lines harbor minority populations of putative stem-like cells, molecularly defined by dye extrusion resulting in the side population phenotype. These findings establish a heterogeneous nature of human cancer cell lines and argue for their stem cell origin. This should be considered when interpreting research involving these model systems.

  2. Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Hyejin Choi

    2015-02-01

    Full Text Available Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments.

  3. Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model.

    Science.gov (United States)

    Choi, Hyejin; Sheng, Jianting; Gao, Dingcheng; Li, Fuhai; Durrans, Anna; Ryu, Seongho; Lee, Sharrell B; Narula, Navneet; Rafii, Shahin; Elemento, Olivier; Altorki, Nasser K; Wong, Stephen T C; Mittal, Vivek

    2015-02-24

    Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments. PMID:25704820

  4. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

    Science.gov (United States)

    Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander; Larsen, Annette K.; de Almeida, Luís Neves; Escargueil, Alexandre; Clairambault, Jean

    2016-06-01

    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  5. Modeling Approaches for Describing Microbial Population Heterogeneity

    OpenAIRE

    Lencastre Fernandes, Rita; Gernaey, Krist; Jensen, Anker Degn; Nopens, Ingmar

    2013-01-01

    Although microbial populations are typically described by averaged properties, individual cells present a certain degree of variability. Indeed, initially clonal microbial populations develop into heterogeneous populations, even when growing in a homogeneous environment. A heterogeneous microbial population consists of cells in different states, and it implies a heterogeneous distribution of activities (e.g. respiration, product yield), including different responses to extracellular stimuli. ...

  6. Modelling nova populations in galaxies

    Science.gov (United States)

    Chen, Hai-Liang; Woods, T. E.; Yungelson, L. R.; Gilfanov, M.; Han, Zhanwen

    2016-05-01

    Theoretical modelling of the evolution of classical and recurrent novae plays an important role in studies of binary evolution, nucleosynthesis and accretion physics. However, from a theoretical perspective the observed statistical properties of novae remain poorly understood. In this paper, we have produced model populations of novae using a hybrid binary population synthesis approach for differing star formation histories (SFHs): a starburst case (elliptical-like galaxies), a constant star formation rate case (spiral-like galaxies) and a composite case (in line with the inferred SFH for M31). We found that the nova rate at 10 Gyr in an elliptical-like galaxy is ˜10-20 times smaller than a spiral-like galaxy with the same mass. The majority of novae in elliptical-like galaxies at the present epoch are characterized by low-mass white dwarfs (WDs), long decay times, relatively faint absolute magnitudes and long recurrence periods. In contrast, the majority of novae in spiral-like galaxies at 10 Gyr have massive WDs, short decay times, are relatively bright and have short recurrence periods. The mass-loss time distribution for novae in our M31-like galaxy is in agreement with observational data for Andromeda. However, it is possible that we underestimate the number of bright novae in our model. This may arise in part due to the present uncertainties in the appropriate bolometric correction for novae.

  7. New Models for Population Protocols

    CERN Document Server

    Michail, Othon

    2010-01-01

    Wireless sensor networks are about to be part of everyday life. Homes and workplaces capable of self-controlling and adapting air-conditioning for different temperature and humidity levels, sleepless forests ready to detect and react in case of a fire, vehicles able to avoid sudden obstacles or possibly able to self-organize routes to avoid congestion, and so on, will probably be commonplace in the very near future. Mobility plays a central role in such systems and so does passive mobility, that is, mobility of the network stemming from the environment itself. The population protocol model was

  8. Single cell motility and trail formation in populations of microglia

    Science.gov (United States)

    Lee, Kyoung Jin

    2009-03-01

    Microglia are a special type of glia cell in brain that has immune responses. They constitute about 20 % of the total glia population within the brain. Compared to other glia cells, microglia are very motile, constantly moving to destroy pathogens and to remove dead neurons. While doing so, they exhibit interesting body shapes, have cell-to-cell communications, and have chemotatic responses to each other. Interestingly, our recent in vitro studies show that their unusual motile behaviors can self-organize to form trails, similar to those in populations of ants. We have studied the changes in the physical properties of these trails by varying the cell population density and by changing the degree of spatial inhomogeneities (``pathogens''). Our experimental observations can be quite faithfully reproduced by a simple mathematical model involving many motile cells whose mechanical motion are driven by actin polymerization and depolymerization process within the individual cell body and by external chemical gradients.

  9. Modelling nova populations in galaxies

    CERN Document Server

    Chen, Hai-Liang; Yungelson, L R; Gilfanov, M; Han, Zhanwen

    2016-01-01

    Theoretical modelling of the evolution of classical and recurrent novae plays an important role in studies of binary evolution, nucleosynthesis and accretion physics. However, from a theoretical perspective the observed statistical properties of novae remain poorly understood. In this paper, we have produced model populations of novae using a hybrid binary population synthesis approach for differing star formation histories (SFHs): a starburst case (elliptical-like galaxies), a constant star formation rate case (spiral-like galaxies) and a composite case (in line with the inferred SFH for M31). We found that the nova rate at 10\\;Gyr in an elliptical-like galaxy is $\\sim 10-20$ times smaller than a spiral-like galaxy with the same mass. The majority of novae in elliptical-like galaxies at the present epoch are characterized by low mass white dwarfs (WDs), long decay times, relatively faint absolute magnitudes and long recurrence periods. In contrast, the majority of novae in spiral-like galaxies at 10\\;Gyr hav...

  10. Matrix population models from 20 studies of perennial plant populations

    Science.gov (United States)

    Ellis, Martha M.; Williams, Jennifer L.; Lesica, Peter; Bell, Timothy J.; Bierzychudek, Paulette; Bowles, Marlin; Crone, Elizabeth E.; Doak, Daniel F.; Ehrlen, Johan; Ellis-Adam, Albertine; McEachern, Kathryn; Ganesan, Rengaian; Latham, Penelope; Luijten, Sheila; Kaye, Thomas N.; Knight, Tiffany M.; Menges, Eric S.; Morris, William F.; den Nijs, Hans; Oostermeijer, Gerard; Quintana-Ascencio, Pedro F.; Shelly, J. Stephen; Stanley, Amanda; Thorpe, Andrea; Tamara, Ticktin; Valverde, Teresa; Weekley, Carl W.

    2012-01-01

    Demographic transition matrices are one of the most commonly applied population models for both basic and applied ecological research. The relatively simple framework of these models and simple, easily interpretable summary statistics they produce have prompted the wide use of these models across an exceptionally broad range of taxa. Here, we provide annual transition matrices and observed stage structures/population sizes for 20 perennial plant species which have been the focal species for long-term demographic monitoring. These data were assembled as part of the "Testing Matrix Models" working group through the National Center for Ecological Analysis and Synthesis (NCEAS). In sum, these data represent 82 populations with >460 total population-years of data. It is our hope that making these data available will help promote and improve our ability to monitor and understand plant population dynamics.

  11. Modeling oscillations and spiral waves in Dictyostelium populations

    Science.gov (United States)

    Noorbakhsh, Javad; Schwab, David J.; Sgro, Allyson E.; Gregor, Thomas; Mehta, Pankaj

    2015-06-01

    Unicellular organisms exhibit elaborate collective behaviors in response to environmental cues. These behaviors are controlled by complex biochemical networks within individual cells and coordinated through cell-to-cell communication. Describing these behaviors requires new mathematical models that can bridge scales—from biochemical networks within individual cells to spatially structured cellular populations. Here we present a family of "multiscale" models for the emergence of spiral waves in the social amoeba Dictyostelium discoideum. Our models exploit new experimental advances that allow for the direct measurement and manipulation of the small signaling molecule cyclic adenosine monophosphate (cAMP) used by Dictyostelium cells to coordinate behavior in cellular populations. Inspired by recent experiments, we model the Dictyostelium signaling network as an excitable system coupled to various preprocessing modules. We use this family of models to study spatially unstructured populations of "fixed" cells by constructing phase diagrams that relate the properties of population-level oscillations to parameters in the underlying biochemical network. We then briefly discuss an extension of our model that includes spatial structure and show how this naturally gives rise to spiral waves. Our models exhibit a wide range of novel phenomena. including a density-dependent frequency change, bistability, and dynamic death due to slow cAMP dynamics. Our modeling approach provides a powerful tool for bridging scales in modeling of Dictyostelium populations.

  12. Fluctuations of cell population in a colonic crypt

    Science.gov (United States)

    Pei, Qi-ming; Zhan, Xuan; Yang, Li-jian; Bao, Chun; Cao, Wei; Li, An-bang; Rozi, Anvar; Jia, Ya

    2014-03-01

    The number of stem cells in a colonic crypt is often very small, which leads to large intrinsic fluctuations in the cell population. Based on the model of cell population dynamics with linear feedback in a colonic crypt, we present a stochastic dynamics of the cell population [including stem cells (SCs), transit amplifying cells (TACs), and fully differentiated cells (FDCs)]. The Fano factor, covariance, and susceptibility formulas of the cell population around the steady state are derived by using the Langevin theory. In the range of physiologically reasonable parameter values, it is found that the stationary populations of TACs and FDCs exhibit an approximately threshold behavior as a function of the net growth rate of TACs, and the reproductions of TACs and FDCs can be classified into three regimens: controlled, crossover, and uncontrolled. With the increasing of the net growth rate of TACs, there is a maximum of the relative intrinsic fluctuations (i.e., the Fano factors) of TACs and FDCs in the crossover region. For a fixed differentiation rate and the net growth rate of SCs, the covariance of fluctuations between SCs and TACs has a maximum in the crossover region. However, the susceptibilities of both TACs and FDCs to the net growth rate of TACs have a minimum in the crossover region.

  13. Incorporating territory compression into population models

    OpenAIRE

    Ridley, J.; Komdeur, J.; Sutherland, WJ; Sutherland, William J.

    2004-01-01

    The ideal despotic distribution, whereby the lifetime reproductive success a territory's owner achieves is unaffected by population density, is a mainstay of behaviour-based population models. We show that the population dynamics of an island population of Seychelles warblers (Acrocephalus sechellensis) cannot be modelled with an ideal despotic distribution, and suggest the effects of both territory shrinkage and territorial disputes on reproductive success must be included to adequately mode...

  14. Disparity energy model using a trained neuronal population

    OpenAIRE

    Martins, Jaime A.; Rodrigues, J. M. F.; du Buf, J. M. H.

    2011-01-01

    Depth information using the biological Disparity Energy Model can be obtained by using a population of complex cells. This model explicitly involves cell parameters like their spatial frequency, orientation, binocular phase and position difference. However, this is a mathematical model. Our brain does not have access to such parameters, it can only exploit responses. Therefore, we use a new model for encoding disparity information implicitly by employing a trained binocular ...

  15. Stimulus-dependent maximum entropy models of neural population codes.

    Directory of Open Access Journals (Sweden)

    Einat Granot-Atedgi

    Full Text Available Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. For large populations, direct sampling of these distributions is impossible, and so we must rely on constructing appropriate models. We show here that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. We introduce the stimulus-dependent maximum entropy (SDME model-a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. We find that the SDME model gives a more accurate account of single cell responses and in particular significantly outperforms uncoupled models in reproducing the distributions of population codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like average surprise and information transmission in a neural population.

  16. [The population problem in global modeling].

    Science.gov (United States)

    Naidenova, P

    1986-01-01

    Developments during the past 15 years in population modeling are critically reviewed. The author notes that while population variables were treated as endogenous in earlier models developed by the Club of Rome, later models have treated such variables as exogenous. The need to link demographic factors to structural changes and economic growth, in accordance with Marxist-Leninist population theory, is noted. (SUMMARY IN ENG AND RUS) PMID:12280533

  17. Eel population and solution model

    OpenAIRE

    Chen, Liangming; Chen, Xinyu; Chen, Yu; Fang, Ping; Huang, Yuyu; Li, Haiyan; Liu, Mingyan; Wang, Cong

    2006-01-01

    Almost two decades before, eel population had not waved quite hugely, but in this twenty years, it is changed. Eel population decreases very obviously on account of five main reasons—pollution, barriers, the change of ocean currents, overfishing, diseases. Base on this phenomena, though our research, we would like to suggest two solution for changing the decline. In short-term, aquaculture should be utilized widely; on the other hand, re-stocking is a quiet nice method for long-term.

  18. Senescent cells in growing tumors: population dynamics and cancer stem cells

    OpenAIRE

    C.A.M. La Porta; Zapperi, S.; Sethna, J. P.

    2012-01-01

    Author Summary It is commonly believed that cell senescence – the loss of replicative capacity of cells – acts as a barrier for tumor growth. Here we follow the evolution of senescence markers in melanoma cells and find that while most cancer cells eventually turn senescent, this is at root irrelevant for the long-term growth rate of a tumor. To demonstrate this, we construct a mathematical population dynamics model incorporating cancer stem cells which is able to reproduce quantitatively the...

  19. Population Balance Modeling of Conjugation in Enterococcus faecalis

    OpenAIRE

    Binagia, Jeremy; Tran, Vu; Shu, Che-Chi; Ramkrishna, Doraiswami

    2014-01-01

    In the bacteria species Enterococcus faecalis, transfer of plasmid pCF10 by conjugation between donor cells that possess sets of genes conferring drug resistance and recipient cells leads to the spread of this resistance in a population. A complex signaling molecule network is responsible for communication between recipient and donor cells. Up to this point, the nature of these signaling molecules has been modeled deterministically from the point of view of an “average” cell. While this view ...

  20. Detecting cell assemblies in large neuronal populations.

    Science.gov (United States)

    Lopes-dos-Santos, Vítor; Ribeiro, Sidarta; Tort, Adriano B L

    2013-11-15

    Recent progress in the technology for single unit recordings has given the neuroscientific community the opportunity to record the spiking activity of large neuronal populations. At the same pace, statistical and mathematical tools were developed to deal with high-dimensional datasets typical of such recordings. A major line of research investigates the functional role of subsets of neurons with significant co-firing behavior: the Hebbian cell assemblies. Here we review three linear methods for the detection of cell assemblies in large neuronal populations that rely on principal and independent component analysis. Based on their performance in spike train simulations, we propose a modified framework that incorporates multiple features of these previous methods. We apply the new framework to actual single unit recordings and show the existence of cell assemblies in the rat hippocampus, which typically oscillate at theta frequencies and couple to different phases of the underlying field rhythm. PMID:23639919

  1. Mathematical Modeling of Extinction of Inhomogeneous Populations.

    Science.gov (United States)

    Karev, G P; Kareva, I

    2016-04-01

    Mathematical models of population extinction have a variety of applications in such areas as ecology, paleontology and conservation biology. Here we propose and investigate two types of sub-exponential models of population extinction. Unlike the more traditional exponential models, the life duration of sub-exponential models is finite. In the first model, the population is assumed to be composed of clones that are independent from each other. In the second model, we assume that the size of the population as a whole decreases according to the sub-exponential equation. We then investigate the "unobserved heterogeneity," i.e., the underlying inhomogeneous population model, and calculate the distribution of frequencies of clones for both models. We show that the dynamics of frequencies in the first model is governed by the principle of minimum of Tsallis information loss. In the second model, the notion of "internal population time" is proposed; with respect to the internal time, the dynamics of frequencies is governed by the principle of minimum of Shannon information loss. The results of this analysis show that the principle of minimum of information loss is the underlying law for the evolution of a broad class of models of population extinction. Finally, we propose a possible application of this modeling framework to mechanisms underlying time perception. PMID:27090117

  2. Modelling urban - rural population growth in China

    OpenAIRE

    Shen, J; N A Spence

    1996-01-01

    The population of China is still growing despite a dramatic decline in fertility in the past two decades. There are marked urban - rural differentials in fertility and, as a result, the pace of urbanization has significant effects on population growth. In this research an attempt is made to model urban - rural population growth in China. A demoeconomic model of urban and rural sectors is calibrated to account for the long-term trend of urbanization in China. Two important components of urban ...

  3. Circadian rhythm and cell population growth

    CERN Document Server

    Clairambault, Jean; Lepoutre, Thomas

    2010-01-01

    Molecular circadian clocks, that are found in all nucleated cells of mammals, are known to dictate rhythms of approximately 24 hours (circa diem) to many physiological processes. This includes metabolism (e.g., temperature, hormonal blood levels) and cell proliferation. It has been observed in tumor-bearing laboratory rodents that a severe disruption of these physiological rhythms results in accelerated tumor growth. The question of accurately representing the control exerted by circadian clocks on healthy and tumour tissue proliferation to explain this phenomenon has given rise to mathematical developments, which we review. The main goal of these previous works was to examine the influence of a periodic control on the cell division cycle in physiologically structured cell populations, comparing the effects of periodic control with no control, and of different periodic controls between them. We state here a general convexity result that may give a theoretical justification to the concept of cancer chronothera...

  4. Perfect Simulation From Nonneutral Population Genetic Models: Variable Population Size and Population Subdivision.

    OpenAIRE

    Fearnhead, Paul

    2006-01-01

    We show how the idea of monotone coupling from the past can produce simple algorithms for simulating samples at a nonneutral locus under a range of demographic models. We specifically consider a biallelic locus and either a general variable population size mode or a general migration model for population subdivision. We investigate the effect of demography on the efficacy of selection and the effect of selection on genetic divergence between populations.

  5. Perturbation analysis of nonlinear matrix population models

    Directory of Open Access Journals (Sweden)

    Hal Caswell

    2008-03-01

    Full Text Available Perturbation analysis examines the response of a model to changes in its parameters. It is commonly applied to population growth rates calculated from linear models, but there has been no general approach to the analysis of nonlinear models. Nonlinearities in demographic models may arise due to density-dependence, frequency-dependence (in 2-sex models, feedback through the environment or the economy, and recruitment subsidy due to immigration, or from the scaling inherent in calculations of proportional population structure. This paper uses matrix calculus to derive the sensitivity and elasticity of equilibria, cycles, ratios (e.g. dependency ratios, age averages and variances, temporal averages and variances, life expectancies, and population growth rates, for both age-classified and stage-classified models. Examples are presented, applying the results to both human and non-human populations.

  6. Characterization and localization of side population cells in the lens

    OpenAIRE

    Oka, Mikako; Toyoda, Chizuko; Kaneko, Yuka; Nakazawa, Yosuke; Aizu-Yokota, Eriko; Takehana, Makoto

    2010-01-01

    Purpose Side population (SP) cells were isolated and the possibility whether lens epithelial cells contain stem cells was investigated. Methods Mouse lens epithelial cells were stained by Hoechst 33342 and then sorted by fluorescence-activated cell sorting (FACS). The expression of stem cell markers in sorted SP cells and the main population of epithelial cells were analyzed by quantitative real-time PCR. Localization of SP cells in the mouse lens was studied by fluorescence microscopy. Resul...

  7. Structured population models in biology and epidemiology

    CERN Document Server

    Ruan, Shigui

    2008-01-01

    This book consists of six chapters written by leading researchers in mathematical biology. These chapters present recent and important developments in the study of structured population models in biology and epidemiology. Topics include population models structured by age, size, and spatial position; size-structured models for metapopulations, macroparasitc diseases, and prion proliferation; models for transmission of microparasites between host populations living on non-coincident spatial domains; spatiotemporal patterns of disease spread; method of aggregation of variables in population dynamics; and biofilm models. It is suitable as a textbook for a mathematical biology course or a summer school at the advanced undergraduate and graduate level. It can also serve as a reference book for researchers looking for either interesting and specific problems to work on or useful techniques and discussions of some particular problems.

  8. Trail networks formed by populations of immune cells

    Science.gov (United States)

    Yang, Taeseok Daniel; Kwon, Tae Goo; Park, Jin-sung; Lee, Kyoung J.

    2014-02-01

    Populations of biological cells that communicate with each other can organize themselves to generate large-scale patterns. Examples can be found in diverse systems, ranging from developing embryos, cardiac tissues, chemotaxing ameba and swirling bacteria. The similarity, often shared by the patterns, suggests the existence of some general governing principle. On the other hand, rich diversity and system-specific properties are exhibited, depending on the type of involved cells and the nature of their interactions. The study on the similarity and the diversity constitutes a rapidly growing field of research. Here, we introduce a new class of self-organized patterns of cell populations that we term as ‘cellular trail networks’. They were observed with populations of rat microglia, the immune cells of the brain and the experimental evidence suggested that haptotaxis is the key element responsible for them. The essential features of the observed patterns are well captured by the mathematical model cells that actively crawl and interact with each other through a decomposing but non-diffusing chemical attractant laid down by the cells. Our finding suggests an unusual mechanism of socially cooperative long-range signaling for the crawling immune cells.

  9. Stellar population models at high spectral resolution

    CERN Document Server

    Maraston, Claudia; Portsmouth, ICG-University of; Kingdom, United

    2011-01-01

    We present new, high-to-intermediate spectral resolution stellar population models, based on four popular libraries of empirical stellar spectra, namely Pickles, ELODIE, STELIB and MILES. These new models are the same as our previous models, but with higher resolution and based on empirical stellar spectra, while keeping other ingredients the same including the stellar energetics, the atmospheric parameters and the treatment of the Thermally-Pulsating Asymptotic Giant Branch and the Horizontal Branch morphology. We further compute very high resolution (R=20,000) models based on the theoretical stellar library MARCS which extends to the near-infrared. We therefore provide merged high resolution stellar population models, extending from ~1000 AA to 25,000 AA. We compare how these libraries perform in stellar population models and highlight spectral regions where discrepancies are found. We confirm our previous findings that the flux around the V-band is lower (in a normalised sense) in models based on empirical...

  10. Modeling Small Stellar Populations Using Starburst99

    Science.gov (United States)

    Vazquez, Gerardo Arturo; Leitherer, Claus

    2015-08-01

    Stellar populations synthesis models have proven to be excellent tools to learn about galaxy evolution. However, modeling small stellar populations (lower than 105 M⊙) has been an intriguing and continuous to be a field of intensive research. In this work, we have developed a new approach to form stars from clusters first, where massive stars are formed from fractions of mass of small stellar clusters. This new approximation is based on the empirical power law (mc-2) for the mass function of clusters between 20-1100 M⊙ found in recent years and the maximum stellar mass that can be formed in a cluster. Incorporating this new approach to form clusters has made us upgrade the way we integrate the stellar properties and the way that the isochrone is produced with a new technique. To produce the new models we have used the most recent version of Starburst99 that incorporates the most recent stellar evolution models with rotation. On the verge of solving nearby stellar populations and observing small stellar populations across the universe, this new approach brings a new scope on trying to disentangle the nature of hyper and supermassive stars in small stellar populations. In this work we present this new approach and the results when these models are applied to very energetic stellar populations such as the cluster in NGC 3603. Our most important result is that we have modeled the ionizing power of this cluster and some others by forming enough supermassive stars in a cluster of ~104 M⊙.

  11. Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells

    DEFF Research Database (Denmark)

    Jørgensen, Claus; Sherman, Andrew; Chen, Ginny I; Pasculescu, Adrian; Poliakov, Alexei; Hsiung, Marilyn; Larsen, Brett; Wilkinson, David G; Linding, Rune; Pawson, Tony

    2009-01-01

    Cells have self-organizing properties that control their behavior in complex tissues. Contact between cells expressing either B-type Eph receptors or their transmembrane ephrin ligands initiates bidirectional signals that regulate cell positioning. However, simultaneously investigating how...... information is processed in two interacting cell types remains a challenge. We implemented a proteomic strategy to systematically determine cell-specific signaling networks underlying EphB2- and ephrin-B1-controlled cell sorting. Quantitative mass spectrometric analysis of mixed populations of EphB2- and...... revealed that signaling between mixed EphB2- and ephrin-B1-expressing cells is asymmetric and that the distinct cell types use different tyrosine kinases and targets to process signals induced by cell-cell contact. We provide systems- and cell-specific network models of contact-initiated signaling between...

  12. Model for Mutation in Bacterial Populations

    Science.gov (United States)

    Donangelo, R.; Fort, H.

    2002-07-01

    We describe the evolution of E. coli populations through a Bak-Sneppen-type model which incorporates random mutations. We show that, for a value of the mutation level which coincides with the one estimated from experiments, this model reproduces the measures of mean fitness relative to that of a common ancestor, performed for over 10 000 bacterial generations.

  13. A model for mutation in bacterial populations

    OpenAIRE

    Donangelo, R.; Fort, H.

    2002-01-01

    We describe the evolution of $E.coli$ populations through a Bak-Sneppen type model which incorporates random mutations. We show that, for a value of the mutation level which coincides with the one estimated from experiments, this model reproduces the measures of mean fitness relative to that of a common ancestor, performed for over 10,000 bacterial generations.

  14. Mechanism-based population modelling for assessment of L-cell function based on total GLP-1 response following an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Møller, Jonas B.; Jusko, William J.; Gao, Wei;

    2011-01-01

    GLP-1 is an insulinotropic hormone that synergistically with glucose gives rise to an increased insulin response. Its secretion is increased following a meal and it is thus of interest to describe the secretion of this hormone following an oral glucose tolerance test (OGTT). The aim of this study...... was to build a mechanism-based population model that describes the time course of total GLP-1 and provides indices for capability of secretion in each subject. The goal was thus to model the secretion of GLP-1, and not its effect on insulin production. Single 75 g doses of glucose were administered orally....... The individual estimates of absorption rate constants were used in the model for GLP-1 secretion. Estimation of parameters was performed using the FOCE method with interaction implemented in NONMEM VI. The final transit/indirect-response model obtained for GLP-1 production following an OGTT included two...

  15. Population genetics inside a cell: Mutations and mitochondrial genome maintenance

    Science.gov (United States)

    Goyal, Sidhartha; Shraiman, Boris; Gottschling, Dan

    2012-02-01

    In realistic ecological and evolutionary systems natural selection acts on multiple levels, i.e. it acts on individuals as well as on collection of individuals. An understanding of evolutionary dynamics of such systems is limited in large part due to the lack of experimental systems that can challenge theoretical models. Mitochondrial genomes (mtDNA) are subjected to selection acting on cellular as well as organelle levels. It is well accepted that mtDNA in yeast Saccharomyces cerevisiae is unstable and can degrade over time scales comparable to yeast cell division time. We utilize a recent technology designed in Gottschling lab to extract DNA from populations of aged yeast cells and deep sequencing to characterize mtDNA variation in a population of young and old cells. In tandem, we developed a stochastic model that includes the essential features of mitochondrial biology that provides a null model for expected mtDNA variation. Overall, we find approximately 2% of the polymorphic loci that show significant increase in frequency as cells age providing direct evidence for organelle level selection. Such quantitative study of mtDNA dynamics is absolutely essential to understand the propagation of mtDNA mutations linked to a spectrum of age-related diseases in humans.

  16. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.

    Science.gov (United States)

    Wang, Dachun; Haviland, David L; Burns, Alan R; Zsigmond, Eva; Wetsel, Rick A

    2007-03-13

    Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute approximately 60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the differentiation of hES cells into an essentially pure (>99%) population of ATII cells (hES-ATII). Purity, as well as biological features and morphological characteristics of normal ATII cells, was demonstrated for the hES-ATII cells, including lamellar body formation, expression of surfactant proteins A, B, and C, alpha-1-antitrypsin, and the cystic fibrosis transmembrane conductance receptor, as well as the synthesis and secretion of complement proteins C3 and C5. Collectively, these data document the successful generation of a pure population of ATII cells derived from hES cells, providing a practical source of ATII cells to explore in disease models their potential in the regeneration and repair of the injured alveolus and in the therapeutic treatment of genetic diseases affecting the lung. PMID:17360544

  17. Multiple cell and population-level interactions with mouse embryonic stem cell heterogeneity.

    Science.gov (United States)

    Cannon, Danielle; Corrigan, Adam M; Miermont, Agnes; McDonel, Patrick; Chubb, Jonathan R

    2015-08-15

    Much of development and disease concerns the generation of gene expression differences between related cells sharing similar niches. However, most analyses of gene expression only assess population and time-averaged levels of steady-state transcription. The mechanisms driving differentiation are buried within snapshots of the average cell, lacking dynamic information and the diverse regulatory history experienced by individual cells. Here, we use a quantitative imaging platform with large time series data sets to determine the regulation of developmental gene expression by cell cycle, lineage, motility and environment. We apply this technology to the regulation of the pluripotency gene Nanog in mouse embryonic stem cells. Our data reveal the diversity of cell and population-level interactions with Nanog dynamics and heterogeneity, and how this regulation responds to triggers of pluripotency. Cell cycles are highly heterogeneous and cycle time increases with Nanog reporter expression, with longer, more variable cycle times as cells approach ground-state pluripotency. Nanog reporter expression is highly stable over multiple cell generations, with fluctuations within cycles confined by an attractor state. Modelling reveals an environmental component to expression stability, in addition to any cell-autonomous behaviour, and we identify interactions of cell density with both cycle behaviour and Nanog. Rex1 expression dynamics showed shared and distinct regulatory effects. Overall, our observations of multiple partially overlapping dynamic heterogeneities imply complex cell and environmental regulation of pluripotent cell behaviour, and suggest simple deterministic views of stem cell states are inappropriate. PMID:26209649

  18. Transmission models of tuberculosis in heterogeneous population

    Institute of Scientific and Technical Information of China (English)

    JIA Zhong-wei; LI Xiao-wen; FENG Dan; CAO Wu-chun

    2007-01-01

    Objective To review the transmission models of tuberculosis in heterogeneous population.Data sources The data used in this review were adopted mainly from the studies of models of tuberculosis reported from 1995 to 2006.Study selection Relevant literature on transmission models of tuberculosis in heterogeneous populations are referenced.Results Casual/random factors and genetic factors are the main reasons for epidemics of tuberculosis in recent years.Mass public transport is playing the primary role in casually close contact which can facilitate the transmission of tuberculosis. Genetic susceptibility not only varies endemic prevalence levels, but also drastically alters the effects of treatment for tuberculosis patients. Detailed studies further exhibit that casual contact and genetic factor are responsible for over 30%-40% of the total new cases in recent years. The prevalence of tuberculosis could double (from 33% to 60%)if a genetically susceptible phenotype is present in only 30% of the population. And some challenges have emerged along with these exciting results.Conclusions Casual/random contact, public transport and genetic susceptibility are responsible for most new tuberculosis cases and a wide variation in endemic tuberculosis levels between regions. Hence, the transmission model of tuberculosis in a heterogeneous population can provide more clues to underlying mechanism of tuberculosis transmission than in a homogeneous population. However, many challenges remain for us in understanding transmission of disease.

  19. Gene expression heterogeneities in embryonic stem cell populations

    DEFF Research Database (Denmark)

    Martinez Arias, Alfonso; Brickman, Joshua M

    2011-01-01

    intrinsic requirement for heterogeneity with stem cell populations. We focus on Embryonic Stem (ES) cells, in vitro derived cell lines from the early embryo that are considered both pluripotent (able to generate all the lineages of the future embryo) and indefinitely self renewing. We examine the relevance......Stem and progenitor cells are populations of cells that retain the capacity to populate specific lineages and to transit this capacity through cell division. However, attempts to define markers for stem cells have met with limited success. Here we consider whether this limited success reflects an...

  20. Modelling biological invasions: Individual to population scales at interfaces

    KAUST Repository

    Belmonte-Beitia, J.

    2013-10-01

    Extracting the population level behaviour of biological systems from that of the individual is critical in understanding dynamics across multiple scales and thus has been the subject of numerous investigations. Here, the influence of spatial heterogeneity in such contexts is explored for interfaces with a separation of the length scales characterising the individual and the interface, a situation that can arise in applications involving cellular modelling. As an illustrative example, we consider cell movement between white and grey matter in the brain which may be relevant in considering the invasive dynamics of glioma. We show that while one can safely neglect intrinsic noise, at least when considering glioma cell invasion, profound differences in population behaviours emerge in the presence of interfaces with only subtle alterations in the dynamics at the individual level. Transport driven by local cell sensing generates predictions of cell accumulations along interfaces where cell motility changes. This behaviour is not predicted with the commonly used Fickian diffusion transport model, but can be extracted from preliminary observations of specific cell lines in recent, novel, cryo-imaging. Consequently, these findings suggest a need to consider the impact of individual behaviour, spatial heterogeneity and especially interfaces in experimental and modelling frameworks of cellular dynamics, for instance in the characterisation of glioma cell motility. © 2013 Elsevier Ltd.

  1. Adaptive dynamics for physiologically structured population models.

    Science.gov (United States)

    Durinx, Michel; Metz, J A J Hans; Meszéna, Géza

    2008-05-01

    We develop a systematic toolbox for analyzing the adaptive dynamics of multidimensional traits in physiologically structured population models with point equilibria (sensu Dieckmann et al. in Theor. Popul. Biol. 63:309-338, 2003). Firstly, we show how the canonical equation of adaptive dynamics (Dieckmann and Law in J. Math. Biol. 34:579-612, 1996), an approximation for the rate of evolutionary change in characters under directional selection, can be extended so as to apply to general physiologically structured population models with multiple birth states. Secondly, we show that the invasion fitness function (up to and including second order terms, in the distances of the trait vectors to the singularity) for a community of N coexisting types near an evolutionarily singular point has a rational form, which is model-independent in the following sense: the form depends on the strategies of the residents and the invader, and on the second order partial derivatives of the one-resident fitness function at the singular point. This normal form holds for Lotka-Volterra models as well as for physiologically structured population models with multiple birth states, in discrete as well as continuous time and can thus be considered universal for the evolutionary dynamics in the neighbourhood of singular points. Only in the case of one-dimensional trait spaces or when N = 1 can the normal form be reduced to a Taylor polynomial. Lastly we show, in the form of a stylized recipe, how these results can be combined into a systematic approach for the analysis of the (large) class of evolutionary models that satisfy the above restrictions. PMID:17943289

  2. Side Population Cells from Human Melanoma Tumors Reveal Diverse Mechanisms for Chemoresistance

    OpenAIRE

    Luo, Yuchun; Ellis, Lixia Z; Dallaglio, Katiuscia; Takeda, Moe; Robinson, William A.; Robinson, Steven; Liu, Weimin; Lewis, Karl D.; McCarter, Martin D; Gonzalez, Rene; David A Norris; Roop, Dennis R.; Spritz, Richard A.; Ahn, Natalie G.; Fujita, Mayumi

    2012-01-01

    Side population (SP) is identified as cells capable of excluding the fluorescent Hoechst dye and anticancer drugs, and represents hematopoietic stem cells and chemoresistant cells from several solid tumors. In this study, we confirmed the presence of SP cells in tumors from melanoma patients. Melanoma SP cells overexpressed ATP-binding-cassette (ABC) transporters, ABCB1 and ABCB5. We generated a direct in vivo xenograft model, and demonstrated that SP cells were resistant to paclitaxel, a sub...

  3. A population genetics model of linkage disequilibrium in admixed populations

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Understanding linkage disequilibrium (LD) created in admixed population and the rate of decay in the disequilibrium over evolution is an important subject in population genetics theory and in disease gene mapping in human populations. The present study represents the theoretical investigation of effects of gene frequencies, levels of LD and admixture proportions of donor populations on the evolutionary dynamics of the LD of the admixed population. We examined the conditions under which the admixed population reached linkage equilibrium or the peak level of the LD. The study reveals the inappropriateness in approximating the dynamics of the LD generated by population admixture by the commonly used formula in literature. An appropriate equation for the dynamics is proposed. The distinct feature of the newly suggested formula is that the value of the nonlinear component of the LD remains constant in the first generation of the population evolution. Comparison between the predicted disequilibrium dynamics shows that the error will be caused by using the old formula, and thus resulting in a misguidance in using the evolutionary information of the admixed population in gene mapping.

  4. Synchronization of glycolytic oscillations in a yeast cell population

    DEFF Research Database (Denmark)

    Dano, S.; Hynne, F.; De Monte, Silvia;

    2001-01-01

    consequently it cannot be addressed at the level of a single enzyme or a single chemical species. In this paper it is shown how this system in a CSTR (continuous flow stirred tank reactor) can be modelled quantitatively as a population of Stuart-Landau oscillators interacting by exchange of metabolites through......The mechanism of active phase synchronization in a suspension of oscillatory yeast cells has remained a puzzle for almost half a century. The difficulty of the problem stems from the fact that the synchronization phenomenon involves the entire metabolic network of glycolysis and fermentation, and...

  5. Phase transitions in a lattice population model

    International Nuclear Information System (INIS)

    We introduce a model for a population on a lattice with diffusion and birth/death according to 2A→3A and A→Φ for a particle A. We find that the model displays a phase transition from an active to an absorbing state which is continuous in 1 + 1 dimensions and of first-order in higher dimensions in agreement with the mean field equation. For the (1 + 1)-dimensional case, we examine the critical exponents and a scaling function for the survival probability and show that it belongs to the universality class of directed percolation. In higher dimensions, we look at the first-order phase transition by plotting a histogram of the population density and use the presence of phase coexistence to find an accurate value for the critical point in 2 + 1 dimensions

  6. MicroSim: Modeling the Swedish Population

    CERN Document Server

    Brouwers, Lisa; Cakici, Baki; Mäkilä, Kalle; Saretok, Paul

    2009-01-01

    This article presents a unique, large-scale and spatially explicit microsimulation model that uses official anonymized register data collected from all individuals living in Sweden. Individuals are connected to households and workplaces and represent crucial links in the Swedish social contact network. This enables significant policy experiments in the domain of epidemic outbreaks. Development of the model started in 2004 at the Swedish Institute for Infectious Disease Control (SMI) in Solna, Sweden with the goal of creating a tool for testing the effects of intervention policies. These interventions include mass vaccination, targeted vaccination, isolation and social distancing. The model was initially designed for simulating smallpox outbreaks. In 2006, it was modified to support simulations of pandemic influenza. All nine millions members of the Swedish population are represented in the model. This article is a technical description of the simulation model; the input data, the simulation engine and the bas...

  7. The model of fungal population dynamics affected by nystatin

    Science.gov (United States)

    Voychuk, Sergei I.; Gromozova, Elena N.; Sadovskiy, Mikhail G.

    Fungal diseases are acute problems of the up-to-day medicine. Significant increase of resistance of microorganisms to the medically used antibiotics and a lack of new effective drugs follows in a growth of dosage of existing chemicals to solve the problem. Quite often such approach results in side effects on humans. Detailed study of fungi-antibiotic dynamics can identify new mechanisms and bring new ideas to overcome the microbial resistance with a lower dosage of antibiotics. In this study, the dynamics of the microbial population under antibiotic treatment was investigated. The effects of nystatin on the population of Saccharomyces cerevisiae yeasts were used as a model system. Nystatin effects were investigated both in liquid and solid media by viability tests. Dependence of nystatin action on osmotic gradient was evaluated in NaCl solutions. Influences of glucose and yeast extract were additionally analyzed. A "stepwise" pattern of the cell death caused by nystatin was the most intriguing. This pattern manifested in periodical changes of the stages of cell death against stages of resistance to the antibiotic. The mathematical model was proposed to describe cell-antibiotic interactions and nystatin viability effects in the liquid medium. The model implies that antibiotic ability to cause a cells death is significantly affected by the intracellular compounds, which came out of cells after their osmotic barriers were damaged

  8. Population dynamics of species-rich ecosystems: the mixture of matrix population models approach

    DEFF Research Database (Denmark)

    Mortier, Frédéric; Rossi, Vivien; Guillot, Gilles;

    2013-01-01

    Matrix population models are widely used to predict population dynamics, but when applied to species-rich ecosystems with many rare species, the small population sample sizes hinder a good fit of species-specific models. This issue can be overcome by assigning species to groups to increase the size...... group species with similar population dynamics....

  9. Coarse-grained analysis of stochastically simulated cell populations with a positive feedback genetic network architecture.

    Science.gov (United States)

    Aviziotis, I G; Kavousanakis, M E; Bitsanis, I A; Boudouvis, A G

    2015-06-01

    Among the different computational approaches modelling the dynamics of isogenic cell populations, discrete stochastic models can describe with sufficient accuracy the evolution of small size populations. However, for a systematic and efficient study of their long-time behaviour over a wide range of parameter values, the performance of solely direct temporal simulations requires significantly high computational time. In addition, when the dynamics of the cell populations exhibit non-trivial bistable behaviour, such an analysis becomes a prohibitive task, since a large ensemble of initial states need to be tested for the quest of possibly co-existing steady state solutions. In this work, we study cell populations which carry the lac operon network exhibiting solution multiplicity over a wide range of extracellular conditions (inducer concentration). By adopting ideas from the so-called "equation-free" methodology, we perform systems-level analysis, which includes numerical tasks such as the computation of coarse steady state solutions, coarse bifurcation analysis, as well as coarse stability analysis. Dynamically stable and unstable macroscopic (population level) steady state solutions are computed by means of bifurcation analysis utilising short bursts of fine-scale simulations, and the range of bistability is determined for different sizes of cell populations. The results are compared with the deterministic cell population balance model, which is valid for large populations, and we demonstrate the increased effect of stochasticity in small size populations with asymmetric partitioning mechanisms. PMID:24929336

  10. Targeting population heterogeneity for optimal cell factories

    DEFF Research Database (Denmark)

    Heins, Anna-Lena; Carlqvist, Magnus; Helmark, S.;

    To achieve an efficient production process, it is essential to optimize both the strain and the cultivation conditions. Traditionally, a microbial population has been considered homogeneous in optimization studies of fermentation processes. However, research has shown that a typical microbial...

  11. A novel population of α-smooth muscle actin-positive cells activated in a rat model of stroke: an analysis of the spatio-temporal distribution in response to ischemia.

    Science.gov (United States)

    Sharma, Varun; Ling, Tina W; Rewell, Sarah S; Hare, David L; Howells, David W; Kourakis, Angela; Wookey, Peter J

    2012-11-01

    In a rat model of stroke, the spatio-temporal distribution of α-smooth muscle actin-positive, (αSMA+) cells was investigated in the infarcted hemisphere (ipsilateral) and compared with the contralateral hemisphere. At day 3 postischemia, αSMA+ cells were concentrated in two main loci within the ipsilateral hemisphere (Area A) in the medial corpus callosum and (Area B) midway through the striatum adjacent to the lateral ventricle. By day 7 and further by day 14, fewer αSMA+ cells remained in Areas A and B but a steady increase in the peri-infarct was observed. αSMA+ cells also expressed glial acidic fibrillary protein [GFAP: αSMA+/GFAP+ (29%); αSMA+/GFAP- (71%) phenotypes] and feline leukemia virus C receptor 2 (FLVCR2), but not ED1(microglia) and established markers of pericytes normally located in vascular wall. αSMA+ cells were also located close to the subventricular zones (SVZ) adjacent to Areas A and B. In conclusion, αSMA+ cells have been identified in a spatial and temporal sequence from the SVZ, at intermediate loci and in the vicinity of the peri-infarct. It is hypothesized that novel populations of αSMA+ precursors of pericytes are born on the SVZ, migrate into the peri-infarct region and are incorporated into new vessels of the peri-infarct regions. PMID:22805872

  12. Progenitor cell populations in the periodontal ligament of mice

    International Nuclear Information System (INIS)

    Stem cells in a variety of renewal tissues exhibit a slow rate of cell proliferation. The periodontal ligament of mouse molars was examined for the presence of slowly cycling progenitor cells to provide evidence for the existence of stem cells in this tissue. A pulse injection of 3H-thymidine was administered and mice were sacrificed between 1 hour and 14 days after injection. Analysis of radioautographs using percentage of labeled cells and grain counts demonstrated that a population of label-retaining cells within 10 micron of blood vessels traversed the cell cycle more slowly than proliferating cells located greater than 10 micron from blood vessels. These data suggest that there is a slowly dividing population of progenitor cells in paravascular sites in mouse molar periodontal ligament which may be stem cells

  13. Sustainability in single-species population models.

    Science.gov (United States)

    Quinn, Terrance J; Collie, Jeremy S

    2005-01-29

    In this paper, we review the concept of sustainability with regard to a single-species, age-structured fish population with density dependence at some stage of its life history. We trace the development of the view of sustainability through four periods. The classical view of sustainability, prevalent in the 1970s and earlier, developed from deterministic production models, in which equilibrium abundance or biomass is derived as a function of fishing mortality. When there is no fishing mortality, the population equilibrates about its carrying capacity. We show that carrying capacity is the result of reproductive and mortality processes and is not a fixed constant unless these processes are constant. There is usually a fishing mortality, F(MSY), which results in MSY, and a higher value, F(ext), for which the population is eventually driven to extinction. For each F between 0 and F(ext), there is a corresponding sustainable population. From this viewpoint, the primary tool for achieving sustainability is the control of fishing mortality. The neoclassical view of sustainability, developed in the 1980s, involved population models with depensation and stochasticity. This view point is in accord with the perception that a population at a low level is susceptible to collapse or to a lack of rebuilding regardless of fishing. Sustainability occurs in a more restricted range from that in the classical view and includes an abundance threshold. A variety of studies has suggested that fishing mortality should not let a population drop below a threshold at 10-20% of carrying capacity. The modern view of sustainability in the 1990s moves further in the direction of precaution. The fishing mortality limit is the former target of F(MSY) (or some proxy), and the target fishing mortality is set lower. This viewpoint further reduces the range of permissible fishing mortalities and resultant desired population sizes. The objective has shifted from optimizing long-term catch to

  14. Androgen receptor expands the population of cancer stem cells in upper urinary tract urothelial cell carcinoma cells

    Science.gov (United States)

    Chen, Chi-Cheng; Hsieh, Teng-Fu; Huang, Chi-Ping; Yu, Ai-Lin; Chang, Wen-Lin; Shyr, Chih-Rong

    2016-01-01

    Androgen receptor (AR) affects the development and progression of upper urinary tract urothelial cell carcinoma (UUTUC). However, the regulatory mechanism exerted by AR to affect UUTUC cells remains unclear. Here we investigated whether AR promotes UUTUC development and progression, possibly by expanding the population of cancer stem cells (CSCs), which are a particular population of cells within cancer cells responsible for tumor initiation, drug resistance and metastasis. We compared UUTUC cells with or without the addition of AR on their CSC population with flow cytometry, colony formation and sphere formation assay to determine the effect of AR on CSC activity, and real-time PCR was used to detect the expression stemness genes and miRNAs. In vivo tumor formation was evaluated with the implantation of cancer cells in nude mice. We found that the addition of AR in UUTUC cells, significantly increased the population of CSC, clonogenicity, sphere formation and the expression of stemness genes (Oct4, Bmi1 and Nanog), altered CSC-related miRNA profile, as well as promoted epithelial mesenchymal transition (EMT). And AR inhibitor, enzalutamide was shown to suppress AR’s effect on tumorsphere formation. Furthermore, in an immune-deficient mouse model, the addition of AR in UUTUC cells also increased the tumor formation capacity. This study will help us better understand the extent to which AR contributes to UUTUC progression by expanding their CSC population and capacity. Our findings could explain high incidence of UUTUC observed in males. And targeting AR may lead to novel therapeutic approaches for genetically diversified urothelial carcinomas in precision medicine era.

  15. Population models for optimising SIT eradication strategies

    International Nuclear Information System (INIS)

    Successful eradication using the Sterile Insect Technique (SIT) relies on first optimising the competitiveness of irradiated insects, and second implementing a strategy of releases in space and time which effectively infiltrates the wild population. The former involves finding a radiation dosage which induces an effective level of sterility, but which minimises damage to the competitive fitness of individuals, and is particularly important in the case of inherited sterility where the population-level effects are not realised for several generations. We used simple, general population models to explore the trade-offs involved in the use of irradiated males for eradication, including both complete and inherited sterility scenarios. The models included different rates of competitiveness and sterility arising from matings between different combinations of wild, irradiated, and irradiated-lineage individuals. The default parameter set was derived from detailed field and laboratory experiments on the painted apple moth, Teia anartoides (Lepidoptera: Lymantriidae). Assuming that insects of irradiated lineage can only successfully mate with wild partners, then the critical overflooding ratio, Φc, defined as the number of irradiated males per wild male needed to prevent population increase, is given in an equation where R is the rate of increase of an uncontrolled population per generation, vS and vY are the relative competitiveness rates of irradiated and irradiated-lineage males respectively, fFS is the relative fecundity of matings between wild females and irradiated males, fFS is that of matings between wild females and irradiated-lineage males, and fXM is that of matings between irradiated-lineage females and wild males. This result suggests that the most important parameters to optimise are the competitiveness and virility of the irradiated males themselves, but this is not necessarily the case when irradiated-lineage males and females are compatible. The model also

  16. Probabilistic models of population evolution scaling limits, genealogies and interactions

    CERN Document Server

    Pardoux, Étienne

    2016-01-01

    This expository book presents the mathematical description of evolutionary models of populations subject to interactions (e.g. competition) within the population. The author includes both models of finite populations, and limiting models as the size of the population tends to infinity. The size of the population is described as a random function of time and of the initial population (the ancestors at time 0). The genealogical tree of such a population is given. Most models imply that the population is bound to go extinct in finite time. It is explained when the interaction is strong enough so that the extinction time remains finite, when the ancestral population at time 0 goes to infinity. The material could be used for teaching stochastic processes, together with their applications. Étienne Pardoux is Professor at Aix-Marseille University, working in the field of Stochastic Analysis, stochastic partial differential equations, and probabilistic models in evolutionary biology and population genetics. He obtai...

  17. Controlling the diversity of cell populations in a stem cell culture

    NARCIS (Netherlands)

    Heo, Inha; Clevers, Hans

    2015-01-01

    Culturing intestinal stem cells into 3D organoids results in heterogeneous cell populations, reflecting the in vivo cell type diversity. In a recent paper published in Nature, Wang et al. established a culture condition for a highly homogeneous population of intestinal stem cells.

  18. A population dynamics analysis of the interaction between adaptive regulatory T cells and antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    David Fouchet

    Full Text Available BACKGROUND: Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks that can be accomplished by a network. METHODOLOGY AND PRINCIPAL FINDINGS: We used a mathematical model to describe a interaction network of adaptive regulatory T cells, in which mature precursor T cells may differentiate into either adaptive regulatory T cells or effector T cells, depending on the activation state of the cell by which the antigen was presented. Using an equilibrium analysis of the mathematical model we show that, for some parameters, the network has two stable equilibrium states: one in which effector T cells are strongly regulated by regulatory T cells and another in which effector T cells are not regulated because the regulatory T cell population is vanishingly small. We then simulate different types of perturbations, such as the introduction of an antigen into a virgin system, and look at the state into which the system falls. We find that whether or not the interaction network switches from the regulated (tolerant state to the unregulated state depends on the strength of the antigenic stimulus and the state from which the network has been perturbed. CONCLUSION/SIGNIFICANCE: Our findings suggest that the interaction network studied in this paper plays an essential part in generating and maintaining tolerance against allergens and self-antigens.

  19. A focus on parietal cells as a renewing cell population

    Institute of Scientific and Technical Information of China (English)

    Sherif; M; Karam

    2010-01-01

    The fact that the acidsecreting parietal cells undergo continuous renewal has been ignored by many gastroenterologists and cell biologists. In the past, it was thought that these cells were static. However, by using 3Hthymidine radioautography in combination with electron microscopy, it was possible to demonstrate that parietal cells belong to a continuously renewing epithelial cell lineage. In the gastric glands, stem cells anchored in the isthmus region are responsible for the production of parietal cells...

  20. Modeling Radicalization Phenomena in Heterogeneous Populations

    CERN Document Server

    Galam, Serge

    2015-01-01

    The phenomenon of radicalization is investigated within an heterogeneous population composed of a core subpopulation, sharing a way of life locally rooted, and a recently immigrated subpopulation of different origins with ways of life which can be partly in conflict with the local one. While core agents are embedded in the country prominent culture and identity, they are not likely to modify their way of life, which make them naturally inflexible about it. On the opposite, the new comers can either decide to live peacefully with the core people adapting their way of life, or to keep strictly on their way and oppose the core population, leading eventually to criminal activities. To study the corresponding dynamics of radicalization we introduce a 3-state agent model with a proportion of inflexible agents and a proportion of flexible ones, which can be either peaceful or opponent. Assuming agents interact via weighted pairs within a Lotka-Volterra like Ordinary Differential Equation framework, the problem is an...

  1. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    OpenAIRE

    Lennard, Thomas W.J.; Meeson, Annette P; Britton, Kelly M.; Kirby, John A.

    2011-01-01

    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative....

  2. Single-Cell Behavior and Population Heterogeneity: Solving an Inverse Problem to Compute the Intrinsic Physiological State Functions

    OpenAIRE

    Spetsieris, Konstantinos; Zygourakis, Kyriacos

    2011-01-01

    The dynamics of isogenic cell populations can be described by cell population balance models that account for phenotypic heterogeneity. To utilize the predictive power of these models, however, we must know the rates of single-cell reaction and division and the bivariate partition probability density function. These three intrinsic physiological state (IPS) functions can be obtained by solving an inverse problem that requires knowledge of the phenotypic distributions for the overall cell popu...

  3. Population 24/7: building time-specific population grid models

    OpenAIRE

    Martin, David; Cockings, Samantha; Leung, Samuel

    2009-01-01

    Many areas of social science research and public policy rely on small area geographical representations of population. Studies of disease prevalence, crime rates, exposure to environmental hazards, transportation modelling and the more applied challenges of emergency planning, service delivery and resource allocation rely fundamentally on statistics relating to the distribution of population. Grid-based population models have considerable advantages for population representation, offering mor...

  4. Human embryonic stem cell lines derived from the Chinese population

    Institute of Scientific and Technical Information of China (English)

    Zhen Fu FANG; Fan JIN; Hui GAI; Ying CHEN; Li WU; Ai Lian LIU; Bin CHEN; Hui Zhen SHENG

    2005-01-01

    Six human embryonic stem cell lines were established from surplus blastocysts. The cell lines expressed alkaline phosphatase and molecules typical of primate embryonic stem cells, including Oct-4, Nanog, TDGF1, Sox2, EBAF,Thy-1, FGF4, Rex-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. Five of the six lines formed embryoid bodies that expressed markers of a variety of cell types; four of them formed teratomas with tissue types representative of all three embryonic germ layers. These human embryonic stem cells are capable of producing clones of undifferentiated morphology, and one of them was propagated to become a subline. Human embryonic stem cell lines from the Chinese population should facilitate stem cell research and may be valuable in studies of population genetics and ecology.

  5. Toward Synthetic Spatial Patterns in Engineered Cell Populations with Chemotaxis.

    Science.gov (United States)

    Duran-Nebreda, Salva; Solé, Ricard V

    2016-07-15

    A major force shaping form and patterns in biology is based in the presence of amplification mechanisms able to generate ordered, large-scale spatial structures out of local interactions and random initial conditions. Turing patterns are one of the best known candidates for such ordering dynamics, and their existence has been proven in both chemical and physical systems. Their relevance in biology, although strongly supported by indirect evidence, is still under discussion. Extensive modeling approaches have stemmed from Turing's pioneering ideas, but further confirmation from experimental biology is required. An alternative possibility is to engineer cells so that self-organized patterns emerge from local communication. Here we propose a potential synthetic design based on the interaction between population density and a diffusing signal, including also directed motion in the form of chemotaxis. The feasibility of engineering such a system and its implications for developmental biology are also assessed. PMID:27009520

  6. A single dividing cell population with imbalanced fate drives oesophageal tumour growth.

    Science.gov (United States)

    Frede, Julia; Greulich, Philip; Nagy, Tibor; Simons, Benjamin D; Jones, Philip H

    2016-09-01

    Understanding the cellular mechanisms of tumour growth is key for designing rational anticancer treatment. Here we used genetic lineage tracing to quantify cell behaviour during neoplastic transformation in a model of oesophageal carcinogenesis. We found that cell behaviour was convergent across premalignant tumours, which contained a single proliferating cell population. The rate of cell division was not significantly different in the lesions and the surrounding epithelium. However, dividing tumour cells had a uniform, small bias in cell fate so that, on average, slightly more dividing than non-dividing daughter cells were generated at each round of cell division. In invasive cancers induced by Kras(G12D) expression, dividing cell fate became more strongly biased towards producing dividing over non-dividing cells in a subset of clones. These observations argue that agents that restore the balance of cell fate may prove effective in checking tumour growth, whereas those targeting cycling cells may show little selectivity. PMID:27548914

  7. [Th9 cells: a new population of helper T cells].

    Science.gov (United States)

    Vegran, Frédérique; Martin, François; Apetoh, Lionel; Ghiringhelli, François

    2016-04-01

    Th9 cells are CD4 T helper cells characterized by their ability to produce IL-9 and IL-21. These cells are obtained from naive CD4(+) T cells cultured in the presence of TGF-β and IL-4. Thus their differentiation results from the balance between the signaling pathways induced by IL-4 in one hand and the one induced by TGF-β in the other hand. These cells are inflammatory cells and were first described in the context of atopic and autoimmune diseases in which they have a pathogenic role. They are also involved in the defense against parasite infections. Recently, some reports defined Th9 anticancer properties through their cytokine secretion. Indeed, their high secretion of IL-9 and IL-21 in the tumor bed contributes to their anticancer functions. These cytokines trigger the activation of dendritic cells, mast cells, natural killer cells, and CD8 T cells to mount an antitumor immune response. PMID:27137696

  8. Stochastic multi-scale models of competition within heterogeneous cellular populations: simulation methods and mean-field analysis

    CERN Document Server

    de la Cruz, Roberto; Spill, Fabian; Alarcón, Tomás

    2016-01-01

    We propose a modelling framework to analyse the stochastic behaviour of heterogeneous, multi-scale cellular populations. We illustrate our methodology with a particular example in which we study a population with an oxygen-regulated proliferation rate. Our formulation is based on an age-dependent stochastic process. Cells within the population are characterised by their age. The age-dependent (oxygen-regulated) birth rate is given by a stochastic model of oxygen-dependent cell cycle progression. We then formulate an age-dependent birth-and-death process, which dictates the time evolution of the cell population. The population is under a feedback loop which controls its steady state size: cells consume oxygen which in turns fuels cell proliferation. We show that our stochastic model of cell cycle progression allows for heterogeneity within the cell population induced by stochastic effects. Such heterogeneous behaviour is reflected in variations in the proliferation rate. Within this set-up, we have established...

  9. Implications of epigenetic variability within a cell population for cell type classification

    Directory of Open Access Journals (Sweden)

    Inna eTabansky

    2015-12-01

    Full Text Available Here we propose a new approach to defining nerve ‘cell types’ in reaction to recent advances in single cell analysis. Among cells previously thought to be equivalent, considerable differences in global gene expression and biased tendencies among differing developmental fates have been demonstrated within multiple lineages. The model of classifying cells into distinct types thus has to be revised to account for this intrinsic variability. A ‘cell type’ could be a group of cells that possess similar, but not necessarily identical properties, variable within a spectrum of epigenetic adjustments that permit its developmental path toward a specific function to be achieved. Thus, the definition of a cell type is becoming more similar to the definition of a species: sharing essential properties with other members of its group, but permitting a certain amount of deviation in aspects that do not seriously impact function. This approach accommodates, even embraces the spectrum of natural variation found in various cell populations and consequently avoids the fallacy of false equivalence. For example, developing neurons will react to their microenvironments with epigenetic changes resulting in slight changes in gene expression and morphology. Addressing the new questions implied here will have significant implications for developmental neurobiology.

  10. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

    To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

  11. Characterization of side population cells from human airway epithelium.

    Science.gov (United States)

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V; Jacoby, David B; Kicic, Anthony; Stick, Stephen M; Knight, Darryl A

    2008-10-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45(-) SP, CD45(+) SP, and non-SP cells were isolated and sorted. CD45(-) SP cells made up 0.12% +/- 0.01% of the total epithelial cell population in normal airway but 4.1% +/- 0.06% of the epithelium in asthmatic airways. All CD45(-) SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45(-) SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45(-) SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and long-term proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium. Disclosure of potential conflicts of interest is found at the end of this article. PMID:18653771

  12. A focus on parietal cells as a renewing cell population

    Directory of Open Access Journals (Sweden)

    Sherif M Karam

    2010-02-01

    Full Text Available The fact that the acid-secreting parietal cells undergo continuous renewal has been ignored by many gastroenterologists and cell biologists. In the past, it was thought that these cells were static. However, by using 3H-thymidine radioautography in combination with electron microscopy, it was possible to demonstrate that parietal cells belong to a continuously renewing epithelial cell lineage. In the gastric glands, stem cells anchored in the isthmus region are responsible for the production of parietal cells. The stem cells give rise to three main progenitors: prepit, preneck and preparietal cells. Parietal cells develop either directly from the non-cycling preparietal cells or less commonly via differentiation of the cycling prepit and preneck cell progenitors. The formation of a parietal cell is a sequential process which involves diminishment of glycocalyx, production of cytoplasmic tubulovesicles, an increase in number and length of microvilli, an increase in number and size of mitochondria, and finally, expansion and invagination of the apical membrane with the formation of an intracellular canalicular system. Little is known about the genetic counterparts of these morphological events. However, the time dimension of parietal cell production and the consequences of its alteration on the biological features of the gastric gland are well documented. The production of a new parietal cell takes about 2 d. However, mature parietal cells have a long lifespan during which they migrate bi-directionally while their functional activity for acid secretion gradually diminishes. Following an average lifespan of about 54 d, in mice, old parietal cells undergo degeneration and elimination. Various approaches for genetic alteration of the development of parietal cells have provided evidence in support of their role as governors of the stem/progenitor cell proliferation and differentiation programs. Revealing the dynamic features and the various roles of

  13. Cell culture models using rat primary alveolar type I cells.

    Science.gov (United States)

    Downs, Charles A; Montgomery, David W; Merkle, Carrie J

    2011-10-01

    There is a lack of cell culture models using primary alveolar type I (AT I) cells. The purpose of this study was to develop cell culture models using rat AT I cells and microvascular endothelial cells from the lung (MVECL). Two types of model systems were developed: single and co-culture systems; additionally a 3-dimensional model system was developed. Pure AT I cell (96.3 ± 2.7%) and MVECL (97.9 ± 1.1%) preparations were used. AT I cell morphology, mitochondrial number and distribution, actin filament arrangement and number of apoptotic cells at confluence, and telomere attrition were characterized. AT I cells maintained their morphometric characteristics through at least population doubling (PD) 35, while demonstrating telomere attrition through at least PD 100. Furthermore, AT I cells maintained the expression of their specific markers, T1α and AQ-5, through PD 42. For the co-cultures, AT I cells were grown on the top and MVECL were grown on the bottom of fibronectin-coated 24-well Transwell Fluroblok™ filter inserts. Neither cell type transmigrated the 1 μm pores. Additionally, AT I cells were grown in a thick layer of Matrigel(®) to create a 3-dimensional model in which primary AT I cells form ring-like structures that resemble an alveolus. The development of these model systems offers the opportunities to investigate AT I cells and their interactions with MVECL in response to pharmacological interventions and in the processes of disease, repair and regeneration. PMID:21624488

  14. Population Balance Models: A useful complementary modelling framework for future WWTP modelling

    DEFF Research Database (Denmark)

    Nopens, Ingmar; Torfs, Elena; Ducoste, Joel;

    2014-01-01

    Population Balance Models (PBMs) represent a powerful modelling framework for the description of the dynamics of properties that are characterised by statistical distributions. This has been demonstrated in many chemical engineering applications. Modelling efforts of several current and future un...

  15. Mathematical Model to Simulate Tuberculosis Disease Population Dynamics

    Directory of Open Access Journals (Sweden)

    O. K. Koriko

    2008-01-01

    Full Text Available A mathematical model to depict Tuberculosis disease population dynamics was presented. The model population was compartmentalised as appropriate and the resulting model equations were solved numerically while different instances of the disease transmission were simulated. The graphical profiles of the various sub-populations with time were presented and discussed based on the results from our simulations. Also, the disease-free and endemic equilibrium of the system were established and analyzed for stability.

  16. Sequential Markov coalescent algorithms for population models with demographic structure

    OpenAIRE

    A. Eriksson; Mahjani, B.; Mehlig, B.

    2009-01-01

    We analyse sequential Markov coalescent algorithms for populations with demographic structure: for a bottleneck model, a population-divergence model, and for a two-island model with migration. The sequential Markov coalescent method is an approximation to the coalescent suggested by McVean and Cardin, and Marjoram and Wall. Within this algorithm we compute, for two individuals randomly sampled from the population, the correlation between times to the most recent common ancestor and the linkag...

  17. A new ODE tumor growth modeling based on tumor population dynamics

    International Nuclear Information System (INIS)

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan

  18. A new ODE tumor growth modeling based on tumor population dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Oroji, Amin; Omar, Mohd bin [Institute of Mathematical Sciences, Faculty of Science University of Malaya, 50603 Kuala Lumpur, Malaysia amin.oroji@siswa.um.edu.my, mohd@um.edu.my (Malaysia); Yarahmadian, Shantia [Mathematics Department Mississippi State University, USA Syarahmadian@math.msstate.edu (United States)

    2015-10-22

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan.

  19. Characterization of Side Population Cells from Human Airway Epithelium

    OpenAIRE

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V; Jacoby, David B.; Kicic, Anthony; Stick, Stephen M.; Knight, Darryl A.

    2008-01-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelia...

  20. Optimal Population Codes for Space: Grid Cells Outperform Place Cells

    OpenAIRE

    Mathis, Alexander; Herz, Andreas V. M.; Stemmler, Martin B

    2012-01-01

    Rodents use two distinct neuronal coordinate systems to estimate their position: place fields in the hippocampus and grid fields in the entorhinal cortex. Whereas place cells spike at only one particular spatial lo- cation, grid cells fire at multiple sites that correspond to the points of an imaginary hexagonal lattice. We study how to best construct place and grid codes, taking the probabilistic nature of neural spiking into account. Which spatial encoding properties of individu...

  1. Modeling human population patterns on tree density

    Directory of Open Access Journals (Sweden)

    M. Yousefpoor

    2016-05-01

    Full Text Available In order to evaluate the possible correlation between the tree density and the human population density, the forested area in Nav Asalem district located in Guilan Province was selected. The descriptors of tree number and basal area per hectare as well as the stand density index were used to determine the tree density, which was conducted from a 2014 forest inventory including 62 cluster (558 plots systematically scattered over 30 % of the forest area. In addition, to determine the density of the human population, circular buffers at intervals of 1 to 7 km from the center of each cluster was considered and population density of each layer was calculated using buffering functions. Statistical results showed that the average basal area, average number of trees and the average stand density index was 23.16 m2/ha, 243 per ha and 178.25 respectively and also different human population density in each buffer. Using Pearson correlation test indicated a significant negative correlation between the stand density index and basal area (DBH≥ 15 cm with human population density. There was no significant relationship between the number of trees per hectare and the human population density except at 7 km. This findings support studies regarding the disturbance has strong correlative with the number of residents per unit area at up to 7 km from clusters and greater control on anthropogenic interventions should be the main priority of sustainable forestry in Hyrcanian forests of northern Iran. Due to the existence of an effective relationship between the components of the tree density and human population in the forest, policy-makers and planners of natural resources could benefit management patterns appropriate to above components to achieve sustainable management.

  2. Modeling bacterial chemotaxis inside a cell

    OpenAIRE

    Ouannes, Nesrine; Djedi, Noureddine; Luga, Hervé; Duthen, Yves

    2014-01-01

    This paper describes a bacterial system that reproduces a population of bacteria that behave by simulating the internal reactions of each bacterial cell. The chemotaxis network of a cell is modulated by a hybrid approach that uses an algebraic model for the receptor clusters activity and an ordinary differential equation for the adaptation dynamics. The experiments are defined in order to simulate bacterial growth in an environment where nutrients are regularly added to it. The results show a...

  3. The evolution of carrying capacity in constrained and expanding tumour cell populations

    Science.gov (United States)

    Gerlee, Philip; Anderson, Alexander R. A.

    2015-10-01

    Cancer cells are known to modify their micro-environment such that it can sustain a larger population, or, in ecological terms, they construct a niche which increases the carrying capacity of the population. It has however been argued that niche construction, which benefits all cells in the tumour, would be selected against since cheaters could reap the benefits without paying the cost. We have investigated the impact of niche specificity on tumour evolution using an individual based model of breast tumour growth, in which the carrying capacity of each cell consists of two components: an intrinsic, subclone-specific part and a contribution from all neighbouring cells. Analysis of the model shows that the ability of a mutant to invade a resident population depends strongly on the specificity. When specificity is low selection is mostly on growth rate, while high specificity shifts selection towards increased carrying capacity. Further, we show that the long-term evolution of the system can be predicted using adaptive dynamics. By comparing the results from a spatially structured versus well-mixed population we show that spatial structure restores selection for carrying capacity even at zero specificity, which poses a solution to the niche construction dilemma. Lastly, we show that an expanding population exhibits spatially variable selection pressure, where cells at the leading edge exhibit higher growth rate and lower carrying capacity than those at the centre of the tumour.

  4. Population Pharmacokinetics of Busulfan in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplant: A Model-Based Dosing Algorithm for Personalized Therapy and Implementation into Routine Clinical Use

    Science.gov (United States)

    Long-Boyle, Janel; Savic, Rada; Yan, Shirley; Bartelink, Imke; Musick, Lisa; French, Deborah; Law, Jason; Horn, Biljana; Cowan, Morton J.; Dvorak, Christopher C.

    2014-01-01

    Background Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared to conventional dosing. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration-at-steady-state, Css) and implement a simple, model-based tool for the initial dosing of busulfan in children undergoing HCT. Patients and Methods Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone HCT with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the non-linear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly, Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Results Modeling of busulfan time-concentration data indicates busulfan CL displays non-linearity in children, decreasing up to approximately 20% between the concentrations of 250–2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan CL were actual body weight and age. The percentage of individuals achieving a therapeutic Css was significantly higher in subjects receiving initial doses based on the population PK model (81%) versus historical controls dosed on conventional guidelines (52%) (p = 0.02). Conclusion When compared to the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults. PMID:25162216

  5. Isolation of basal and mucous cell populations from rabbit trachea

    International Nuclear Information System (INIS)

    The application of a unit gravity sedimentation procedure to monodispersed rabbit tracheal cells resulted in the isolation of enriched (2-fold to 2.5-fold) basal and mucous cell populations. Cellular integrity was confirmed by a trypan blue dye exclusion index of 93%, [3H] leucine incorporation, and ultrastructural analysis. Unit gravity sedimentation is an affective and rapid procedure for obtaining viable, homogeneous preparations of basal and mucous cells that may be used for in vitro studies of cellular proliferation, differentiation, and glycoprotein biosynthesis in respiratory mucous epithelia

  6. A spatial ecosystem and populations dynamics model (SEAPODYM) Modeling of tuna and tuna-like populations

    Science.gov (United States)

    Lehodey, Patrick; Senina, Inna; Murtugudde, Raghu

    2008-09-01

    An enhanced version of the spatial ecosystem and population dynamics model SEAPODYM is presented to describe spatial dynamics of tuna and tuna-like species in the Pacific Ocean at monthly resolution over 1° grid-boxes. The simulations are driven by a bio-physical environment predicted from a coupled ocean physical-biogeochemical model. This new version of SEAPODYM includes expanded definitions of habitat indices, movements, and natural mortality based on empirical evidences. A thermal habitat of tuna species is derived from an individual heat budget model. The feeding habitat is computed according to the accessibility of tuna predator cohorts to different vertically migrating and non-migrating micronekton (mid-trophic) functional groups. The spawning habitat is based on temperature and the coincidence of spawning fish with presence or absence of predators and food for larvae. The successful larval recruitment is linked to spawning stock biomass. Larvae drift with currents, while immature and adult tuna can move of their own volition, in addition to being advected by currents. A food requirement index is computed to adjust locally the natural mortality of cohorts based on food demand and accessibility to available forage components. Together these mechanisms induce bottom-up and top-down effects, and intra- (i.e. between cohorts) and inter-species interactions. The model is now fully operational for running multi-species, multi-fisheries simulations, and the structure of the model allows a validation from multiple data sources. An application with two tuna species showing different biological characteristics, skipjack ( Katsuwonus pelamis) and bigeye ( Thunnus obesus), is presented to illustrate the capacity of the model to capture many important features of spatial dynamics of these two different tuna species in the Pacific Ocean. The actual validation is presented in a companion paper describing the approach to have a rigorous mathematical parameter optimization

  7. Noise and Epigenetic Inheritance of Single-Cell Division Times Influence Population Fitness.

    Science.gov (United States)

    Cerulus, Bram; New, Aaron M; Pougach, Ksenia; Verstrepen, Kevin J

    2016-05-01

    The fitness effect of biological noise remains unclear. For example, even within clonal microbial populations, individual cells grow at different speeds. Although it is known that the individuals' mean growth speed can affect population-level fitness, it is unclear how or whether growth speed heterogeneity itself is subject to natural selection. Here, we show that noisy single-cell division times can significantly affect population-level growth rate. Using time-lapse microscopy to measure the division times of thousands of individual S. cerevisiae cells across different genetic and environmental backgrounds, we find that the length of individual cells' division times can vary substantially between clonal individuals and that sublineages often show epigenetic inheritance of division times. By combining these experimental measurements with mathematical modeling, we find that, for a given mean division time, increasing heterogeneity and epigenetic inheritance of division times increases the population growth rate. Furthermore, we demonstrate that the heterogeneity and epigenetic inheritance of single-cell division times can be linked with variation in the expression of catabolic genes. Taken together, our results reveal how a change in noisy single-cell behaviors can directly influence fitness through dynamics that operate independently of effects caused by changes to the mean. These results not only allow a better understanding of microbial fitness but also help to more accurately predict fitness in other clonal populations, such as tumors. PMID:27068419

  8. Adding Value to Ecological Risk Assessment with Population Modeling

    DEFF Research Database (Denmark)

    Forbes, Valery E.; Calow, Peter; Grimm, Volker;

    2011-01-01

    population models can provide a powerful basis for expressing ecological risks that better inform the environmental management process and thus that are more likely to be used by managers. Here we provide at least five reasons why population modeling should play an important role in bridging the gap between...

  9. MIUSCAT: extended MILES spectral coverage. I. Stellar populations synthesis models

    OpenAIRE

    Vazdekis, A.; Ricciardelli, E.; Cenarro, A. J.; Rivero-González, J. G.; Díaz-García, L. A.; Falcón-Barroso, J.

    2012-01-01

    We extend the spectral range of our stellar population synthesis models based on the MILES and CaT empirical stellar spectral libraries. For this purpose we combine these two libraries with the Indo-U.S. to construct composite stellar spectra to feed our models. The spectral energy distributions (SEDs) computed with these models and the originally published models are combined to construct composite SEDs for single-age, single-metallicity stellar populations (SSPs) covering the range 3465 - 9...

  10. Transcriptional and phenotypical heterogeneity of Trypanosoma cruzi cell populations.

    Science.gov (United States)

    Seco-Hidalgo, Víctor; De Pablos, Luis Miguel; Osuna, Antonio

    2015-12-01

    Trypanosoma cruzi has a complex life cycle comprising pools of cell populations which circulate among humans, vectors, sylvatic reservoirs and domestic animals. Recent experimental evidence has demonstrated the importance of clonal variations for parasite population dynamics, survival and evolution. By limiting dilution assays, we have isolated seven isogenic clonal cell lines derived from the Pan4 strain of T. cruzi. Applying different molecular techniques, we have been able to provide a comprehensive characterization of the expression heterogeneity in the mucin-associated surface protein (MASP) gene family, where all the clonal isogenic populations were transcriptionally different. Hierarchical cluster analysis and sequence comparison among different MASP cDNA libraries showed that, despite the great variability in MASP expression, some members of the transcriptome (including MASP pseudogenes) are conserved, not only in the life-cycle stages but also among different strains of T. cruzi. Finally, other important aspects for the parasite, such as growth, spontaneous metacyclogenesis or excretion of different catabolites, were also compared among the clones, demonstrating that T. cruzi populations of cells are also phenotypically heterogeneous. Although the evolutionary strategy that sustains the MASP expression polymorphism remains unknown, we suggest that MASP clonal variability and phenotypic heterogeneities found in this study might provide an advantage, allowing a rapid response to environmental pressure or changes during the life cycle of T. cruzi. PMID:26674416

  11. Population balance models: a useful complementary modelling framework for future WWTP modelling

    DEFF Research Database (Denmark)

    Nopens, Ingmar; Torfs, Elena; Ducoste, Joel;

    2015-01-01

    Population balance models (PBMs) represent a powerful modelling framework for the description of the dynamics of properties that are characterised by distributions. This distribution of properties under transient conditions has been demonstrated in many chemical engineering applications. Modellin...

  12. Changes in the population of perivascular cells in the bone tissue remodeling zones under microgravity

    Science.gov (United States)

    Katkova, Olena; Rodionova, Natalia; Shevel, Ivan

    2016-07-01

    Microgravity and long-term hypokinesia induce reduction both in bone mass and mineral saturation, which can lead to the development of osteoporosis and osteopenia. (Oganov, 2003). Reorganizations and adaptive remodeling processes in the skeleton bones occur in the topographical interconnection with blood capillaries and perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel, Fee, 1980; Rodionova, 1989, 2006) have shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic. Hence the study of populations of perivascular stromal cells in areas of destructive changes is actual. Perivascular cells from metaphysis of the rat femoral bones under conditions of modeling microgravity were studied using electron microscopy and cytochemistry (hindlimb unloading, 28 days duration) and biosatellite «Bion-M1» (duration of flight from April 19 till May 19, 2013 on C57, black mice). It was revealed that both control and test groups populations of the perivascular cells are not homogeneous in remodeling adaptive zones. These populations comprise of adjacent to endothelium poorly differentiated forms and isolated cells with signs of differentiation (specific increased volume of rough endoplasmic reticulum in cytoplasm). Majority of the perivascular cells in the control group (modeling microgravity) reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In poorly differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of experimental animals reaction to the alkaline phosphatase is registered not in all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. Under microgravity some poorly differentiated perivascular

  13. Accommodating environmental variation in population models: metaphysiological biomass loss accounting.

    Science.gov (United States)

    Owen-Smith, Norman

    2011-07-01

    1. There is a pressing need for population models that can reliably predict responses to changing environmental conditions and diagnose the causes of variation in abundance in space as well as through time. In this 'how to' article, it is outlined how standard population models can be modified to accommodate environmental variation in a heuristically conducive way. This approach is based on metaphysiological modelling concepts linking populations within food web contexts and underlying behaviour governing resource selection. Using population biomass as the currency, population changes can be considered at fine temporal scales taking into account seasonal variation. Density feedbacks are generated through the seasonal depression of resources even in the absence of interference competition. 2. Examples described include (i) metaphysiological modifications of Lotka-Volterra equations for coupled consumer-resource dynamics, accommodating seasonal variation in resource quality as well as availability, resource-dependent mortality and additive predation, (ii) spatial variation in habitat suitability evident from the population abundance attained, taking into account resource heterogeneity and consumer choice using empirical data, (iii) accommodating population structure through the variable sensitivity of life-history stages to resource deficiencies, affecting susceptibility to oscillatory dynamics and (iv) expansion of density-dependent equations to accommodate various biomass losses reducing population growth rate below its potential, including reductions in reproductive outputs. Supporting computational code and parameter values are provided. 3. The essential features of metaphysiological population models include (i) the biomass currency enabling within-year dynamics to be represented appropriately, (ii) distinguishing various processes reducing population growth below its potential, (iii) structural consistency in the representation of interacting populations and

  14. Modelling familial dysautonomia in human induced pluripotent stem cells

    OpenAIRE

    Lee, Gabsang; Studer, Lorenz

    2011-01-01

    Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of...

  15. Modeling human population patterns on tree density

    OpenAIRE

    M. Yousefpoor; Rostamie Shahraji, T; Eslam Bonyad, A; Salahi, M

    2016-01-01

    In order to evaluate the possible correlation between the tree density and the human population density, the forested area in Nav Asalem district located in Guilan Province was selected. The descriptors of tree number and basal area per hectare as well as the stand density index were used to determine the tree density, which was conducted from a 2014 forest inventory including 62 cluster (558 plots) systematically scattered over 30 % of the forest area. In addition, to determine the density o...

  16. Cell population-specific expression analysis of human cerebellum

    Directory of Open Access Journals (Sweden)

    Kuhn Alexandre

    2012-11-01

    Full Text Available Abstract Background Interpreting gene expression profiles obtained from heterogeneous samples can be difficult because bulk gene expression measures are not resolved to individual cell populations. We have recently devised Population-Specific Expression Analysis (PSEA, a statistical method that identifies individual cell types expressing genes of interest and achieves quantitative estimates of cell type-specific expression levels. This procedure makes use of marker gene expression and circumvents the need for additional experimental information like tissue composition. Results To systematically assess the performance of statistical deconvolution, we applied PSEA to gene expression profiles from cerebellum tissue samples and compared with parallel, experimental separation methods. Owing to the particular histological organization of the cerebellum, we could obtain cellular expression data from in situ hybridization and laser-capture microdissection experiments and successfully validated computational predictions made with PSEA. Upon statistical deconvolution of whole tissue samples, we identified a set of transcripts showing age-related expression changes in the astrocyte population. Conclusions PSEA can predict cell-type specific expression levels from tissues homogenates on a genome-wide scale. It thus represents a computational alternative to experimental separation methods and allowed us to identify age-related expression changes in the astrocytes of the cerebellum. These molecular changes might underlie important physiological modifications previously observed in the aging brain.

  17. Tumor-Initiating Cells Are Enriched in CD44hi Population in Murine Salivary Gland Tumor

    OpenAIRE

    Shukun Shen; Wenjun Yang; Zhugang Wang; Xia Lei; Liqun Xu; Yang Wang; Lizhen Wang; Lei Huang; Zhiwei Yu; Xinhong Zhang; Jiang Li; Yan Chen; Xiaoping Zhao; Xuelai Yin; Chenping Zhang

    2011-01-01

    Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44(high) (CD44(hi)) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44(hi) tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU), at a...

  18. Clonal genotype and population structure inference from single-cell tumor sequencing.

    Science.gov (United States)

    Roth, Andrew; McPherson, Andrew; Laks, Emma; Biele, Justina; Yap, Damian; Wan, Adrian; Smith, Maia A; Nielsen, Cydney B; McAlpine, Jessica N; Aparicio, Samuel; Bouchard-Côté, Alexandre; Shah, Sohrab P

    2016-07-01

    Single-cell DNA sequencing has great potential to reveal the clonal genotypes and population structure of human cancers. However, single-cell data suffer from missing values and biased allelic counts as well as false genotype measurements owing to the sequencing of multiple cells. We describe the Single Cell Genotyper (https://bitbucket.org/aroth85/scg), an open-source software based on a statistical model coupled with a mean-field variational inference method, which can be used to address these problems and robustly infer clonal genotypes. PMID:27183439

  19. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury.

    Science.gov (United States)

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  20. Evidence of distinct tumour-propagating cell populations with different properties in primary human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Federico Colombo

    Full Text Available BACKGROUND AND AIMS: Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC compartments within human hepatocellular carcinoma (HCC. METHODS: After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ/⁻ mice. RESULTS: The primary cell populations (hcc-1, -2 and -3 and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8 differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features. CONCLUSIONS: Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution.

  1. Sensitivity analysis of periodic matrix population models.

    Science.gov (United States)

    Caswell, Hal; Shyu, Esther

    2012-12-01

    Periodic matrix models are frequently used to describe cyclic temporal variation (seasonal or interannual) and to account for the operation of multiple processes (e.g., demography and dispersal) within a single projection interval. In either case, the models take the form of periodic matrix products. The perturbation analysis of periodic models must trace the effects of parameter changes, at each phase of the cycle, on output variables that are calculated over the entire cycle. Here, we apply matrix calculus to obtain the sensitivity and elasticity of scalar-, vector-, or matrix-valued output variables. We apply the method to linear models for periodic environments (including seasonal harvest models), to vec-permutation models in which individuals are classified by multiple criteria, and to nonlinear models including both immediate and delayed density dependence. The results can be used to evaluate management strategies and to study selection gradients in periodic environments. PMID:23316494

  2. A quantitative model of honey bee colony population dynamics.

    Directory of Open Access Journals (Sweden)

    David S Khoury

    Full Text Available Since 2006 the rate of honey bee colony failure has increased significantly. As an aid to testing hypotheses for the causes of colony failure we have developed a compartment model of honey bee colony population dynamics to explore the impact of different death rates of forager bees on colony growth and development. The model predicts a critical threshold forager death rate beneath which colonies regulate a stable population size. If death rates are sustained higher than this threshold rapid population decline is predicted and colony failure is inevitable. The model also predicts that high forager death rates draw hive bees into the foraging population at much younger ages than normal, which acts to accelerate colony failure. The model suggests that colony failure can be understood in terms of observed principles of honey bee population dynamics, and provides a theoretical framework for experimental investigation of the problem.

  3. Augmenting superpopulation capture-recapture models with population assignment data

    Science.gov (United States)

    Wen, Zhi; Pollock, Kenneth; Nichols, James; Waser, Peter

    2011-01-01

    Ecologists applying capture-recapture models to animal populations sometimes have access to additional information about individuals' populations of origin (e.g., information about genetics, stable isotopes, etc.). Tests that assign an individual's genotype to its most likely source population are increasingly used. Here we show how to augment a superpopulation capture-recapture model with such information. We consider a single superpopulation model without age structure, and split each entry probability into separate components due to births in situ and immigration. We show that it is possible to estimate these two probabilities separately. We first consider the case of perfect information about population of origin, where we can distinguish individuals born in situ from immigrants with certainty. Then we consider the more realistic case of imperfect information, where we use genetic or other information to assign probabilities to each individual's origin as in situ or outside the population. We use a resampling approach to impute the true population of origin from imperfect assignment information. The integration of data on population of origin with capture-recapture data allows us to determine the contributions of immigration and in situ reproduction to the growth of the population, an issue of importance to ecologists. We illustrate our new models with capture-recapture and genetic assignment data from a population of banner-tailed kangaroo rats Dipodomys spectabilis in Arizona.

  4. Periodic solutions of nonautonomous differential systems modeling obesity population

    Energy Technology Data Exchange (ETDEWEB)

    Arenas, Abraham J. [Departamento de Matematicas y Estadistica, Universidad de Cordoba Monteria (Colombia)], E-mail: aarenas@sinu.unicordoba.edu.co; Gonzalez-Parra, Gilberto [Departamento de Calculo, Universidad de los Andes, Merida (Venezuela, Bolivarian Republic of)], E-mail: gcarlos@ula.ve; Jodar, Lucas [Instituto de Matematica Multidisciplinar, Universidad Politecnica de Valencia Edificio 8G, 2o, 46022 Valencia (Spain)], E-mail: ljodar@imm.upv.es

    2009-10-30

    In this paper we study the periodic behaviour of the solutions of a nonautonomous model for obesity population. The mathematical model represented by a nonautonomous system of nonlinear ordinary differential equations is used to model the dynamics of obese populations. Numerical simulations suggest periodic behaviour of subpopulations solutions. Sufficient conditions which guarantee the existence of a periodic positive solution are obtained using a continuation theorem based on coincidence degree theory.

  5. Efficient Checking of Individual Rewards Properties in Markov Population Models

    OpenAIRE

    Bortolussi, Luca; Hillston, Jane

    2015-01-01

    In recent years fluid approaches to the analysis of Markov populations models have been demonstrated to have great pragmatic value. Initially developed to estimate the behaviour of the system in terms of the expected values of population counts, the fluid approach has subsequently been extended to more sophisticated interrogations of models through its embedding within model checking procedures. In this paper we extend recent work on checking CSL properties of individual agents within a Marko...

  6. Classification method for heterogeneity in monoclonal cell population

    Science.gov (United States)

    Aburatani, S.; Tashiro, K.; Kuhara, S.

    2015-09-01

    Monoclonal cell populations are known to be composed of heterogeneous subpopulations, thus complicating the data analysis. To gain clear insights into the mechanisms of cellular systems, biological data from a homogeneous cell population should be obtained. In this study, we developed a method based on Latent Profile Analysis (LPA) combined with Confirmatory Factor Analysis (CFA) to divide mixed data into classes, depending on their heterogeneity. In general cluster analysis, the number of measured points is a constraint, and thereby the data must be classified into fewer groups than the number of samples. By our newly developed method, the measured data can be divided into groups depending on their latent effects, without constraints. Our method is useful to clarify all types of omics data, including transcriptome, proteome and metabolic information.

  7. Modeling Radicalization Phenomena in Heterogeneous Populations.

    Science.gov (United States)

    Galam, Serge; Javarone, Marco Alberto

    2016-01-01

    The phenomenon of radicalization is investigated within a mixed population composed of core and sensitive subpopulations. The latest includes first to third generation immigrants. Respective ways of life may be partially incompatible. In case of a conflict core agents behave as inflexible about the issue. In contrast, sensitive agents can decide either to live peacefully adjusting their way of life to the core one, or to oppose it with eventually joining violent activities. The interplay dynamics between peaceful and opponent sensitive agents is driven by pairwise interactions. These interactions occur both within the sensitive population and by mixing with core agents. The update process is monitored using a Lotka-Volterra-like Ordinary Differential Equation. Given an initial tiny minority of opponents that coexist with both inflexible and peaceful agents, we investigate implications on the emergence of radicalization. Opponents try to turn peaceful agents to opponents driving radicalization. However, inflexible core agents may step in to bring back opponents to a peaceful choice thus weakening the phenomenon. The required minimum individual core involvement to actually curb radicalization is calculated. It is found to be a function of both the majority or minority status of the sensitive subpopulation with respect to the core subpopulation and the degree of activeness of opponents. The results highlight the instrumental role core agents can have to hinder radicalization within the sensitive subpopulation. Some hints are outlined to favor novel public policies towards social integration. PMID:27166677

  8. Modeling Radicalization Phenomena in Heterogeneous Populations.

    Directory of Open Access Journals (Sweden)

    Serge Galam

    Full Text Available The phenomenon of radicalization is investigated within a mixed population composed of core and sensitive subpopulations. The latest includes first to third generation immigrants. Respective ways of life may be partially incompatible. In case of a conflict core agents behave as inflexible about the issue. In contrast, sensitive agents can decide either to live peacefully adjusting their way of life to the core one, or to oppose it with eventually joining violent activities. The interplay dynamics between peaceful and opponent sensitive agents is driven by pairwise interactions. These interactions occur both within the sensitive population and by mixing with core agents. The update process is monitored using a Lotka-Volterra-like Ordinary Differential Equation. Given an initial tiny minority of opponents that coexist with both inflexible and peaceful agents, we investigate implications on the emergence of radicalization. Opponents try to turn peaceful agents to opponents driving radicalization. However, inflexible core agents may step in to bring back opponents to a peaceful choice thus weakening the phenomenon. The required minimum individual core involvement to actually curb radicalization is calculated. It is found to be a function of both the majority or minority status of the sensitive subpopulation with respect to the core subpopulation and the degree of activeness of opponents. The results highlight the instrumental role core agents can have to hinder radicalization within the sensitive subpopulation. Some hints are outlined to favor novel public policies towards social integration.

  9. Modeling Radicalization Phenomena in Heterogeneous Populations

    Science.gov (United States)

    2016-01-01

    The phenomenon of radicalization is investigated within a mixed population composed of core and sensitive subpopulations. The latest includes first to third generation immigrants. Respective ways of life may be partially incompatible. In case of a conflict core agents behave as inflexible about the issue. In contrast, sensitive agents can decide either to live peacefully adjusting their way of life to the core one, or to oppose it with eventually joining violent activities. The interplay dynamics between peaceful and opponent sensitive agents is driven by pairwise interactions. These interactions occur both within the sensitive population and by mixing with core agents. The update process is monitored using a Lotka-Volterra-like Ordinary Differential Equation. Given an initial tiny minority of opponents that coexist with both inflexible and peaceful agents, we investigate implications on the emergence of radicalization. Opponents try to turn peaceful agents to opponents driving radicalization. However, inflexible core agents may step in to bring back opponents to a peaceful choice thus weakening the phenomenon. The required minimum individual core involvement to actually curb radicalization is calculated. It is found to be a function of both the majority or minority status of the sensitive subpopulation with respect to the core subpopulation and the degree of activeness of opponents. The results highlight the instrumental role core agents can have to hinder radicalization within the sensitive subpopulation. Some hints are outlined to favor novel public policies towards social integration. PMID:27166677

  10. Model for Measuring the Entrepreneurship of the Population

    Directory of Open Access Journals (Sweden)

    Šarūnė Beinoraitė

    2014-09-01

    Full Text Available Population entrepreneurship is an important factor in the progress of economic development. This paper proposes a model of entrepreneurship measurement for comparing the level of entrepreneurship. The model consists of two main components, including criteria for the selection and determination of entrepreneurship by adapting the multi­criteria evaluation method TOPSIS. The most important criteria for identifying entrepreneurship cover the dynamics of the unemployment rate, the population of personal characteristics, geographical location, broadband Internet penetration per 1000 inhabitants, issued business licenses per thousand population, competitiveness, innovation, registered enterprises per thousand population, the promotion of a entrepreneurship program, the average wage level, the number of loans taken for business per thousand population, the number of bankrupt enterprises per thousand population, the level of education, the subscription of newspapers and magazines on business.

  11. Mapping enteroendocrine cell populations in transgenic mice reveals an unexpected degree of complexity in cellular differentiation within the gastrointestinal tract

    OpenAIRE

    1990-01-01

    The gastrointestinal tract is lined with a monolayer of cells that undergo perpetual and rapid renewal. Four principal, terminally differentiated cell types populate the monolayer, enterocytes, goblet cells, Paneth cells, and enteroendocrine cells. This epithelium exhibits complex patterns of regional differentiation, both from crypt- to-villus and from duodenum-to-colon. The "liver" fatty acid binding protein (L-FABP) gene represents a useful model for analyzing the molecular basis for intes...

  12. Modelling hunting strategies for the conservation of wild rabbit populations

    OpenAIRE

    Angulo, Elena; Villafuerte, Rafael

    2003-01-01

    Recently, European wild rabbit (Oryctolagus cuniculus) populations have undergone a sharp decline that may be exacerbated by hunting. We investigate the effects of the timing of hunting on the conservation of wild rabbit using a model for rabbit population dynamics. Scenarios with different hunting rates and age strategies were simulated for different population qualities. We interviewed hunters to ascertain the degree to which they would accept a change in the timing of hunting. We also invest...

  13. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Kelly M. [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); Kirby, John A. [Institute of Cellular Medicine, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Lennard, Thomas W.J. [Faculty of Medical Sciences, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Meeson, Annette P., E-mail: annette.meeson@ncl.ac.uk [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); North East England Stem Cell Institute, Bioscience Centre, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom)

    2011-04-19

    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis.

  14. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    International Nuclear Information System (INIS)

    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis

  15. Modeling Stem Cell Induction Processes

    OpenAIRE

    Filipe Grácio; Joaquim Cabral; Bruce Tidor

    2012-01-01

    Technology for converting human cells to pluripotent stem cell using induction processes has the potential to revolutionize regenerative medicine. However, the production of these so called iPS cells is still quite inefficient and may be dominated by stochastic effects. In this work we build mass-action models of the core regulatory elements controlling stem cell induction and maintenance. The models include not only the network of transcription factors NANOG, OCT4, SOX2, but also important e...

  16. A two population model of prion transport through a tunnelling nanotube.

    Science.gov (United States)

    Kuznetsov, I A; Kuznetsov, A V

    2014-11-01

    This article develops a two prion population model that simulates prion trafficking between an infected dendritic cell and a neuron. The situation when the two cells are connected by a tunnelling nanotube (TNT) is simulated. Two mechanisms of prion transport are considered: lateral diffusion in the TNT membrane and active actin-dependent transport inside endocytic vesicles that are propelled by myosin Va molecular motors. Analytical solutions describing prion concentrations and fluxes are obtained. Numerical results are compared with those predicted by a single prion population model that relies on a single reaction-diffusion equation and accounts for the two modes of prion transport in an effective way. PMID:23477810

  17. Characterization of Side Cell Populations Obtained from Human Amnion Mesenchymal Cells

    Institute of Scientific and Technical Information of China (English)

    LI Ning; PIAO Zhengfu; Mamoru Kobayashi; Koji Sasaki; DING Shu-qin; Aiko Kikuchi; Isao Kamo; Norio Sakuragawa

    2009-01-01

    Human amnion mesenchymal cells (AMCs) contain multipotent cells. To enrich such multipotent stem cells, we applied to AMCs the new method for the isolation of side population (SP) cells used for the enrichment of multipotent stem cells from many tissues. We succeeded in obtaining SP cells from AMCs (AMC-SP cells). AMC-SP cells were found in 0.2% of AMCs, irrespective of the length of pregnant period, ranging from 37 to 40 weeks. Cell cycle analyses uggested that AMC-SP cells belonged to a cell population that proliferated very slowly and/or was in a quiescent state in the amniotic membrane. Upon culturing, they proliferated with 40 to 80 cell doublings. However, they did not form colonies in a soft agarose culture, whereas HepG2 cells, representative human hepatoma cells formed many large colonies. These results suggest that AMC-SP cells that have considerable value for the use of regenerative medicine can be managed safely in vitro.

  18. An age structured model for obesity prevalence dynamics in populations

    Directory of Open Access Journals (Sweden)

    Gilberto González Parra

    2010-08-01

    Full Text Available Objective. Modeling the correlation of the development of obesity in a population with age and time and predict the dynamics of the correlation of the development of obesity in a population with age and time under different scenarios in Valencia (Spain. Materials and methods. An age structured mathematical model is used to describe the future dynamics of obesity prevalence for different ages in human population with excess weight. Simulation of the model with parameters estimated using the Health Survey of the Region of Valencia 2000 (4.319 interviews and Health Survey of the Region of Valencia 2005 (4.012 interviews. The model considers only overweight and obese populations since these subpopulations are the most relevant on obesity health concern. Results. The model allows predicting and studying the prevalence of obesity for each age. Results showed an increasing trend of obesity in the following years in well accordance with the trend observed in several countries. Conclusions. Based on the numerical simulations it is possible to conclude that the age structured mathematical model is suitable to forecast the obesity epidemic in each age group in different countries. Additionally, this type of models may be applied to study other characteristics of other populations such animal populations.

  19. Statistical and Energetic Constraints in Population Synthesis Models

    OpenAIRE

    Buzzoni, Alberto

    1998-01-01

    Physical and numerical constraints in building up self-consistent population synthesis models are briefly analysed discussing their application to most of the current synthesis codes widely adopted in Galactic and extragalactic studies.

  20. PBPK and population modelling to interpret urine cadmium concentrations of the French population

    International Nuclear Information System (INIS)

    As cadmium accumulates mainly in kidney, urinary concentrations are considered as relevant data to assess the risk related to cadmium. The French Nutrition and Health Survey (ENNS) recorded the concentration of cadmium in the urine of the French population. However, as with all biomonitoring data, it needs to be linked to external exposure for it to be interpreted in term of sources of exposure and for risk management purposes. The objective of this work is thus to interpret the cadmium biomonitoring data of the French population in terms of dietary and cigarette smoke exposures. Dietary and smoking habits recorded in the ENNS study were combined with contamination levels in food and cigarettes to assess individual exposures. A PBPK model was used in a Bayesian population model to link this external exposure with the measured urinary concentrations. In this model, the level of the past exposure was corrected thanks to a scaling function which account for a trend in the French dietary exposure. It resulted in a modelling which was able to explain the current urinary concentrations measured in the French population through current and past exposure levels. Risk related to cadmium exposure in the general French population was then assessed from external and internal critical values corresponding to kidney effects. The model was also applied to predict the possible urinary concentrations of the French population in 2030 assuming there will be no more changes in the exposures levels. This scenario leads to significantly lower concentrations and consequently lower related risk. - Highlights: • Interpretation of urine cadmium concentrations in France • PBPK and Bayesian population modelling of cadmium exposure • Assessment of the historic time-trend of the cadmium exposure in France • Risk assessment from current and future external and internal exposure

  1. PBPK and population modelling to interpret urine cadmium concentrations of the French population

    Energy Technology Data Exchange (ETDEWEB)

    Béchaux, Camille, E-mail: Camille.bechaux@anses.fr [ANSES, French Agency for Food, Environmental and Occupational Health Safety, 27-31 Avenue du Général Leclerc, 94701 Maisons-Alfort (France); Bodin, Laurent [ANSES, French Agency for Food, Environmental and Occupational Health Safety, 27-31 Avenue du Général Leclerc, 94701 Maisons-Alfort (France); Clémençon, Stéphan [Telecom ParisTech, 46 rue Barrault, 75634 Paris Cedex 13 (France); Crépet, Amélie [ANSES, French Agency for Food, Environmental and Occupational Health Safety, 27-31 Avenue du Général Leclerc, 94701 Maisons-Alfort (France)

    2014-09-15

    As cadmium accumulates mainly in kidney, urinary concentrations are considered as relevant data to assess the risk related to cadmium. The French Nutrition and Health Survey (ENNS) recorded the concentration of cadmium in the urine of the French population. However, as with all biomonitoring data, it needs to be linked to external exposure for it to be interpreted in term of sources of exposure and for risk management purposes. The objective of this work is thus to interpret the cadmium biomonitoring data of the French population in terms of dietary and cigarette smoke exposures. Dietary and smoking habits recorded in the ENNS study were combined with contamination levels in food and cigarettes to assess individual exposures. A PBPK model was used in a Bayesian population model to link this external exposure with the measured urinary concentrations. In this model, the level of the past exposure was corrected thanks to a scaling function which account for a trend in the French dietary exposure. It resulted in a modelling which was able to explain the current urinary concentrations measured in the French population through current and past exposure levels. Risk related to cadmium exposure in the general French population was then assessed from external and internal critical values corresponding to kidney effects. The model was also applied to predict the possible urinary concentrations of the French population in 2030 assuming there will be no more changes in the exposures levels. This scenario leads to significantly lower concentrations and consequently lower related risk. - Highlights: • Interpretation of urine cadmium concentrations in France • PBPK and Bayesian population modelling of cadmium exposure • Assessment of the historic time-trend of the cadmium exposure in France • Risk assessment from current and future external and internal exposure.

  2. Defining priorities for dog population management through mathematical modeling.

    Science.gov (United States)

    Santos Baquero, O; Akamine, L A; Amaku, M; Ferreira, F

    2016-01-01

    We simulated dog population dynamics for a thirty-years period using a logistic growth model. Through sensitivity analyses, we determined the influence of the parameters used in the model. Carrying capacity was the most influential parameter in all simulations. In the owned-dog population, the influence of immigration, abandonment and births was 19%, 16% and 6% of the influence of the carrying capacity, respectively. In the sterilized owned-dog population, the influence of abandonment, female and male sterilization was 37%, 30% and 27% of the influence of the carrying capacity. In the stray population, the influence of abandonment, carrying capacity of the owned-dog population and adoption was 10%, 9% and 6% of the influence of the carrying capacity. In the sterilized stray population, the influence of births, female sterilization and male sterilization was 45%, 15% and 13% of the influence of the carrying capacity. Other parameters had lower influence values. Modification of the carrying capacity requires different interventions for the owned- and stray-dog populations. Dog trade control is a way to reduce immigration. The evaluation of sterilization effects must focus on the variations in the infertile population fraction. Adoption may improve the effects of the reduction in carrying capacity on the stray-dog population. PMID:26652574

  3. Population and Development Planning (PDP) Model: The 1998 Update

    OpenAIRE

    Orbeta, Aniceto Jr. C.; Belizario, Mildred; Lavina, Edith

    1999-01-01

    This paper presents an update of the Population and Development Planning (PDP) model. The PDP model is an economic-demographic model designed to capture the long-term interactions between economic and demographic variables. Also presented in the paper are results of diagnostic and policy simulation runs.

  4. Parameter Estimates in Differential Equation Models for Population Growth

    Science.gov (United States)

    Winkel, Brian J.

    2011-01-01

    We estimate the parameters present in several differential equation models of population growth, specifically logistic growth models and two-species competition models. We discuss student-evolved strategies and offer "Mathematica" code for a gradient search approach. We use historical (1930s) data from microbial studies of the Russian biologist,…

  5. Toxicity of chlorinated phenoxyacetic acid herbicides in the experimental eukaryotic model Saccharomyces cerevisiae: role of pH and of growth phase and size of the yeast cell population.

    Science.gov (United States)

    Cabral, M G; Viegas, C A; Teixeira, M C; Sá-Correia, I

    2003-04-01

    The inhibitory effect of the herbicides 2-methyl-4-chlorophenoxyacetic acid (MCPA) and 2,4-dichlorophenoxyacetic acid (2,4-D) in Saccharomyces cerevisiae growth is strongly dependent on medium pH (range 2.5-6.5). Consistent with the concept that the toxic form is the liposoluble undissociated form, at values close to their pK(a) (3.07 and 2.73, respectively) the toxicity is high, decreasing with the increase of external pH. In addition, the toxicity of identical concentrations of the undissociated acid form is pH independent, as observed with 2,4-dichlorophenol (2,4-DCP), an intermediate of 2,4-D degradation. Consequently, at pH values above 3.5 (approximately one unit higher than 2,4-D pK(a)), 2,4-DCP becomes more toxic than the original herbicide. A dose-dependent inhibition of growth kinetics and increased duration of growth latency is observed following sudden exposure of an unadapted yeast cell population to the presence of the herbicides. This contrasts with the effect of 2,4-DCP, which essentially affects growth kinetics. Experimental evidences suggest that the acid herbicides toxicity is not exclusively dependent on the liposolubility of the toxic form, as may essentially be the case of 2,4-DCP. An unadapted yeast cell population at the early stationary-phase of growth under nutrient limitation is significantly more resistant to short-term herbicide induced death than an exponential-phase population. Consequently, the duration of growth latency is reduced, as observed with the increase of the size of the herbicide stressed population. However, these physiological parameters have no significant effect either on growth kinetics, following growth resumption under herbicide stress, or on the growth curve of yeast cells previously adapted to the herbicides, indicating that their role is exerted at the level of cell adaptation. PMID:12586155

  6. Model stars for the modelling of galaxies: $\\alpha$-enhancement in stellar populations models

    CERN Document Server

    Coelho, P

    2008-01-01

    Stellar population (SP) models are an essential tool to understand the observations of galaxies and clusters. One of the main ingredients of a SP model is a library of stellar spectra, and both empirical and theoretical libraries can been used for this purpose. Here I will start by giving a short overview of the pros and cons of using theoretical libraries, i.e. model stars, to produce our galaxy models. Then I will address the question on how theoretical libraries can be used to model stellar populations, in particular to explore the effect of $\\alpha$-enhancement on spectral observables.

  7. Modelling the Dynamics of an Aedes albopictus Population

    CERN Document Server

    Basuki, Thomas Anung; Barbuti, Roberto; Maggiolo-Schettini, Andrea; Milazzo, Paolo; Rossi, Elisabetta; 10.4204/EPTCS.33.2

    2010-01-01

    We present a methodology for modelling population dynamics with formal means of computer science. This allows unambiguous description of systems and application of analysis tools such as simulators and model checkers. In particular, the dynamics of a population of Aedes albopictus (a species of mosquito) and its modelling with the Stochastic Calculus of Looping Sequences (Stochastic CLS) are considered. The use of Stochastic CLS to model population dynamics requires an extension which allows environmental events (such as changes in the temperature and rainfalls) to be taken into account. A simulator for the constructed model is developed via translation into the specification language Maude, and used to compare the dynamics obtained from the model with real data.

  8. Demographics of reintroduced populations: estimation, modeling, and decision analysis

    Science.gov (United States)

    Converse, Sarah J.; Moore, Clinton T.; Armstrong, Doug P.

    2013-01-01

    Reintroduction can be necessary for recovering populations of threatened species. However, the success of reintroduction efforts has been poorer than many biologists and managers would hope. To increase the benefits gained from reintroduction, management decision making should be couched within formal decision-analytic frameworks. Decision analysis is a structured process for informing decision making that recognizes that all decisions have a set of components—objectives, alternative management actions, predictive models, and optimization methods—that can be decomposed, analyzed, and recomposed to facilitate optimal, transparent decisions. Because the outcome of interest in reintroduction efforts is typically population viability or related metrics, models used in decision analysis efforts for reintroductions will need to include population models. In this special section of the Journal of Wildlife Management, we highlight examples of the construction and use of models for informing management decisions in reintroduced populations. In this introductory contribution, we review concepts in decision analysis, population modeling for analysis of decisions in reintroduction settings, and future directions. Increased use of formal decision analysis, including adaptive management, has great potential to inform reintroduction efforts. Adopting these practices will require close collaboration among managers, decision analysts, population modelers, and field biologists.

  9. The Statistical Modeling of the Trends Concerning the Romanian Population

    Directory of Open Access Journals (Sweden)

    Gabriela OPAIT

    2014-11-01

    Full Text Available This paper reflects the statistical modeling concerning the resident population in Romania, respectively the total of the romanian population, through by means of the „Least Squares Method”. Any country it develops by increasing of the population, respectively of the workforce, which is a factor of influence for the growth of the Gross Domestic Product (G.D.P.. The „Least Squares Method” represents a statistical technique for to determine the trend line of the best fit concerning a model.

  10. Small populations corrections for selection-mutation models

    CERN Document Server

    Jabin, Pierre-Emmanuel

    2012-01-01

    We consider integro-differential models describing the evolution of a population structured by a quantitative trait. Individuals interact competitively, creating a strong selection pressure on the population. On the other hand, mutations are assumed to be small. Following the formalism of Diekmann, Jabin, Mischler, and Perthame, this creates concentration phenomena, typically consisting in a sum of Dirac masses slowly evolving in time. We propose a modification to those classical models that takes the effect of small populations into accounts and corrects some abnormal behaviours.

  11. GLOBAL ATTRACTIVITY OF POPULATION MODELS WITH DELAYS AND DIFFUSION

    Institute of Scientific and Technical Information of China (English)

    QIU Zhipeng

    2005-01-01

    In this paper, the asymptotic behavior of three types of population models with delays and diffusion is studied. The first represents one species growth in the patchΩand periodic environment and with delays recruitment, the second models a single species dispersal among the m patches of a heterogeneous environment, and the third models the spread of bacterial infections. Sufficient conditions for the global attractivity of periodic solution are obtained by the method of monotone theory and strongly concave operators.Some earlier results are extended to population models with delays and diffusion.

  12. Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population

    Science.gov (United States)

    Giachino, Claudio; Basak, Onur; Lugert, Sebastian; Knuckles, Philip; Obernier, Kirsten; Fiorelli, Roberto; Frank, Stephan; Raineteau, Olivier; Alvarez–Buylla, Arturo; Taylor, Verdon

    2014-01-01

    Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V-SVZ) of rodents produce neurons throughout life while those in humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal and the generation of neurons. Using genetic markers and lineage tracing, we identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a striking heterogeneity including activated, brain lipid binding protein (BLBP, FABP7) expressing stem cells. BLBP+ NSCs are mitotically active components of pinwheel structures in the lateral ventricle walls and persistently generate neurons in adulthood. BLBP+ NSCs express epidermal growth factor (EGF) receptor, proliferate in response to EGF, and are a major clonogenic population in the SVZ. We also find BLBP expressed by proliferative ventricular and sub-ventricular progenitors in the fetal and postnatal human brain. Loss of BLBP+ stem/progenitor cells correlates with reduced neurogenesis in aging rodents and postnatal humans. These findings of molecular heterogeneity and proliferative differences subdivide the NSC population and have implications for neurogenesis in the forebrain of mammals during aging. PMID:23964022

  13. Merging Mixture Components for Cell Population Identification in Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Greg Finak

    2009-01-01

    Full Text Available We present a framework for the identification of cell subpopulations in flow cytometry data based on merging mixture components using the flowClust methodology. We show that the cluster merging algorithm under our framework improves model fit and provides a better estimate of the number of distinct cell subpopulations than either Gaussian mixture models or flowClust, especially for complicated flow cytometry data distributions. Our framework allows the automated selection of the number of distinct cell subpopulations and we are able to identify cases where the algorithm fails, thus making it suitable for application in a high throughput FCM analysis pipeline. Furthermore, we demonstrate a method for summarizing complex merged cell subpopulations in a simple manner that integrates with the existing flowClust framework and enables downstream data analysis. We demonstrate the performance of our framework on simulated and real FCM data. The software is available in the flowMerge package through the Bioconductor project.

  14. Efficient Analysis of Systems Biology Markup Language Models of Cellular Populations Using Arrays.

    Science.gov (United States)

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

    The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime. PMID:26912276

  15. Biological characteristics of side population cells in a self-established human ovarian cancer cell line

    Science.gov (United States)

    WEI, ZHENTONG; LV, SHUANG; WANG, YISHU; SUN, MEIYU; CHI, GUANGFAN; GUO, JUN; SONG, PEIYE; FU, XIAOYU; ZHANG, SONGLING; LI, YULIN

    2016-01-01

    The aim of the present study was to establish an ovarian cancer (OC) cell line from ascites of an ovarian serous cystadenocarcinoma patient and investigate the biological characteristics of its side population (SP) cells. The OC cell line was established by isolating, purifying and subculturing primary cells from ascites of an ovarian serous cystadenocarcinoma patient (stage IIIc; grade 3). SP and non-SP (NSP) cells were isolated by fluorescence-activated cell sorting and cultured in serum-free medium and soft agar to compare the tumorsphere and colony formation capacities. Furthermore, SP and NSP cell tumorigenesis was examined by subcutaneous and intraperitoneal injection of the cells to non-obese diabetic/severe combined immune deficiency (NOD/SCID) mice. Drug resistance to cisplatin was examined by cell counting kit-8. The OC cell line was successfully established from ascites of an ovarian serous cystadenocarcinoma patient, which exhibited properties similar to primary tumors subsequent to >50 passages and >2 years of culture. The SP cell ratio was 0.38% in the OC cell line, and a similar SP cell ratio (0.39%) was observed when sorted SP cells were cultured for 3 weeks. Compared with NSP cells, SP cells exhibited increased abilities in differentiation and tumorsphere and colony formation, in addition to the formation of xenografted tumors and ascites and metastasis of the tumors in NOD/SCID mice, even at low cell numbers (3.0×103 cells). The xenografted tumors demonstrated histological features similar to primary tumors and expressed the ovarian serous cystadenocarcinoma marker CA125. In addition, SP cells demonstrated a significantly stronger drug resistance to cisplatin compared with NSP and unsorted cells, while treatment with verapamil, an inhibitor of ATP-binding cassette transporters, potently abrogated SP cell drug resistance. In conclusion, the present study verified SP cells from an established OC cell line and characterized the cells with self

  16. Spike correlations in a songbird agree with a simple markov population model.

    Directory of Open Access Journals (Sweden)

    Andrea P Weber

    2007-12-01

    Full Text Available The relationships between neural activity at the single-cell and the population levels are of central importance for understanding neural codes. In many sensory systems, collective behaviors in large cell groups can be described by pairwise spike correlations. Here, we test whether in a highly specialized premotor system of songbirds, pairwise spike correlations themselves can be seen as a simple corollary of an underlying random process. We test hypotheses on connectivity and network dynamics in the motor pathway of zebra finches using a high-level population model that is independent of detailed single-neuron properties. We assume that neural population activity evolves along a finite set of states during singing, and that during sleep population activity randomly switches back and forth between song states and a single resting state. Individual spike trains are generated by associating with each of the population states a particular firing mode, such as bursting or tonic firing. With an overall modification of one or two simple control parameters, the Markov model is able to reproduce observed firing statistics and spike correlations in different neuron types and behavioral states. Our results suggest that song- and sleep-related firing patterns are identical on short time scales and result from random sampling of a unique underlying theme. The efficiency of our population model may apply also to other neural systems in which population hypotheses can be tested on recordings from small neuron groups.

  17. Ab initio phenomenological simulation of the growth of large tumor cell populations

    CERN Document Server

    Chignola, R; Milotti, E; Pellegrina, C D; Chignola, Roberto; Fabbro, Alessio Del; Milotti, Edoardo; Pellegrina, Chiara Dalla

    2007-01-01

    In a previous paper we have introduced a phenomenological model of cell metabolism and of the cell cycle to simulate the behavior of large tumor cell populations (Chignola R and Milotti E, Phys. Biol. 2 (2005) 8-22). Here we describe a refined and extended version of the model that includes some of the complex interactions between cells and their surrounding environment. The present version takes into consideration several additional energy-consuming biochemical pathways such as protein and DNA synthesis, the tuning of extracellular pH and of the cell membrane potential. The control of the cell cycle - that was previously modeled by means of ad hoc thresholds - has been directly addressed here by considering checkpoints from proteins that act as targets for phosphorylation on multiple sites. As simulated cells grow, they can now modify the chemical composition of the surrounding environment which in turn acts as a feedback mechanism to tune cell metabolism and hence cell proliferation: in this way we obtain g...

  18. Modeling: driving fuel cells

    Directory of Open Access Journals (Sweden)

    Michael Francis

    2002-05-01

    Fuel cells were invented in 1839 by Sir William Grove, a Welsh judge and gentleman scientist, as a result of his experiments on the electrolysis of water. To put it simply, fuel cells are electrochemical devices that take hydrogen gas from fuel, combine it with oxygen from the air, and generate electricity and heat, with water as the only by-product.

  19. Isolation of Side Population Cells and Detection of ABCG2 from SW480

    Institute of Scientific and Technical Information of China (English)

    LIU Hai-guang; PAN Yi-fei; GUO Gui-long; HU Xiao-qu; HUANG Ka-te; ZHANG Xiao-hua

    2007-01-01

    Objective: Side population cells (SP cells) are a new type of stem cells. They mainly express ABCG2/BCRP1 and have the ability to eliminate DNA dye Hoechst33342. Many studies showed that side population cells were able of self-renewal, differentiation and carcinogenesis in cancers. Our investigation aimed at isolation of side population cells and ABCG2 positive subpopulation from colon cancer cell line SW480 and identification of their characteristics of cancer stem cells. Methods: side population cells and non-side population cells of colon cancer cell line SW480 were isolated with DNA dye Hoechst33342 and their cell cycles were measured by flow cytometry. Expression of ABCG2 of SW480 was measured by immunohistochemistry and immunofluorescence, and its proportion was measured by flow cytometry. Results: SW480 contained 2.29% side population cells. The fraction of side population cells decreased greatly to 0.40% by treatment with verapamil. The fraction of side population cells in S-G2M cell cycle was 16.14%, which was much lower than the fraction (34.05%) of non-side population cells in S-G2M. In SW480, ABCG2 positive cells, which proportion was 9.66%, were small, circular or oval, lack of psuedopods, similar to poor differentiation. On the contrary, the ABCG2 negative cells were large, polygonal, with many psuedopods, similar to high differentiation. Conclusion: our assay identified that side population cells did exist in SW480 and had a quiescence characteristic of stem cells. ABCG2 positive subpopulation occupied about 9.66% of SW480 and may have the ability to promote cell self-renewal and inhibit cell differentiation. Therefore, to isolate ABCG2 positive subpopulation from side population cells may be an alternative to study colorectal cancer stem cells.

  20. Mixture models for studying stellar populations. I. Univariate mixture models, parameter estimation, and the number of discrete population components

    International Nuclear Information System (INIS)

    A unified approach to the analysis of stellar populations through the application of finite mixture models is presented, and the statistical properties of univariate finite mixture models are examined. A review is presented of the analysis methods that are available, with emphasis on methods for estimating the parameters that describe the underlying stellar populations and for determining the number of discrete stellar populations. Attention is restricted to five variables: U, V, W, Fe/H, and age. Parameter and error estimation is demonstrated in two simulation experiments designed to assess the detectability of a thick disk in samples of solar neighborhood stars. 159 refs

  1. Computational modeling of the spatiotemporal dynamics of cancer stem cells

    Science.gov (United States)

    Signoriello, Alexandra; Bosenberg, Marcus; Shattuck, Mark; O'Hern, Corey

    2015-03-01

    Cancer stem cells can differentiate into any cell type in a particular tumor, and thus can reform a tumor even when seeded from a single cell. Despite their importance, the identification of stem cells, their interactions, and how and why they malfunction to cause cancer and form tumors are not well understood. We have developed discrete element modeling (DEM) simulations to investigate the role of stem cells in the formation of heterogeneous cell populations in melanoma tumors. The DEM simulations include elastic, excluded volume, and signaling interactions between cells and rates for cell differentiation, apoptosis, and growth. The DEM is calibrated to results from experimental studies of melanoma tumor growth in mouse models. We use the simulations to generate virtual tumors and study their morphology and cell subtype populations as a function of time.

  2. Transition to quorum sensing in an Agrobacterium population: A stochastic model.

    Directory of Open Access Journals (Sweden)

    Andrew B Goryachev

    2005-09-01

    Full Text Available Understanding of the intracellular molecular machinery that is responsible for the complex collective behavior of multicellular populations is an exigent problem of modern biology. Quorum sensing, which allows bacteria to activate genetic programs cooperatively, provides an instructive and tractable example illuminating the causal relationships between the molecular organization of gene networks and the complex phenotypes they control. In this work we--to our knowledge for the first time--present a detailed model of the population-wide transition to quorum sensing using the example of Agrobacterium tumefaciens. We construct a model describing the Ti plasmid quorum-sensing gene network and demonstrate that it behaves as an "on-off" gene expression switch that is robust to molecular noise and that activates the plasmid conjugation program in response to the increase in autoinducer concentration. This intracellular model is then incorporated into an agent-based stochastic population model that also describes bacterial motion, cell division, and chemical communication. Simulating the transition to quorum sensing in a liquid medium and biofilm, we explain the experimentally observed gradual manifestation of the quorum-sensing phenotype by showing that the transition of individual model cells into the "on" state is spread stochastically over a broad range of autoinducer concentrations. At the same time, the population-averaged values of critical autoinducer concentration and the threshold population density are shown to be robust to variability between individual cells, predictable and specific to particular growth conditions. Our modeling approach connects intracellular and population scales of the quorum-sensing phenomenon and provides plausible answers to the long-standing questions regarding the ecological and evolutionary significance of the phenomenon. Thus, we demonstrate that the transition to quorum sensing requires a much higher threshold

  3. Transition to Quorum Sensing in an Agrobacterium Population: A Stochastic Model.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Understanding of the intracellular molecular machinery that is responsible for the complex collective behavior of multicellular populations is an exigent problem of modern biology. Quorum sensing, which allows bacteria to activate genetic programs cooperatively, provides an instructive and tractable example illuminating the causal relationships between the molecular organization of gene networks and the complex phenotypes they control. In this work we-to our knowledge for the first time-present a detailed model of the population-wide transition to quorum sensing using the example of Agrobacterium tumefaciens. We construct a model describing the Ti plasmid quorum-sensing gene network and demonstrate that it behaves as an "on-off" gene expression switch that is robust to molecular noise and that activates the plasmid conjugation program in response to the increase in autoinducer concentration. This intracellular model is then incorporated into an agent-based stochastic population model that also describes bacterial motion, cell division, and chemical communication. Simulating the transition to quorum sensing in a liquid medium and biofilm, we explain the experimentally observed gradual manifestation of the quorum-sensing phenotype by showing that the transition of individual model cells into the "on" state is spread stochastically over a broad range of autoinducer concentrations. At the same time, the population-averaged values of critical autoinducer concentration and the threshold population density are shown to be robust to variability between individual cells, predictable and specific to particular growth conditions. Our modeling approach connects intracellular and population scales of the quorum-sensing phenomenon and provides plausible answers to the long-standing questions regarding the ecological and evolutionary significance of the phenomenon. Thus, we demonstrate that the transition to quorum sensing requires a much higher threshold cell

  4. Side population cells isolated from KATO Ⅲ human gastric cancer cell line have cancer stem cell-like characteristics

    Institute of Scientific and Technical Information of China (English)

    Jun-Jun She; Peng-Ge Zhang; Xuan Wang; Xiang-Ming Che; Zi-Ming Wang

    2012-01-01

    AIM:To investigate whether the side population (SP)cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer.METHODS:We analyzed the presence of SP cells in different human gastric carcinoma cell lines,and then isolated and identified the SP cells from the KATO Ⅲ human gastric cancer cell line by flow cytometry.The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays.The related genes were determined by reverse transcription polymerase chain reaction.To compare tumorigenic ability,SP and non-side population (NSP) cells from the KATO Ⅲ human gastric cancer cell line were subcutaneously injected into nude mice.RESULTS:SP cells from the total population accounted for 0.57% in KATO Ⅲ,1.04% in Hs-746T,and 0.02% in AGS (CRL-1739).SP cells could grow clonally and have self-renewal capability in conditioned media.The expression of ABCG2,MDRI,Bmi-1 and Oct-4 was different between SP and NSP cells.However,there was no apparent difference between SP and NSP cells when they were injected into nude mice.CONCLUSION:SP cells have some cancer stem celllike characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.

  5. Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside" pattern of cell sorting

    Directory of Open Access Journals (Sweden)

    Ajioka Itsuki

    2007-09-01

    Full Text Available Abstract Background Development of multicellular organisms proceeds from a single fertilized egg as the combined effect of countless numbers of cellular interactions among highly dynamic cells. Since at least a reminiscent pattern of morphogenesis can be recapitulated in a reproducible manner in reaggregation cultures of dissociated embryonic cells, which is known as cell sorting, the cells themselves must possess some autonomous cell behaviors that assure specific and reproducible self-organization. Understanding of this self-organized dynamics of heterogeneous cell population seems to require some novel approaches so that the approaches bridge a gap between molecular events and morphogenesis in developmental and cell biology. A conceptual cell model in a computer may answer that purpose. We constructed a dynamical cell model based on autonomous cell behaviors, including cell shape, growth, division, adhesion, transformation, and motility as well as cell-cell signaling. The model gives some insights about what cellular behaviors make an appropriate global pattern of the cell population. Results We applied the model to "inside and outside" pattern of cell-sorting, in which two different embryonic cell types within a randomly mixed aggregate are sorted so that one cell type tends to gather in the central region of the aggregate and the other cell type surrounds the first cell type. Our model can modify the above cell behaviors by varying parameters related to them. We explored various parameter sets with which the "inside and outside" pattern could be achieved. The simulation results suggested that direction of cell movement responding to its neighborhood and the cell's mobility are important for this specific rearrangement. Conclusion We constructed an in silico cell model that mimics autonomous cell behaviors and applied it to cell sorting, which is a simple and appropriate phenomenon exhibiting self-organization of cell population. The model

  6. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia

    2011-01-01

    Objective: There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs) has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods: Side population(SP) cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting (FACS) was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results: Lung cancer cells could grow in a serum-free Medium(SFM) as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion: SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of

  7. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia

    2010-01-01

    Objective:There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs)has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods:Side population(SP)cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting(FACS)was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results:Lung cancer cells could grow in a serum-free Medium(SFM)as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion:SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of cancer stem

  8. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    Directory of Open Access Journals (Sweden)

    Martins-Neves Sara R

    2012-04-01

    Full Text Available Abstract Background Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. Methods CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. Results The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. Conclusions MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.

  9. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    International Nuclear Information System (INIS)

    Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma

  10. A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations

    CERN Document Server

    Chignola, R; Chignola, Roberto; Milotti, Edoardo

    2005-01-01

    A major goal of modern computational biology is to simulate the collective behaviour of large cell populations starting from the intricate web of molecular interactions occurring at the microscopic level. In this paper we describe a simplified model of cell metabolism, growth and proliferation, suitable for inclusion in a multicell simulator, now under development (Chignola R and Milotti E 2004 Physica A 338 261-6). Nutrients regulate the proliferation dynamics of tumor cells which adapt their behaviour to respond to changes in the biochemical composition of the environment. This modeling of nutrient metabolism and cell cycle at a mesoscopic scale level leads to a continuous flow of information between the two disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with modern computers and tested experimentally.

  11. Multistability in simplest models of the population dynamics

    Science.gov (United States)

    Zhdanova, Oksana L.; Frisman, Efim Ya.

    2016-06-01

    The investigation of dynamics behavior of population number and genetic structure has been conducted for a homogeneous limited population influenced by density-dependent selection in single di-allelic genetic locus. The detailed investigation of the mechanisms of the loss of stability in the considered model is carried out. It is shown that coexistence of several different asymptotic dynamic regimes (with own attraction basins) is possible in numerous enough parametric regions which are meaningful biologically.

  12. Techniques for modelling population-related raster databases

    OpenAIRE

    Martin, D.; I Bracken

    1991-01-01

    In this paper the refinement and application of a technique for the generation of surface models of population and related information are examined. With use of this technique the efficient generation of geographically extensive, high-resolution surfaces is described. The resulting database facilitates a range of improved spatial analyses. Some of these are more flexible means of accomplishing conventional tasks, such as the computation of incidence rates and the estimation of population for ...

  13. A polarised population of dynamic microtubules mediates homeostatic length control in animal cells.

    Directory of Open Access Journals (Sweden)

    Remigio Picone

    Full Text Available Because physical form and function are intimately linked, mechanisms that maintain cell shape and size within strict limits are likely to be important for a wide variety of biological processes. However, while intrinsic controls have been found to contribute to the relatively well-defined shape of bacteria and yeast cells, the extent to which individual cells from a multicellular animal control their plastic form remains unclear. Here, using micropatterned lines to limit cell extension to one dimension, we show that cells spread to a characteristic steady-state length that is independent of cell size, pattern width, and cortical actin. Instead, homeostatic length control on lines depends on a population of dynamic microtubules that lead during cell extension, and that are aligned along the long cell axis as the result of interactions of microtubule plus ends with the lateral cell cortex. Similarly, during the development of the zebrafish neural tube, elongated neuroepithelial cells maintain a relatively well-defined length that is independent of cell size but dependent upon oriented microtubules. A simple, quantitative model of cellular extension driven by microtubules recapitulates cell elongation on lines, the steady-state distribution of microtubules, and cell length homeostasis, and predicts the effects of microtubule inhibitors on cell length. Together this experimental and theoretical analysis suggests that microtubule dynamics impose unexpected limits on cell geometry that enable cells to regulate their length. Since cells are the building blocks and architects of tissue morphogenesis, such intrinsically defined limits may be important for development and homeostasis in multicellular organisms.

  14. Single-cell protein dynamics reproduce universal fluctuations in cell populations

    CERN Document Server

    Brenner, Naama; Rotella, James S; Salman, Hanna

    2015-01-01

    Protein fluctuations in cell populations have recently been shown to exhibit a universal distribution shape under a broad range of biological realizations. Here, measuring protein content in individual bacteria continuously over ~70 generations, we show that single-cell trajectories fluctuate around their average with the same distribution shape as the population, i.e. their relative fluctuations are ergodic. Analysis of these temporal trajectories reveals that one effective random variable, sampled once each cell cycle, suffices to reconstruct the distribution from the trajectory. This in turn implies that cellular microscopic processes are strongly buffered and population-level protein distributions are insensitive to details of the intracellular dynamics. Probing them thus requires searching for novel universality-breaking experimental perturbations.

  15. Cell competition modifies adult stem cell and tissue population dynamics in a JAKSTAT dependent manner

    OpenAIRE

    Kolahgar, Golnar; Suijkerbuijk, Saskia J. E.; Kucinski, Iwo; Poirier, Enzo Z.; Mansour, Sarah; Simons, Benjamin D.; Piddini, Eugenia

    2015-01-01

    Summary Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem...

  16. A simple add-on microfluidic appliance for accurately sorting small populations of cells with high fidelity

    International Nuclear Information System (INIS)

    Current advances in single cell sequencing, gene expression and proteomics require the isolation of single cells, frequently from a very small source population. In this work we describe the design and characterization of a manually operated microfluidic cell sorter that (1) can accurately sort single or small groups of cells from very small cell populations with minimal losses, (2) that is easy to operate and that can be used in any laboratory that has a basic fluorescent microscope and syringe pump, (3) that can be assembled within minutes, (4) that can sort cells in very short time (minutes) with minimum cell stress, (5) that is cheap and reusable. This microfluidic sorter is made from hard plastic material (PMMA) into which microchannels are directly milled with hydraulic diameter of 70 µm. Inlet and outlet reservoirs are drilled through the chip. Sorting occurs through hydrodynamic switching ensuring low hydrodynamic shear stresses, which were modeled and experimentally confirmed to be below the cell damage threshold. Manually operated, the maximum sorting frequencies were approximately 10 cells min−1. Experiments verified that cell sorting operations could be achieved in as little as 15 min, including the assembly and testing of the sorter. In only one out of ten sorting experiments the sorted cells were contaminated with another cell type. This microfluidic cell sorter represents an important capability for protocols requiring fast isolation of single cells from small number of rare cell populations. (technical note)

  17. A hybrid model of molecular regulation and population dynamics for yeast autophagy.

    Science.gov (United States)

    Jin, Huiqin; Lei, Jinzhi

    2016-08-01

    Autophagy is an evolutionarily conserved lysosome-based degradation process that is involved in maintaining cellular homeostasis and stress responses. Dysregulation of autophagy is known to associate with many diseases. In this paper, we establish a Hybrid model of Molecular regulation and Population dynamics (HMP model) for yeast autophagy to study how autophagy regulation at molecular level affects the cell population dynamics under the stress of starvation. The model includes interactions between amino acids, TORC1, Atg1 complex, and Atg8 lipidation at the molecular level, and cell death and division at the cell behavior level. Two feedback loops are involved in autophagy induction, in which the negative feedback of TORC1 activation has been known previously, and the positive feedback between TORC1 and Atg1 complex formation is introduced according to the similarity of Drosophila and mammalian cells. We demonstrate that the two feedback loops play distinct roles in autophagy regulation. The positive feedback is pro-survival, whereas the negative feedback has little effect on the survival of population during starvation. In addition, autophagy deficient cells can be rescued from starvation by amino acid exchanges from their neighboring wild type cells. PMID:27103581

  18. Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

    Institute of Scientific and Technical Information of China (English)

    Hai-hong ZHANG; Ai-zhen CAI; Xue-ming WEI; Li DING; Feng-zhi LI; Ai-ming ZHENG; Da-jiang DAI

    2013-01-01

    Objective:Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer.Many kinds of cell lines and tissues have demonstrated the presence of SP cells,including several gastric cancer cell lines.This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45.Methods:We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells.Results:This study found that the SP cells had higher clone formation efficiency than major population (MP) cells.Five stemness-related gene expression profiles,including OCT-4,SOX-2,NANOG,CD44,and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2,were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).Western blot was used to show the difference of protein expression between SP and MP cells.Both results show that there was significantly higher protein expression in SP cells than in MP cells.When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice,SP cells show higher tumorigenesis tendency than MP cells.Conclusions:These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

  19. CFD Simulation of Nanosufur Crystallization Incorporating Population Balance Modeling

    OpenAIRE

    Fatemeh Golkhou; Mahmod Tajee Hamed Mosavian

    2013-01-01

    A physical vapor condensation process for synthesizing nanosized sulfur powder as a precursor for various industries was simulated by the use of computational ?uid dynamic (CFD) modeling. The phase change, swirl flow and heat transfer taking place inside the cyclone are analyzed along with particle formation via gas condensation method. The population balance model is a mathematical framework for the modeling of crystal size distribution (CSD) and the study of gas-phase changes leading to nuc...

  20. Stochastic resonance in a generalized Von Foerster population growth model

    International Nuclear Information System (INIS)

    The stochastic dynamics of a population growth model, similar to the Von Foerster model for human population, is studied. The influence of fluctuating environment on the carrying capacity is modeled as a multiplicative dichotomous noise. It is established that an interplay between nonlinearity and environmental fluctuations can cause single unidirectional discontinuous transitions of the mean population size versus the noise amplitude, i.e., an increase of noise amplitude can induce a jump from a state with a moderate number of individuals to that with a very large number, while by decreasing the noise amplitude an opposite transition cannot be effected. An analytical expression of the mean escape time for such transitions is found. Particularly, it is shown that the mean transition time exhibits a strong minimum at intermediate values of noise correlation time, i.e., the phenomenon of stochastic resonance occurs. Applications of the results in ecology are also discussed

  1. Multiple bifurcations and periodic 'bubbling' in a delay population model

    International Nuclear Information System (INIS)

    In this paper, the flip bifurcation and periodic doubling bifurcations of a discrete population model without delay influence is firstly studied and the phenomenon of Feigenbaum's cascade of periodic doublings is also observed. Secondly, we explored the Neimark-Sacker bifurcation in the delay population model (two-dimension discrete dynamical systems) and the unique stable closed invariant curve which bifurcates from the nontrivial fixed point. Finally, a computer-assisted study for the delay population model is also delved into. Our computer simulation shows that the introduction of delay effect in a nonlinear difference equation derived from the logistic map leads to much richer dynamic behavior, such as stable node → stable focus → an lower-dimensional closed invariant curve (quasi-periodic solution, limit cycle) or/and stable periodic solutions → chaotic attractor by cascading bubbles (the combination of potential period doubling and reverse period-doubling) and the sudden change between two different attractors, etc

  2. Modelling population dynamics model formulation, fitting and assessment using state-space methods

    CERN Document Server

    Newman, K B; Morgan, B J T; King, R; Borchers, D L; Cole, D J; Besbeas, P; Gimenez, O; Thomas, L

    2014-01-01

    This book gives a unifying framework for estimating the abundance of open populations: populations subject to births, deaths and movement, given imperfect measurements or samples of the populations.  The focus is primarily on populations of vertebrates for which dynamics are typically modelled within the framework of an annual cycle, and for which stochastic variability in the demographic processes is usually modest. Discrete-time models are developed in which animals can be assigned to discrete states such as age class, gender, maturity,  population (within a metapopulation), or species (for multi-species models). The book goes well beyond estimation of abundance, allowing inference on underlying population processes such as birth or recruitment, survival and movement. This requires the formulation and fitting of population dynamics models.  The resulting fitted models yield both estimates of abundance and estimates of parameters characterizing the underlying processes.  

  3. An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population

    OpenAIRE

    Benn, Peter; Curnow, Kirsten J.; Chapman, Steven; Michalopoulos, Steven N.; Hornberger, John; Rabinowitz, Matthew

    2015-01-01

    Objective Analyze the economic value of replacing conventional fetal aneuploidy screening approaches with non-invasive prenatal testing (NIPT) in the general pregnancy population. Methods Using decision-analysis modeling, we compared conventional screening to NIPT with cell-free DNA (cfDNA) analysis in the annual US pregnancy population. Sensitivity and specificity for fetal aneuploidies, trisomy 21, trisomy 18, trisomy 13, and monosomy X, were estimated using published data and modeling of b...

  4. Sickle cell disease in the Kurdish population of northern Iraq.

    Science.gov (United States)

    Al-Allawi, Nasir A S; Jalal, Sana D; Nerwey, Farida F; Al-Sayan, Galawezh O O; Al-Zebari, Sahima S M; Alshingaly, Awny A; Markous, Raji D; Jubrael, Jaladet M S; Hamamy, Hanan

    2012-01-01

    Epidemiological studies have revealed that sickle cell disease patients are clustered in two geographical areas in Iraq, one among the Arabs in the extreme south, another among the Kurdish population in the extreme north, where they constitute major health problems. However, no studies have focused on the genotypes responsible for sickle cell disease or the β-globin gene haplotypes associated with it. For the latter purpose, a total of 103 unrelated Kurdish sickle cell disease patients were evaluated by restriction fragment length polymorphism (RFLP) for the sickle cell mutation, followed by multiplex polymerase chain reaction (PCR) and reverse hybridization for β- and α-thalassemia (β- and α-thal) mutations, whenever indicated. Results showed that the most common genotype was sickle cell anemia (68.0%) followed by Hb S/β(0)-thal and Hb S/β(+)-thal at frequencies of 24.2 and 7.8%, respectively. Eight β-thal mutations were associated with the latter two genotypes including: IVS-II-1 (G>A), IVS-I-110 (G>A), codon 8 (-AA), codon 44 (-C), codon 22 (-7 bp), IVS-I-1 (G>A), codon 30 (G>C) and IVS-I-6 (T>C). In Hb SS patients, the -α(3.7) deletion was documented in 10.0% and was the only α-thal mutation detected. Furthermore, 5' β-globin gene cluster haplotyping of 128 β(S) chromosomes revealed that the most common haplotype seen in 69.5% was the Benin haplotype, followed by the Arab-Indian haplotype in 12.5%. These latter findings closely resemble reports from neighboring Turkey, Syria, Jordan, Lebanon and Mediterranean countries, suggesting a possible common origin, but are in contrast to findings from the Eastern Arabian Peninsula and Iran. PMID:22686351

  5. Stochastic models of cell motility

    DEFF Research Database (Denmark)

    Gradinaru, Cristian

    2012-01-01

    interdisciplinary field focusing on the study of biological processes at the nanoscale level, with a range of technological applications in medicine and biological research, has emerged. The work presented in this thesis is at the interface of cell biology, image processing, and stochastic modeling. The stochastic...... coefficient. By adding a persistence component to simple random motion I introduce the standard Ornstein-Uhlenbeck process. I build on this commonly used cell motility model to address the challenges of working with real-life data: positional (centroid coordinate measuring) error and time discretization (due...... generalizing the Orstein-Uhlenbeck process to study cell motility on anisotropic substrates. I apply the general model to analyze cell motility on a series of anisotropic substrates and discuss the implications of our observations. This work is potentially useful to cell biologists by addressing their need for...

  6. Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Ju, Yeun-Jin; Shin, Hyun-Jin; Park, Jeong-Eun; Juhn, Kyoung-Mi; Woo, Seon Rang; Kim, Hee-Young; Han, Young-Hoon; Hwang, Sang-Gu; Hong, Sung-Hee; Kang, Chang-Mo [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Yoo, Young-Do [Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Park, Won-Bong [Division of Natural Science, Seoul Women' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul (Korea, Republic of); Park, Gil Hong, E-mail: ghpark@korea.ac.kr [Department of Biochemistry, College of Medicine, Korea University, Seoul (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2010-11-12

    Research highlights: {yields} In our present manuscript, we have clearly showed an interesting but problematic obstacle of a radiosensitization strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this radiosensitization occasionally arise. {yields} The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. {yields} The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. {yields} P53 status is not associated with the occurrence of unsensitized clone. {yields} Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC{sup -/-} cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC{sup -/-} clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.

  7. Immunophenotyping of immune cell populations in the raccoon (Procyon lotor).

    Science.gov (United States)

    Heinrich, Franziska; Jungwirth, Nicole; Carlson, Regina; Tipold, Andrea; Böer, Michael; Scheibe, Thomas; Molnár, Viktor; von Dörnberg, Katja; Spitzbarth, Ingo; Puff, Christina; Wohlsein, Peter; Baumgärtner, Wolfgang

    2015-12-15

    The raccoon (Procyon lotor) is a highly adaptable carnivore that has rapidly conquered Europe over the last decades and represents a potential candidate as pathogen reservoir, bearing the risk for transmission of infectious agents, as zoonosis or spill-over, to other wild life and domestic animals and man. Comprehensive investigations of infectious diseases in raccoons require a detailed knowledge of the participating immune cell populations. To close this gap of knowledge, various antibodies were tested for cross-reactivity with leukocytes in lymphoid organs and peripheral blood of raccoons using immunohistochemistry and flow cytometry, respectively. Eight out of 16 antibodies, directed against CD3, CD79α, Pax-5, IgG, CD44, MHC class II, myeloid/histiocyte antigen (MAC387), and Iba-1 exhibited a specific immunoreaction with cells in distinct anatomical compartments in formalin-fixed paraffin-embedded lymphoid tissues. Flow cytometric analysis revealed that 7 out of 18 antibodies directed against CD11c, CD14, CD21, CD44, CD79α, MHC class I and II cross-reacted with peripheral blood-derived raccoon leukocytes. Summarized, the usefulness of several cross-reacting antibodies was determined for the characterization of raccoon immune cells in immunohistochemistry and flow cytometry, offering the opportunity to study the raccoon immune system under normal and diseased conditions. PMID:26672912

  8. Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition

    International Nuclear Information System (INIS)

    Research highlights: → In our present manuscript, we have clearly showed an interesting but problematic obstacle of a radiosensitization strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this radiosensitization occasionally arise. → The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. → The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. → P53 status is not associated with the occurrence of unsensitized clone. → Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC-/- cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC-/- clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.

  9. Learning with Admixture: Modeling, Optimization, and Applications in Population Genetics

    DEFF Research Database (Denmark)

    Cheng, Jade Yu

    2016-01-01

    including population splits, effective population sizes, gene flow, etc. Since joining the CoalHMM development team in 2014, I have mainly contributed in two directions: 1) improving optimizations through heuristic-based evolutionary algorithms and 2) modeling of historical admixture events. Ohana, meaning...... data. Ohana's admixture module is based on classical structure modeling but uses new optimization subroutines through quadratic programming, which outperform the current state-of-the-art software in both speed and accuracy. Ohana presents a new method for phylogenetic tree inference using Gaussian...

  10. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    Institute of Scientific and Technical Information of China (English)

    Jian-Hua Yu; Jing-Tao Dong; Yong-Qian Jia; Neng-Gang Jiang; Ting-Ting Zeng; Hong Xu; Xian-Ming Mo

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease.We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development,including IL-7Rα (CD127),cytoplasmic CD79a (cCD79a),CD19,VpreB (CD179a),and slgM,which are successive and essential for progression of B cells along their developmental pathway.Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous,with the leukemic cell population differing from case to case.Through the comprehensive analysis of immunophenotypic patterns,the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis,therapeutic monitoring,and individualized therapies for common ALL.

  11. A mouse model of intestinal stem cell function and regeneration

    OpenAIRE

    Slorach, E M; Campbell, F. C.; Dorin, J. R.

    1999-01-01

    We present here an in vivo mouse model for intestinal stem cell function and differentiation that uses postnatal intestinal epithelial cell aggregates to generate a differentiated murine small intestinal mucosa with full crypt-villus architecture. The process of neomucosal formation is highly similar to that of intestinal regeneration. Both in vivo grafting and primary culture of these cells reveal two different epithelial cell populations, which display properties consistent with intestinal ...

  12. Measuring and modelling cell-to-cell variation in uptake of gold nanoparticles

    OpenAIRE

    Jeynes, JCG; Jeynes, C.; Merchant, MJ; Kirkby, KJ

    2013-01-01

    The cell-to-cell variation of gold nanoparticle (GNP) uptake is important for therapeutic applications. We directly counted the GNPs in hundreds of individual cells, and showed that the large variation from cell-to-cell could be directly modelled by assuming log-normal distributions of both cell mass and GNP rate of uptake. This was true for GNPs non-specifically bound to fetal bovine serum or conjugated to a cell penetrating peptide. Within a population of cells, GNP content varied naturally...

  13. Tumor-initiating cells are enriched in CD44(hi population in murine salivary gland tumor.

    Directory of Open Access Journals (Sweden)

    Shukun Shen

    Full Text Available Tumor-initiating cells (T-ICs discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1 transgenic mouse model of a salivary gland tumor, we identified CD44(high (CD44(hi tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44(hi tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU, at a lower rate than their CD44(negative (CD44(neg counterparts, and also retained BrdU for a long period of time. Cell surface maker analysis revealed that 25% of the CD44(hi tumor cells co-express other cancer stem cell markers such as CD133 and CD117. As few as 500 CD44(hi tumor cells were sufficient to initiate pleomorphic adenomas in one third of the wildtype mice, whereas more than 1×10(4 CD44(neg cells were needed for the same purpose. In NIH 3T3 cells, Plag1 was capable of activating the gene transcription of Egr1, a known upregulator for CD44. Furthermore, deletion of sequence 81-96 in the Egr1 promoter region abolished the effect of Plag1 on Egr1 upregulation. Our results establish the existence of T-ICs in murine salivary gland tumors, and suggest a potential molecular mechanism for CD44 upregulation.

  14. Robust detection of alternative splicing in a population of single cells.

    Science.gov (United States)

    Welch, Joshua D; Hu, Yin; Prins, Jan F

    2016-05-01

    Single cell RNA-seq experiments provide valuable insight into cellular heterogeneity but suffer from low coverage, 3' bias and technical noise. These unique properties of single cell RNA-seq data make study of alternative splicing difficult, and thus most single cell studies have restricted analysis of transcriptome variation to the gene level. To address these limitations, we developed SingleSplice, which uses a statistical model to detect genes whose isoform usage shows biological variation significantly exceeding technical noise in a population of single cells. Importantly, SingleSplice is tailored to the unique demands of single cell analysis, detecting isoform usage differences without attempting to infer expression levels for full-length transcripts. Using data from spike-in transcripts, we found that our approach detects variation in isoform usage among single cells with high sensitivity and specificity. We also applied SingleSplice to data from mouse embryonic stem cells and discovered a set of genes that show significant biological variation in isoform usage across the set of cells. A subset of these isoform differences are linked to cell cycle stage, suggesting a novel connection between alternative splicing and the cell cycle. PMID:26740580

  15. Modeling population access to New Zealand public hospitals

    Directory of Open Access Journals (Sweden)

    Skelly Chris

    2002-11-01

    Full Text Available Abstract This paper demonstrates a method for estimating the geographical accessibility of public hospitals. Cost path analysis was used to determine the minimum travel time and distance to the closest hospital via a road network. This analysis was applied to 38,000 census enumeration district centroids in New Zealand allowing geographical access to be linked to local populations. Average time and distance statistics have been calculated for local populations by modeling the total travel of a population if everybody visited a hospital once. These types of statistics can be generated for different population groups and enable comparisons to be made between regions. This study has shown that the northern and southern parts of New Zealand have high average travel times to hospital services.

  16. The MIUSCAT stellar population models: constraints from optical photometry

    Science.gov (United States)

    Ricciardelli, E.; Vazdekis, A.; Cenarro, A. J.; Falcón-Barroso, J.

    2013-05-01

    We present the spectral extension of our stellar population synthesis models based on the MILES and CaT empirical stellar spectral libraries. For this purpose we combine these two libraries with the Indo-US to construct composite stellar spectra to feed our models. The spectral energy distributions (SEDs) computed with these models and the originally published models are combined to construct composite SEDs for single-age, single-metallicity stellar populations (SSPs) covering the range λλ3465 -- 9469 Å at resolution FWHM =2.51 Å. We also show a comprehensive comparison of the MIUSCAT models with photometric data of globular clusters and early-type galaxies. The models compare remarkably well with the integrated colours of Milky Way globular clusters in the optical range. On the other hand we find that the colour relations of nearby early-type galaxies are still a challenge for present-day stellar population synthesis models. We investigate a number of possible explanations and establish the importance of α-enhanced models to bring down the discrepancy with observations.

  17. Mathematical Model for Photovoltaic Cells

    OpenAIRE

    Wafaa ABD EL-BASIT; Ashraf Mosleh ABD El–MAKSOOD; Fouad Abd El-Moniem Saad SOLIMAN

    2013-01-01

    The study of photovoltaic systems in an efficient manner requires a precise knowledge of the (I-V) and (P-V) characteristic curves of photovoltaic modules. So, the aim of the present paper is to estimate such characteristics based on different operating conditions. In this concern, a simple one diode mathematical model was implemented using MATLAB script. The output characteristics of PV cell depend on the environmental conditions. For any solar cell, the model parameters are function of the ...

  18. Birth-death branching models. Application to African elephant populations.

    Science.gov (United States)

    Corbacho, Casimiro; Molina, Manuel; Mota, Manuel; Ramos, Alfonso

    2013-09-01

    Branching models have a long history of biological applications, particularly in population dynamics. In this work, our interest is the development of mathematical models to describe the demographic dynamics of socially structured animal populations, focusing our attention on lineages, usually matrilines, as the basic structure in the population. Significant efforts have been made to develop models based on the assumption that all individuals behave identically with respect to reproduction. However, the reproduction phase has a large random component that involves not only demographic but also environmental factors that change across range distribution of species. In the present work, we introduce new classes of birth-death branching models which take such factors into account. We assume that both, the offspring probability distribution and the death probabilities may be different in each generation, changing either predictably or unpredictably in relation to habitat features. We consider the genealogical tree generated by observation of the process until a pre-set generation. We determine the probability distributions of the random variables representing the number of dead or living individuals having at least one ancestor alive, living individuals whose ancestors are all dead, and dead individuals whose ancestors are all dead, explicitly obtaining their principal moments. Also, we derive the probability distributions corresponding to the partial and total numbers of such biological variables, obtaining in particular the distribution of the total number of matriarchs in the genealogical tree. We apply the proposed models to describe the demographic dynamics of African elephant populations living in different habitats. PMID:23648183

  19. Expression of genes encoding multi-transmembrane proteins in specific primate taste cell populations.

    Directory of Open Access Journals (Sweden)

    Bryan D Moyer

    expressed in primate taste buds provides new insights into the processes of taste cell development, signal transduction, and information coding. Discrete taste cell populations exhibit highly specific gene expression patterns, supporting a model whereby each mature taste receptor cell is responsible for sensing, transmitting, and coding a specific taste quality.

  20. Stochastic population and epidemic models persistence and extinction

    CERN Document Server

    Allen, Linda J S

    2015-01-01

    This monograph provides a summary of the basic theory of branching processes for single-type and multi-type processes. Classic examples of population and epidemic models illustrate the probability of population or epidemic extinction obtained from the theory of branching processes. The first chapter develops the branching process theory, while in the second chapter two applications to population and epidemic processes of single-type branching process theory are explored. The last two chapters present multi-type branching process applications to epidemic models, and then continuous-time and continuous-state branching processes with applications. In addition, several MATLAB programs for simulating stochastic sample paths  are provided in an Appendix. These notes originated as part of a lecture series on Stochastics in Biological Systems at the Mathematical Biosciences Institute in Ohio, USA. Professor Linda Allen is a Paul Whitfield Horn Professor of Mathematics in the Department of Mathematics and Statistics ...

  1. The high redshift galaxy population in hierarchical galaxy formation models

    CERN Document Server

    Kitzbichler, M G; Kitzbichler, Manfred G.; White, Simon D. M.

    2006-01-01

    We compare observations of the high redshift galaxy population to the predictions of the galaxy formation model of Croton et al. (2006). This model, implemented on the Millennium Simulation of the concordance LCDM cosmogony, introduces "radio mode" feedback from the central galaxies of groups and clusters in order to obtain quantitative agreement with the luminosity, colour, morphology and clustering properties of the low redshift galaxy population. Here we compare the predictions of this same model to the observed counts and redshift distributions of faint galaxies, as well as to their inferred luminosity and mass functions out to redshift 5. With the exception of the mass functions, all these properties are sensitive to modelling of dust obscuration. A simple but plausible treatment gives moderately good agreement with most of the data, although the predicted abundance of relatively massive (~M*) galaxies appears systematically high at high redshift, suggesting that such galaxies assemble earlier in this mo...

  2. Accounting for randomness in measurement and sampling in studying cancer cell population dynamics.

    Science.gov (United States)

    Ghavami, Siavash; Wolkenhauer, Olaf; Lahouti, Farshad; Ullah, Mukhtar; Linnebacher, Michael

    2014-10-01

    Knowing the expected temporal evolution of the proportion of different cell types in sample tissues gives an indication about the progression of the disease and its possible response to drugs. Such systems have been modelled using Markov processes. We here consider an experimentally realistic scenario in which transition probabilities are estimated from noisy cell population size measurements. Using aggregated data of FACS measurements, we develop MMSE and ML estimators and formulate two problems to find the minimum number of required samples and measurements to guarantee the accuracy of predicted population sizes. Our numerical results show that the convergence mechanism of transition probabilities and steady states differ widely from the real values if one uses the standard deterministic approach for noisy measurements. This provides support for our argument that for the analysis of FACS data one should consider the observed state as a random variable. The second problem we address is about the consequences of estimating the probability of a cell being in a particular state from measurements of small population of cells. We show how the uncertainty arising from small sample sizes can be captured by a distribution for the state probability. PMID:25257023

  3. Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance.

    Science.gov (United States)

    Naito, Hisamichi; Wakabayashi, Taku; Kidoya, Hiroyasu; Muramatsu, Fumitaka; Takara, Kazuhiro; Eino, Daisuke; Yamane, Keitaro; Iba, Tomohiro; Takakura, Nobuyuki

    2016-06-01

    Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor-like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor-like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200-10. ©2016 AACR. PMID:27197162

  4. Limitations of a TCP model incorporating population heterogeneity

    International Nuclear Information System (INIS)

    The variation between individuals in their dose-response characteristics complicates attempts to extract estimates of radiobiological parameters (e.g. α, β, etc) from fits to clinical dose-response data. The use of 'population' dose-response models that explicitly account for this variability is necessary to avoid obtaining skewed parameter estimates. In this work, we evaluated an example of a 'population' tumour control probability (TCP) model in terms of its ability to provide reliable parameter estimates. This was accomplished by performing fits of this population model to 'pseudo' data sets, which were generated with Monte Carlo techniques and based on preset values for the various radiobiological parameters. The fitting exercises illustrated considerable correlations between the model parameters. Especially significant was the large correlation observed between the parameter μ = α/σα used to characterize the level of population heterogeneity in radiosensitivity and the α/β parameter typically used to describe the response to fractionation. The results imply that fits to clinical data may not be able to distinguish between tumours exhibiting a high degree of heterogeneity and a strong β-mechanism and those containing little heterogeneity and having a weak β-mechanism. One implication is that basing the design of optimal fractionation regimes on such fitting results may be error-prone. If in vitro assays are to be used to independently determine biologically reasonable ranges for parameter values, an accurate knowledge of the relationship between in vitro and in vivo dose-response characteristics is required

  5. CELLULAR AND POPULATION PLASTICITY OF HELPER CD4 T CELL RESPONSES

    Directory of Open Access Journals (Sweden)

    Gesham eMagombedze

    2013-08-01

    Full Text Available Vertebrates are constantly exposed to pathogens, and the adaptive immunity has most likely evolved to control and clear such infectious agents. CD4 T cells are the major players in the adaptive immune response to pathogens. Following recognition of pathogen-derived antigens naïve CD4 T cells differentiate into effectors which then control pathogen replication either directly by killing pathogen-infected cells or by assisting with generation of cytotoxic T lymphocytes or pathogen-specific antibodies. Pathogen-specific effector CD4 T cells are highly heterogeneous in terms of cytokines they produce. Three major subtypes of effector CD4 T cells have been identified: T-helper 1 (Th1 cells producing IFN-g and TNF-α, Th2 cells producing IL-4 and IL-10, and Th17 cells producing IL-17. How this heterogeneity is maintained and what regulates changes in effector T cell composition during chronic infections remains poorly understood. In this review we discuss recent advances in our understanding of CD4 T cell differentiation in response to microbial infections. We propose that a change in the phenotype of pathogen-specific effector CD4 T cells during chronic infections, for example, from Th1 to Th2 response as observed in Mycobacteriumavium ssp. paratuberculosis (MAP infection of ruminants, can be achieved by conversion of T cells from one effector subset to another (cellular plasticity or due to differences in kinetics (differentiation, proliferation, death of different effector T cell subsets (population plasticity. We also shortly review mathematical models aimed at describing CD4 T cell differentiation and outline areas for future experimental and theoretical research.

  6. Predicting population dynamics with analytical, simulation and supercomputer models

    Energy Technology Data Exchange (ETDEWEB)

    Onstad, D.W.

    1987-07-01

    A set of epizootiological models describing the influence of a microsporidian disease on the population dynamics of an herbivorous insect demonstrate the similarities and differences between the three major approaches now available for ecological modeling. Simulation modeling allows the incorporation of randomness or the timing of discrete events in the temporal dynamics. More complex models incorporating both temporal and spatial dynamics in variable and heterogeneous environments require the use of supercomputers. Under a number of realistic circumstances, the qualitative predictions of the approaches may differ.

  7. Prediction Model for Gastric Cancer Incidence in Korean Population

    OpenAIRE

    Eom, Bang Wool; Joo, Jungnam; Kim, Sohee; Shin, Aesun; Yang, Hye-Ryung; Park, Junghyun; Choi, Il Ju; Kim, Young-Woo; Kim, Jeongseon; Nam, Byung-Ho

    2015-01-01

    Background Predicting high risk groups for gastric cancer and motivating these groups to receive regular checkups is required for the early detection of gastric cancer. The aim of this study is was to develop a prediction model for gastric cancer incidence based on a large population-based cohort in Korea. Method Based on the National Health Insurance Corporation data, we analyzed 10 major risk factors for gastric cancer. The Cox proportional hazards model was used to develop gender specific ...

  8. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    Science.gov (United States)

    Stampfer, Martha R; Garbe, James C

    2015-02-24

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  9. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Garbe, James C.

    2016-06-28

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  10. Two-Step Regulation of a Meristematic Cell Population Acting in Shoot Branching in Arabidopsis.

    Science.gov (United States)

    Shi, Bihai; Zhang, Cui; Tian, Caihuan; Wang, Jin; Wang, Quan; Xu, Tengfei; Xu, Yan; Ohno, Carolyn; Sablowski, Robert; Heisler, Marcus G; Theres, Klaus; Wang, Ying; Jiao, Yuling

    2016-07-01

    Shoot branching requires the establishment of new meristems harboring stem cells; this phenomenon raises questions about the precise regulation of meristematic fate. In seed plants, these new meristems initiate in leaf axils to enable lateral shoot branching. Using live-cell imaging of leaf axil cells, we show that the initiation of axillary meristems requires a meristematic cell population continuously expressing the meristem marker SHOOT MERISTEMLESS (STM). The maintenance of STM expression depends on the leaf axil auxin minimum. Ectopic expression of STM is insufficient to activate axillary buds formation from plants that have lost leaf axil STM expressing cells. This suggests that some cells undergo irreversible commitment to a developmental fate. In more mature leaves, REVOLUTA (REV) directly up-regulates STM expression in leaf axil meristematic cells, but not in differentiated cells, to establish axillary meristems. Cell type-specific binding of REV to the STM region correlates with epigenetic modifications. Our data favor a threshold model for axillary meristem initiation, in which low levels of STM maintain meristematic competence and high levels of STM lead to meristem initiation. PMID:27398935

  11. Model cell membranes

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Nylander, Tommy; Cardenas Gomez, Marite

    2014-01-01

    The high complexity of biological membranes has motivated the development and application of a wide range of model membrane systems to study biochemical and biophysical aspects of membranes in situ under well defined conditions. The aim is to provide fundamental understanding of processes control...

  12. CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Al-Shammary, Asma; Skagen, Peter;

    2015-01-01

    Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and...... prospective isolation of mouse bone marrow osteoprogenitors....... prospective isolation of BMSCs and committed progenitors are lacking. Here, we compared the transcriptome profile of CD markers expressed at baseline and during the course of osteoblast and adipocyte differentiation of two well-characterized osteogenic-committed murine BMSCs (mBMSC(Bone)) and adipogenic...

  13. Physical models of cell motility

    CERN Document Server

    2016-01-01

    This book surveys the most recent advances in physics-inspired cell movement models. This synergetic, cross-disciplinary effort to increase the fidelity of computational algorithms will lead to a better understanding of the complex biomechanics of cell movement, and stimulate progress in research on related active matter systems, from suspensions of bacteria and synthetic swimmers to cell tissues and cytoskeleton.Cell motility and collective motion are among the most important themes in biology and statistical physics of out-of-equilibrium systems, and crucial for morphogenesis, wound healing, and immune response in eukaryotic organisms. It is also relevant for the development of effective treatment strategies for diseases such as cancer, and for the design of bioactive surfaces for cell sorting and manipulation. Substrate-based cell motility is, however, a very complex process as regulatory pathways and physical force generation mechanisms are intertwined. To understand the interplay between adhesion, force ...

  14. Can modeling improve estimation of desert tortoise population densities?

    Science.gov (United States)

    Nussear, K.E.; Tracy, C.R.

    2007-01-01

    The federally listed desert tortoise (Gopherus agassizii) is currently monitored using distance sampling to estimate population densities. Distance sampling, as with many other techniques for estimating population density, assumes that it is possible to quantify the proportion of animals available to be counted in any census. Because desert tortoises spend much of their life in burrows, and the proportion of tortoises in burrows at any time can be extremely variable, this assumption is difficult to meet. This proportion of animals available to be counted is used as a correction factor (g0) in distance sampling and has been estimated from daily censuses of small populations of tortoises (6-12 individuals). These censuses are costly and produce imprecise estimates of g0 due to small sample sizes. We used data on tortoise activity from a large (N = 150) experimental population to model activity as a function of the biophysical attributes of the environment, but these models did not improve the precision of estimates from the focal populations. Thus, to evaluate how much of the variance in tortoise activity is apparently not predictable, we assessed whether activity on any particular day can predict activity on subsequent days with essentially identical environmental conditions. Tortoise activity was only weakly correlated on consecutive days, indicating that behavior was not repeatable or consistent among days with similar physical environments. ?? 2007 by the Ecological Society of America.

  15. A mammary repopulating cell population characterized in mammary anlagen reveals essential mammary stroma for morphogenesis.

    Science.gov (United States)

    Song, Jiazhe; Xue, Kai; She, Ji; Ding, Fangrong; Li, Song; Shangguan, Rulan; Dai, Yunping; Du, Liying; Li, Ning

    2014-09-10

    The cells with mammary repopulating capability can achieve mammary gland morphogenesis in a suitable cellular microenvironment. Using cell surface markers of CD24, CD29 and CD49f, mouse mammary repopulating unit (MRU) has been identified in adult mammary epithelium and late embryonic mammary bud epithelium. However, embryonic MRU remains to be fully characterized at earlier mammary anlagen stage. Here we isolated discrete populations of E14.5 mouse mammary anlagen cells. Only Lin(-)CD24(med)CD29(+) cell population was predicted as E14.5 MRU by examining their capacities of forming mammosphere and repopulating cleared mammary fat pad in vivo. However, when we characterized gene expressions of this E14.5 cell population by comparing with adult mouse MRU (Lin(-)CD24(+)CD29(hi)), the gene profiling of these two cell populations exhibited great differences. Real-time PCR and immunostaining assays uncovered that E14.5 Lin(-)CD24(med)CD29(+) cell population was a heterogeneous stroma-enriched cell population. Then, limiting dilutions and single-cell assays also confirmed that E14.5 Lin(-)CD24(med)CD29(+) cell population possessed low proportion of stem cells. In summary, heterogeneous Lin(-)CD24(med)CD29(+) cell population exhibited mammary repopulating ability in E14.5 mammary anlagen, implying that only suitable mammary stroma could enable mammary gland morphogenesis, which relied on the interaction between rare stem cells and microenvironment. PMID:24954407

  16. IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells

    OpenAIRE

    Saenz, Steven A.; Siracusa, Mark C.; Monticelli, Laurel A.; Ziegler, Carly G. K.; Kim, Brian S.; Brestoff, Jonathan R.; Peterson, Lance W.; Wherry, E. John; Goldrath, Ananda W; Bhandoola, Avinash; Artis, David

    2013-01-01

    The predominantly epithelial cell–derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) can promote CD4+ Th2 cell–dependent immunity, inflammation, and tissue repair at barrier surfaces through the induction of multiple innate immune cell populations. IL-25 and IL-33 were previously shown to elicit four innate cell populations, named natural helper cells, nuocytes, innate type 2 helper cells, and multipotent progenitor type 2 (MPPtype2) cells, now collectively termed group 2...

  17. Modeling the impact of granular embedding media, and pulling versus pushing cells on growing cell clones

    International Nuclear Information System (INIS)

    In this paper, we explore how potential biomechanical influences on cell cycle entrance and cell migration affect the growth dynamics of cell populations. We consider cell populations growing in free, granular and tissue-like environments using a mathematical single-cell-based model. In a free environment we study the effect of pushing movements triggered by proliferation versus active pulling movements of cells stretching cell-cell contacts on the multi-cellular kinetics and the cell population morphotype. By growing cell clones embedded in agarose gel or cells of another type, one can mimic aspects of embedding tissues. We perform simulation studies of cell clones expanding in an environment of granular objects and of chemically inert cells. In certain parameter ranges, we find the formation of invasive fingers reminiscent of viscous fingering. Since the simulation studies are highly computation-time consuming, we mainly study one-cell-thick monolayers and show that for selected parameter settings the results also hold for multi-cellular spheroids. Finally, we compare our model to the experimentally observed growth dynamics of multi-cellular spheroids in agarose gel. (paper)

  18. Populism

    OpenAIRE

    Abts, Koenraad; van Kessel, Stijn

    2015-01-01

    Populism is a concept applied to a wide range of political movements and actors across the globe. There is, at the same time, considerable confusion about the attributes and manifestation of populism, as well as its impact on democracy. This contribution identifies the defining elements of the populist ideology and discusses the varieties in which populism manifests itself, for instance as a component of certain party families. We finally discuss various normative interpretations of populism,...

  19. Stochastic population oscillations in spatial predator-prey models

    Energy Technology Data Exchange (ETDEWEB)

    Taeuber, Uwe C, E-mail: tauber@vt.edu [Department of Physics, Virginia Tech, Blacksburg, VA 24061-0435 (United States)

    2011-09-15

    It is well-established that including spatial structure and stochastic noise in models for predator-prey interactions invalidates the classical deterministic Lotka-Volterra picture of neutral population cycles. In contrast, stochastic models yield long-lived, but ultimately decaying erratic population oscillations, which can be understood through a resonant amplification mechanism for density fluctuations. In Monte Carlo simulations of spatial stochastic predator-prey systems, one observes striking complex spatio-temporal structures. These spreading activity fronts induce persistent correlations between predators and prey. In the presence of local particle density restrictions (finite prey carrying capacity), there exists an extinction threshold for the predator population. The accompanying continuous non-equilibrium phase transition is governed by the directed-percolation universality class. We employ field-theoretic methods based on the Doi-Peliti representation of the master equation for stochastic particle interaction models to (i) map the ensuing action in the vicinity of the absorbing state phase transition to Reggeon field theory, and (ii) to quantitatively address fluctuation-induced renormalizations of the population oscillation frequency, damping, and diffusion coefficients in the species coexistence phase.

  20. A mathematical model of syphilis transmission in an MSM population.

    Science.gov (United States)

    Saad-Roy, C M; Shuai, Zhisheng; van den Driessche, P

    2016-07-01

    Syphilis is caused by the bacterium Treponema pallidum subspecies pallidum, and is a sexually transmitted disease with multiple stages. A model of transmission of syphilis in an MSM population (there has recently been a resurgence of syphilis in such populations) that includes infection stages and treatment is formulated as a system of ordinary differential equations. The control reproduction number is calculated, and it is proved that if this threshold parameter is below one, syphilis dies out; otherwise, if it is greater than one, it is shown that there exists a unique endemic equilibrium and that for certain special cases, this equilibrium is globally asymptotically stable. Using data from the literature on MSM populations, numerical methods are used to determine the variation and robustness of the control reproduction number with respect to the model parameters, and to determine adequate treatment rates for syphilis eradication. By assuming a closed population and no return to susceptibility, an epidemic model is obtained. Final outbreak sizes are numerically determined for various parameter values, and its variation and robustness to parameter value changes is also investigated. Results quantify the importance of early treatment for syphilis control. PMID:27071977

  1. Two-Population Dynamics in a Growing Network Model

    CERN Document Server

    Ivanova, Kristinka

    2011-01-01

    We introduce a growing network evolution model with nodal attributes. The model describes the interactions between potentially violent V and non-violent N agents who have different affinities in establishing connections within their own population versus between the populations. The model is able to generate all stable triads observed in real social systems. In the framework of rate equations theory, we employ the mean-field approximation to derive analytical expressions of the degree distribution and the local clustering coefficient for each type of nodes. Analytical derivations agree well with numerical simulation results. The assortativity of the potentially violent network qualitatively resembles the connectivity pattern in terrorist networks that was recently reported. The assortativity of the network driven by aggression shows clearly different behavior than the assortativity of the networks with connections of non-aggressive nature in agreement with recent empirical results of an online social system.

  2. Bifurcations of travelling waves in population taxis models

    International Nuclear Information System (INIS)

    A penetrating analysis of the wave dynamic modes of a conceptual population system described by the 'reaction - taxis - diffusion' and 'reaction - autotaxis - cross-diffusion' polynomial models is carried out for the case of increasing degrees of the reaction and taxis (autotaxis) functions. It is shown that a 'suitable' nonlinear taxis can affect the wave front sets and generate nonmonotone waves, such as trains and pulses which represent the exact solutions of the model system. Parametric critical points whose neighborhood displays the full spectrum of possible model wave regimes are identified and a wave mode systematization in the form of bifurcation diagrams is given. This enables standard criteria of approach to 'dangerous boundaries' to be developed. As possible applications, 'pulsing density patches' in forest insect populations as well as plankton communities and some other examples are discussed. (from the current literature)

  3. A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp.

    Science.gov (United States)

    Iohara, Koichiro; Zheng, Li; Wake, Hiroaki; Ito, Masataka; Nabekura, Junichi; Wakita, Hideaki; Nakamura, Hiroshi; Into, Takeshi; Matsushita, Kenji; Nakashima, Misako

    2008-09-01

    Cell therapy with stem cells and endothelial progenitor cells (EPCs) to stimulate vasculogenesis as a potential treatment for ischemic disease is an exciting area of research in regenerative medicine. EPCs are present in bone marrow, peripheral blood, and adipose tissue. Autologous EPCs, however, are obtained by invasive biopsy, a potentially painful procedure. An alternative approach is proposed in this investigation. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. We isolated a highly vasculogenic subfraction of side population (SP) cells based on CD31 and CD146, from dental pulp. The CD31(-);CD146(-) SP cells, demonstrating CD34+ and vascular endothelial growth factor-2 (VEGFR2)/Flk1+, were similar to EPCs. These cells were distinct from the hematopoietic lineage as CD11b, CD14, and CD45 mRNA were not expressed. They showed high proliferation and migration activities and multilineage differentiation potential including vasculogenic potential. In models of mouse hind limb ischemia, local transplantation of this subfraction of SP cells resulted in successful engraftment and an increase in the blood flow including high density of capillary formation. The transplanted cells were in proximity of the newly formed vasculature and expressed several proangiogenic factors, such as VEGF-A, G-CSF, GM-CSF, and MMP3. Conditioned medium from this subfraction showed the mitogenic and antiapoptotic activity on human umbilical vein endothelial cells. In conclusion, subfraction of SP cells from dental pulp is a new stem cell source for cell-based therapy to stimulate angiogenesis/vasculogenesis during tissue regeneration. PMID:18583536

  4. Computational models of populations of bacteria and lytic phage.

    Science.gov (United States)

    Krysiak-Baltyn, Konrad; Martin, Gregory J O; Stickland, Anthony D; Scales, Peter J; Gras, Sally L

    2016-11-01

    The use of phages to control and reduce numbers of unwanted bacteria can be traced back to the early 1900s, when phages were explored as a tool to treat infections before the wide scale use of antibiotics. Recently, phage therapy has received renewed interest as a method to treat multiresistant bacteria. Phages are also widely used in the food industry to prevent the growth of certain bacteria in foods, and are currently being explored as a tool for use in bioremediation and wastewater treatment. Despite the large body of biological research on phages, relatively little attention has been given to computational modeling of the population dynamics of phage and bacterial interactions. The earliest model was described by Campbell in the 1960s. Subsequent modifications to this model include partial or complete resistance, multiple phage binding sites, and spatial heterogeneity. This review provides a general introduction to modeling of the population dynamics of bacteria and phage. The review introduces the basic model and relevant concepts and evaluates more complex variations of the basic model published to date, including a model of disease epidemics caused by infectious bacteria. Finally, the shortcomings and potential ways to improve the models are discussed. PMID:26828960

  5. Modeling evolutionary games in populations with demographic structure

    DEFF Research Database (Denmark)

    Li, Xiang-Yi; Giaimo, Stefano; Baudisch, Annette;

    2015-01-01

    interactions, but usually omits life history and the demographic structure of the population. Here we show how an integration of both aspects can substantially alter the underlying evolutionary dynamics. We study the replicator dynamics of strategy interactions in life stage structured populations. Individuals......Classic life history models are often based on optimization algorithms, focusing on the adaptation of survival and reproduction to the environment, while neglecting frequency dependent interactions in the population. Evolutionary game theory, on the other hand, studies frequency dependent strategy...... have two basic strategic behaviours, interacting in pairwise games. A player may condition behaviour on the life stage of its own, or that of the opponent, or the matching of life stages between both players. A strategy is thus defined as the set of rules that determines a player׳s life stage dependent...

  6. Delayed population models with Allee effects and exploitation.

    Science.gov (United States)

    Liz, Eduardo; Ruiz-Herrera, Alfonso

    2015-02-01

    Allee effects make populations more vulnerable to extinction, especially under severe harvesting or predation. Using a delay-differential equation modeling the evolution of a single-species population subject to constant effort harvesting, we show that the interplay between harvest strength and Allee effects leads not only to collapses due to overexploitation; large delays can interact with Allee effects to produce extinction at population densities that would survive for smaller time delays. In case of bistability, our estimations on the basins of attraction of the two coexisting attractors improve some recent results in this direction. Moreover, we show that the persistent attractor can exhibit bubbling: a stable equilibrium loses its stability as harvesting effort increases, giving rise to sustained oscillations, but higher mortality rates stabilize the equilibrium again. PMID:25811339

  7. A model combining oscillations and attractor dynamics for generation of grid cell firing

    Directory of Open Access Journals (Sweden)

    Michael E Hasselmo

    2012-05-01

    Full Text Available Different models have been able to account for different features of the data on grid cell firing properties, including the relationship of grid cells to cellular properties and network oscillations. This paper describes a model that combines elements of two major classes of models of grid cells: models using interference of oscillations and models using attractor dynamics. This model includes a population of units with oscillatory input representing input from the medial septum. These units are termed heading angle cells because their connectivity depends upon heading angle in the environment as well as the spatial phase coded by the cell. These cells project to a population of grid cells. The sum of the heading angle input results in standing waves of circularly symmetric input to the grid cell population. Feedback from the grid cell population increases the activity of subsets of the heading angle cells, resulting in the network settling into activity patterns that resemble the patterns of firing fields in a population of grid cells. The properties of heading angle cells firing as conjunctive grid-by-head-direction cells can shift the grid cell firing according to movement velocity. The pattern of interaction of oscillations requires use of separate populations that fire on alternate cycles of the net theta rhythmic input to grid cells, similar to recent neurophysiological data on theta cycle skipping in medial entorhinal cortex.

  8. The New Standard Stellar Population Models (NSSPM) -- The Prologue

    CERN Document Server

    Lee, H; Trager, S C; Dotter, A; Chaboyer, B; Ferguson, J W; Jevremovic, D; Baron, E; Coelho, P; Briley, M M; Lee, Hyun-chul; Worthey, Guy; Trager, Scott C.; Dotter, Aaron; Chaboyer, Brian; Ferguson, Jason W.; Jevremovic, Darko; Baron, Eddie; Coelho, Paula; Briley, Michael M.

    2007-01-01

    We are developing a brand new stellar population models with flexible chemistry (isochrones plus stellar colors and spectra) in order to set a new standard of completeness and excellence. Here we present preliminary results to assess the effects of stellar evolution models and stellar model atmosphere to the well-known Lick indices at constant heavy element mass fraction Z that self-consistently account for varying heavy element mixtures. We have enhanced chemical elements one by one. Our ultimate goal is to demonstrate 10% absolute mean ages for a sample of local galaxies derived from an integrated light spectrum.

  9. Defense of single-factor models of population regulation

    International Nuclear Information System (INIS)

    I reject a multifactorial approach to the study of the regulation of animal populations for two reasons. First, a mechanism suggested by Chitty, that has natural selection at its base, has not been adequately tested. Second, the multifactorial model suggested by Lidicker is untestable because of its vagueness. As a middle ground, I suggest a model that has natural selection as its mechanism, but is multifacturial because it allows many parameters to be the selective agents. I particularly emphasize prediction and selective dispersal. Methods to test this model are suggested

  10. A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell-division capability in populations of isogenic cells of Chlamydomonas reinhardtii.

    Science.gov (United States)

    Damodaran, Shima P; Eberhard, Stephan; Boitard, Laurent; Rodriguez, Jairo Garnica; Wang, Yuxing; Bremond, Nicolas; Baudry, Jean; Bibette, Jérôme; Wollman, Francis-André

    2015-01-01

    To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers) and a significant subpopulation of slowly dividing cells (slow-growers). These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes. PMID:25760649

  11. A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell-division capability in populations of isogenic cells of Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Shima P Damodaran

    Full Text Available To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers and a significant subpopulation of slowly dividing cells (slow-growers. These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes.

  12. Increasing accuracy of dispersal kernels in grid-based population models

    Science.gov (United States)

    Slone, D.H.

    2011-01-01

    Dispersal kernels in grid-based population models specify the proportion, distance and direction of movements within the model landscape. Spatial errors in dispersal kernels can have large compounding effects on model accuracy. Circular Gaussian and Laplacian dispersal kernels at a range of spatial resolutions were investigated, and methods for minimizing errors caused by the discretizing process were explored. Kernels of progressively smaller sizes relative to the landscape grid size were calculated using cell-integration and cell-center methods. These kernels were convolved repeatedly, and the final distribution was compared with a reference analytical solution. For large Gaussian kernels (σ > 10 cells), the total kernel error was population took to reach a defined goal, the discrete model results were comparable to the analytical reference. With Gaussian kernels that had σ ≤ 0.12 using the cell integration method, or σ ≤ 0.22 using the cell center method, the kernel error was greater than 10%, which resulted in invasion times that were orders of magnitude different than theoretical results. A goal-seeking routine was developed to adjust the kernels to minimize overall error. With this, corrections for small kernels were found that decreased overall kernel error to <10-11 and invasion time error to <5%.

  13. Mathematical Model for Photovoltaic Cells

    Directory of Open Access Journals (Sweden)

    Wafaa ABD EL-BASIT

    2013-11-01

    Full Text Available The study of photovoltaic systems in an efficient manner requires a precise knowledge of the (I-V and (P-V characteristic curves of photovoltaic modules. So, the aim of the present paper is to estimate such characteristics based on different operating conditions. In this concern, a simple one diode mathematical model was implemented using MATLAB script. The output characteristics of PV cell depend on the environmental conditions. For any solar cell, the model parameters are function of the irradiance and the temperature values of the site where the panel is placed. In this paper, the numerical values of the equivalent circuit parameters are generated by the program. As well, the dependence of the cells electrical parameters are analyzed under the influence of different irradiance and temperature levels. The variation of slopes of the (I–V curves of a cell at short-circuit and open-circuit conditions with intensity of illumination in small span of intensity and different temperature levels have been applied to determine the cell parameters, shunt resistance, series resistance. The results show that the efficiency of solar cells has an inverse relationship with temperature, irradiance levels are affected by the change of the photo-generation current and the series resistance in the single diode model.

  14. A random graph model of density thresholds in swarming cells.

    Science.gov (United States)

    Jena, Siddhartha G

    2016-03-01

    Swarming behaviour is a type of bacterial motility that has been found to be dependent on reaching a local density threshold of cells. With this in mind, the process through which cell-to-cell interactions develop and how an assembly of cells reaches collective motility becomes increasingly important to understand. Additionally, populations of cells and organisms have been modelled through graphs to draw insightful conclusions about population dynamics on a spatial level. In the present study, we make use of analogous random graph structures to model the formation of large chain subgraphs, representing interactions between multiple cells, as a random graph Markov process. Using numerical simulations and analytical results on how quickly paths of certain lengths are reached in a random graph process, metrics for intercellular interaction dynamics at the swarm layer that may be experimentally evaluated are proposed. PMID:26893102

  15. Modelling food and population dynamics in honey bee colonies.

    Directory of Open Access Journals (Sweden)

    David S Khoury

    Full Text Available Honey bees (Apis mellifera are increasingly in demand as pollinators for various key agricultural food crops, but globally honey bee populations are in decline, and honey bee colony failure rates have increased. This scenario highlights a need to understand the conditions in which colonies flourish and in which colonies fail. To aid this investigation we present a compartment model of bee population dynamics to explore how food availability and bee death rates interact to determine colony growth and development. Our model uses simple differential equations to represent the transitions of eggs laid by the queen to brood, then hive bees and finally forager bees, and the process of social inhibition that regulates the rate at which hive bees begin to forage. We assume that food availability can influence both the number of brood successfully reared to adulthood and the rate at which bees transition from hive duties to foraging. The model predicts complex interactions between food availability and forager death rates in shaping colony fate. Low death rates and high food availability results in stable bee populations at equilibrium (with population size strongly determined by forager death rate but consistently increasing food reserves. At higher death rates food stores in a colony settle at a finite equilibrium reflecting the balance of food collection and food use. When forager death rates exceed a critical threshold the colony fails but residual food remains. Our model presents a simple mathematical framework for exploring the interactions of food and forager mortality on colony fate, and provides the mathematical basis for more involved simulation models of hive performance.

  16. Moving across the border: modeling migratory bat populations

    Science.gov (United States)

    Ruscena, Wiederholt; López-Hoffman, Laura; Cline, Jon; Medellin, Rodrigo; Cryan, Paul M.; Russell, Amy; McCracken, Gary; Diffendorfer, Jay; Semmens, Darius J.

    2013-01-01

    The migration of animals across long distances and between multiple habitats presents a major challenge for conservation. For the migratory Mexican free-tailed bat (Tadarida brasiliensis mexicana), these challenges include identifying and protecting migratory routes and critical roosts in two countries, the United States and Mexico. Knowledge and conservation of bat migratory routes is critical in the face of increasing threats from climate change and wind turbines that might decrease migratory survival. We employ a new modeling approach for bat migration, network modeling, to simulate migratory routes between winter habitat in southern Mexico and summer breeding habitat in northern Mexico and the southwestern United States. We use the model to identify key migratory routes and the roosts of greatest conservation value to the overall population. We measure roost importance by the degree to which the overall bat population declined when the roost was removed from the model. The major migratory routes—those with the greatest number of migrants—were between winter habitat in southern Mexico and summer breeding roosts in Texas and the northern Mexican states of Sonora and Nuevo Leon. The summer breeding roosts in Texas, Sonora, and Nuevo Leon were the most important for maintaining population numbers and network structure – these are also the largest roosts. This modeling approach contributes to conservation efforts by identifying the most influential areas for bat populations, and can be used as a tool to improve our understanding of bat migration for other species. We anticipate this approach will help direct coordination of habitat protection across borders.

  17. A stage-based model of manatee population dynamics

    Science.gov (United States)

    Runge, M.C.; Langtimm, C.A.; Kendall, W.L.

    2004-01-01

    A stage-structured population model for the Florida manatee (Trichechus manatus latirostris) was developed that explicitly incorporates uncertainty in parameter estimates. The growth rates calculated with this model reflect the status of the regional populations over the most recent 10-yr period. The Northwest and Upper St. Johns River regions have growth rates (8) of 1.037 (95% interval, 1.016?1.056) and 1.062 (1.037?1.081), respectively. The Southwest region has a growth rate of 0.989 (0.946?1.024), suggesting this population has been declining at about 1.1% per year. The estimated growth rate in the Atlantic region is 1.010 (0.988?1.029), but there is some uncertainty about whether adult survival rates have been constant over the last 10 yr; using the mean survival rates from the most recent 5-yr period, the estimated growth rate in this region is 0.970 (0.938?0.998). Elasticity analysis indicates that the most effective management actions should seek to increase adult survival rates. Decomposition of the uncertainty in the growth rates indicates that uncertainty about population status can best be reduced through increased monitoring of adult survival rate.

  18. A descriptive study of plasma cell dyscrasias in Egyptian population

    International Nuclear Information System (INIS)

    Background: Plasma cell dyscrasias (PCDs) refer to a spectrum of disorders characterized by the monoclonal proliferation of lymphoplasmacytic cells in the bone marrow and, sometimes, tissue deposition of monoclonal immunoglobulins or their components. These disorders include multiple myeloma (MM) and Waldenstrom’s macroglobulinemia, as well as rare conditions such as light-chain deposition disease (LCDD) and heavy-chain diseases (HCDs). The worldwide annual incidence of MM is estimated at 86,000, which is approximately 0.8% of all new cancer cases. Purpose: Our retrospective study aims to highlight the immunologic and epidemiological features of PCDs mainly MM in Egyptian patients and compare our results with those of other populations. Methods: Two hundred seventeen Egyptian patients with PCD were enrolled in the study. Serum, urine protein electrophoresis and immunofixation were used to demonstrate M protein. Results: One hundred thirty-eight patients (63.6%) had IgG monoclonal band, 38 patients (17.5%) had IgA, 12 patients (5.5%) had Waldenstrom’s macroglobulinemia (IgM monoclonal band) and 29 patients (13.4%) were light chain myeloma. One hundred fifty-one (70%) were Kappa chain positive and 66 patients (30%) were lumbda positive. Conventional cytogenetics was available for 40 patients; of them12 patients (30%) showed 13q-. Mean OS was 37.5 months (1-84 months). Survival analysis was statistically insignificant according to age, sex and ISS or type of treatment (P value >0.05). Conclusion: Long term follow up is required to further define the role of different therapeutic lines of treatment including ASCT in the various stages of PCD based on OS data.

  19. Isolation of adult human pluripotent stem cells from mesenchymal cell populations and their application to liver damages.

    Science.gov (United States)

    Wakao, Shohei; Kitada, Masaaki; Kuroda, Yasumasa; Dezawa, Mari

    2012-01-01

    We have found a novel type of pluripotent stem cells, Multilineage-differentiating stress enduring (Muse) cells that can be isolated from mesenchymal cell populations. Muse cells are characterized by stress tolerance, expression of pluripotency markers, self-renewal, and the ability to differentiate into endodermal-, mesodermal-, and ectodermal-lineage cells from a single cell, demonstrating that they are pluripotent stem cells. They can be isolated as cells positive for stage-specific embryonic antigen-3, a human pluripotent stem cell marker. Here, we introduce the isolation method for Muse cells and the effect of transplantation of these cells on chronic liver diseases. PMID:22167642

  20. Stochastic adaptation and fold-change detection: from single-cell to population behavior

    Directory of Open Access Journals (Sweden)

    Leier André

    2011-02-01

    Full Text Available Abstract Background In cell signaling terminology, adaptation refers to a system's capability of returning to its equilibrium upon a transient response. To achieve this, a network has to be both sensitive and precise. Namely, the system must display a significant output response upon stimulation, and later on return to pre-stimulation levels. If the system settles at the exact same equilibrium, adaptation is said to be 'perfect'. Examples of adaptation mechanisms include temperature regulation, calcium regulation and bacterial chemotaxis. Results We present models of the simplest adaptation architecture, a two-state protein system, in a stochastic setting. Furthermore, we consider differences between individual and collective adaptive behavior, and show how our system displays fold-change detection properties. Our analysis and simulations highlight why adaptation needs to be understood in terms of probability, and not in strict numbers of molecules. Most importantly, selection of appropriate parameters in this simple linear setting may yield populations of cells displaying adaptation, while single cells do not. Conclusions Single cell behavior cannot be inferred from population measurements and, sometimes, collective behavior cannot be determined from the individuals. By consequence, adaptation can many times be considered a purely emergent property of the collective system. This is a clear example where biological ergodicity cannot be assumed, just as is also the case when cell replication rates are not homogeneous, or depend on the cell state. Our analysis shows, for the first time, how ergodicity cannot be taken for granted in simple linear examples either. The latter holds even when cells are considered isolated and devoid of replication capabilities (cell-cycle arrested. We also show how a simple linear adaptation scheme displays fold-change detection properties, and how rupture of ergodicity prevails in scenarios where transitions between

  1. BSim: an agent-based tool for modeling bacterial populations in systems and synthetic biology.

    Directory of Open Access Journals (Sweden)

    Thomas E Gorochowski

    Full Text Available Large-scale collective behaviors such as synchronization and coordination spontaneously arise in many bacterial populations. With systems biology attempting to understand these phenomena, and synthetic biology opening up the possibility of engineering them for our own benefit, there is growing interest in how bacterial populations are best modeled. Here we introduce BSim, a highly flexible agent-based computational tool for analyzing the relationships between single-cell dynamics and population level features. BSim includes reference implementations of many bacterial traits to enable the quick development of new models partially built from existing ones. Unlike existing modeling tools, BSim fully considers spatial aspects of a model allowing for the description of intricate micro-scale structures, enabling the modeling of bacterial behavior in more realistic three-dimensional, complex environments. The new opportunities that BSim opens are illustrated through several diverse examples covering: spatial multicellular computing, modeling complex environments, population dynamics of the lac operon, and the synchronization of genetic oscillators. BSim is open source software that is freely available from http://bsim-bccs.sf.net and distributed under the Open Source Initiative (OSI recognized MIT license. Developer documentation and a wide range of example simulations are also available from the website. BSim requires Java version 1.6 or higher.

  2. BSim: an agent-based tool for modeling bacterial populations in systems and synthetic biology.

    Science.gov (United States)

    Gorochowski, Thomas E; Matyjaszkiewicz, Antoni; Todd, Thomas; Oak, Neeraj; Kowalska, Kira; Reid, Stephen; Tsaneva-Atanasova, Krasimira T; Savery, Nigel J; Grierson, Claire S; di Bernardo, Mario

    2012-01-01

    Large-scale collective behaviors such as synchronization and coordination spontaneously arise in many bacterial populations. With systems biology attempting to understand these phenomena, and synthetic biology opening up the possibility of engineering them for our own benefit, there is growing interest in how bacterial populations are best modeled. Here we introduce BSim, a highly flexible agent-based computational tool for analyzing the relationships between single-cell dynamics and population level features. BSim includes reference implementations of many bacterial traits to enable the quick development of new models partially built from existing ones. Unlike existing modeling tools, BSim fully considers spatial aspects of a model allowing for the description of intricate micro-scale structures, enabling the modeling of bacterial behavior in more realistic three-dimensional, complex environments. The new opportunities that BSim opens are illustrated through several diverse examples covering: spatial multicellular computing, modeling complex environments, population dynamics of the lac operon, and the synchronization of genetic oscillators. BSim is open source software that is freely available from http://bsim-bccs.sf.net and distributed under the Open Source Initiative (OSI) recognized MIT license. Developer documentation and a wide range of example simulations are also available from the website. BSim requires Java version 1.6 or higher. PMID:22936991

  3. Spatial Modeling of Indian Agriculture, Economic Activity and Population under Climate Change

    Science.gov (United States)

    McCord, G. C.

    2010-12-01

    We present a spatial model of economic activity and human population built on physical geography that takes particular account of its effects through agricultural productivity and transport costs for trade. A major component of this work is an agricultural model, driven in part by high-resolution climate data and model output. We put forward India as the initial region for this modeling work; India is a relatively data-rich country, it exhibits significant within-country spatial and temporal variation in agricultural productivity, urbanization rates, and population growth rates, and the climate dynamics of the monsoon are well-studied and expected to change on decadal time scales. Agricultural productivity is modeled as a function of soil, climate, and technology variables. Farmers locate optimally given varying geography and transport costs; in turn, food availability defines urbanization rates and economic activity in non-agricultural sectors. This “social system” integrated assessment model is a step towards a valuable policy tool, but requires a significant mobilization of data and a grid-cell-level system of equations to describe the underlying dynamics of the model. We test against past trends of social-natural system progression in demography, human location, income, food production, etc., and argue that the model could be used to assess future trends under varying climate change scenarios, and eventually serve to model feedbacks through effects on migration, population growth rates, or economic activity.

  4. Hierarchical population model with a carrying capacity distribution

    CERN Document Server

    Indekeu, J O

    2002-01-01

    A time- and space-discrete model for the growth of a rapidly saturating local biological population $N(x,t)$ is derived from a hierarchical random deposition process previously studied in statistical physics. Two biologically relevant parameters, the probabilities of birth, $B$, and of death, $D$, determine the carrying capacity $K$. Due to the randomness the population depends strongly on position, $x$, and there is a distribution of carrying capacities, $\\Pi (K)$. This distribution has self-similar character owing to the imposed hierarchy. The most probable carrying capacity and its probability are studied as a function of $B$ and $D$. The effective growth rate decreases with time, roughly as in a Verhulst process. The model is possibly applicable, for example, to bacteria forming a "towering pillar" biofilm. The bacteria divide on randomly distributed nutrient-rich regions and are exposed to random local bactericidal agent (antibiotic spray). A gradual overall temperature change away from optimal growth co...

  5. A simulation model for stem cells differentiation into specialized cells of non-connective tissues.

    Science.gov (United States)

    Pisu, Massimo; Concas, Alessandro; Fadda, Sarah; Cincotti, Alberto; Cao, Giacomo

    2008-10-01

    A novel mathematical model to simulate stem cells differentiation into specialized cells of non-connective tissues is proposed. The model is based upon material balances for growth factors coupled with a mass-structured population balance describing cell growth, proliferation and differentiation. The proposed model is written in a general form and it may be used to simulate a generic cell differentiation pathway during in vitro cultivation when specific growth factors are used. Literature experimental data concerning the differentiation of central nervous stem cells into astrocytes are successfully compared with model results, thus demonstrating the validity of the proposed model as well as its predictive capability. Finally, sensitivity analysis of model parameters is also performed in order to clarify what mechanisms most strongly influence differentiation and cell types distribution. PMID:18667361

  6. Characterization of rabbit limbal epithelial side population cells using RNA sequencing and single-cell qRT-PCR.

    Science.gov (United States)

    Kameishi, Sumako; Umemoto, Terumasa; Matsuzaki, Yu; Fujita, Masako; Okano, Teruo; Kato, Takashi; Yamato, Masayuki

    2016-05-01

    Corneal epithelial stem cells reside in the limbus, a transitional zone between the cornea and conjunctiva, and are essential for maintaining homeostasis in the corneal epithelium. Although our previous studies demonstrated that rabbit limbal epithelial side population (SP) cells exhibit stem cell-like phenotypes with Hoechst 33342 staining, the different characteristics and/or populations of these cells remain unclear. Therefore, in this study, we determined the gene expression profiles of limbal epithelial SP cells by RNA sequencing using not only present public databases but also contigs that were created by de novo transcriptome assembly as references for mapping. Our transcriptome data indicated that limbal epithelial SP cells exhibited a stem cell-like phenotype compared with non-SP cells. Importantly, gene ontology analysis following RNA sequencing demonstrated that limbal epithelial SP cells exhibited significantly enhanced expression of mesenchymal/endothelial cell markers rather than epithelial cell markers. Furthermore, single-cell quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) demonstrated that the limbal epithelial SP population consisted of at least two immature cell populations with endothelial- or mesenchymal-like phenotypes. Therefore, our present results may propose the presence of a novel population of corneal epithelial stem cells distinct from conventional epithelial stem cells. PMID:26546824

  7. MIUSCAT: extended MILES spectral coverage. I. Stellar populations synthesis models

    CERN Document Server

    Vazdekis, A; Cenarro, A J; Rivero-González, J G; Díaz-García, L A; Falcón-Barroso, J

    2012-01-01

    We extend the spectral range of our stellar population synthesis models based on the MILES and CaT empirical stellar spectral libraries. For this purpose we combine these two libraries with the Indo-U.S. to construct composite stellar spectra to feed our models. The spectral energy distributions (SEDs) computed with these models and the originally published models are combined to construct composite SEDs for single-age, single-metallicity stellar populations (SSPs) covering the range 3465 - 9469\\AA at moderately high, and uniform, resolution (FWHM=2.51\\AA). The colours derived from these SSP SEDs provide good fits to Galactic globular cluster data. We find that the colours involving redder filters are very sensitive to the IMF, as well as a number of features and molecular bands throughout the spectra. To illustrate the potential use of these models we focus on the NaI doublet at 8200 \\AA and with the aid of the newly synthesized SSP model SEDs we define a new IMF-sensitive index that is based on this feature...

  8. T Cell Epitope Immunotherapy Induces a CD4+ T Cell Population with Regulatory Activity

    Directory of Open Access Journals (Sweden)

    Verhoef Adrienne

    2005-01-01

    Full Text Available Background Synthetic peptides, representing CD4+ T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. Methods and Findings In this study we address the mechanism of action of peptide immunotherapy (PIT in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4+ cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4neg PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4+ and CD8+ PBMCs. Conclusion This study provides evidence for the induction of a population of CD4+ T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen.

  9. Integration of manatee life-history data and population modeling

    Science.gov (United States)

    Eberhardt, L.L.; O'Shea, Thomas J.

    1995-01-01

    Aerial counts and the number of deaths have been a major focus of attention in attempts to understand the population status of the Florida manatee (Trichechus manatus latirostris). Uncertainties associated with these data have made interpretation difficult. However, knowledge of manatee life-history attributes increased and now permits the development of a population model. We describe a provisional model based on the classical approach of Lotka. Parameters in the model are based on data from'other papers in this volume and draw primarily on observations from the Crystal River, Blue Spring, and Adantic Coast areas. The model estimates X (the finite rate ofincrease) at each study area, and application ofthe delta method provides estimates of variance components and partial derivatives ofX with respectto key input parameters (reproduction, adult survival, and early survival). In some study areas, only approximations of some parameters are available. Estimates of X and coefficients of variation (in parentheses) of manatees were 1.07 (0.009) in the Crystal River, 1.06 (0.012) at Blue Spring, and 1.01 (0.012) on the Atlantic Coast. Changing adult survival has a major effect on X. Early-age survival has the smallest effect. Bootstrap comparisons of population growth estimates from trend counts in the Crystal River and at Blue Spring and the reproduction and survival data suggest that the higher, observed rates from counts are probably not due to chance. Bootstrapping for variance estimates based on reproduction and survival data from manatees at Blue Spring and in the Crystal River provided estimates of X, adult survival, and rates of reproduction that were similar to those obtained by other methods. Our estimates are preliminary and suggestimprovements for future data collection and analysis. However, results support efforts to reduce mortality as the most effective means to promote the increased growth necessary for the eventual recovery of the Florida manatee

  10. Surviving the ratchet : Modelling deleterious mutations in asexual populations

    OpenAIRE

    Söderberg, Jonas

    2011-01-01

    One of the most unforgiving processes in nature is that of Muller's ratchet, a seemingly irreversible accumulation of deleterious mutations that all organisms have to deal with or face extinction. The most obvious way to avoid fitness collapse is recombination, though asexual populations usually do not have the luxury of recombining freely.  With the aid of computational and mathematical models, we have studied other situations where this threat is averted and the organism can survive the rat...

  11. A predictive model of criminality in civil psychiatric populations

    OpenAIRE

    Evans, Laura; Ioannou, Maria; Hammond, Laura

    2015-01-01

    Purpose The purpose of this paper is to develop a predictive model of criminal risk in civil psychiatric populations, by determining the relative impacts of psychopathy, drug use, impulsivity and intelligence on levels of criminality. Design/methodology/approach The sample consisted of 871 civil psychiatric patients, selected from the MacArthur Violence Risk Assessment Study, who had been diagnosed with a mental illness or personality disorder, and hospitalised less than 21 days. Ea...

  12. Interactional models for adults of two populations with maturation delays

    Institute of Scientific and Technical Information of China (English)

    HE Ze-rong; LI Jian-quan

    2008-01-01

    This paper is concerned with interactional models for adults of two species delayed by their mature periods. The existence and local stability of equilibria are discussed thoroughly for competitive systems, cooperative systems and predator-prey systems, respectively. For systems with interaction of competition and cooperation, it is found that the two populations are uniformly persistent if the positive equilibrium is stable. For predator-prey interaction, however, some further conditions are needed to guarantee the persistence of the systems.

  13. Encoding through patterns: regression tree-based neuronal population models.

    Science.gov (United States)

    Haslinger, Robert; Pipa, Gordon; Lewis, Laura D; Nikolić, Danko; Williams, Ziv; Brown, Emery

    2013-08-01

    Although the existence of correlated spiking between neurons in a population is well known, the role such correlations play in encoding stimuli is not. We address this question by constructing pattern-based encoding models that describe how time-varying stimulus drive modulates the expression probabilities of population-wide spike patterns. The challenge is that large populations may express an astronomical number of unique patterns, and so fitting a unique encoding model for each individual pattern is not feasible. We avoid this combinatorial problem using a dimensionality-reduction approach based on regression trees. Using the insight that some patterns may, from the perspective of encoding, be statistically indistinguishable, the tree divisively clusters the observed patterns into groups whose member patterns possess similar encoding properties. These groups, corresponding to the leaves of the tree, are much smaller in number than the original patterns, and the tree itself constitutes a tractable encoding model for each pattern. Our formalism can detect an extremely weak stimulus-driven pattern structure and is based on maximizing the data likelihood, not making a priori assumptions as to how patterns should be grouped. Most important, by comparing pattern encodings with independent neuron encodings, one can determine if neurons in the population are driven independently or collectively. We demonstrate this method using multiple unit recordings from area 17 of anesthetized cat in response to a sinusoidal grating and show that pattern-based encodings are superior to those of independent neuron models. The agnostic nature of our clustering approach allows us to investigate encoding by the collective statistics that are actually present rather than those (such as pairwise) that might be presumed. PMID:23607564

  14. CellCODE: a robust latent variable approach to differential expression analysis for heterogeneous cell populations

    OpenAIRE

    Chikina, Maria; Zaslavsky, Elena; Sealfon, Stuart C.

    2015-01-01

    Motivation: Identifying alterations in gene expression associated with different clinical states is important for the study of human biology. However, clinical samples used in gene expression studies are often derived from heterogeneous mixtures with variable cell-type composition, complicating statistical analysis. Considerable effort has been devoted to modeling sample heterogeneity, and presently, there are many methods that can estimate cell proportions or pure cell-type expression from m...

  15. The cell-stretcher: A novel device for the mechanical stimulation of cell populations

    Science.gov (United States)

    Seriani, S.; Del Favero, G.; Mahaffey, J.; Marko, D.; Gallina, P.; Long, C. S.; Mestroni, L.; Sbaizero, O.

    2016-08-01

    Mechanical stimulation appears to be a critical modulator for many aspects of biology, both of living tissue and cells. The cell-stretcher, a novel device for the mechanical uniaxial stimulation of populations of cells, is described. The system is based on a variable stroke cam-lever-tappet mechanism which allows the delivery of cyclic stimuli with frequencies of up to 10 Hz and deformation between 1% and 20%. The kinematics is presented and a simulation of the dynamics of the system is shown, in order to compute the contact forces in the mechanism. The cells, following cultivation and preparation, are plated on an ad hoc polydimethylsiloxane membrane which is then loaded on the clamps of the cell-stretcher via force-adjustable magnetic couplings. In order to show the viability of the experimentation and biocompatibility of the cell-stretcher, a set of two in vitro tests were performed. Human epithelial carcinoma cell line A431 and Adult Mouse Ventricular Fibroblasts (AMVFs) from a dual reporter mouse were subject to 0.5 Hz, 24 h cyclic stretching at 15% strain, and to 48 h stimulation at 0.5 Hz and 15% strain, respectively. Visual analysis was performed on A431, showing definite morphological changes in the form of cellular extroflections in the direction of stimulation compared to an unstimulated control. A cytometric analysis was performed on the AMVF population. Results show a post-stimulation live-dead ratio deviance of less than 6% compared to control, which proves that the environment created by the cell-stretcher is suitable for in vitro experimentation.

  16. Cauchy problem for multiscale conservation laws: Application to structured cell populations

    CERN Document Server

    Shang, Peipei

    2010-01-01

    In this paper, we study a vector conservation law that models the growth and selection of ovarian follicles. During each ovarian cycle, only a definite number of follicles ovulate, while the others undergo a degeneration process called atresia. This work is motivated by a multiscale mathematical model starting on the cellular scale, where ovulation or atresia result from a hormonally controlled selection process. A two-dimensional conservation law describes the age and maturity structuration of the follicular cell populations. The densities intersect through a coupled hyperbolic system between different follicles and cell phases, which results in a vector conservation law and coupling boundary conditions. The maturity velocity functions possess both a local and nonlocal character. We prove the existence and uniqueness of the weak solution to the Cauchy problem with bounded initial and boundary data.

  17. Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

    Science.gov (United States)

    Goldar, A.; Arneodo, A.; Audit, B.; Argoul, F.; Rappailles, A.; Guilbaud, G.; Petryk, N.; Kahli, M.; Hyrien, O.

    2016-03-01

    We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

  18. Deterministic versus stochastic aspects of superexponential population growth models

    Science.gov (United States)

    Grosjean, Nicolas; Huillet, Thierry

    2016-08-01

    Deterministic population growth models with power-law rates can exhibit a large variety of growth behaviors, ranging from algebraic, exponential to hyperexponential (finite time explosion). In this setup, selfsimilarity considerations play a key role, together with two time substitutions. Two stochastic versions of such models are investigated, showing a much richer variety of behaviors. One is the Lamperti construction of selfsimilar positive stochastic processes based on the exponentiation of spectrally positive processes, followed by an appropriate time change. The other one is based on stable continuous-state branching processes, given by another Lamperti time substitution applied to stable spectrally positive processes.

  19. ON SKEW-NORMAL MODEL FOR ECONOMICALLY ACTIVE POPULATION

    Directory of Open Access Journals (Sweden)

    OLOSUNDE AKINLOLU A

    2011-04-01

    Full Text Available The literature related to skew-symmetric distribution have grown rapidly in recent years but at the moment no publication on its applications concerning the description of economically active data with this type of probability models. In this paper, we provided an extension to this skew-normal distribution, which is also part of the family of skewed class of normal but with additional shape parameters δ. Some properties of this distribution are presented and finally, we considered fitting it to economically active population data. The model exhibited a better behaviour when compared to normal and skew normal distributions.

  20. Border Collision Bifurcations in a Generalized Model of Population Dynamics

    OpenAIRE

    Lilia M. Ladino; Cristiana Mammana; Elisabetta Michetti; Jose C. Valverde

    2016-01-01

    We analyze the dynamics of a generalized discrete time population model of a two-stage species with recruitment and capture. This generalization, which is inspired by other approaches and real data that one can find in literature, consists in considering no restriction for the value of the two key parameters appearing in the model, that is, the natural death rate and the mortality rate due to fishing activity. In the more general case the feasibility of the system has been preserved by posing...

  1. A model with competition between the cell lines in leukemia under treatment

    Energy Technology Data Exchange (ETDEWEB)

    Halanay, A.; Cândea, D.; Rădulescu, R. [POLITEHNICA University of Bucharest Department of Mathematics and Informatics Splaiul Independentei 313 RO-060042 Bucharest (Romania)

    2014-12-10

    The evolution of leukemia is modeled with a delay differential equation model of four cell populations: two populations (healthy and leukemic) ) of stem-like cells involving a larger category consisting of proliferating stem and progenitor cells with self-renew capacity and two populations (healthy and leukemic) of mature cells, considering the competition of healthy vs. leukemic cell populations and three types of division that a stem-like cell can exhibit: self-renew, asymmetric division and differentiation. In the model it is assumed that the treatment acts on the proliferation rate of the leukemic stem cells and on the apoptosis of stem and mature cells. The emphasis in this model is on establishing relevant parameters for chronic and acute manifestations of leukemia. Stability of equilibria is investigated and sufficient conditions for local asymptotic stability will be given using a Lyapunov-Krasovskii functional.

  2. A model with competition between the cell lines in leukemia under treatment

    International Nuclear Information System (INIS)

    The evolution of leukemia is modeled with a delay differential equation model of four cell populations: two populations (healthy and leukemic) ) of stem-like cells involving a larger category consisting of proliferating stem and progenitor cells with self-renew capacity and two populations (healthy and leukemic) of mature cells, considering the competition of healthy vs. leukemic cell populations and three types of division that a stem-like cell can exhibit: self-renew, asymmetric division and differentiation. In the model it is assumed that the treatment acts on the proliferation rate of the leukemic stem cells and on the apoptosis of stem and mature cells. The emphasis in this model is on establishing relevant parameters for chronic and acute manifestations of leukemia. Stability of equilibria is investigated and sufficient conditions for local asymptotic stability will be given using a Lyapunov-Krasovskii functional

  3. CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

    International Nuclear Information System (INIS)

    The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133+) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133+ subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133+ cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133+ / CD133- subpopulations

  4. A paradox in individual-based models of populations.

    Science.gov (United States)

    van der Meer, Jaap

    2016-01-01

    The standard dynamic energy budget model is widely used to describe the physiology of individual animals. It assumes that assimilation rate scales with body surface area, whereas maintenance rate scales with body volume. When the model is used as the building block of a population model, only limited dynamical behaviour, the so-called juvenile-driven cycles, emerges. The reason is that in the model juveniles are competitively superior over adults, because juveniles have a higher surface area-to-volume ratio. Maintenance requirements for adults are therefore relatively large, and a reduced assimilation rate as a result of lowered food levels will easily become insufficient. Here, an alternative dynamic energy budget model is introduced that gives rise to adult-driven cycles, which may be closer to what is often observed in reality. However, this comes at the price of a rather odd description of the individual, in that maintenance scales with body area and assimilation rate with body volume, resulting in unbounded exponential body growth. I make a plea to solve the paradox and come up with reliable descriptions at both the individual and the population level. PMID:27413533

  5. Modeling evolutionary games in populations with demographic structure.

    Science.gov (United States)

    Li, Xiang-Yi; Giaimo, Stefano; Baudisch, Annette; Traulsen, Arne

    2015-09-01

    Classic life history models are often based on optimization algorithms, focusing on the adaptation of survival and reproduction to the environment, while neglecting frequency dependent interactions in the population. Evolutionary game theory, on the other hand, studies frequency dependent strategy interactions, but usually omits life history and the demographic structure of the population. Here we show how an integration of both aspects can substantially alter the underlying evolutionary dynamics. We study the replicator dynamics of strategy interactions in life stage structured populations. Individuals have two basic strategic behaviours, interacting in pairwise games. A player may condition behaviour on the life stage of its own, or that of the opponent, or the matching of life stages between both players. A strategy is thus defined as the set of rules that determines a player׳s life stage dependent behaviours. We show that the diversity of life stage structures and life stage dependent strategies can promote each other, and the stable frequency of basic strategic behaviours can deviate from game equilibrium in populations with life stage structures. PMID:26055649

  6. A Retrospective Analysis of Oral Langerhans Cell Histiocytosis in an Iranian Population: a 20-year Evaluation

    OpenAIRE

    Saede Atarbashi Moghadam; Ali Lotfi; Batool Piroozhashemi; Sepideh Mokhtari

    2015-01-01

    Statement of the Problem: Langerhans cell histiocytosis is a rare disease with unknown pathogenesis and is characterized by local or disseminated proliferation of Langerhans cells. There is no previous investigation on prevalence of oral Langerhans cell histiocytosis in Iranian population. Purpose: The purpose of this study was to assess the relative frequency of oral Langerhans cell histiocytosis in an Iranian population and to compare the data with previous reports. Materials and Meth...

  7. Richards-like two species population dynamics model.

    Science.gov (United States)

    Ribeiro, Fabiano; Cabella, Brenno Caetano Troca; Martinez, Alexandre Souto

    2014-12-01

    The two-species population dynamics model is the simplest paradigm of inter- and intra-species interaction. Here, we present a generalized Lotka-Volterra model with intraspecific competition, which retrieves as particular cases, some well-known models. The generalization parameter is related to the species habitat dimensionality and their interaction range. Contrary to standard models, the species coupling parameters are general, not restricted to non-negative values. Therefore, they may represent different ecological regimes, which are derived from the asymptotic solution stability analysis and are represented in a phase diagram. In this diagram, we have identified a forbidden region in the mutualism regime, and a survival/extinction transition with dependence on initial conditions for the competition regime. Also, we shed light on two types of predation and competition: weak, if there are species coexistence, or strong, if at least one species is extinguished. PMID:25112794

  8. Nonlinear Stochastic Modelling of Antimicrobial resistance in Bacterial Populations

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber

    This thesis applies mathematical modelling and statistical methods to investigate the dynamics and mechanisms of bacterial evolution. More specifically it is concerned with the evolution of antibiotic resistance in bacteria populations, which is an increasing problem for the treatment of infections...... in humans and animals. To prevent the evolution and spread of resistance, there is a need for further understanding of its dynamics. A grey-box modelling approach based on stochastic differential equations is the main and innovative method applied to study bacterial systems in this thesis. Through...... for bacterial growth in an environment with multiple substrates. Models based on stochastic differential equations are also used in studies of mutation and conjugation. Mutation and conjugation are important mechanisms for the development of resistance. Earlier models for conjugation have described...

  9. CML Mouse Model Generated from Leukemia Stem Cells.

    Science.gov (United States)

    Hu, Yiguo

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a high number of well-differentiated neutrophils in peripheral blood and myeloid cells in bone marrow (BM). CML is derived from the hematopoietic stem cells (HSCs) with the Philadelphia chromosome (Ph(+), t(9;22)-(q34;q11)), resulting in generating a fusion oncogene, BCR/ABL1. HSCs with Ph(+) are defined as leukemia stem cells (LSCs), a subpopulation cell at the apex of hierarchies in leukemia cells and responsible for the disease continuous propagation. Several kinds of CML models have been developed to reveal the mechanism of CML pathogenesis and evaluate therapeutic drugs in the past three decades. Here, we describe the procedures to generate a CML mouse model by introducing BCR/ABL1 into Lin(-)Sca1(+) cKit(+) population cells purified from mouse bone marrow. In CML retroviral transduction/transplantation mouse models, this modified model can mimic CML pathogenesis on high fidelity. PMID:27581136

  10. Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population.

    Science.gov (United States)

    Lugthart, Gertjan; Melsen, Janine E; Vervat, Carly; van Ostaijen-Ten Dam, Monique M; Corver, Willem E; Roelen, Dave L; van Bergen, Jeroen; van Tol, Maarten J D; Lankester, Arjan C; Schilham, Marco W

    2016-07-01

    Knowledge of human NK cells is based primarily on conventional CD56(bright) and CD56(dim) NK cells from blood. However, most cellular immune interactions occur in lymphoid organs. Based on the coexpression of CD69 and CXCR6, we identified a third major NK cell subset in lymphoid tissues. This population represents 30-60% of NK cells in marrow, spleen, and lymph node but is absent from blood. CD69(+)CXCR6(+) lymphoid tissue NK cells have an intermediate expression of CD56 and high expression of NKp46 and ICAM-1. In contrast to circulating NK cells, they have a bimodal expression of the activating receptor DNAX accessory molecule 1. CD69(+)CXCR6(+) NK cells do not express the early markers c-kit and IL-7Rα, nor killer cell Ig-like receptors or other late-differentiation markers. After cytokine stimulation, CD69(+)CXCR6(+) NK cells produce IFN-γ at levels comparable to CD56(dim) NK cells. They constitutively express perforin but require preactivation to express granzyme B and exert cytotoxicity. After hematopoietic stem cell transplantation, CD69(+)CXCR6(+) lymphoid tissue NK cells do not exhibit the hyperexpansion observed for both conventional NK cell populations. CD69(+)CXCR6(+) NK cells constitute a separate NK cell population with a distinct phenotype and function. The identification of this NK cell population in lymphoid tissues provides tools to further evaluate the cellular interactions and role of NK cells in human immunity. PMID:27226093

  11. Synthetic stellar populations: single stellar populations, stellar interior models and primordial proto-galaxies

    CERN Document Server

    Jiménez, R; Dunlop, J; Padoan, P; Peacock, J; Jimenez, Raul; Donald, James Mac; Dunlop, James; Padoan, Paolo; Peacock, John

    2004-01-01

    We present a new set of stellar interior and synthesis models for predicting the integrated emission from stellar populations in star clusters and galaxies of arbitrary age and metallicity. This work differs from existing spectral synthesis codes in a number of important ways, namely (1) the incorporation of new stellar evolutionary tracks, with sufficient resolution in mass to sample rapid stages of stellar evolution; (2) a physically consistent treatment of evolution in the HR diagram, including the approach to the main sequence and the effects of mass loss on the giant and horizontal-branch phases. Unlike several existing models, ours yield consistent ages when used to date a coeval stellar population from a wide range of spectral features and colour indexes. We rigorously discuss degeneracies in the age-metallicity plane and show that inclusion of spectral features blueward of 4500 AA, suffices to break any remaining degeneracy and that with moderate S/N spectra (10 per 20AA, resolution element) age and m...

  12. Molecular analysis of endothelial progenitor cell (EPC subtypes reveals two distinct cell populations with different identities

    Directory of Open Access Journals (Sweden)

    Simpson David A

    2010-05-01

    Full Text Available Abstract Background The term endothelial progenitor cells (EPCs is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular fingerprint for two EPC subtypes: early EPCs (eEPCs and outgrowth endothelial cells (OECs. Methods Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types. Results Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN with links to immunity and inflammation (TLRs, CD14, HLAs, whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs. Conclusions This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.

  13. Coupling of wall boiling with discrete population balance model

    International Nuclear Information System (INIS)

    A coupling between a polydisperse population balance method (Multiple Size Group Model - MUSIG) and the RPI wall boiling model for nucleate subcooled boiling has been implemented in ANSYS CFX. It allows more accurate prediction of the interfacial area density for mass, momentum and energy transfer between phases in comparison to the usual local-monodisperse bubble size assumption and underlying bulk bubble diameter correlations as they are commonly used in boiling flow applications like e.g. the prediction of subcooled nucleate boiling in rod bundles and fuel assemblies of PWR. The paper outlines the methodology of the coupled CFD model, which automatically avoids possible inconsistencies in the model formulation for the heated wall, when the generated steam bubbles on the heater surface are injected exactly in the bubble size class corresponding to the predicted bubble departure diameter. The coupling of the RPI wall boiling model and the MUSIG model has been implemented for both homogenous/inhomogeneous variants of the MUSIG model. The paper presents the validation of the coupled modeling approach for the well known test case of nucleate subcooled boiling of R113 refrigerant in a circular annulus with inner heated rod based on the experiments of Roy et al. ANSYS CFX results with the newly implemented approach as well as comparison to data and locally-monodisperse simulations are provided. (author)

  14. Endothelial Progenitor Cell Fraction Contained in Bone Marrow-Derived Mesenchymal Stem Cell Populations Impairs Osteogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Fabian Duttenhoefer

    2015-01-01

    Full Text Available In bone tissue engineering (TE endothelial cell-osteoblast cocultures are known to induce synergies of cell differentiation and activity. Bone marrow mononucleated cells (BMCs are a rich source of mesenchymal stem cells (MSCs able to develop an osteogenic phenotype. Endothelial progenitor cells (EPCs are also present within BMC. In this study we investigate the effect of EPCs present in the BMC population on MSCs osteogenic differentiation. Human BMCs were isolated and separated into two populations. The MSC population was selected through plastic adhesion capacity. EPCs (CD34+ and CD133+ were removed from the BMC population and the resulting population was named depleted MSCs. Both populations were cultured over 28 days in osteogenic medium (Dex+ or medium containing platelet lysate (PL. MSC population grew faster than depleted MSCs in both media, and PL containing medium accelerated the proliferation for both populations. Cell differentiation was much higher in Dex+ medium in both cases. Real-time RT-PCR revealed upregulation of osteogenic marker genes in depleted MSCs. Higher values of ALP activity and matrix mineralization analyses confirmed these results. Our study advocates that absence of EPCs in the MSC population enables higher osteogenic gene expression and matrix mineralization and therefore may lead to advanced bone neoformation necessary for TE constructs.

  15. Modelling multi-pulse population dynamics from ultrafast spectroscopy.

    Directory of Open Access Journals (Sweden)

    Luuk J G W van Wilderen

    Full Text Available Current advanced laser, optics and electronics technology allows sensitive recording of molecular dynamics, from single resonance to multi-colour and multi-pulse experiments. Extracting the occurring (bio- physical relevant pathways via global analysis of experimental data requires a systematic investigation of connectivity schemes. Here we present a Matlab-based toolbox for this purpose. The toolbox has a graphical user interface which facilitates the application of different reaction models to the data to generate the coupled differential equations. Any time-dependent dataset can be analysed to extract time-independent correlations of the observables by using gradient or direct search methods. Specific capabilities (i.e. chirp and instrument response function for the analysis of ultrafast pump-probe spectroscopic data are included. The inclusion of an extra pulse that interacts with a transient phase can help to disentangle complex interdependent pathways. The modelling of pathways is therefore extended by new theory (which is included in the toolbox that describes the finite bleach (orientation effect of single and multiple intense polarised femtosecond pulses on an ensemble of randomly oriented particles in the presence of population decay. For instance, the generally assumed flat-top multimode beam profile is adapted to a more realistic Gaussian shape, exposing the need for several corrections for accurate anisotropy measurements. In addition, the (selective excitation (photoselection and anisotropy of populations that interact with single or multiple intense polarised laser pulses is demonstrated as function of power density and beam profile. Using example values of real world experiments it is calculated to what extent this effectively orients the ensemble of particles. Finally, the implementation includes the interaction with multiple pulses in addition to depth averaging in optically dense samples. In summary, we show that mathematical

  16. flowCL: ontology-based cell population labelling in flow cytometry

    OpenAIRE

    Courtot, Mélanie; Meskas, Justin; Diehl, Alexander D.; Droumeva, Radina; Gottardo, Raphael; Jalali, Adrin; Taghiyar, Mohammad Jafar; Maecker, Holden T; McCoy, J. Philip; Ruttenberg, Alan; Scheuermann, Richard H.; Brinkman, Ryan R

    2014-01-01

    Motivation: Finding one or more cell populations of interest, such as those correlating to a specific disease, is critical when analysing flow cytometry data. However, labelling of cell populations is not well defined, making it difficult to integrate the output of algorithms to external knowledge sources.

  17. Phenotype overlap in glial cell populations: astroglia, oligodendroglia and NG-2(+ cells

    Directory of Open Access Journals (Sweden)

    Robert eFern

    2015-05-01

    Full Text Available The extent to which NG-2(+ cells form a distinct population separate from astrocytes is central to understanding whether this important cell class is wholly an oligodendrocyte precursor cell (OPC or has additional functions akin to those classically ascribed to astrocytes. Early immuno-staining studies indicate that NG-2(+ cells do not express the astrocyte marker GFAP, but orthogonal reconstructions of double-labelled confocal image stacks here reveal a significant degree of co-expression in individual cells within post-natal day 10 (P10 rat optic nerve (RON and rat cortex. Extensive scanning of various antibody/fixation/embedding approaches identified a protocol for selective post-embedded immuno-gold labelling. This first ultrastructural characterization of identified NG-2(+ cells revealed populations of both OPCs and astrocytes in P10 RON. NG-2(+ astrocytes had classic features including the presence of glial filaments but low levels of glial filament expression were also found in OPCs and myelinating oligodendrocytes. P0 RONs contained few OPCs but positively identified astrocytes were observed to ensheath pre-myelinated axons in a fashion previously described as a definitive marker of the oligodendrocyte lineage. Astrocyte ensheathment was also apparent in P10 RONs, was absent from developing nodes of Ranvier and was never associated with compact myelin. Astrocyte processes were also shown to encapsulate some oligodendrocyte somata. The data indicate that common criteria for delineating astrocytes and oligodendroglia are insufficiently robust and that astrocyte features ascribed to OPCs are likely to arise from misidentification.

  18. Amplification of the spleen macrophage population in malaria: possible role of a factor chemotactic for blood mononuclear cells

    International Nuclear Information System (INIS)

    The mechanism of amplification of the splenic macrophages' population was investigated using mice infected with malaria as a model of an obligate intravascular infection. It was observed that these macrophages derived from blood monocytes rather than by local proliferation in the spleen. A factor, chemotactic for blood mononuclear cells, was present in spleen cells shortly after infection and preceded detectable increases in spleen macrophage number by 48 hours. This factor, in concert with spleen derived macrophage migration inhibition factor, may be important in the amplification of splenic macrophage population in intravascular infections

  19. Fucolipid metabolism as a function of cell population density in normal and murine sarcoma virus-transformed rat cells

    International Nuclear Information System (INIS)

    The incorporation of isotopically labeled fucose into the lipids of normal and murine sarcoma virus-transformed rat cells as a function of cell population density was examined. When normal cells were seeded at low cell density, the levels of the major fucolipids, i.e., fucolipids III and IV, were substantially reduced, but then they increased as the cells approached confluency. This variation in synthesis of fucolipids III and IV appeared to be primarily related to cell density and not to cell growth. Chase experiments revealed that the reduced level of fucolipids III and IV in sparse normal cells is due to decreased synthesis rather than to increased catabolism. In contrast to the observations with normal rat cells, the high level of fucolipid III and the low level of fucolipid IV in murine sarcoma virus-transformed rat cells was shown to be independent of cell population density

  20. PEM Fuel Cells - Fundamentals, Modeling and Applications

    OpenAIRE

    Maher A.R. Sadiq Al-Baghdadi

    2013-01-01

    Part I: Fundamentals Chapter 1: Introduction. Chapter 2: PEM fuel cell thermodynamics, electrochemistry, and performance. Chapter 3: PEM fuel cell components. Chapter 4: PEM fuel cell failure modes. Part II: Modeling and Simulation Chapter 5: PEM fuel cell models based on semi-empirical simulation. Chapter 6: PEM fuel cell models based on computational fluid dynamics. Part III: Applications Chapter 7: PEM fuel cell system design and applications.

  1. PEM Fuel Cells - Fundamentals, Modeling and Applications

    Directory of Open Access Journals (Sweden)

    Maher A.R. Sadiq Al-Baghdadi

    2013-01-01

    Full Text Available Part I: Fundamentals Chapter 1: Introduction. Chapter 2: PEM fuel cell thermodynamics, electrochemistry, and performance. Chapter 3: PEM fuel cell components. Chapter 4: PEM fuel cell failure modes. Part II: Modeling and Simulation Chapter 5: PEM fuel cell models based on semi-empirical simulation. Chapter 6: PEM fuel cell models based on computational fluid dynamics. Part III: Applications Chapter 7: PEM fuel cell system design and applications.

  2. A population-level model from the microscopic dynamics in Escherichia coli chemotaxis via Langevin approximation

    International Nuclear Information System (INIS)

    Recent extensive studies of Escherichia coli (E. coli) chemotaxis have achieved a deep understanding of its microscopic control dynamics. As a result, various quantitatively predictive models have been developed to describe the chemotactic behavior of E. coli motion. However, a population-level partial differential equation (PDE) that rationally incorporates such microscopic dynamics is still insufficient. Apart from the traditional Keller–Segel (K–S) equation, many existing population-level models developed from the microscopic dynamics are integro-PDEs. The difficulty comes mainly from cell tumbles which yield a velocity jumping process. Here, we propose a Langevin approximation method that avoids such a difficulty without appreciable loss of precision. The resulting model not only quantitatively reproduces the results of pathway-based single-cell simulators, but also provides new inside information on the mechanism of E. coli chemotaxis. Our study demonstrates a possible alternative in establishing a simple population-level model that allows for the complex microscopic mechanisms in bacterial chemotaxis

  3. Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling.

    Directory of Open Access Journals (Sweden)

    Matthieu Jacobs

    2016-03-01

    Full Text Available Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-estimation studies to distinguish between competing PD models are lacking. This study compared the ability of static and dynamic in vitro infection models to distinguish between models with different resistance mechanisms and support accurate and precise parameter estimation. Monte Carlo simulations (MCS were performed for models with one susceptible bacterial population without (M1 or with a resting stage (M2, a one population model with adaptive resistance (M5, models with pre-existing susceptible and resistant populations without (M3 or with (M4 inter-conversion, and a model with two pre-existing populations with adaptive resistance (M6. For each model, 200 datasets of the total bacterial population were simulated over 24h using static antibiotic concentrations (256-fold concentration range or over 48h under dynamic conditions (dosing every 12h; elimination half-life: 1h. Twelve-hundred random datasets (each containing 20 curves for static or four curves for dynamic conditions were generated by bootstrapping. Each dataset was estimated by all six models via population PD modeling to compare bias and precision. For M1 and M3, most parameter estimates were unbiased (<10% and had good imprecision (<30%. However, parameters for adaptive resistance and inter-conversion for M2, M4, M5 and M6 had poor bias and large imprecision under static and dynamic conditions. For datasets that only contained viable counts of the total population, common statistical criteria and diagnostic plots did not support sound identification of the true resistance mechanism. Therefore, it seems advisable to quantify resistant bacteria and characterize their MICs and resistance mechanisms to support extended simulations and translate from in vitro experiments to animal infection models and

  4. Population transcriptomics with single-cell resolution: a new field made possible by microfluidics: a technology for high throughput transcript counting and data-driven definition of cell types.

    Science.gov (United States)

    Plessy, Charles; Desbois, Linda; Fujii, Teruo; Carninci, Piero

    2013-02-01

    Tissues contain complex populations of cells. Like countries, which are comprised of mixed populations of people, tissues are not homogeneous. Gene expression studies that analyze entire populations of cells from tissues as a mixture are blind to this diversity. Thus, critical information is lost when studying samples rich in specialized but diverse cells such as tumors, iPS colonies, or brain tissue. High throughput methods are needed to address, model and understand the constitutive and stochastic differences between individual cells. Here, we describe microfluidics technologies that utilize a combination of molecular biology and miniaturized labs on chips to study gene expression at the single cell level. We discuss how the characterization of the transcriptome of each cell in a sample will open a new field in gene expression analysis, population transcriptomics, that will change the academic and biomedical analysis of complex samples by defining them as quantified populations of single cells. PMID:23281054

  5. Model of two infectious diseases in nettle caterpillar population

    Science.gov (United States)

    Firdausi, F. Z.; Nuraini, N.

    2016-04-01

    Palm oil is a vital commodity to the economy of Indonesia. The area of oil palm plantations in Indonesia has increased from year to year. However, the effectiveness of palm oil production is reduced by pest infestation. One of the pest which often infests oil palm plantations is nettle caterpillar. The pest control used in this study is biological control, viz. biological agents given to oil palm trees. This paper describes a mathematical model of two infectious diseases in nettle caterpillar population. The two infectious diseases arise due to two biological agents, namely Bacillus thuringiensis bacterium and parasite which usually attack nettle caterpillars. The derivation of the model constructed in this paper is obtained from ordinary differential equations without time delay. The equilibrium points are analyzed. Two of three equilibrium points are stable if the Routh-Hurwitz criteria are fulfilled. In addition, this paper also presents the numerical simulation of the model which has been constructed.

  6. CFD Simulation of Nanosufur Crystallization Incorporating Population Balance Modeling

    Directory of Open Access Journals (Sweden)

    Fatemeh Golkhou

    2013-01-01

    Full Text Available A physical vapor condensation process for synthesizing nanosized sulfur powder as a precursor for various industries was simulated by the use of computational ?uid dynamic (CFD modeling. The phase change, swirl flow and heat transfer taking place inside the cyclone are analyzed along with particle formation via gas condensation method. The population balance model is a mathematical framework for the modeling of crystal size distribution (CSD and the study of gas-phase changes leading to nucleation of the first solid particles. In this paper the Direct Quadrature Method of Moments is used for solving the transport equations of the moments of the size distribution. The temperature, velocity and particle size distribution ranges inside the cyclone were computed. The results show the formation of nanosulfur particles in 1-7 nm range.

  7. flowCL: ontology-based cell population labelling in flow cytometry

    Science.gov (United States)

    Courtot, Mélanie; Meskas, Justin; Diehl, Alexander D.; Droumeva, Radina; Gottardo, Raphael; Jalali, Adrin; Taghiyar, Mohammad Jafar; Maecker, Holden T.; McCoy, J. Philip; Ruttenberg, Alan; Scheuermann, Richard H.; Brinkman, Ryan R.

    2015-01-01

    Motivation: Finding one or more cell populations of interest, such as those correlating to a specific disease, is critical when analysing flow cytometry data. However, labelling of cell populations is not well defined, making it difficult to integrate the output of algorithms to external knowledge sources. Results: We developed flowCL, a software package that performs semantic labelling of cell populations based on their surface markers and applied it to labelling of the Federation of Clinical Immunology Societies Human Immunology Project Consortium lyoplate populations as a use case. Conclusion: By providing automated labelling of cell populations based on their immunophenotype, flowCL allows for unambiguous and reproducible identification of standardized cell types. Availability and implementation: Code, R script and documentation are available under the Artistic 2.0 license through Bioconductor (http://www.bioconductor.org/packages/devel/bioc/html/flowCL.html). Contact: rbrinkman@bccrc.ca Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25481008

  8. Cell cycle delays in synchronized cell populations following irradiation with heavy ions

    International Nuclear Information System (INIS)

    Mammalian cells subjected to irradiation with heavy ions were investigated for cell cycle delays. The ions used for this purpose included Ne ions in the LET range of 400 keV/μm just as well as uranium ions of 16225 keV/μm. The qualitative changes in cell cycle progression seen after irradiation with Ne ions (400 keV/μm) were similar to those observed in connection with X-rays. Following irradiation with extremely heavy ions (lead, uranium) the majority of cells were even at 45 hours still found to be in the S phase or G2M phase of the first cycle. The delay cross section 'σ-delay' was introduced as a quantity that would permit quantitative comparisons to be carried out between the changes in cell progression and other effects of radiation. In order to evaluate the influence of the number of hits on the radiation effect observed, the size of the cell nucleus was precisely determined with reference to the cycle phase and local cell density. A model to simulate those delay effects was designed in such a way that account is taken of this probability of hit and that the results can be extrapolated from the delay effects after X-irradiation. On the basis of the various probabilities of hit for cells at different cycle stages a model was developed to ascertain the intensified effect following fractionated irradiation with heavy ions. (orig./MG)

  9. PKreport: report generation for checking population pharmacokinetic model assumptions

    Directory of Open Access Journals (Sweden)

    Li Jun

    2011-05-01

    Full Text Available Abstract Background Graphics play an important and unique role in population pharmacokinetic (PopPK model building by exploring hidden structure among data before modeling, evaluating model fit, and validating results after modeling. Results The work described in this paper is about a new R package called PKreport, which is able to generate a collection of plots and statistics for testing model assumptions, visualizing data and diagnosing models. The metric system is utilized as the currency for communicating between data sets and the package to generate special-purpose plots. It provides ways to match output from diverse software such as NONMEM, Monolix, R nlme package, etc. The package is implemented with S4 class hierarchy, and offers an efficient way to access the output from NONMEM 7. The final reports take advantage of the web browser as user interface to manage and visualize plots. Conclusions PKreport provides 1 a flexible and efficient R class to store and retrieve NONMEM 7 output, 2 automate plots for users to visualize data and models, 3 automatically generated R scripts that are used to create the plots; 4 an archive-oriented management tool for users to store, retrieve and modify figures, 5 high-quality graphs based on the R packages, lattice and ggplot2. The general architecture, running environment and statistical methods can be readily extended with R class hierarchy. PKreport is free to download at http://cran.r-project.org/web/packages/PKreport/index.html.

  10. Border Collision Bifurcations in a Generalized Model of Population Dynamics

    Directory of Open Access Journals (Sweden)

    Lilia M. Ladino

    2016-01-01

    Full Text Available We analyze the dynamics of a generalized discrete time population model of a two-stage species with recruitment and capture. This generalization, which is inspired by other approaches and real data that one can find in literature, consists in considering no restriction for the value of the two key parameters appearing in the model, that is, the natural death rate and the mortality rate due to fishing activity. In the more general case the feasibility of the system has been preserved by posing opportune formulas for the piecewise map defining the model. The resulting two-dimensional nonlinear map is not smooth, though continuous, as its definition changes as any border is crossed in the phase plane. Hence, techniques from the mathematical theory of piecewise smooth dynamical systems must be applied to show that, due to the existence of borders, abrupt changes in the dynamic behavior of population sizes and multistability emerge. The main novelty of the present contribution with respect to the previous ones is that, while using real data, richer dynamics are produced, such as fluctuations and multistability. Such new evidences are of great interest in biology since new strategies to preserve the survival of the species can be suggested.

  11. Establishment and characterization of primary lung cancer cell lines from Chinese population

    Institute of Scientific and Technical Information of China (English)

    Chao ZHENG; Yi-hua SUN; Xiao-lei YE; Hai-quan CHEN; Hong-bin JI

    2011-01-01

    Aim: To establish and characterize primary lung cancer cell lines from Chinese population.Methods: Lung cancer specimens or pleural effusions were collected from Chinese lung cancer patients and cultured in vitro with ACL4 medium (for non-small cell lung carcinomas (NSCLC)) or HITES medium (for small cell lung carcinomas (SCLC)) supplemented with 5%FBS. All cell lines were maintained in culture for more than 25 passages. Most of these cell lines were further analyzed for oncogenic mutations, karyotype, cell growth kinetics, and tumorigenicity in nude mice.Results: Eight primary cell lines from Chinese lung cancer patients were established and characterized, including seven NSCLC cell lines and one SCLC cell line. Five NSCLC cell lines were found to harbor epidermal growth factor receptor (EGFR) kinase domain mutations.Conclusion: These well-characterized primary lung cancer cell lines from Chinese population provide a unique platform for future studies of the ethnic differences in lung cancer biology and drug response.

  12. Epidemic Oscillations in a Meta-Population Model

    Directory of Open Access Journals (Sweden)

    Dong Hu

    2013-05-01

    Full Text Available The individual mobility and the underlying spatial structure of populations play an important role in epidemic spreading processes. In this study, effects of these two factors on epidemic dynamics in metapopulation systems are investigated by using a discrete Susceptible-Infective-Recovered-Susceptible (SIRS model. Our extensive numerical Monte Carlo simulations show that both irregular and regular oscillations can be observed, depending on the life cycles of epidemic diseases. Furthermore, the amplitudes of regular oscillations are enlarged by decreasing the move cycle. It is also found that heterogeneous connectivity patterns among subpopulations result in a global infection under fast movement, compared to homogeneous connectivity patterns.

  13. Effect of Intrinsic Noise on the Phenotype of Cell Populations Featuring Solution Multiplicity: An Artificial lac Operon Network Paradigm.

    Science.gov (United States)

    Aviziotis, Ioannis G; Kavousanakis, Michail E; Boudouvis, Andreas G

    2015-01-01

    Heterogeneity in cell populations originates from two fundamentally different sources: the uneven distribution of intracellular content during cell division, and the stochastic fluctuations of regulatory molecules existing in small amounts. Discrete stochastic models can incorporate both sources of cell heterogeneity with sufficient accuracy in the description of an isogenic cell population; however, they lack efficiency when a systems level analysis is required, due to substantial computational requirements. In this work, we study the effect of cell heterogeneity in the behaviour of isogenic cell populations carrying the genetic network of lac operon, which exhibits solution multiplicity over a wide range of extracellular conditions. For such systems, the strategy of performing solely direct temporal solutions is a prohibitive task, since a large ensemble of initial states needs to be tested in order to drive the system--through long time simulations--to possible co-existing steady state solutions. We implement a multiscale computational framework, the so-called "equation-free" methodology, which enables the performance of numerical tasks, such as the computation of coarse steady state solutions and coarse bifurcation analysis. Dynamically stable and unstable solutions are computed and the effect of intrinsic noise on the range of bistability is efficiently investigated. The results are compared with the homogeneous model, which neglects all sources of heterogeneity, with the deterministic cell population balance model, as well as with a stochastic model neglecting the heterogeneity originating from intrinsic noise effects. We show that when the effect of intrinsic source of heterogeneity is intensified, the bistability range shifts towards higher extracellular inducer concentration values. PMID:26185999

  14. Effect of Intrinsic Noise on the Phenotype of Cell Populations Featuring Solution Multiplicity: An Artificial lac Operon Network Paradigm.

    Directory of Open Access Journals (Sweden)

    Ioannis G Aviziotis

    Full Text Available Heterogeneity in cell populations originates from two fundamentally different sources: the uneven distribution of intracellular content during cell division, and the stochastic fluctuations of regulatory molecules existing in small amounts. Discrete stochastic models can incorporate both sources of cell heterogeneity with sufficient accuracy in the description of an isogenic cell population; however, they lack efficiency when a systems level analysis is required, due to substantial computational requirements. In this work, we study the effect of cell heterogeneity in the behaviour of isogenic cell populations carrying the genetic network of lac operon, which exhibits solution multiplicity over a wide range of extracellular conditions. For such systems, the strategy of performing solely direct temporal solutions is a prohibitive task, since a large ensemble of initial states needs to be tested in order to drive the system--through long time simulations--to possible co-existing steady state solutions. We implement a multiscale computational framework, the so-called "equation-free" methodology, which enables the performance of numerical tasks, such as the computation of coarse steady state solutions and coarse bifurcation analysis. Dynamically stable and unstable solutions are computed and the effect of intrinsic noise on the range of bistability is efficiently investigated. The results are compared with the homogeneous model, which neglects all sources of heterogeneity, with the deterministic cell population balance model, as well as with a stochastic model neglecting the heterogeneity originating from intrinsic noise effects. We show that when the effect of intrinsic source of heterogeneity is intensified, the bistability range shifts towards higher extracellular inducer concentration values.

  15. Risk Factors for Renal Cell Cancer in a Japanese Population

    OpenAIRE

    Washio, Masakazu; Mori, Mitsuru

    2009-01-01

    The incidence of renal cell cancer has been increasing worldwide. Although the incidence of renal cell cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. In this paper, we would like to introduce the result of our studies, which evaluate the risk factors for renal cell cancer in Japan. Hypertension, diabetes mellitus, kidney diseases, fondness for fatty food and black tea showed an increased risk of renal cell carcinoma whil...

  16. Explicit kinetic heterogeneity: mechanistic models for interpretation of labeling data in heterogeneous populations

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory

    2008-01-01

    Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system. Deuterium, in the form of deuterated glucose or heavy water, can be used to measure rates of proliferation and death of lymphocytes in vivo. Inferring these rates from labeling and delabeling curves has been subject to considerable debate with different groups suggesting different mathematical models for that purpose. We show that the three models that are most commonly used are in fact mathematically identical and differ only in their interpretation of the estimated parameters. By extending these previous models, we here propose a more mechanistic approach for the analysis of data from deuterium labeling experiments. We construct a model of 'kinetic heterogeneity' in which the total cell population consists of many sub-populations with different rates of cell turnover. In this model, for a given distribution of the rates of turnover, the predicted fraction of labeled DNA accumulated and lost can be calculated. Our model reproduces several previously made experimental observations, such as a negative correlation between the length of the labeling period and the rate at which labeled DNA is lost after label cessation. We demonstrate the reliability of the new explicit kinetic heterogeneity model by applying it to artificially generated datasets, and illustrate its usefulness by fitting experimental data. In contrast to previous models, the explicit kinetic heterogeneity model (1) provides a mechanistic way of interpreting labeling data; (2) allows for a non-exponential loss of labeled cells during delabeling, and (3) can be used to describe data with variable labeling length.

  17. Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling.

    Science.gov (United States)

    Jacobs, Matthieu; Grégoire, Nicolas; Couet, William; Bulitta, Jurgen B

    2016-03-01

    Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-estimation studies to distinguish between competing PD models are lacking. This study compared the ability of static and dynamic in vitro infection models to distinguish between models with different resistance mechanisms and support accurate and precise parameter estimation. Monte Carlo simulations (MCS) were performed for models with one susceptible bacterial population without (M1) or with a resting stage (M2), a one population model with adaptive resistance (M5), models with pre-existing susceptible and resistant populations without (M3) or with (M4) inter-conversion, and a model with two pre-existing populations with adaptive resistance (M6). For each model, 200 datasets of the total bacterial population were simulated over 24h using static antibiotic concentrations (256-fold concentration range) or over 48h under dynamic conditions (dosing every 12h; elimination half-life: 1h). Twelve-hundred random datasets (each containing 20 curves for static or four curves for dynamic conditions) were generated by bootstrapping. Each dataset was estimated by all six models via population PD modeling to compare bias and precision. For M1 and M3, most parameter estimates were unbiased (sound identification of the true resistance mechanism. Therefore, it seems advisable to quantify resistant bacteria and characterize their MICs and resistance mechanisms to support extended simulations and translate from in vitro experiments to animal infection models and ultimately patients. PMID:26967893

  18. A Model Combining Oscillations and Attractor Dynamics for Generation of Grid Cell Firing

    OpenAIRE

    Michael E Hasselmo; Brandon, Mark P.

    2012-01-01

    Different models have been able to account for different features of the data on grid cell firing properties, including the relationship of grid cells to cellular properties and network oscillations. This paper describes a model that combines elements of two major classes of models of grid cells: models using interference of oscillations and models using attractor dynamics. This model includes a population of units with oscillatory input representing input from the medial septum. These units ...

  19. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K., E-mail: mishima-k@dent.showa-u.ac.jp

    2013-05-01

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.

  20. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities

  1. The stem cell population of the human colon crypt: analysis via methylation patterns.

    Directory of Open Access Journals (Sweden)

    Pierre Nicolas

    2007-03-01

    Full Text Available The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism. In a stem cell-niche scenario, sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cells within a niche and the niche succession time, the methylation/demethylation process, and the randomness due to sampling. As a consequence, methylation pattern studies can reveal niche characteristics but also require appropriate statistical methods. The analysis of methylation patterns sampled from colon crypts is a prototype of such a study. Previous analyses were based on forward simulation of the cell content of the whole crypt and subsequent comparisons between simulated and experimental data using a few statistics as a proxy to summarize the data. In this paper we develop a more powerful method to analyze these data based on coalescent modelling and Bayesian inference. Results support a scenario where the colon crypt is maintained by a high number of stem cells; the posterior indicates a number greater than eight and the posterior mode is between 15 and 20. The results also provide further evidence for synergistic effects in the methylation/demethylation process that could for the first time be quantitatively assessed through their long-term consequences such as the coexistence of hypermethylated and hypomethylated patterns in the same colon crypt.

  2. Birthdating studies reshape models for pituitary gland cell specification.

    Science.gov (United States)

    Davis, Shannon W; Mortensen, Amanda H; Camper, Sally A

    2011-04-15

    The intermediate and anterior lobes of the pituitary gland are derived from an invagination of oral ectoderm that forms Rathke's pouch. During gestation proliferating cells are enriched around the pouch lumen, and they appear to delaminate as they exit the cell cycle and differentiate. During late mouse gestation and the postnatal period, anterior lobe progenitors re-enter the cell cycle and expand the populations of specialized, hormone-producing cells. At birth, all cell types are present, and their localization appears stratified based on cell type. We conducted a birth dating study of Rathke's pouch derivatives to determine whether the location of specialized cells at birth is correlated with the timing of cell cycle exit. We find that all of the anterior lobe cell types initiate differentiation concurrently with a peak between e11.5 and e13.5. Differentiation of intermediate lobe melanotropes is delayed relative to anterior lobe cell types. We discovered that specialized cell types are not grouped together based on birth date and are dispersed throughout the anterior lobe. Thus, the apparent stratification of specialized cells at birth is not correlated with cell cycle exit. Thus, the currently popular model of cell specification, dependent upon timing of extrinsic, directional gradients of signaling molecules, needs revision. We propose that signals intrinsic to Rathke's pouch are necessary for cell specification between e11.5 and e13.5 and that cell-cell communication likely plays an important role in regulating this process. PMID:21262217

  3. Simplified Model for the Population Dynamics Involved in a Malaria Crisis

    International Nuclear Information System (INIS)

    We adapt a simple model of predator-prey to the population involved in a crisis of malaria. The study is made only in the stream blood inside the human body except for the liver. Particularly we look at the dynamics of the malaria parasites 'merozoites' and their interaction with the blood components, more specifically the red blood cells (RBC) and the immune response grouped under the white blood cells (WBC). The stability analysis of the system reveals an important practical direction to investigate as regards the ratio WBC over RBC since it is a fundamental parameter that characterizes stable regions. The model numerically presents a wide range of possible features of the disease. Even with its simplified form, the model not only recovers well-known results but in addition predicts possible hidden phenomenon and an interesting clinical feature a malaria crisis. (author)

  4. Noise-induced extinction in Bazykin-Berezovskaya population model

    Science.gov (United States)

    Bashkirtseva, Irina; Ryashko, Lev

    2016-07-01

    A nonlinear Bazykin-Berezovskaya prey-predator model under the influence of parametric stochastic forcing is considered. Due to Allee effect, this conceptual population model even in the deterministic case demonstrates both local and global bifurcations with the change of predator mortality. It is shown that random noise can transform system dynamics from the regime of coexistence, in equilibrium or periodic modes, to the extinction of both species. Geometry of attractors and separatrices, dividing basins of attraction, plays an important role in understanding the probabilistic mechanisms of these stochastic phenomena. Parametric analysis of noise-induced extinction is carried out on the base of the direct numerical simulation and new analytical stochastic sensitivity functions technique taking into account the arrangement of attractors and separatrices.

  5. Mathematical model of temephos resistance in Aedes aegypti mosquito population

    Science.gov (United States)

    Aldila, D.; Nuraini, N.; Soewono, E.; Supriatna, A. K.

    2014-03-01

    Aedes aegypti is the main vector of dengue disease in many tropical and sub-tropical countries. Dengue became major public concern in these countries due to the unavailability of vaccine or drugs for dengue disease in the market. Hence, the only way to control the spread of DF and DHF is by controlling the vectors carrying the disease, for instance with fumigation, temephos or genetic manipulation. Many previous studies conclude that Aedes aegypti may develop resistance to many kind of insecticide, including temephos. Mathematical model for transmission of temephos resistance in Aedes aegypti population is discussed in this paper. Nontrivial equilibrium point of the system and the corresponding existence are shown analytically. The model analysis have shown epidemiological trends condition that permits the coexistence of nontrivial equilibrium is given analytically. Numerical results are given to show parameter sensitivity and some cases of worsening effect values for illustrating possible conditions in the field.

  6. Coculture with endothelial cells reduces the population of cycling LeX neural precursors but increases that of quiescent cells with a side population phenotype

    International Nuclear Information System (INIS)

    Neural stem cell proliferation and differentiation are regulated by external cues from their microenvironment. As endothelial cells are closely associated with neural stem cell in brain germinal zones, we investigated whether endothelial cells may interfere with neurogenesis. Neural precursor cells (NPC) from telencephalon of EGFP mouse embryos were cocultured in direct contact with endothelial cells. Endothelial cells did not modify the overall proliferation and apoptosis of neural cells, albeit they transiently delayed spontaneous apoptosis. These effects appeared to be specific to endothelial cells since a decrease in proliferation and a raise in apoptosis were observed in cocultures with fibroblasts. Endothelial cells stimulated the differentiation of NPC into astrocytes and into neurons, whereas they reduced differentiation into oligodendrocytes in comparison to adherent cultures on polyornithine. Determination of NPC clonogenicity and quantification of LeX expression, a marker for NPC, showed that endothelial cells decreased the number of cycling NPC. On the other hand, the presence of endothelial cells increased the number of neural cells having 'side population' phenotype, another marker reported on NPC, which we have shown to contain quiescent cells. Thus, we show that endothelial cells may regulate neurogenesis by acting at different level of NPC differentiation, proliferation and quiescence

  7. Chase-and-run between adjacent cell populations promotes directional collective migration

    Science.gov (United States)

    Theveneau, Eric; Steventon, Benjamin; Scarpa, Elena; Garcia, Simon; Trepat, Xavier; Streit, Andrea; Mayor, Roberto

    2016-01-01

    Collective cell migration in morphogenesis and cancer progression often involves the coordination of multiple cell types. How reciprocal interactions between adjacent cell populations lead to new emergent behaviours remains unknown. Here we studied the interaction between Neural Crest (NC) cells, a highly migratory cell population, and placodal cells, an epithelial tissue that contributes to sensory organs. We found that NC cells “chase” placodal cells by chemotaxis, while placodal cells “run” when contacted by NC. Chemotaxis to Sdf1 underlies the chase, while repulsion involving PCP and N-Cadherin signalling is responsible for the run. This “chase-and-run” requires the generation of asymmetric forces, which depend on local inhibition of focal adhesions. The cell interactions described here are essential for correct NC migration and for segregation of placodes in vivo and are likely to represent a general mechanism of coordinated migration. PMID:23770678

  8. 3-Bromopyruvate inhibits cell proliferation and induces apoptosis in CD133+ population in human glioma.

    Science.gov (United States)

    Xu, Dong-Qiang; Tan, Xiao-Yu; Zhang, Bao-Wei; Wu, Tao; Liu, Ping; Sun, Shao-Jun; Cao, Yin-Guang

    2016-03-01

    The study was aimed to investigate the role of 3-bromopyruvate in inhibition of CD133+ U87 human glioma cell population growth. The results demonstrated that 3-bromopyruvate inhibited the viability of both CD133+ and parental cells derived from U87 human glioma cell line. However, the 3-bromopyruvate-induced inhibition in viability was more prominent in CD133+ cells at 10 μM concentration after 48 h. Treatment of CD133+ cells with 3-bromopyruvate caused reduction in cell population and cell size, membrane bubbling, and degradation of cell membranes. Hoechst 33258 staining showed condensation of chromatin material and fragmentation of DNA in treated CD133+ cells after 48 h. 3-Bromopyruvate inhibited the migration rate of CD133+ cells significantly compared to the parental cells. Flow cytometry revealed that exposure of CD133+ cells to 3-bromopyruvate increased the cell population in S phase from 24.5 to 37.9 % with increase in time from 12 to 48 h. In addition, 3-bromopyruvate significantly enhanced the expression of Bax and cleaved caspase 3 in CD133+ cells compared to the parental cells. Therefore, 3-bromopyruvate is a potent chemotherapeutic agent for the treatment of glioma by targeting stem cells selectively. PMID:26453119

  9. Sexual Reproduction in a Simple Growth Population Model

    Science.gov (United States)

    Lemos, Carlos Gentil Oro; Santos, Marcio

    2012-05-01

    One of the most important characteristics in the survival of a species is related to the kind of reproduction responsible for the offspring generation. However, only in the last years the role played by sexual reproduction has been investigated. Then, for a better understanding of this kind of process we introduce, in this work, a surface reaction model that describes the role of the sexual reproduction. In our model two different elements of the species, representing male and female, can interact to reproduce a new element. The sex of this new element is chosen with a given probability and in order to take into account the mortality rate we introduce another kind of individual. The value of the spatial density of this element remains constant during the time evolution of the system. The model is studied using Monte Carlo simulations and mean field approximation. Depending on the values of the control parameters of the model, the system can attain two stationary states: In one of them the population survives and in the other it can be extinguished. Besides, accordingly to our results, the phase diagram of the model shows a discontinuous transition between these two states.

  10. Modeling particle population balances in fluidized-bed wood gasifiers

    International Nuclear Information System (INIS)

    An unsteady model is developed for the particle size distribution in fluidized-bed reactors including fragmentation, abrasion, elutriation and the chemical reactions of wood gasification. Based on the assumption of constant conditions (gas composition, temperature, velocity) of the surrounding atmosphere, an analytical solution is developed for the distribution of sizes belonging to the classes of mother and fine particles. It is found that for the typical feed sizes (minimum above 3 × 10−2 mm) and the usual maximum size of fine particles (2.4 × 10−3 mm), the behavior of fine particles is quasi-steady with respect to mother particles. The numerical solution of the quasi-steady formulation of particle population balances is also coupled with a two-phase (bubble and emulsion), three-zone (bed, splash zone and freeboard) model for a bubbling fluidized-bed reactor, giving predictions of the producer gas composition in agreement with measurements for air gasification of wood. - Highlights: • Particle size distribution in fluidized-bed gasifiers is modeled. • Fragmentation, abrasion, elutriation and the chemical reactions of wood gasification are described. • A quasi-steady behavior of the fine particles with respect to mother particles is found. • The particle size distribution model is coupled with a transport model for a bubbling fluidized bed. • Good agreement is obtained between measurements and predictions for highly variable operating conditions

  11. Comparison of manufactured and modeled solar cell

    OpenAIRE

    Strachala, D.; Hylský, J.

    2015-01-01

    The aim of the work is to compare the model of monocrystalline silicon solar cell in PC1D with the real solar cell structure in terms of using a model in manufacture process. Real solar cell was firstly measured and analyzed to determine input parameters for a simulation and then realized in free available PC1D software. Degree of conformity of modeled and real solar cell was in the end established for basic prediction of solar cell parameters before manufacturing process.

  12. Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells.

    Science.gov (United States)

    Kegel, Victoria; Deharde, Daniela; Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

    2016-01-01

    Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine(1). Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models. PMID:27077489

  13. Aging and Immortality in a Cell Proliferation Model

    CERN Document Server

    Antal, T; Trugman, S A; Redner, S

    2007-01-01

    We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.

  14. Awareness of Stem cells & Health Implications of SHED found in Pediatric Dentition among Indian Population

    OpenAIRE

    Goomer, Pallvi; Sidhu, Arshpreet Kaur; Tuli, Preety; Kansal, Shinam; Bansal, Kanishka; Thakre, Gauri R

    2014-01-01

    Background: Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED (stem cells from human exfoliated deciduous teeth) were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. The present study was carried out to assess the knowledge, awareness...

  15. An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy

    DEFF Research Database (Denmark)

    Bach, Lars Arve; Bentzen, Søren; Alsner, Jan;

    2001-01-01

    interpretations of gene therapy. Two prototypical strategies for gene therapy are suggested, both of them leading to extinction of the malignant phenotype: one approach would be to reduce the relative proportion of the cooperating malignant cell type below a certain critical value. Another approach would be to......Evolutionary games have been applied as simple mathematical models of populations where interactions between individuals control the dynamics. Recently, it has been proposed to use this type of model to describe the evolution of tumour cell populations with interactions between cells. We extent the...... analysis to allow for synergistic effects between cells. A mathematical model of a tumour cell population is presented in which population-level synergy is assumed to originate through the interaction of triplets of cells. A threshold of two cooperating cells is assumed to be required to produce a...

  16. Nuisance Source Population Modeling for Radiation Detection System Analysis

    International Nuclear Information System (INIS)

    A major challenge facing the prospective deployment of radiation detection systems for homeland security applications is the discrimination of radiological or nuclear 'threat sources' from radioactive, but benign, 'nuisance sources'. Common examples of such nuisance sources include naturally occurring radioactive material (NORM), medical patients who have received radioactive drugs for either diagnostics or treatment, and industrial sources. A sensitive detector that cannot distinguish between 'threat' and 'benign' classes will generate false positives which, if sufficiently frequent, will preclude it from being operationally deployed. In this report, we describe a first-principles physics-based modeling approach that is used to approximate the physical properties and corresponding gamma ray spectral signatures of real nuisance sources. Specific models are proposed for the three nuisance source classes - NORM, medical and industrial. The models can be validated against measured data - that is, energy spectra generated with the model can be compared to actual nuisance source data. We show by example how this is done for NORM and medical sources, using data sets obtained from spectroscopic detector deployments for cargo container screening and urban area traffic screening, respectively. In addition to capturing the range of radioactive signatures of individual nuisance sources, a nuisance source population model must generate sources with a frequency of occurrence consistent with that found in actual movement of goods and people. Measured radiation detection data can indicate these frequencies, but, at present, such data are available only for a very limited set of locations and time periods. In this report, we make more general estimates of frequencies for NORM and medical sources using a range of data sources such as shipping manifests and medical treatment statistics. We also identify potential data sources for industrial source frequencies, but leave the task of

  17. Nuisance Source Population Modeling for Radiation Detection System Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sokkappa, P; Lange, D; Nelson, K; Wheeler, R

    2009-10-05

    A major challenge facing the prospective deployment of radiation detection systems for homeland security applications is the discrimination of radiological or nuclear 'threat sources' from radioactive, but benign, 'nuisance sources'. Common examples of such nuisance sources include naturally occurring radioactive material (NORM), medical patients who have received radioactive drugs for either diagnostics or treatment, and industrial sources. A sensitive detector that cannot distinguish between 'threat' and 'benign' classes will generate false positives which, if sufficiently frequent, will preclude it from being operationally deployed. In this report, we describe a first-principles physics-based modeling approach that is used to approximate the physical properties and corresponding gamma ray spectral signatures of real nuisance sources. Specific models are proposed for the three nuisance source classes - NORM, medical and industrial. The models can be validated against measured data - that is, energy spectra generated with the model can be compared to actual nuisance source data. We show by example how this is done for NORM and medical sources, using data sets obtained from spectroscopic detector deployments for cargo container screening and urban area traffic screening, respectively. In addition to capturing the range of radioactive signatures of individual nuisance sources, a nuisance source population model must generate sources with a frequency of occurrence consistent with that found in actual movement of goods and people. Measured radiation detection data can indicate these frequencies, but, at present, such data are available only for a very limited set of locations and time periods. In this report, we make more general estimates of frequencies for NORM and medical sources using a range of data sources such as shipping manifests and medical treatment statistics. We also identify potential data sources for industrial

  18. Bioluminescence imaging of leukemia cell lines in vitro and in mouse xenografts: effects of monoclonal and polyclonal cell populations on intensity and kinetics of photon emission

    Directory of Open Access Journals (Sweden)

    Christoph Sandra

    2013-01-01

    Full Text Available Abstract Background We investigated the utility of bioluminescence imaging (BLI using firefly luciferase in monoclonal and polyclonal populations of leukemia cells in vitro and in vivo. Methods Monoclonal and polyclonal human lymphoid and myeloid leukemia cell lines transduced with firefly luciferase were used for BLI. Results Kinetics and dynamics of bioluminescence signal were cell line dependent. Luciferase expression decreased significantly over time in polyclonal leukemia cells in vitro. Transplantation of polyclonal luciferase-tagged cells in mice resulted in inconsistent signal intensity. After selection of monoclonal cell populations, luciferase activity was stable, equal kinetic and dynamic of bioluminescence intensity and strong correlation between cell number and light emission in vitro were observed. We obtained an equal development of leukemia burden detected by luciferase activity in NOD-scid-gamma mice after transplantation of monoclonal populations. Conclusion The use of monoclonal leukemia cells selected for stable and equal luciferase activity is recommended for experiments in vitro and xenograft mouse models. The findings are highly significant for bioluminescence imaging focused on pre-clinical drug development.

  19. An example of population-level risk assessments for small mammals using individual-based population models

    DEFF Research Database (Denmark)

    Schmitt, Walter; Auteri, Domenica; Bastiansen, Finn;

    2016-01-01

    This article presents a case study demonstrating the application of 3 individual-based, spatially explicit population models (IBMs, also known as agent-based models) in ecological risk assessments to predict long-term effects of a pesticide to populations of small mammals. The 3 IBMs each used...... differing internal model design and scenarios, results indicated in all 3 cases low population sensitivity unless FungicideX was applied at very high (×10) rates. Recovery from local population impacts was generally fast. Only when patch extinctions occured in simulations of intentionally high acute toxic...... a hypothetical fungicide (FungicideX) in different scenarios: spraying in cereals (common vole, Microtus arvalis), spraying in orchards (field vole, Microtus agrestis), and cereal seed treatment (wood mouse, Apodemus sylvaticus). Each scenario used existing model landscapes, which differed greatly in size...

  20. The propagation of uncertainties in stellar population synthesis modeling III: model calibration, comparison, and evaluation

    OpenAIRE

    Conroy, Charlie; Gunn, James E.

    2009-01-01

    Stellar population synthesis (SPS) provides the link between the stellar and dust content of galaxies and their observed spectral energy distributions. In the present work we perform a comprehensive calibration of our own flexible SPS (FSPS) model against a suite of data. Several public SPS models are intercompared, including the models of Bruzual & Charlot (BC03), Maraston (M05) and FSPS. The relative strengths and weaknesses of these models are evaluated, with the following conclusions: 1) ...

  1. Development of some intestinal endocrine cell populations in water buffalo

    Directory of Open Access Journals (Sweden)

    L. Castaldo

    2010-02-01

    Full Text Available The occurrence and distribution of different endocrine cell types in the gastrointestinal tract of large and small domestic mammals have been extensively studied (Ceccarelli et al. 1995; Agungpriyono et al.2000. Some studies have been also carried out on the ontogeny of gut endocrine cells in mammals (Ono et al. 1994, and only few in ruminant. (Kitamura et al. 1985; Guilloteau et al. 1997. In order to complete a previous study regarding postnatal development of intestinal endocrine cells (Lucini et al. 1999, in this study we report the appearance and distribution of some endocrine cell types in the gut of water buffalo during foetal development.

  2. 75 FR 54351 - Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop

    Science.gov (United States)

    2010-09-07

    ... HUMAN SERVICES Food and Drug Administration Cell and Gene Therapy Clinical Trials in Pediatric... public workshop entitled ``Cell and Gene Therapy Clinical Trials in Pediatric Populations.'' The purpose... therapy clinical researchers, and other stakeholders regarding best practices related to cell and...

  3. Active house: A contemporary housing model for flood affected population

    Directory of Open Access Journals (Sweden)

    Stratimirović Tatjana

    2015-01-01

    Full Text Available The effectiveness of architectural knowledge in the struggle for a better future can be seen in the attitude that a good design or a good architectural solution, does not belong solely to the privileged ones as an improvement of the basic requirements, rather quite the opposite, that it is created as a response to a need. The goal of physical and emotional wellbeing, combined with a long term strategy for reducing the negative impact of the built environment by converting it into a positive influence upon the natural ecosystem, brings together and advances bioclimatic principles, architectural design and sustainable construction in the contemporary housing model dubbed the Active House. The Active House Workshop was held, as part of a wider student initiative New Housing Models for Flood Affected Population, at the University of Belgrade - Faculty of Architecture. The purpose of the campaign was to provide help to flood affected communities and assistance in efforts for repairing buildings in Serbia, hit by the severe floods of May 2014. Students came up with nine design solutions for small family homes, which incorporate the principles of Active House into existing construction techniques. In an architectural context, when concerning repair work after flooding, the need to consider problems related to contemporary living conditions through the ‘active’ category is seen in a new understanding of nature which allows the replacement of a passive restoration model, with an active models for designing in interaction with the environment.

  4. Nuclear β-catenin and CD44 upregulation characterize invasive cell populations in non-aggressive MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    novel model for breast cancer metastasis without requiring constitutive EMT and are categorized as a 'metastable phenotype', which can be distinguished from both epithelial and mesenchymal cells. The alterations and characteristics of MCF-7-14 cells, especially nuclear β-catenin and CD44 upregulation, may characterize invasive cell populations in breast cancer

  5. Glioblastoma formation from cell population depleted of Prominin1-expressing cells.

    Directory of Open Access Journals (Sweden)

    Kenji Nishide

    Full Text Available Prominin1 (Prom1, also known as CD133 in human has been widely used as a marker for cancer stem cells (CSCs, which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM. However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreER(TM, and generated glioma-initiating cells (GICs-LD by overexpressing both the SV40 Large T antigen and an oncogenic H-Ras(L61 in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs-LD (GICs-DTA form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.

  6. A dynamic urban air pollution population exposure assessment study using model and population density data derived by mobile phone traffic

    Science.gov (United States)

    Gariazzo, Claudio; Pelliccioni, Armando; Bolignano, Andrea

    2016-04-01

    A dynamic city-wide air pollution exposure assessment study has been carried out for the urban population of Rome, Italy, by using time resolved population distribution maps, derived by mobile phone traffic data, and modelled air pollutants (NO2, O3 and PM2.5) concentrations obtained by an integrated air dispersion modelling system. More than a million of persons were tracked during two months (March and April 2015) for their position within the city and its surroundings areas, with a time resolution of 15 min and mapped over an irregular grid system with a minimum resolution of 0.26 × 0.34 Km2. In addition, demographics information (as gender and age ranges) were available in a separated dataset not connected with the total population one. Such BigData were matched in time and space with air pollution model results and then used to produce hourly and daily resolved cumulative population exposures during the studied period. A significant mobility of population was identified with higher population densities in downtown areas during daytime increasing of up to 1000 people/Km2 with respect to nigh-time one, likely produced by commuters, tourists and working age population. Strong variability (up to ±50% for NO2) of population exposures were detected as an effect of both mobility and time/spatial changing in pollutants concentrations. A comparison with the correspondent stationary approach based on National Census data, allows detecting the inability of latter in estimating the actual variability of population exposure. Significant underestimations of the amount of population exposed to daily PM2.5 WHO guideline was identified for the Census approach. Very small differences (up to a few μg/m3) on exposure were detected for gender and age ranges population classes.

  7. Regeneration of transplanted intact cell populations in lethally irradiated hydra

    International Nuclear Information System (INIS)

    A single irradiation of the hydra Pelmatohydra robusta with 0.4 to 10 kR of x rays induced no lethal effects at all, while animals exposed to 40 kR ceased to produce a bud within 24 hr and died within a limited period of time, varying from 10 to 14 days at 250C, and from 28 to 50 days at 100C. This lethal dose of x rays inhibited the proliferation of the cells completely and destroyed interstitial cells. When a small cell mass, which was too small to regenerate alone, was transplanted from the subhypostomal region of an intact animal into the subhypostomal region of the irradiated hydra, the recipient began to produce buds by the proliferation of the graft cells. However, the transplantation of intact peduncle tissue, in which mitotic figures and interstitial cells rarely occurred, failed to produce new buds

  8. Transcriptional modulation in a leukocyte-depleted splenic cell population during prion disease.

    Science.gov (United States)

    Huzarewich, Rhiannon L C H; Medina, Sarah; Robertson, Catherine; Parchaliuk, Debra; Booth, Stephanie A

    2011-01-01

    Prion replication in the periphery precedes neuroinvasion in many experimental rodent scrapie models, and in natural sheep scrapie and chronic wasting disease (CWD) in cervids. Prions propagate in the germinal centers of secondary lymphoid organs and are strongly associated with follicular dendritic cells (FDC) and possibly circulating dendritic cells and macrophages. Given the importance of lymphoid organs in prion disease transmission and pathogenesis, gene expression studies may reveal host factors or biological pathways related to prion replication and accumulation. A procedure was developed to enrich for FDC, dendritic cells, and macrophages prior to the investigation of transcriptional alterations in murine splenic cells during prion pathogenesis. In total, 1753 transcripts exhibited fold changes greater than three (false discovery rates less than 2%) in this population isolated from spleens of prion-infected versus uninfected mice. The gene for the small leucine-rich proteoglycan decorin (DCN) was one of the genes most overexpressed in infected mice, and the splenic protein levels mirrored this in mice infected with scrapie as well as bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD). A number of groups of functionally related genes were also significantly decreased in infected spleens. These included genes related to iron metabolism and homeostasis, pathways that have also been implicated in prion pathogenesis in the brain. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as a pool of potential surrogate markers for the early detection and diagnosis of some prion diseases. PMID:22043911

  9. Unexpected diversity in populations of the many-celled magnetotactic prokaryote.

    Science.gov (United States)

    Simmons, Sheri L; Edwards, Katrina J

    2007-01-01

    The many-celled magnetotactic prokaryote (MMP) is an uncultivated, highly motile aggregate of 10-30 cells containing numerous chains of greigite (Fe(3)S(4)) magnetosomes. It is unique to marine environments and is abundant in slightly sulfidic sediments of the Little Sippewissett salt marsh (Falmouth, MA). We sequenced 16s rDNA genes from a natural population of MMP and found five lineages separated by at least 5% sequence divergence. Fluorescent in situ hybridization probes for three of these lineages showed significant variation in their relative abundances across a seasonal cycle in marsh productivity. The MMP should therefore be considered a separate genus in the delta-proteobacteria rather than a single species as previously thought. All cells in each aggregate express identical SSU rRNAs, suggesting that the aggregates are composed of a single MMP phylotype. This observation supports a model of the MMP as comprised of clonal cells which reproduce by binary fission of the aggregate. PMID:17227425

  10. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate

    OpenAIRE

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B.; Fuxe, Jonas; Shoshan, Maria

    2012-01-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility...

  11. Differentiation of Effector CD4 T Cell Populations*

    OpenAIRE

    Zhu, Jinfang; Yamane, Hidehiro; Paul, William E.

    2010-01-01

    CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and r...

  12. Indium 111 white blood cell scanning in the pediatric population

    International Nuclear Information System (INIS)

    Indium-111 leukocyte scanning is a reliable means of locating acute infection in adults, but its use in the pediatric population has not been extensively documented. The results of scans on 30 children retrospectively reviewed are presented. Acute infections were detected in 15 to 16 patients (94% sensitivity) with one false negative scan. There were 8 truly negative and 6 falsely positive studies (57% specificity). (orig.)

  13. A critical stress model for cell motility

    OpenAIRE

    Mehrayin Mehrnush; Farmanzad Farhad; Mozafari Masoud; Vashaee Daryoosh; Tayebi Lobat

    2012-01-01

    Abstract A detailed theoretical model that combines the conventional viscoelastic continuum description of cell motion with a dynamic active stress is presented. The model describes the ameboid cells movement comprising of protrusion and adhesion of the front edge followed by detachment and movement of the tail. Unlike the previous viscoelastic descriptions in which the cell movement is steady, the presented model describes the “walking” of the cell in response to specific active stress compo...

  14. Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation

    OpenAIRE

    Wright, Pamela B.; McEntegart, Anne; McCarey, David; McInnes, Iain B.; Siebert, Stefan; Milling, Simon W F

    2015-01-01

    Objective. AS is a systemic inflammatory disease of the SpA family. Polymorphisms at loci including HLA-B27, IL-23R and ERAP-1 directly implicate immune mechanisms in AS pathogenesis. Previously, in an SpA model, we identified HLA-B27–mediated effects on dendritic cells that promoted disease-associated Th17 cells. Here we extend these studies to AS patients using deep immunophenotyping of candidate pathogenic cell populations. The aim of our study was to functionally characterize the immune p...

  15. Multifunction Co-culture Model for Evaluating Cell–Cell Interactions

    OpenAIRE

    Bogdanowicz, Danielle R.; Lu, Helen H.

    2014-01-01

    Interactions within the same cell population (homotypic) and between different cell types (heterotypic) are essential for tissue development, repair, and homeostasis. To elucidate the underlying mechanisms of these cellular interactions, co-culture models have been used extensively to investigate the role of cell–cell physical contact, autocrine and/or paracrine interactions on cell function, as well as stem cell differentiation. Specifically, the mixed co-culture model is often optimal for i...

  16. Modeling the Role of the Cell Cycle in Regulating Proteus mirabilis Swarm-Colony Development

    OpenAIRE

    Ayati, Bruce P

    2005-01-01

    We present models and computational results which indicate that the spatial and temporal regularity seen in Proteus mirabilis swarm-colony development is largely an expression of a sharp age of dedifferentiation in the cell cycle from motile swarmer cells to immotile dividing cells (also called swimmer or vegetative cells.) This contrasts strongly with reaction-diffusion models of Proteus behavior that ignore or average out the age structure of the cell population and instead use only density...

  17. Modelling future oil production, population and the economy

    Energy Technology Data Exchange (ETDEWEB)

    Laherrere, Jean

    2003-07-01

    Most published data on energy, population and the economy are unreliable. In many cases, authors have political motives, selectively choosing data from a wide range of uncertainty to give a desired image. In addition to the uncertainty of the measurements themselves, as in the case of population or the confidentiality of the oil reserves, they often indulge in manipulation. A so-called hedonistic factor distorts the calculation of GDP in the United States; and the definition of the Proved Reserves by the Securities and Exchange Commission gives rise to 'reserve growth'. OPEC misreports its oil reserves because its quotas depend upon the reported reserves, and the reserves were overestimated in the Soviet Union because economic and technical constraints were ignored. Our present culture of eternal growth makes the word 'decline' politically incorrect, but constant growth is unsustainable in a finite world. Growth is the Santa Claus of the modern age who is supposed to provide welfare and retirement for our children and us. All natural events, when measured over their full life, can be modelled under one or more cycles, as in the Fourier analysis. This cyclical nature corresponds with the finite nature of the Universe; everything that is born will die, whether we speak of the solar system, the Earth, or human species. What goes up must come down. The Russian population is already declining and Europe's will soon do so too. This basic understanding was recognised by the celebrated King Hubbert when he made his famous prediction in 1956 that US oil production would peak in 1970. But, in fact, he oversimplified by showing a single peak. In reality, US oil production had a secondary peak (93% of the first one) in 1985, reflecting the entry of Alaskan production, which itself peaked in 1988. A symmetrical oil cycle reflects a large number of independent producers, acting randomly, but in many cases economic and political factors disturb the

  18. Connecting multiple spatial scales to decode the population activity of grid cells

    OpenAIRE

    Stemmler, Martin; Mathis, Alexander; Andreas V. M Herz

    2015-01-01

    Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from m...

  19. Genetic diversity in normal cell populations is the earliest stage of oncogenesis leading to intra-tumor heterogeneity

    Directory of Open Access Journals (Sweden)

    Cory L Howk

    2013-04-01

    Full Text Available Random mutations and epigenetic alterations provide a rich substrate for microevolutionary phenomena to occur in proliferating epithelial tissues. Genetic diversity resulting from random mutations in normal cells is critically important for understanding the genetic basis of oncogenesis. However, evaluation of the cell-specific role of individual (epi-genetic alterations in living tissues is extremely difficult from a direct experimental perspective. We have developed a theoretical model for uterine epithelial cell proliferation. Computational simulations have shown that a base-line mutation rate of two mutations per cell division is sufficient to explain sporadic endometrial cancer as a rare evolutionary consequence with an incidence similar to that reported in SEER data. Simulation of the entire oncogenic process has allowed us to analyze the features of the tumor initiating cells and their clonal expansion. Analysis of the malignant features of individual cancer cells, such as de-differentiation status, proliferation potential, and immortalization status, permits a mathematical characterization of malignancy and a comparison of intra-tumor heterogeneity between individual tumors. We found, under the conditions specified, that cancer stem cells account for approximately 7% of the total cancer cell population. Taken together, our mathematical modeling describes the genetic diversity and evolution in a normal cell population at the early stages of oncogenesis and characterizes intra-tumor heterogeneity. This model has explored the role of accumulation of a large number of genetic alterations in oncogenesis as an alternative to traditional biological approaches emphasizing the driving role of a small number of genetic mutations, and this accumulation, along with environmental factors, has a significant impact on the growth advantage of and selection pressure on individual cancer cells and the resulting tumor composition and progression.

  20. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

    Directory of Open Access Journals (Sweden)

    Kaoru Miyazaki

    Full Text Available BACKGROUND: Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay. METHODOLOGY/PRINCIPAL FINDINGS: ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells. CONCLUSIONS/SIGNIFICANCE: We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo

  1. Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

    International Nuclear Information System (INIS)

    Granulosa cell tumours (GCTs) are frequently seen in menopausal women and are relatively indolent. Although the physiological properties of normal granulosa cells have been studied extensively, little is known about the molecular mechanism of GCT progression. Here, we characterise the unique behavioural properties of a granulosa tumour cell line, KGN cells, for the molecular analysis of GCT progression. Population doubling was carried out to examine the proliferation capacity of KGN cells. Moreover, the invasive capacity of these cells was determined using the in vitro invasion assay. The expression level of tumour markers in KGN cells at different passages was then determined by Western blot analysis. Finally, the growth and metastasis of KGN cells injected subcutaneously (s.c.) into nude mice was observed 3 months after injection. During in vitro culture, the advanced passage KGN cells grew 2-fold faster than the early passage cells, as determined by the population doubling assay. Moreover, we found that the advanced passage cells were 2-fold more invasive than the early passage cells. The expression pattern of tumour markers, such as p53, osteopontin, BAX and BAG-1, supported the notion that with passage, KGN cells became more aggressive. Strikingly, KGN cells at both early and advanced passages metastasized to the bowel when injected s.c. into nude mice. In addition, more tumour nodules were formed when the advanced passage cells were implanted. KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo

  2. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

    Directory of Open Access Journals (Sweden)

    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  3. The Future of Whole-Cell Modeling

    OpenAIRE

    Macklin, Derek N.; Ruggero, Nicholas A.; Covert, Markus W.

    2014-01-01

    Integrated whole-cell modeling is poised to make a dramatic impact on molecular and systems biology, bioengineering, and medicine — once certain obstacles are overcome. From our group’s experience building a whole-cell model of Mycoplasma genitalium, we identified several significant challenges to building models of more complex cells. Here we review and discuss these challenges in seven areas: (1) experimental interrogation, (2) data curation, (3) model building and integration, (4) accelera...

  4. In vitro expansion of the mammary stem/progenitor cell population by xanthosine treatment

    Directory of Open Access Journals (Sweden)

    Choudhary Ratan K

    2012-06-01

    Full Text Available Abstract Background Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore are of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo, and hepatic and hair follicle stem cells in vitro. In the latter, xanthosine promoted the symmetrical division of hepatic and hair follicle stem cells. The objective of this study was to determine if treating primary cultures of bovine mammary epithelial cells (MEC with xanthosine increases the stem/progenitor cell population by promoting symmetrical division of mammary stem cells. Results In vitro treatment with xanthosine increased the population of MEC during the exponential phase of cell growth, reducing the doubling time from 86 h in control cultures to 60 h in xanthosine-treated cultures. The bromodeoxyuridine (BrdU labeling index and the proportion of MEC in S-phase both were increased by xanthosine treatment, indicating that increased cell accretion was due to increased cell proliferation. Analysis of daughter-pairs indicated that xanthosine promoted a shift from asymmetric to symmetric cell division. Moreover, the 30 % increase in symmetric cell division was concomitant with an increase in the proportion of MEC that were positive for a putative stem cell marker (FNDC3B and a trend toward increased telomerase activity. These results suggest that xanthosine treatment in vitro can increase cell proliferation, promote symmetric cell division and enhance stem/progenitor cell activity. Conclusions Xanthosine treatment increased the proliferation rate of bovine MEC in vitro. This was likely to be mediated by an increase in the proportion of stem/progenitor cells in the MEC population due to promotion of symmetrical stem cell division by xanthosine.

  5. Microfluidic isolation of cancer-cell-derived microvesicles from hetergeneous extracellular shed vesicle populations.

    Science.gov (United States)

    Santana, Steven M; Antonyak, Marc A; Cerione, Richard A; Kirby, Brian J

    2014-12-01

    Extracellular shed vesicles, including exosomes and microvesicles, are disseminated throughout the body and represent an important conduit of cell communication. Cancer-cell-derived microvesicles have potential as a cancer biomarker as they help shape the tumor microenvironment to promote the growth of the primary tumor and prime the metastatic niche. It is likely that, in cancer cell cultures, the two constituent extracellular shed vesicle subpopulations, observed in dynamic light scattering, represent an exosome population and a cancer-cell-specific microvesicle population and that extracellular shed vesicle size provides information about provenance and cargo. We have designed and implemented a novel microfluidic technology that separates microvesicles, as a function of diameter, from heterogeneous populations of cancer-cell-derived extracellular shed vesicles. We measured cargo carried by the microvesicle subpopulation processed through this microfluidic platform. Such analyses could enable future investigations to more accurately and reliably determine provenance, functional activity, and mechanisms of transformation in cancer. PMID:25342569

  6. Networks and Models with Heterogeneous Population Structure in Epidemiology

    Science.gov (United States)

    Kao, R. R.

    Heterogeneous population structure can have a profound effect on infectious disease dynamics, and is particularly important when investigating “tactical” disease control questions. At times, the nature of the network involved in the transmission of the pathogen (bacteria, virus, macro-parasite, etc.) appears to be clear; however, the nature of the network involved is dependent on the scale (e.g. within-host, between-host, or between-population), the nature of the contact, which ranges from the highly specific (e.g. sexual acts or needle sharing at the person-to-person level) to almost completely non-specific (e.g. aerosol transmission, often over long distances as can occur with the highly infectious livestock pathogen foot-and-mouth disease virus—FMDv—at the farm-to-farm level, e.g. Schley et al. in J. R. Soc. Interface 6:455-462, 2008), and the timescale of interest (e.g. at the scale of the individual, the typical infectious period of the host). Theoretical approaches to examining the implications of particular network structures on disease transmission have provided critical insight; however, a greater challenge is the integration of network approaches with data on real population structures. In this chapter, some concepts in disease modelling will be introduced, the relevance of selected network phenomena discussed, and then results from real data and their relationship to network analyses summarised. These include examinations of the patterns of air traffic and its relation to the spread of SARS in 2003 (Colizza et al. in BMC Med., 2007; Hufnagel et al. in Proc. Natl. Acad. Sci. USA 101:15124-15129, 2004), the use of the extensively documented Great Britain livestock movements network (Green et al. in J. Theor. Biol. 239:289-297, 2008; Robinson et al. in J. R. Soc. Interface 4:669-674, 2007; Vernon and Keeling in Proc. R. Soc. Lond. B, Biol. Sci. 276:469-476, 2009) and the growing interest in combining contact structure data with phylogenetics to

  7. Modeling Rett Syndrome with Stem Cells

    OpenAIRE

    Walsh, Ryan M.; Hochedlinger, Konrad

    2010-01-01

    The discovery that somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) raised the exciting possibility of modeling diseases with patient-specific cells. Marchetto et al. (2010) now use iPSC technology to generate, characterize, and treat an in vitro model for the autism spectrum disorder, Rett syndrome.

  8. Identification of a population of cells with hematopoietic stem cell properties in mouse aorta-gonad-mesonephros cultures

    International Nuclear Information System (INIS)

    The aorta-gonad-mesonephros (AGM) region is a primary source of definitive hematopoietic cells in the midgestation mouse embryo. In cultures of dispersed AGM regions, adherent cells containing endothelial cells are observed first, and then non-adherent hematopoietic cells are produced. Here we report on the characterization of hematopoietic cells that emerge in the AGM culture. Based on the expression profiles of CD45 and c-Kit, we defined three cell populations: CD45low c-Kit+ cells that had the ability to form hematopoietic cell colonies in methylcellulose media and in co-cultures with stromal cells; CD45low c-Kit- cells that showed a granulocyte morphology; CD45high c-Kitlow/- that exhibited a macrophage morphology. In co-cultures of OP9 stromal cells and freshly prepared AGM cultures, CD45low c-Kit+ cells from the AGM culture had the abilities to reproduce CD45low c-Kit+ cells and differentiate into CD45low c-Kit- and CD45high c-Kitlow/- cells, whereas CD45low c-Kit- and CD45high c-Kitlow/- did not produce CD45low c-Kit+ cells. Furthermore, CD45low c-Kit+ cells displayed a long-term repopulating activity in adult hematopoietic tissue when transplanted into the liver of irradiated newborn mice. These results indicate that CD45low c-Kit+ cells from the AGM culture have the potential to reconstitute multi-lineage hematopoietic cells

  9. Characterization of bone cells isolated on discontinuous Percoll gradients: distribution in sequentially derived populations.

    Science.gov (United States)

    Wong, G L; Ng, M C; Calabrese, D W; Swartzendruber, D E

    1991-09-01

    Bone cell populations obtained by sequential digestion of newborn mouse calvariae remain morphologically heterogeneous despite well-documented biochemical differences. Fractionation of these populations on Percoll gradient reveal three major cell groups of low, intermediate, and high buoyant density (1.056, 1.070, and 1.095 g/ml) that are present in different ratios in early and late released populations. Cells of low and intermediate density dominate in early released populations. In contrast, late released populations contain mostly high-density cells. Basal levels of alkaline phosphatase are highest in cells of intermediate buoyant density. All cells respond to PTH with cAMP production and morphologic transformation, but biochemical responses to PTH, such as secretion of insulin-like growth factor I (IGF-I) and stimulation of alkaline phosphatase activity, occur mostly in cells of intermediate density. These data suggest that (1) subclasses of osteoblasts can be further separated by density and (2) PTH effects on alkaline phosphatase activity and IGF-I secretion are probably expressed by osteoblasts of a certain subclass and/or stage of development. PMID:1665004

  10. A differential equation with state-dependent delay from cell population biology

    Science.gov (United States)

    Getto, Philipp; Waurick, Marcus

    2016-04-01

    We analyze a differential equation, describing the maturation of a stem cell population, with a state-dependent delay, which is implicitly defined via the solution of an ODE. We elaborate smoothness conditions for the model ingredients, in particular vital rates, that guarantee the existence of a local semiflow and allow to specify the linear variational equation. The proofs are based on theoretical results of Hartung et al. combined with implicit function arguments in infinite dimensions. Moreover we elaborate a criterion for global existence for differential equations with state-dependent delay. To prove the result we adapt a theorem by Hale and Lunel to the C1-topology and use a result on metric spaces from Diekmann et al.

  11. Microselection - Affinity Selecting Antibodies against a Single Rare Cell in a Heterogeneous Population

    DEFF Research Database (Denmark)

    Sørensen, Morten Draeby; Agerholm, Inge Errebo; Christensen, Britta; Kølvraa, Steen; Kristensen, Peter

    2010-01-01

    antibodies. Here we have generated a microselection method allowing antibody selection, by phage display, targeting a single cell in a heterogeneous population. One K562 cell (female origin) was positioned on glass-slide among millions of lymphocytes from male donor, identifying the K562 cell by FISH (XX......). Several single cell selections were performed on such individual slides. The phage particles bound to the target cell is protected by a minute disc, while inactivating all remaining phage by UV-irradiation; leaving only the phage bound to the target cell viable. We hereby retrieved up to eight antibodies...

  12. Demographic population model for American shad: will access to additional habitat upstream of dams increase population sizes?

    Science.gov (United States)

    Harris, Julianne E.; Hightower, Joseph E.

    2012-01-01

    American shad Alosa sapidissima are in decline in their native range, and modeling possible management scenarios could help guide their restoration. We developed a density-dependent, deterministic, stage-based matrix model to predict the population-level results of transporting American shad to suitable spawning habitat upstream of dams on the Roanoke River, North Carolina and Virginia. We used data on sonic-tagged adult American shad and oxytetracycline-marked American shad fry both above and below dams on the Roanoke River with information from other systems to estimate a starting population size and vital rates. We modeled the adult female population over 30 years under plausible scenarios of adult transport, effective fecundity (egg production), and survival of adults (i.e., to return to spawn the next year) and juveniles (from spawned egg to age 1). We also evaluated the potential effects of increased survival for adults and juveniles. The adult female population size in the Roanoke River was estimated to be 5,224. With no transport, the model predicted a slow population increase over the next 30 years. Predicted population increases were highest when survival was improved during the first year of life. Transport was predicted to benefit the population only if high rates of effective fecundity and juvenile survival could be achieved. Currently, transported adults and young are less likely to successfully out-migrate than individuals below the dams, and the estimated adult population size is much smaller than either of two assumed values of carrying capacity for the lower river; therefore, transport is not predicted to help restore the stock under present conditions. Research on survival rates, density-dependent processes, and the impacts of structures to increase out-migration success would improve evaluation of the potential benefits of access to additional spawning habitat for American shad.

  13. Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease

    Science.gov (United States)

    Li, Wei; Liu, Liangyi; Gomez, Aurelie; Zhang, Jilu; Ramadan, Abdulraouf; Zhang, Qing; Choi, Sung W.; Zhang, Peng; Greenson, Joel K.; Liu, Chen; Jiang, Di; Virts, Elizabeth; Kelich, Stephanie L.; Chu, Hong Wei; Flynn, Ryan; Blazar, Bruce R.; Hanenberg, Helmut; Hanash, Samir; Paczesny, Sophie

    2016-01-01

    Gastrointestinal graft-versus-host-disease (GI-GVHD) is a life-threatening complication occurring after allogeneic hematopoietic cell transplantation (HCT), and a blood biomarker that permits stratification of HCT patients according to their risk of developing GI-GVHD would greatly aid treatment planning. Through in-depth, large-scale proteomic profiling of presymptomatic samples, we identified a T cell population expressing both CD146, a cell adhesion molecule, and CCR5, a chemokine receptor that is upregulated as early as 14 days after transplantation in patients who develop GI-GVHD. The CD4+CD146+CCR5+ T cell population is Th17 prone and increased by ICOS stimulation. shRNA knockdown of CD146 in T cells reduced their transmigration through endothelial cells, and maraviroc, a CCR5 inhibitor, reduced chemotaxis of the CD4+CD146+CCR5+ T cell population toward CCL14. Mice that received CD146 shRNA–transduced human T cells did not lose weight, showed better survival, and had fewer CD4+CD146+CCR5+ T cells and less pathogenic Th17 infiltration in the intestine, even compared with mice receiving maraviroc with control shRNA– transduced human T cells. Furthermore, the frequency of CD4+CD146+CCR5+ Tregs was increased in GI-GVHD patients, and these cells showed increased plasticity toward Th17 upon ICOS stimulation. Our findings can be applied to early risk stratification, as well as specific preventative therapeutic strategies following HCT. PMID:27195312

  14. Delay of cell cycle progression after X-irradiation of synchronized populations of human cells (NHIK 3025) in culture

    International Nuclear Information System (INIS)

    The effect of X-irradiation on the cell cycle progression of synchronized populations of the human cell line NHIK 3035 has been studied in terms of the radiation-induced delay of DNA replication and cell division. Results were obtained by flow cytometric measurements of histograms of cellular DNA content and parallel use of conventional methods for cell cycle analysis, such as pulse labelling with (3H) thymidine and counting of cell numbers. The two sets of methods were generally in good agreement, but the advantages of employing two independent techniques are pointed out. Irradiation was found to have a minor influence on DNA replication. As compared with unirradiated populations, half-completed DNA replication was 20-30 min delayed in populations given 580 rad in mid-G1 or 290 rad in early S. Cell cycle progression was markedly delayed in G2. The sensitivity induction of this delay was 0.6 min/rad for populations irradiated in mid-G1, and 1.4 min/rad for populations irradiated in early S. (author)

  15. Neurochemical phenotype and birthdating of specific cell populations in the chick retina

    Directory of Open Access Journals (Sweden)

    Karin da Costa calaza

    2010-09-01

    Full Text Available The chick embryo is one of the most traditional models in developing neuroscience and its visual system has been one of the most exhaustively studied. The retina has been used as a model for studying the development of the nervous system. Here, we describe the morphological features that characterize each stage of the retina development and studies of the neurogenesis period of some specific neurochemical subpopulations of retinal cells by using a combination of immunohistochemistry and autoradiography of tritiated-thymidine. It could be concluded that the proliferation period of dopaminergic, GABAergic, cholinoceptive and GABAceptive cells does not follow a common rule of the neurogenesis. In addition, some specific neurochemical cell groups can have a restrict proliferation period when compared to the total cell population.O embrião de galinha é um dos mais tradicionais modelosde estudos da neurociência do desenvolvimento e seu sistema visual tem sido um dos mais exaustivamente estudado. Aretina tem sido utilizada como modelo para estudar o desenvolvimento do sistema nervoso. Aqui, nós descrevemos as características morfológicas que caracterizam cada estádio da retina em desenvolvimento e os estudos do período de neurogênese de algumas subpopulações de células neuroquímicamente específicas da retina usando uma combinação de imunohistoquímica e autoradiografia de timidina-tritiada. Conclui-se que o período de proliferação das células dopaminérgicas, GABAérgicas, colinoceptivas e GABAceptivas não segue uma regra comum. Além disso, alguns grupos celulares neuroquimicamente distintos podem ter um período de proliferaçãomais restrito quando comparado ao da população total destas células.

  16. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    Energy Technology Data Exchange (ETDEWEB)

    Lushaj, Entela B., E-mail: lushaj@surgery.wisc.edu [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States); Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States)

    2012-06-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  17. Estimation of the target stem-cell population size in chronic myeloid leukemogenesis

    International Nuclear Information System (INIS)

    Estimation of the number of hematopoietic stem cells capable of causing chronic myeloid leukemia (CML) is relevant to the development of biologically based risk models of radiation-induced CML. Through a comparison of the age structure of CML incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program and the age structure of chromosomal translocations found in healthy subjects, the number of CML target stem cells is estimated for individuals above 20 years of age. The estimation involves three steps. First, CML incidence among adults is fit to an exponentially increasing function of age. Next, assuming a relatively short waiting time distribution between BCR-ABL induction and the appearance of CML, an exponential age function with rate constants fixed to the values found for CML is fitted to the translocation data. Finally, assuming that translocations are equally likely to occur between any two points in the genome, the parameter estimates found in the first two steps are used to estimate the number of target stem cells for CML. The population-averaged estimates of this number are found to be 1.86 x 108 for men and 1.21 x 108 for women; the 95% confidence intervals of these estimates are (1.34 x 108, 2.50 x 108) and (0.84 x 108, 1.83 x 108), respectively. (orig.)

  18. The epidermis comprises autonomous compartments maintained by distinct stem cell populations

    DEFF Research Database (Denmark)

    Page, Mahalia E; Lombard, Patrick; Ng, Felicia;

    2013-01-01

    populations. In contrast, upon wounding, stem cell progeny from multiple compartments acquire lineage plasticity and make permanent contributions to regenerating tissue. We further show that oncogene activation in Lrig1(+ve) cells drives hyperplasia but requires auxiliary stimuli for tumor formation...

  19. Entrainment and Control of Bacterial Populations: An in Silico Study over a Spatially Extended Agent Based Model.

    Science.gov (United States)

    Mina, Petros; Tsaneva-Atanasova, Krasimira; Bernardo, Mario di

    2016-07-15

    We extend a spatially explicit agent based model (ABM) developed previously to investigate entrainment and control of the emergent behavior of a population of synchronized oscillating cells in a microfluidic chamber. Unlike most of the work in models of control of cellular systems which focus on temporal changes, we model individual cells with spatial dependencies which may contribute to certain behavioral responses. We use the model to investigate the response of both open loop and closed loop strategies, such as proportional control (P-control), proportional-integral control (PI-control) and proportional-integral-derivative control (PID-control), to heterogeinities and growth in the cell population, variations of the control parameters and spatial effects such as diffusion in the spatially explicit setting of a microfluidic chamber setup. We show that, as expected from the theory of phase locking in dynamical systems, open loop control can only entrain the cell population in a subset of forcing periods, with a wide variety of dynamical behaviors obtained outside these regions of entrainment. Closed-loop control is shown instead to guarantee entrainment in a much wider region of control parameter space although presenting limitations when the population size increases over a certain threshold. In silico tracking experiments are also performed to validate the ability of classical control approaches to achieve other reference behaviors such as a desired constant output or a linearly varying one. All simulations are carried out in BSim, an advanced agent-based simulator of microbial population which is here extended ad hoc to include the effects of control strategies acting onto the population. PMID:27110835

  20. Combined CFD/Population Balance Model for Gas Hydrate Particle Size Prediction in Turbulent Pipeline Flow

    Science.gov (United States)

    Balakin, Boris V.; Hoffmann, Alex C.; Kosinski, Pawel; Istomin, Vladimir A.; Chuvilin, Evgeny M.

    2010-09-01

    A combined computational fluid dynamics/population balance model (CFD-PBM) is developed for gas hydrate particle size prediction in turbulent pipeline flow. The model is based on a one-moment population balance technique, which is coupled with flow field parameters computed using commercial CFD software. The model is calibrated with a five-moment, off-line population balance model and validated with experimental data produced in a low-pressure multiphase flow loop.

  1. Predators inhibit brain cell proliferation in natural populations of electric fish, Brachyhypopomus occidentalis.

    Science.gov (United States)

    Dunlap, Kent D; Tran, Alex; Ragazzi, Michael A; Krahe, Rüdiger; Salazar, Vielka L

    2016-02-10

    Compared with laboratory environments, complex natural environments promote brain cell proliferation and neurogenesis. Predators are one important feature of many natural environments, but, in the laboratory, predatory stimuli tend to inhibit brain cell proliferation. Often, laboratory predatory stimuli also elevate plasma glucocorticoids, which can then reduce brain cell proliferation. However, it is unknown how natural predators affect cell proliferation or whether glucocorticoids mediate the neurogenic response to natural predators. We examined brain cell proliferation in six populations of the electric fish, Brachyhypopomus occidentalis, exposed to three forms of predator stimuli: (i) natural variation in the density of predatory catfish; (ii) tail injury, presumably from predation attempts; and (iii) the acute stress of capture. Populations with higher predation pressure had lower density of proliferating (PCNA+) cells, and fish with injured tails had lower proliferating cell density than those with intact tails. However, plasma cortisol did not vary at the population level according to predation pressure or at the individual level according to tail injury. Capture stress significantly increased cortisol, but only marginally decreased cell proliferation. Thus, it appears that the presence of natural predators inhibits brain cell proliferation, but not via mechanisms that depend on changes in basal cortisol levels. This study is the first demonstration of predator-induced alteration of brain cell proliferation in a free-living vertebrate. PMID:26842566

  2. Optimized Stem Cell Detection Using the DyeCycle-Triggered Side Population Phenotype

    Science.gov (United States)

    Boesch, Maximilian; Wolf, Dominik; Sopper, Sieghart

    2016-01-01

    Tissue and cancer stem cells are highly attractive target populations for regenerative medicine and novel potentially curative anticancer therapeutics. In order to get a better understanding of stem cell biology and function, it is essential to reproducibly identify these stem cells from biological samples for subsequent characterization or isolation. ABC drug transporter expression is a hallmark of stem cells. This is utilized to identify (cancer) stem cells by exploiting their dye extrusion properties, which is referred to as the “side population assay.” Initially described for high-end flow cytometers equipped with ultraviolet lasers, this technique is now also amenable for a broader scientific community, owing to the increasing availability of violet laser-furnished cytometers and the advent of DyeCycle Violet (DCV). Here, we describe important technical aspects of the DCV-based side population assay and discuss potential pitfalls and caveats helping scientists to establish a valid and reproducible DCV-based side population assay. In addition, we investigate the suitability of blue laser-excitable DyeCycle dyes for side population detection. This knowledge will help to improve and standardize detection and isolation of stem cells based on their expression of ABC drug transporters. PMID:26798352

  3. Morphokinetics of mesenterial lymphatic node cell populations at exposure of gold nanoparticles in experiment

    Directory of Open Access Journals (Sweden)

    O.V. Zlobina

    2012-12-01

    Full Text Available The influence of gold nanoparticles with different size (1-3 nm, 15 nm and 50 nm on the morphokinetics of mesenterial lymphatic node cell populations of healthy laboratory animals was investigated. It was established that the oral administration of gold nanoparticles caused the changes of morphokinetics of mesenterial lymphatic node cell populations. The morphological reorganizations in the mesenterial lymphatic nodes testified about activation of migration processes, the proliferation and differentiation processes of immunocompetent cells, which assumes the presence of immunomodulating action of gold nanoparticles.

  4. From individual behavior to metapopulation dynamics: unifying the patchy population and classic metapopulation models.

    OpenAIRE

    Ovaskainen, Otso; Hanski, Ilkka

    2004-01-01

    Spatially structured populations in patchy habitats show much variation in migration rate, from patchy populations in which individuals move repeatedly among habitat patches to classic metapopulations with infrequent migration among discrete populations. To establish a common framework for population dynamics in patchy habitats, we describe an individual-based model (IBM) involving a diffusion approximation of correlated random walk of individual movements. As an example, we apply the model t...

  5. Ecological effects of ionizing radiation on population and ecosystem: a computational model ecosystem study

    International Nuclear Information System (INIS)

    Ecosystem is a self-sustaining system of complexity, and their responses to the impacts are synergistic and subjected to the demographic stochasticity of the species, environmental stochasticity and randomness. Environmental fate and effects of radiation has ranged from observable DNA damage of the cell to the fare on tissues, individual, population, community and ecosystems. The quantitative, systematic individual-based model, SIM-COSM was developed to simulate impacts of radiation exposure and other toxicants on an aquatic microbial ecosystem (microcosm). The microcosm consists of heterotroph ciliate protozoa (Tetrahymena thermophila B) as a consumer, autotroph flagellate algae (Euglena gracilis Z) as a producer and saprotroph bacteria (Escherichia coli DH5) as a decomposer. The symbiosis among microbes is self-organized by realizing material cycle and sustained for more than 2 years after inoculation. The system can not afford to lose any one of the microbes to maintain its sustainability. Experimental ecotoxicological tests for (a) gamma radiation, (b) Manganese ions and (c) Gadolinium are summarized. Population dynamics of microbes in Microcosm and its computer simulations by SIM-COSM are shown together in a figure. Population dynamics in Microcosm and SIM-COSM exposed to 500 Gy of gamma-radiation at 50 days after inoculation are shown also in a figure. To take the effects on the interactions between species and environment into account, one option is to put the ecotoxicity tests as experimental micro ecosystem study and theoretical model ecosystem analysis. (M. Suetake)

  6. Data-driven modelling of structured populations a practical guide to the integral projection model

    CERN Document Server

    Ellner, Stephen P; Rees, Mark

    2016-01-01

    This book is a “How To” guide for modeling population dynamics using Integral Projection Models (IPM) starting from observational data. It is written by a leading research team in this area and includes code in the R language (in the text and online) to carry out all computations. The intended audience are ecologists, evolutionary biologists, and mathematical biologists interested in developing data-driven models for animal and plant populations. IPMs may seem hard as they involve integrals. The aim of this book is to demystify IPMs, so they become the model of choice for populations structured by size or other continuously varying traits. The book uses real examples of increasing complexity to show how the life-cycle of the study organism naturally leads to the appropriate statistical analysis, which leads directly to the IPM itself. A wide range of model types and analyses are presented, including model construction, computational methods, and the underlying theory, with the more technical material in B...

  7. Ability of matrix models to explain the past and predict the future of plant populations.

    Science.gov (United States)

    McEachern, Kathryn; Crone, Elizabeth E.; Ellis, Martha M.; Morris, William F.; Stanley, Amanda; Bell, Timothy; Bierzychudek, Paulette; Ehrlen, Johan; Kaye, Thomas N.; Knight, Tiffany M.; Lesica, Peter; Oostermeijer, Gerard; Quintana-Ascencio, Pedro F.; Ticktin, Tamara; Valverde, Teresa; Williams, Jennifer I.; Doak, Daniel F.; Ganesan, Rengaian; Thorpe, Andrea S.; Menges, Eric S.

    2013-01-01

    Uncertainty associated with ecological forecasts has long been recognized, but forecast accuracy is rarely quantified. We evaluated how well data on 82 populations of 20 species of plants spanning 3 continents explained and predicted plant population dynamics. We parameterized stage-based matrix models with demographic data from individually marked plants and determined how well these models forecast population sizes observed at least 5 years into the future. Simple demographic models forecasted population dynamics poorly; only 40% of observed population sizes fell within our forecasts' 95% confidence limits. However, these models explained population dynamics during the years in which data were collected; observed changes in population size during the data-collection period were strongly positively correlated with population growth rate. Thus, these models are at least a sound way to quantify population status. Poor forecasts were not associated with the number of individual plants or years of data. We tested whether vital rates were density dependent and found both positive and negative density dependence. However, density dependence was not associated with forecast error. Forecast error was significantly associated with environmental differences between the data collection and forecast periods. To forecast population fates, more detailed models, such as those that project how environments are likely to change and how these changes will affect population dynamics, may be needed. Such detailed models are not always feasible. Thus, it may be wiser to make risk-averse decisions than to expect precise forecasts from models.

  8. Including excitons in semiconductor solar cell modelling

    OpenAIRE

    Burgelman, Marc; Minnaert, Ben

    2005-01-01

    Excitons are marginally important in classical semiconductor device physics, and their treatment is not included in standard solar cell modelling. However, in organic semiconductors and solar cells, the role of excitons is essential, as the primary effect of light absorption is exciton generation, and free electrons and holes are created by exciton dissociation. First steps to include excitons in solar cell modelling were presented by Green 1996 and Zhang 1998. Their model was restricted to a...

  9. Evaluation of observation-fused regional air quality model results for population air pollution exposure estimation.

    Science.gov (United States)

    Chen, Gang; Li, Jingyi; Ying, Qi; Sherman, Seth; Perkins, Neil; Rajeshwari, Sundaram; Mendola, Pauline

    2014-07-01

    In this study, Community Multiscale Air Quality (CMAQ) model was applied to predict ambient gaseous and particulate concentrations during 2001 to 2010 in 15 hospital referral regions (HRRs) using a 36-km horizontal resolution domain. An inverse distance weighting based method was applied to produce exposure estimates based on observation-fused regional pollutant concentration fields using the differences between observations and predictions at grid cells where air quality monitors were located. Although the raw CMAQ model is capable of producing satisfying results for O3 and PM2.5 based on EPA guidelines, using the observation data fusing technique to correct CMAQ predictions leads to significant improvement of model performance for all gaseous and particulate pollutants. Regional average concentrations were calculated using five different methods: 1) inverse distance weighting of observation data alone, 2) raw CMAQ results, 3) observation-fused CMAQ results, 4) population-averaged raw CMAQ results and 5) population-averaged fused CMAQ results. It shows that while O3 (as well as NOx) monitoring networks in the HRRs are dense enough to provide consistent regional average exposure estimation based on monitoring data alone, PM2.5 observation sites (as well as monitors for CO, SO2, PM10 and PM2.5 components) are usually sparse and the difference between the average concentrations estimated by the inverse distance interpolated observations, raw CMAQ and fused CMAQ results can be significantly different. Population-weighted average should be used to account for spatial variation in pollutant concentration and population density. Using raw CMAQ results or observations alone might lead to significant biases in health outcome analyses. PMID:24747248

  10. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

    OpenAIRE

    Ryoichi Tashima; Satsuki Mikuriya; Daisuke Tomiyama; Miho Shiratori-Hayashi; Tomohiro Yamashita; Yuta Kohro; Hidetoshi Tozaki-Saitoh; Kazuhide Inoue; Makoto Tsuda

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controver...

  11. Mechanism of murine epidermal maintenance: Cell division and the Voter Model

    CERN Document Server

    Klein, Allon M; Jones, Philip H; Simons, Benjamin D

    2007-01-01

    This paper presents an interesting experimental example of voter-model statistics in biology. In recent work on mouse tail-skin, where proliferating cells are confined to a two-dimensional layer, we showed that cells proliferate and differentiate according to a simple stochastic model of cell division involving just one type of proliferating cell that may divide both symmetrically and asymmetrically. Curiously, these simple rules provide excellent predictions of the cell population dynamics without having to address their spatial distribution. Yet, if the spatial behaviour of cells is addressed by allowing cells to diffuse at random, one deduces that density fluctuations destroy tissue confluence, implying some hidden degree of spatial regulation in the physical system. To infer the mechanism of spatial regulation, we consider a two-dimensional model of cell fate that preserves the overall population dynamics. By identifying the resulting behaviour with a three-species variation of the "Voter" model, we predi...

  12. Cell population kinetics and dose-time relationships for post-irradiation injury of the brachial plexus in man

    International Nuclear Information System (INIS)

    Collected data on radiation-induced lesions of the brachial plexus were analyzed on the assuption that this reaction arises from depletion of some unidentified cell population in the irradiated tissues. A multi-probit search program was used to derive best-fitting cell kinetic parameters in a composite multi-target model for cellular radiation lethality and repopulation. From these parameters, a comprehensive iso-effect table, for a wide range of treatment schedules including daily treatment as well as fractionation at shorter and longer intervals, was constructed. The table provides a useful set of tolerance dosage limits for late effects in irradiation peripheral nerve. (Auth.)

  13. An agent-based computational model for tuberculosis spreading on age-structured populations

    Science.gov (United States)

    Graciani Rodrigues, C. C.; Espíndola, Aquino L.; Penna, T. J. P.

    2015-06-01

    In this work we present an agent-based computational model to study the spreading of the tuberculosis (TB) disease on age-structured populations. The model proposed is a merge of two previous models: an agent-based computational model for the spreading of tuberculosis and a bit-string model for biological aging. The combination of TB with the population aging, reproduces the coexistence of health states, as seen in real populations. In addition, the universal exponential behavior of mortalities curves is still preserved. Finally, the population distribution as function of age shows the prevalence of TB mostly in elders, for high efficacy treatments.

  14. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate.

    Science.gov (United States)

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B; Fuxe, Jonas; Shoshan, Maria

    2012-12-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations. PMID:22954696

  15. Heterogeneous populations of bone marrow stem cells--are we spotting on the same cells from the different angles?

    Directory of Open Access Journals (Sweden)

    Janina Ratajczak

    2004-10-01

    Full Text Available Accumulated evidence suggests that in addition to hematopoietic stem cells (HSC, bone marrow (BM also harbors endothelial stem cells (ESC, mesenchymal stem cells (MSC, multipotential adult progenitor cells (MAPC, pluripotent stem cells (PCS as well as tissue committed stem cells (TCSC recently identified by us. In this review we discuss the similarities and differences between these cell populations. Furthermore, we will present the hypothesis that all of these versatile BM derived stem cells are in fact different subpopulations of TCSC. These cells accumulate in bone marrow during ontogenesis and being a mobile population of cells are released from BM into peripheral blood after tissue injury to regenerate damaged organs. Furthermore, since BM is a "hideout" for TCSC, their presence in preparations of bone marrow derived mononuclear cells should be considered before experimental evidence is interpreted simply as trans-differentiation or plasticity of HSC. Finally, our observation that the number of TCSC accumulate in the bone marrow of young animals and their numbers decrease during senescence provides a new insight into aging and may explain why the regeneration processes becomes less effective in older individuals.

  16. Emodin as an effective agent in targeting cancer stem-like side population cells of gallbladder carcinoma.

    Science.gov (United States)

    Li, Xin-xing; Dong, Ying; Wang, Wei; Wang, Hao-lu; Chen, Yu-ying; Shi, Gui-ying; Yi, Jing; Wang, Jian

    2013-02-15

    Side population (SP) cells are previously identified from bone marrow based on their capacity to efflux of the fluorescent dye Hoechst 33342. Recent studies demonstrate that SP cells isolated from various cancer cell lines and primary tumors possess stem-cell-like properties. Thus, targeting tumor SP cells may provide new strategies for treatment in clinic. We previously showed that 1,3,8-trihydroxy-6-methylanthraquinone (emodin), a reactive oxygen species (ROS) generator, enhanced sensitivity of gallbladder cancer SGC-996 cells to cisplatin (CDDP) via generation of ROS and downregulation of multidrug-resistance-associated protein 1 (MRP1). To determine whether emodin also acts effectively on cancer stem cells of gallbladder carcinoma, we use SP cells as a model of cancer stem-cell-like cells. Here, we found that emodin, via ROS-related mechanism and suppressing the function of ATP-binding cassette super-family G member (ABCG2), which is known to be associated with Hoechst dye efflux activity of SP cells, not only reduced the ratio, inhibited clone formation, and eliminated sphere formation of SP cells effectively, but also promoted obviously the intracellular accumulation of doxorubicin, the main substrate of the efflux pump ABCG2. In addition, emodin could sensitize CDDP, via inhibition of expression of ABCG2, to overcome chemoresistance of SP cells. Importantly, similar to the experiment in vitro, emodin/CDDP co-treatment in vivo suppressed the tumor growth derived from SP cells through downregulating ABCG2 expression. Our results suggest that emodin is an effective agent targeting cancer stem-like SP cells of gallbladder carcinoma, either alone or acts as a chemotherapy enhancer. PMID:22974371

  17. Generalized breakup and coalescence models for population balance modelling of liquid-liquid flows

    CERN Document Server

    Traczyk, Marcin; Thompson, Chris

    2015-01-01

    Population balance framework is a useful tool that can be used to describe size distribution of droplets in a liquid-liquid dispersion. Breakup and coalescence models provide closures for mathematical formulation of the population balance equation (PBE) and are crucial for accu- rate predictions of the mean droplet size in the flow. Number of closures for both breakup and coalescence can be identified in the literature and most of them need an estimation of model parameters that can differ even by several orders of magnitude on a case to case basis. In this paper we review the fundamental assumptions and derivation of breakup and coalescence ker- nels. Subsequently, we rigorously apply two-stage optimization over several independent sets of experiments in order to identify model parameters. Two-stage identification allows us to estab- lish new parametric dependencies valid for experiments that vary over large ranges of important non-dimensional groups. This be adopted for optimization of parameters in breakup...

  18. The elite and stochastic model for iPS cell generation: multilineage-differentiating stress enduring (Muse) cells are readily reprogrammable into iPS cells.

    Science.gov (United States)

    Wakao, Shohei; Kitada, Masaaki; Dezawa, Mari

    2013-01-01

    Induced pluripotent stem (iPS) cells have attracted a great deal of attention, although the mechanism by which they are generated is still not fully understood. Currently, two theories, the stochastic and elite models, have been proposed. Some reports provide theoretical support for the stochastic model. Other reports, however, support the elite model. For example, some human fibroblasts, such as Multilineage-differentiating stress enduring (Muse) cells, are reported to be pluripotent and a primary source of iPS cells. Thus, the mechanism of iPS cell generation continues to be debated. In this review, we discuss the properties of the original cell source, such as the components of the original populations and the potential of each population to become iPS cells, and further discuss the implications of the two theories for iPS cell research. PMID:22693162

  19. Ionizing irradiation not only inactivates clonogenic potential in primary normal human diploid lens epithelial cells but also stimulates cell proliferation in a subset of this population.

    Directory of Open Access Journals (Sweden)

    Yuki Fujimichi

    Full Text Available Over the past century, ionizing radiation has been known to induce cataracts in the crystalline lens of the eye, but its mechanistic underpinnings remain incompletely understood. This study is the first to report the clonogenic survival of irradiated primary normal human lens epithelial cells and stimulation of its proliferation. Here we used two primary normal human cell strains: HLEC1 lens epithelial cells and WI-38 lung fibroblasts. Both strains were diploid, and a replicative lifespan was shorter in HLEC1 cells. The colony formation assay demonstrated that the clonogenic survival of both strains decreases similarly with increasing doses of X-rays. A difference in the survival between two strains was actually insignificant, although HLEC1 cells had the lower plating efficiency. This indicates that the same dose inactivates the same fraction of clonogenic cells in both strains. Intriguingly, irradiation enlarged the size of clonogenic colonies arising from HLEC1 cells in marked contrast to those from WI-38 cells. Such enhanced proliferation of clonogenic HLEC1 cells was significant at ≥2 Gy, and manifested as increments of ≤2.6 population doublings besides sham-irradiated controls. These results suggest that irradiation of HLEC1 cells not only inactivates clonogenic potential but also stimulates proliferation of surviving uniactivated clonogenic cells. Given that the lens is a closed system, the stimulated proliferation of lens epithelial cells may not be a homeostatic mechanism to compensate for their cell loss, but rather should be regarded as abnormal. This is because these findings are consistent with the early in vivo evidence documenting that irradiation induces excessive proliferation of rabbit lens epithelial cells and that suppression of lens epithelial cell divisions inhibits radiation cataractogenesis in frogs and rats. Thus, our in vitro model will be useful to evaluate the excessive proliferation of primary normal human lens

  20. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

    Directory of Open Access Journals (Sweden)

    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  1. Attenuated Toxoplasma gondii Stimulates Immunity to Pancreatic Cancer by Manipulation of Myeloid Cell Populations.

    Science.gov (United States)

    Sanders, Kiah L; Fox, Barbara A; Bzik, David J

    2015-08-01

    Suppressive myeloid cells represent a significant barrier to the generation of productive antitumor immune responses to many solid tumors. Eliminating or reprogramming suppressive myeloid cells to abrogate tumor-associated immune suppression is a promising therapeutic approach. We asked whether treatment of established aggressive disseminated pancreatic cancer with the immunotherapeutic attenuated Toxoplasma gondii vaccine strain CPS would trigger tumor-associated myeloid cells to generate therapeutic antitumor immune responses. CPS treatment significantly decreased tumor-associated macrophages and markedly increased dendritic cell infiltration of the pancreatic tumor microenvironment. Tumor-resident macrophages and dendritic cells, particularly cells actively invaded by CPS, increased expression of costimulatory molecules CD80 and CD86 and concomitantly boosted their production of IL12. CPS treatment increased CD4(+) and CD8(+) T-cell infiltration into the tumor microenvironment, activated tumor-resident T cells, and increased IFNγ production by T-cell populations. CPS treatment provided a significant therapeutic benefit in pancreatic tumor-bearing mice. This therapeutic benefit depended on IL12 and IFNγ production, MyD88 signaling, and CD8(+) T-cell populations. Although CD4(+) T cells exhibited activated effector phenotypes and produced IFNγ, CD4(+) T cells as well as natural killer cells were not required for the therapeutic benefit. In addition, CD8(+) T cells isolated from CPS-treated tumor-bearing mice produced IFNγ after re-exposure to pancreatic tumor antigen, suggesting this immunotherapeutic treatment stimulated tumor cell antigen-specific CD8(+) T-cell responses. This work highlights the potency and immunotherapeutic efficacy of CPS treatment and demonstrates the significance of targeting tumor-associated myeloid cells as a mechanism to stimulate more effective immunity to pancreatic cancer. PMID:25804437

  2. Functional and phenotypic differences of pure populations of stem cell-derived astrocytes and neuronal precursor cells.

    Science.gov (United States)

    Kleiderman, Susanne; Sá, João V; Teixeira, Ana P; Brito, Catarina; Gutbier, Simon; Evje, Lars G; Hadera, Mussie G; Glaab, Enrico; Henry, Margit; Sachinidis, Agapios; Alves, Paula M; Sonnewald, Ursula; Leist, Marcel

    2016-05-01

    Availability of homogeneous astrocyte populations would facilitate research concerning cell plasticity (metabolic and transcriptional adaptations; innate immune responses) and cell cycle reactivation. Current protocols to prepare astrocyte cultures differ in their final content of immature precursor cells, preactivated cells or entirely different cell types. A new method taking care of all these issues would improve research on astrocyte functions. We found here that the exposure of a defined population of pluripotent stem cell-derived neural stem cells (NSC) to BMP4 results in pure, nonproliferating astrocyte cultures within 24-48 h. These murine astrocytes generated from embryonic stem cells (mAGES) expressed the positive markers GFAP, aquaporin 4 and GLT-1, supported neuronal function, and acquired innate immune functions such as the response to tumor necrosis factor and interleukin 1. The protocol was applicable to several normal or disease-prone pluripotent cell lines, and the corresponding mAGES all exited the cell cycle and lost most of their nestin expression, in contrast to astrocytes generated by serum-addition or obtained as primary cultures. Comparative gene expression analysis of mAGES and NSC allowed quantification of differences between the two cell types and a definition of an improved marker set to define astrocytes. Inclusion of several published data sets in this transcriptome comparison revealed the similarity of mAGES with cortical astrocytes in vivo. Metabolic analysis of homogeneous NSC and astrocyte populations revealed distinct neurochemical features: both cell types synthesized glutamine and citrate, but only mature astrocytes released these metabolites. Thus, the homogeneous cultures allowed an improved definition of NSC and astrocyte features. PMID:26689134

  3. Data Driven Approach for High Resolution Population Distribution and Dynamics Models

    Energy Technology Data Exchange (ETDEWEB)

    Bhaduri, Budhendra L [ORNL; Bright, Eddie A [ORNL; Rose, Amy N [ORNL; Liu, Cheng [ORNL; Urban, Marie L [ORNL; Stewart, Robert N [ORNL

    2014-01-01

    High resolution population distribution data are vital for successfully addressing critical issues ranging from energy and socio-environmental research to public health to human security. Commonly available population data from Census is constrained both in space and time and does not capture population dynamics as functions of space and time. This imposes a significant limitation on the fidelity of event-based simulation models with sensitive space-time resolution. This paper describes ongoing development of high-resolution population distribution and dynamics models, at Oak Ridge National Laboratory, through spatial data integration and modeling with behavioral or activity-based mobility datasets for representing temporal dynamics of population. The model is resolved at 1 km resolution globally and describes the U.S. population for nighttime and daytime at 90m. Integration of such population data provides the opportunity to develop simulations and applications in critical infrastructure management from local to global scales.

  4. Discovery of Power-Law Growth in the Self-Renewal of Heterogeneous Glioma Stem Cell Populations.

    Directory of Open Access Journals (Sweden)

    Michiya Sugimori

    Full Text Available Accumulating evidence indicates that cancer stem cells (CSCs drive tumorigenesis. This suggests that CSCs should make ideal therapeutic targets. However, because CSC populations in tumors appear heterogeneous, it remains unclear how CSCs might be effectively targeted. To investigate the mechanisms by which CSC populations maintain heterogeneity during self-renewal, we established a glioma sphere (GS forming model, to generate a population in which glioma stem cells (GSCs become enriched. We hypothesized, based on the clonal evolution concept, that with each passage in culture, heterogeneous clonal sublines of GSs are generated that progressively show increased proliferative ability.To test this hypothesis, we determined whether, with each passage, glioma neurosphere culture generated from four different glioma cell lines become progressively proliferative (i.e., enriched in large spheres. Rather than monitoring self-renewal, we measured heterogeneity based on neurosphere clone sizes (#cells/clone. Log-log plots of distributions of clone sizes yielded a good fit (r>0.90 to a straight line (log(% total clones = k*log(#cells/clone indicating that the system follows a power-law (y = xk with a specific degree exponent (k = -1.42. Repeated passaging of the total GS population showed that the same power-law was maintained over six passages (CV = -1.01 to -1.17. Surprisingly, passage of either isolated small or large subclones generated fully heterogeneous populations that retained the original power-law-dependent heterogeneity. The anti-GSC agent Temozolomide, which is well known as a standard therapy for glioblastoma multiforme (GBM, suppressed the self-renewal of clones, but it never disrupted the power-law behavior of a GS population.Although the data above did not support the stated hypothesis, they did strongly suggest a novel mechanism that underlies CSC heterogeneity. They indicate that power-law growth governs the self-renewal of heterogeneous

  5. An individual-based model of zebrafish population dynamics accounting for energy dynamics.

    Directory of Open Access Journals (Sweden)

    Rémy Beaudouin

    Full Text Available Developing population dynamics models for zebrafish is crucial in order to extrapolate from toxicity data measured at the organism level to biological levels relevant to support and enhance ecological risk assessment. To achieve this, a dynamic energy budget for individual zebrafish (DEB model was coupled to an individual based model of zebrafish population dynamics (IBM model. Next, we fitted the DEB model to new experimental data on zebrafish growth and reproduction thus improving existing models. We further analysed the DEB-model and DEB-IBM using a sensitivity analysis. Finally, the predictions of the DEB-IBM were compared to existing observations on natural zebrafish populations and the predicted population dynamics are realistic. While our zebrafish DEB-IBM model can still be improved by acquiring new experimental data on the most uncertain processes (e.g. survival or feeding, it can already serve to predict the impact of compounds at the population level.

  6. Modelling the Effects of Pollution on a Population and a Resource in a Polluted Environment

    OpenAIRE

    Victoria Maystruk; Kenzu Abdella

    2011-01-01

    A model for the effect of pollution on an animal population partially dependent on a plant resource is examined. Using a system of ordinary differential equations, the model tracks and relates changes in an animal population and its internal pollution levels, a plant population and its internal pollution levels, and the overall environmental pollution level. The model system is analysed using standard mathematical techniques, including the direct Lyapunov method and numerical simulations. Cri...

  7. Photoreactivation of ultraviolet irradiated non-dividing populations of ICR 2A frog cells

    International Nuclear Information System (INIS)

    Ultraviolet (UV) irradiation of non-dividing populations of ICR 2A frog cells led to their detachment from the surface of the culture dish and eventual lysis. Exposure of the cells to photoreactivating light after UV irradiation prevented cell killing and was accompanied by a loss of endonuclease sensitive sites from DNA. This photoreversal did not take place when the cells were exposed at 40C to photoreactivating light indicating that the reversal was the result of photoenzymatic repair. As the action of photoreactivating enzyme is specific for the repair of pyrimidine dimers in DNA, the results suggest that pyrimidine dimers in DNA are the critical lesions leading to the death of non-dividing populations of UV irradiated cells. (author)

  8. A computational model of amoeboid cell migration.

    Science.gov (United States)

    Lim, Fong Yin; Koon, Yen Ling; Chiam, Keng-Hwee

    2013-10-01

    We present a two-dimensional computational model of amoeboid cell migration characterised by cell shape changes due to the formation and extension of protrusions known as blebs. Using this model, we numerically study the deformation of the cell membrane during blebbing, as well as the effects of obstacles, such as protein fibres in the extracellular matrix, on the motion of the blebbing cell. The model is established in the framework of Stokes flow. Cell membrane deformation is coupled to membrane tension, membrane bending, membrane-cortex adhesion and cortical activities via the intracellular and extracellular fluid field described by the Stokes equation. By assuming that actin monomers move at constant speed towards the membrane and polymerise when they approach the membrane, our model shows that the cell movement in unconfined space can be sustained. We also study how a migrating cell interacts with obstacles hydrodynamically, allowing us to model cell migration in confined environments and to investigate the effects of confinement on the cell migration speed. Our model can be used to further study how tumour cells move through the extracellular matrix during cancer metastasis. PMID:23342988

  9. Population dynamics during cell proliferation and neuronogenesis in the developing murine neocortex

    Science.gov (United States)

    Nowakowski, Richard S.; Caviness, Verne S Jr; Takahashi, Takao; Hayes, Nancy L.

    2002-01-01

    During the development of the neocortex, cell proliferation occurs in two specialized zones adjacent to the lateral ventricle. One of these zones, the ventricular zone, produces most of the neurons of the neocortex. The proliferating population that resides in the ventricular zone is a pseudostratified ventricular epithelium (PVE) that looks uniform in routine histological preparations, but is, in fact, an active and dynamically changing population. In the mouse, over the course of a 6-day period, the PVE produces approximately 95% of the neurons of the adult neocortex. During this time, the cell cycle of the PVE population lengthens from about 8 h to over 18 h and the progenitor population passes through a total of 11 cell cycles. This 6-day, 11-cell cycle period comprises the "neuronogenetic interval" (NI). At each passage through the cell cycle, the proportion of daughter cells that exit the cell cycle (Q cells) increases from 0 at the onset of the NI to 1 at the end of the NI. The proportion of daughter cells that re-enter the cell cycle (P cells) changes in a complementary fashion from 1 at the onset of the NI to 0 at the end of the NI. This set of systematic changes in the cell cycle and the output from the proliferative population of the PVE allows a quantitative and mathematical treatment of the expansion of the PVE and the growth of the cortical plate that nicely accounts for the observed expansion and growth of the developing neocortex. In addition, we show that the cells produced during a 2-h window of development during specific cell cycles reside in a specific set of laminae in the adult cortex, but that the distributions of the output from consecutive cell cycles overlap. These dynamic events occur in all areas of the PVE underlying the neocortex, but there is a gradient of maturation that begins in the rostrolateral neocortex near the striatotelencephalic junction and which spreads across the surface of the neocortex over a period of 24-36 h. The

  10. Modeling Agassiz's Desert Tortoise Population Response to Anthropogenic Stressors

    Science.gov (United States)

    Mojave Desert tortoise (Gopherus agassizii) populations are exposed to a variety of anthropogenic threats, which vary in nature, severity, and frequency. Tortoise management in conservation areas can be compromised when the relative importance of these threats is not well underst...

  11. Decision Support Population Modeling for Piping Plover Recovery

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Nest exclosures are a common management tool used to increase nest success of the threatened U.S. Atlantic Coast Piping Plover (Charadrius melodus) population....

  12. Radiation-induced chromosome aberrations in cell populations from rat tracheal epithelium

    International Nuclear Information System (INIS)

    To determine cells at risk in the respiratory tract for the induction of cancer, it is essential to know not only the dose of toxic agent to the cells but also the sensitivity of each cell type to the agent. The purpose of this study is to define the radiation sensitivity of cells in the airway epithelium of the rat as the first step in determining the cells at risk for cancer induction by radiation. Tracheal epithelial cells were isolated, sorted by flow cytometry, grown in defined medium and exposed to graded doses of X rays. Survival and the frequency of chromosome aberrations were determined in the total cell population, in the sorted secretary and in the sorted basal cells. There was no difference in radiation-induced cytotoxicity of each cell type. The frequency of chromosome aberrations was determined by linear regression analysis and found to be 0.37 ± 0.01 aberrations/cell/Gy for the unsorted cells and 0.26 ± 0.02 for the sorted secretary cells. Because of the low number and cloning efficiency of basal cells, no data on X-ray-induced chromosome aberrations in these cells is available at the present time. There was a linear decrease in the chromatid-type aberration frequency as a function of time after the radiation exposure. The data suggest that, in terms of radiation sensitivity, all three cell populations are very similar. Thus, if there are differences in the response to a toxic agent such as radon, the differences should reflect differences in radiation dose to the cells. (author)

  13. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells

    OpenAIRE

    Wang, Dachun; Haviland, David L.; Burns, Alan R.; Zsigmond, Eva; Wetsel, Rick A.

    2007-01-01

    Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute ≈60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the ...

  14. Active Gel Model of Amoeboid Cell Motility

    CERN Document Server

    Callan-Jones, A C

    2013-01-01

    We develop a model of amoeboid cell motility based on active gel theory. Modeling the motile apparatus of a eukaryotic cell as a confined layer of finite length of poroelastic active gel permeated by a solvent, we first show that, due to active stress and gel turnover, an initially static and homogeneous layer can undergo a contractile-type instability to a polarized moving state in which the rear is enriched in gel polymer. This agrees qualitatively with motile cells containing an actomyosin-rich uropod at their rear. We find that the gel layer settles into a steadily moving, inhomogeneous state at long times, sustained by a balance between contractility and filament turnover. In addition, our model predicts an optimal value of the gel-susbstrate adhesion leading to maximum layer speed, in agreement with cell motility assays. The model may be relevant to motility of cells translocating in complex, confining environments that can be mimicked experimentally by cell migration through microchannels.

  15. Gaining insight in the interaction of zinc and population density with a combined dynamic energy budget and population model.

    Science.gov (United States)

    Klok, Chris

    2008-12-01

    Laboratory tests are typically conducted under optimal conditions testing the single effect of a toxicant In the field, due to suboptimal conditions, density dependence can both diminish and enhance effects of toxicants on populations. A review of the literature indicated that general insight on interaction of density and toxicants is lacking, and therefore no predictions on their combined action can be made. In this paper the influence of zinc was tested at different population densities on the demographic rates: growth, reproduction, and survival in the earthworm Lumbricus rubellus. Changes in these rates were extrapolated with a combined Dynamic energy budget (DEB) and a population model to assess consequences at the population level. Inference from the DEB model indicated that density decreased the assimilation of food whereas zinc increased the maintenance costs. The combined effects of density and zinc resulted in a decrease in the intrinsic rate of population increase which suddenly dropped to zero at combinations of zinc and density where development is so strongly retarded that individuals do not mature. This already happened at zinc levels where zinc induced mortality is low and therefore density enhances zinc effects and density dependent compensation is not expected. PMID:19192801

  16. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-08-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  17. The future of whole-cell modeling.

    Science.gov (United States)

    Macklin, Derek N; Ruggero, Nicholas A; Covert, Markus W

    2014-08-01

    Integrated whole-cell modeling is poised to make a dramatic impact on molecular and systems biology, bioengineering, and medicine--once certain obstacles are overcome. From our group's experience building a whole-cell model of Mycoplasma genitalium, we identified several significant challenges to building models of more complex cells. Here we review and discuss these challenges in seven areas: first, experimental interrogation; second, data curation; third, model building and integration; fourth, accelerated computation; fifth, analysis and visualization; sixth, model validation; and seventh, collaboration and community development. Surmounting these challenges will require the cooperation of an interdisciplinary group of researchers to create increasingly sophisticated whole-cell models and make data, models, and simulations more accessible to the wider community. PMID:24556244

  18. New malignancies after squamous cell carcinoma and melanomas: a population-based study from Norway

    International Nuclear Information System (INIS)

    Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers. All invasive cutaneous malignant melanomas (CMM, N = 28 069) and squamous cell carcinomas (SCC, N = 24 620) diagnosed in Norway during 1955–2008 were included. Rates of new primary cancers in skin cancer survivors were compared to rates of primary malignancies in the general population using standardized incidence ratios (SIR). Discrete-time logistic regression models were applied to individual-level data to estimate cancer risk among those with and without a prior skin cancer, accounting for residential region, education, income, parenthood, marital status and parental cancer status, using a 20% random sample of the entire Norwegian population as reference. Further analyses of the skin cancer cohort were undertaken to determine risk factors related to subsequent cancers. During follow-up, 9608 new primary cancers occurred after an initial skin cancer. SIR analyses showed 50% and 90% increased risks for any cancer after CMM and SCC, respectively (p < 0.01). The logistic regression model suggested even stronger increase after SCC (130%). The highest risk was seen for subsequent skin cancers, but several non-skin cancers were also diagnosed in excess: oral, lung, colon, breast, prostate, thyroid, leukemia, lymphoma and central nervous system. Factors that were associated with increased risk of subsequent cancers include male sex, older age, lower residential latitude, being married and low education and income. Parental cancer did not increase the risk of a subsequent cancer after SCC, but was a significant predictor among younger CMM survivors. Our results provide information on shared environmental and genetic risk factors for first and later cancers and may help to identify

  19. Cytotoxic mechanisms of murine lymphokine-activated killer cells: functional and biochemical characterization of homogeneous populations of spleen LAK cells.

    Science.gov (United States)

    Zychlinsky, A; Joag, S; Liu, C C; Young, J D

    1990-04-01

    A highly purified population of murine lymphokine-activated killer (LAK) cells was obtained by selecting plastic-adherent splenocytes after incubation in high doses of recombinant IL-2. The population obtained was shown to be more than 95% positive for the cell marker asialo-GM1, and negative for both Lyt-1 (CD5) and Lyt-2 (CD8). The cells presented typical large granular lymphocyte morphology, and killed NK-susceptible target cells in an exclusively calcium-dependent fashion. A target cell DNA fragmentation activity of LAK cells could be detected even before target cell death. The presence of Hanukkah Factor/granzyme A/serine esterase 1, CTLA-1/granzyme B/serine esterase 2, and pore-forming protein (PFP/perforin) in these LAK cells was demonstrated by Northern blot analysis, suggesting that these markers are not exclusively associated with cytotoxic T lymphocytes. On immunoblots, antibodies specific for a lymphocyte PFP/perforin reacted with a 70-kDa protein of LAK cells. PFP/perforin was localized by immunofluorescence to the cell granules. A 50-kDa protein antigenically related to the macrophage cytokine tumor necrosis factor (TNF) was detected by immunoblotting and localized by immunofluorescence to both the cell granules and the cytosol. No RNA for TNF, however, could be detected using TNF-specific probes, suggesting that LAK cells may contain a cytotoxic factor which is related to, but distinct from, TNF. The work presented here demonstrates that cytotoxic mediators identified in cell lines are also present in primary cell cultures. PMID:1690083

  20. Models for Natural Killer Cell Repertoire Formation

    Directory of Open Access Journals (Sweden)

    Ramit Mehr

    2003-01-01

    Full Text Available Natural killer (NK cells lyse only cells that do not express sufficient levels of self class I MHC molecules. Inhibition of lysis is mediated by inhibitory receptors expressed by NK cells, such as the murine Ly49 receptors, that bind to MHC class I molecules. Since inhibitory receptor genes and MHC class I genes are located on different chromosomes, and are hence not automatically co-inherited, NK cells apparently adapt to the MHC environment during their development. Two models have been proposed to account for this “education” process of NK cells. The two-step selection model postulates that developing NK cells initiate the stable expression of a random set of Ly49 genes, and then undergo two selection steps, one for cells that express a sufficient number of self-MHC receptors, and one against cells that express too many inhibitory receptors. The sequential model postulates that a cell keeps initiating the stable expression of additional inhibitory receptors until a sufficient expression level of self-MHC specific receptors is reached, and the cell matures. In this study we implement both models in computer simulations, and compare simulation results to experimental data, in order to evaluate the relative plausibility of the two models.

  1. Minimal model for stem-cell differentiation

    Science.gov (United States)

    Goto, Yusuke; Kaneko, Kunihiko

    2013-09-01

    To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed.

  2. Minimal model for stem-cell differentiation.

    Science.gov (United States)

    Goto, Yusuke; Kaneko, Kunihiko

    2013-09-01

    To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed. PMID:24125305

  3. Isolated CD39 Expression on CD4+ T Cells Denotes both Regulatory and Memory Populations

    OpenAIRE

    Zhou, Q.; Yan, J.; Putheti, P.; Wu, Y.; X. Sun; Toxavidis, V.; Tigges, J.; Kassam, N.; Enjyoji, K.; Robson, S C; Strom, T. B.; Gao, W.

    2009-01-01

    Foxp3+ regulatory T cells (Tregs) express both ectoenzymes CD39 and CD73, which in tandem hydrolyze pericellular ATP into adenosine, an immunoinhibitory molecule that contributes to Treg suppressive function. Using Foxp3GFP knockin mice, we noted that the mouse CD4+CD39+ T-cell pool contains two roughly equal size Foxp3+ and Foxp3− populations. While Foxp3+CD39+ cells are CD73bright and are the bone fide Tregs, Foxp3−CD39+ cells do not have suppressive activity and are CD44+CD62L−CD25−CD73dim...

  4. Label-free detection of neuronal differentiation in cell populations using high-throughput live-cell imaging of PC12 cells.

    Directory of Open Access Journals (Sweden)

    Sebastian Weber

    Full Text Available Detection of neuronal cell differentiation is essential to study cell fate decisions under various stimuli and/or environmental conditions. Many tools exist that quantify differentiation by neurite length measurements of single cells. However, quantification of differentiation in whole cell populations remains elusive so far. Because such populations can consist of both proliferating and differentiating cells, the task to assess the overall differentiation status is not trivial and requires a high-throughput, fully automated approach to analyze sufficient data for a statistically significant discrimination to determine cell differentiation. We address the problem of detecting differentiation in a mixed population of proliferating and differentiating cells over time by supervised classification. Using nerve growth factor induced differentiation of PC12 cells, we monitor the changes in cell morphology over 6 days by phase-contrast live-cell imaging. For general applicability, the classification procedure starts out with many features to identify those that maximize discrimination of differentiated and undifferentiated cells and to eliminate features sensitive to systematic measurement artifacts. The resulting image analysis determines the optimal post treatment day for training and achieves a near perfect classification of differentiation, which we confirmed in technically and biologically independent as well as differently designed experiments. Our approach allows to monitor neuronal cell populations repeatedly over days without any interference. It requires only an initial calibration and training step and is thereafter capable to discriminate further experiments. In conclusion, this enables long-term, large-scale studies of cell populations with minimized costs and efforts for detecting effects of external manipulation of neuronal cell differentiation.

  5. Morphokinetics of mesenterial lymphatic node cell populations in exposure of gold nanoparticles within experimental work

    Directory of Open Access Journals (Sweden)

    Dykman L.A.

    2011-06-01

    Full Text Available The research goal is to investigate the influence of gold nanoparticles with different size (1-3 nm, 15 nm and 50 nm on the morphokinetics of mesenterial lymphatic node cell populations of healthy laboratory animals. Experiment included 24 white rats. The investigation was conducted in 4 groups of animals. The animals were administered the gold nanoparticles orally for 15 days. It was established that the oral administration of gold nanoparticles caused the changes of morphokinetics of mesenterial lymphatic node cell populations. The morphological alterations in the mesenterial lymphatic nodes assisted in activation of migration processes, the proliferation and differentiation. The immu-nomodulatory action of gold nanoparticles was proved

  6. Cytoview: Development of a cell modelling framework

    Indian Academy of Sciences (India)

    Prashant Khodade; Samta Malhotra; Nirmal Kumar; M Sriram Iyengar; N Balakrishnan; Nagasuma Chandra

    2007-08-01

    The biological cell, a natural self-contained unit of prime biological importance, is an enormously complex machine that can be understood at many levels. A higher-level perspective of the entire cell requires integration of various features into coherent, biologically meaningful descriptions. There are some efforts to model cells based on their genome, proteome or metabolome descriptions. However, there are no established methods as yet to describe cell morphologies, capture similarities and differences between different cells or between healthy and disease states. Here we report a framework to model various aspects of a cell and integrate knowledge encoded at different levels of abstraction, with cell morphologies at one end to atomic structures at the other. The different issues that have been addressed are ontologies, feature description and model building. The framework describes dotted representations and tree data structures to integrate diverse pieces of data and parametric models enabling size, shape and location descriptions. The framework serves as a first step in integrating different levels of data available for a biological cell and has the potential to lead to development of computational models in our pursuit to model cell structure and function, from which several applications can flow out.

  7. 24/7 population modelling for enhanced assessment of exposure to natural hazards

    OpenAIRE

    Smith, Alan; Martin, David; Cockings, Samantha

    2013-01-01

    There is a growing need for accurate spatio-temporal population estimates free from arbitrary administrative boundaries and temporal divisions to make enhanced assessments of population exposure to natural hazards. The approach proposed here combines the use of a spatio-temporal gridded population model to estimate temporary variations in population with natural hazard exposure estimations. It has been exemplified through a Southampton (UK) centred application using Environment Agency flood m...

  8. Further analyses of human kidney cell populations separated on the space shuttle

    Science.gov (United States)

    Stewart, Robin M.; Todd, Paul; Cole, Kenneth D.; Morrison, Dennis R.

    Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120°C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantitation of plasminogen activators in these samples. These assays of frozen culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator producing cells from non-producing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one another.

  9. Multi-level behaviours in agent-based simulation: colonic crypt cell populations

    Science.gov (United States)

    Chen, Chih-Chun; Nagl, Sylvia B.; Clack, Christopher D.

    Agent-based modelling and simulation is now beginning to establish itself as a suitable technique for studying biological systems. However, a major issue in using agent-based simulations to study complex systems such as those in Systems Biology is the fact that simulations are `opaque'. While we have knowledge of individuals' behaviour through agent rules and have techniques for evaluating global behaviour by aggregating the states of individuals, methods for identifying the interactive mechanisms giving rise to this global behaviour are lacking. Formulating precise hypotheses about these multi-level behaviours is also difficult without an established formalism for describing them. The complex event formalism allows relationships between agent-rule-generated events to be defined so that behaviours at different levels of abstraction to be described. Complex event types define categories of these behaviours, which can then be detected in simulation, giving us computational method for distinguishing between alternative interactive mechanisms underlying a higher level behaviour. We apply the complex event formalism to an agent-based model of cell populations in the colonic crypt and demonstrate how competition and selection events can be identified in simulation at both the individual and clonal level, allowing us to computationally test hypotheses about the interactive mechanisms underlying a clone's success.

  10. Discrete two-sex models of population dynamics: On modelling the mating function

    Science.gov (United States)

    Bessa-Gomes, Carmen; Legendre, Stéphane; Clobert, Jean

    2010-09-01

    Although sexual reproduction has long been a central subject of theoretical ecology, until recently its consequences for population dynamics were largely overlooked. This is now changing, and many studies have addressed this issue, showing that when the mating system is taken into account, the population dynamics depends on the relative abundance of males and females, and is non-linear. Moreover, sexual reproduction increases the extinction risk, namely due to the Allee effect. Nevertheless, different studies have identified diverse potential consequences, depending on the choice of mating function. In this study, we investigate the consequences of three alternative mating functions that are frequently used in discrete population models: the minimum; the harmonic mean; and the modified harmonic mean. We consider their consequences at three levels: on the probability that females will breed; on the presence and intensity of the Allee effect; and on the extinction risk. When we consider the harmonic mean, the number of times the individuals of the least abundant sex mate exceeds their mating potential, which implies that with variable sex-ratios the potential reproductive rate is no longer under the modeller's control. Consequently, the female breeding probability exceeds 1 whenever the sex-ratio is male-biased, which constitutes an obvious problem. The use of the harmonic mean is thus only justified if we think that this parameter should be re-defined in order to represent the females' breeding rate and the fact that females may reproduce more than once per breeding season. This phenomenon buffers the Allee effect, and reduces the extinction risk. However, when we consider birth-pulse populations, such a phenomenon is implausible because the number of times females can reproduce per birth season is limited. In general, the minimum or modified harmonic mean mating functions seem to be more suitable for assessing the impact of mating systems on population dynamics.

  11. Approaches for cytogenetic and molecular analyses of small flow-sorted cell populations from childhood leukemia bone marrow samples

    DEFF Research Database (Denmark)

    Obro, Nina Friesgaard; Madsen, Hans Ole; Ryder, Lars Peter; Andersen, Mette Klarskov; Schmiegelow, Kjeld; Marquart, Hanne Vibeke

    defined cell populations with subsequent analyses of leukemia-associated cytogenetic and molecular marker. The approaches described here optimize the use of the same tube of unfixed, antibody-stained BM cells for flow-sorting of small cell populations and subsequent exploratory FISH and PCR-based analyses....

  12. Resolving archaeological populations with Sr-isotope mixing models

    International Nuclear Information System (INIS)

    Strontium isotope analysis of tooth enamel is a useful provenancing technique to investigate the childhood origins and residential mobility of ancient people. However, where different geographical target regions have similar biosphere 87Sr/86Sr it is often difficult to resolve the 87Sr/86Sr ranges of two different groups of people and establish what constitutes the local range at each site. Here a multi-period study is presented from the Outer Hebrides, Scotland and an investigation of Neolithic and Early Bronze Age populations from the Yorkshire Wolds, NE England. The aim is to demonstrate that, despite complex human dietary strategies, simple mixing systems with only two end-members do occur in archaeological human populations in certain geological provinces and, despite overlapping 87Sr/86Sr ranges, it is possible to separate two populations based on the structure within the data set

  13. Stochastic biophysical modeling of irradiated cells

    CERN Document Server

    Fornalski, Krzysztof Wojciech

    2014-01-01

    The paper presents a computational stochastic model of virtual cells irradiation, based on Quasi-Markov Chain Monte Carlo method and using biophysical input. The model is based on a stochastic tree of probabilities for each cell of the entire colony. Biophysics of the cells is described by probabilities and probability distributions provided as the input. The adaptation of nucleation and catastrophe theories, well known in physics, yields sigmoidal relationships for carcinogenic risk as a function of the irradiation. Adaptive response and bystander effect, incorporated into the model, improves its application. The results show that behavior of virtual cells can be successfully modeled, e.g. cancer transformation, creation of mutations, radioadaptation or radiotherapy. The used methodology makes the model universal and practical for simulations of general processes. Potential biophysical curves and relationships are also widely discussed in the paper. However, the presented theoretical model does not describe ...

  14. Peripheral Immune Cell Populations Associated with Cognitive Deficits and Negative Symptoms of Treatment-Resistant Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Emilio Fernandez-Egea

    Full Text Available Hypothetically, psychotic disorders could be caused or conditioned by immunological mechanisms. If so, one might expect there to be peripheral immune system phenotypes that are measurable in blood cells as biomarkers of psychotic states.We used multi-parameter flow cytometry of venous blood to quantify and determine the activation state of 73 immune cell subsets for 18 patients with chronic schizophrenia (17 treated with clozapine, and 18 healthy volunteers matched for age, sex, BMI and smoking. We used multivariate methods (partial least squares to reduce dimensionality and define populations of differentially co-expressed cell counts in the cases compared to controls.Schizophrenia cases had increased relative numbers of NK cells, naïve B cells, CXCR5+ memory T cells and classical monocytes; and decreased numbers of dendritic cells (DC, HLA-DR+ regulatory T-cells (Tregs, and CD4+ memory T cells. Likewise, within the patient group, more severe negative and cognitive symptoms were associated with decreased relative numbers of dendritic cells, HLA-DR+ Tregs, and CD4+ memory T cells. Motivated by the importance of central nervous system dopamine signalling for psychosis, we measured dopamine receptor gene expression in separated CD4+ cells. Expression of the dopamine D3 (DRD3 receptor was significantly increased in clozapine-treated schizophrenia and covaried significantly with differentiated T cell classes in the CD4+ lineage.Peripheral immune cell populations and dopaminergic signalling are disrupted in clozapine-treated schizophrenia. Immuno-phenotypes may provide peripherally accessible and mechanistically specific biomarkers of residual cognitive and negative symptoms in this treatment-resistant subgroup of patients.

  15. An Atypical Splenic B Cell Progenitor Population Supports Antibody Production during Plasmodium Infection in Mice.

    Science.gov (United States)

    Ghosh, Debopam; Wikenheiser, Daniel J; Kennedy, Brian; McGovern, Kathryn E; Stuart, Johnasha D; Wilson, Emma H; Stumhofer, Jason S

    2016-09-01

    Hematopoietic stem and progenitor cells (HSPCs) function to replenish the immune cell repertoire under steady-state conditions and in response to inflammation due to infection or stress. Whereas the bone marrow serves as the primary niche for hematopoiesis, extramedullary mobilization and differentiation of HSPCs occur in the spleen during acute Plasmodium infection, a critical step in the host immune response. In this study, we identified an atypical HSPC population in the spleen of C57BL/6 mice, with a lineage(-)Sca-1(+)c-Kit(-) (LSK(-)) phenotype that proliferates in response to infection with nonlethal Plasmodium yoelii 17X. Infection-derived LSK(-) cells upon transfer into naive congenic mice were found to differentiate predominantly into mature follicular B cells. However, when transferred into infection-matched hosts, infection-derived LSK(-) cells gave rise to B cells capable of entering into a germinal center reaction, and they developed into memory B cells and Ab-secreting cells that were capable of producing parasite-specific Abs. Differentiation of LSK(-) cells into B cells in vitro was enhanced in the presence of parasitized RBC lysate, suggesting that LSK(-) cells expand and differentiate in direct response to the parasite. However, the ability of LSK(-) cells to differentiate into B cells was not dependent on MyD88, as myd88(-/-) LSK(-) cell expansion and differentiation remained unaffected after Plasmodium infection. Collectively, these data identify a population of atypical lymphoid progenitors that differentiate into B lymphocytes in the spleen and are capable of contributing to the ongoing humoral immune response against Plasmodium infection. PMID:27448588

  16. Phototheranostics of CD44-positive cell populations in triple negative breast cancer

    Science.gov (United States)

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M.

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44high/CD24low, and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. PMID:27302409

  17. Phototheranostics of CD44-positive cell populations in triple negative breast cancer.

    Science.gov (United States)

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44(high)/CD24(low), and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. PMID:27302409

  18. A model of the trapped electron population for solar minimum

    Science.gov (United States)

    Teague, M. J.; Vette, J. I.

    1974-01-01

    A model is presented of the trapped electron environment of solar minimum conditions. Solar maximum models have been presented for the inner radiation zone (AE-5 1967), and for the outer radiation zone (AE-4 1967). The present solar minimum model consists of an inner zone model (AE-5 1975 Projected) with an epoch of 1975, and an outer zone model with an epoch of 1964. With only minor modifications this latter model is identical to the AE-4 1964 model presented previous. The model, however, has not previously been issued in computer form. AE-4 1964 is based upon satellite data, while the inner zone solar minimum model AE-5 1975 Projected consists entirely of extrapolations from AE-5 1967. While the two components of the solar minimum model have epochs 11 years part, it is assumed that any differences between the successive solar minima are smaller than the model error, and the complete model is associated with an epoch of 1975.

  19. Simulation Model Driven Engineering for Manufacturing Cell

    OpenAIRE

    Hibino, Hironori; Inukai, Toshihiro; Yoshida, Yukishige

    2010-01-01

    In our research, the simulation model driven engineering for manufacturing cell (SMDE-MC) is proposed. The purposes of SMDE-MC are to support the manufacturing engineering processes based on the simulation model and to extend the range of control applications and simulation applications using the PC based control. SMDE-MC provides the simulation model which controls and monitors the manufacturing cell directly using PC based control in the manufacturing system execution phase. Then when the s...

  20. Unrelated hematopoietic stem cell transplantation in the pediatric population: single institution experience

    Directory of Open Access Journals (Sweden)

    Daniela Hespanha Marinho

    2015-08-01

    Full Text Available OBJECTIVE: Hematopoietic stem cell transplantation has been successfully used to treat the pediatric population with malignant and non-malignant hematological diseases. This paper reports the results up to 180 days after the procedure of all unrelated hematopoietic stem cell transplantations in pediatric patients that were performed in one institution.METHODS: A retrospective review was performed of all under 18-year-old patients who received unrelated transplantations between 1995 and 2009. Data were analyzed using the log-rank test, Cox stepwise model, Kaplan-Meier method, Fine and Gray model and Fisher's exact test.RESULTS: This study included 118 patients (46.8% who received bone marrow and 134 (53.2% who received umbilical cord blood transplants. Engraftment occurred in 89.47% of the patients that received bone marrow and 65.83% of those that received umbilical cord blood (p-value < 0.001. Both neutrophil and platelet engraftments were faster in the bone marrow group. Acute graft-versus-host disease occurred in 48.6% of the patients without statistically significant differences between the two groups (p-value = 0.653. Chronic graft-versus-host disease occurred in 9.2% of the patients with a higher incidence in the bone marrow group (p-value = 0.007. Relapse occurred in 24% of the 96 patients with malignant disease with 2-year cumulative incidences of 45% in the bone marrow group and 25% in the umbilical cord blood group (p-value = 0.117. Five-year overall survival was 47%, with an average survival time of 1207 days, and no significant differences between the groups (p-value = 0.4666.CONCLUSION: Despite delayed engraftment in the umbilical cord blood group, graft-versus-host disease, relapse and survival were similar in both groups.

  1. Fluctuations of population dynamics model parameters: View on the problem of climate change

    OpenAIRE

    L.V. Nedorezov

    2012-01-01

    In current publication the statistical method of analysis of population time series in considered. This method is based on analysis of dynamics of non-linear ecological model parameter estimations in time, and devoted to investigation of influence of change of weather conditions on population dynamics (on the other words, it is devoted to analysis of climate change from the standpoint of separated population dynamics). Estimations of model parameters were obtained for parts (which contains 12...

  2. On a System Modelling a Population with Two Age Groups

    Directory of Open Access Journals (Sweden)

    Hongliang Gao

    2014-01-01

    Full Text Available A system of first order ordinary differential equations describing a population divided into juvenile and adult age groups is studied. The system is not cooperative but its linear part is, and this makes it possible to establish the existence and nonexistence results of positive solutions for the system in terms of the principal eigenvalue of the corresponding linearized system.

  3. Neuronal population dynamic model:An analytic approach

    Institute of Scientific and Technical Information of China (English)

    Wentao Huang; Licheng Jiao; Yuelei Xu; Shiping Ma; Jianhua Jia

    2009-01-01

    rom this,the stationary solution and the firing rate of the stationary states are given.Last,by the Fourier transform,the time dependent solution is also obtained.This method can be used to analyze the various dynamic behaviors of neuronal populations.

  4. Advancing population ecology with integral projection models: a practical guide

    DEFF Research Database (Denmark)

    Merow, Cory; Dahlgren, Johan; Metcall, C. Jessica E.;

    2014-01-01

    (e.g., environment). By combining regressions of vital rates, an IPM provides mechanistic insight into emergent ecological patterns such as population dynamics, species geographic distributions, or life history strategies. Here, we review important resources for building IPMs and provide a...

  5. Cancer stem cells and cisplatin-resistant cells isolated from non-small-lung cancer cell lines constitute related cell populations

    Science.gov (United States)

    Lopez-Ayllon, Blanca D; Moncho-Amor, Veronica; Abarrategi, Ander; de Cáceres, Inmaculada Ibañez; Castro-Carpeño, Javier; Belda-Iniesta, Cristobal; Perona, Rosario; Sastre, Leandro

    2014-01-01

    Lung cancer is the top cause of cancer-related deceases. One of the reasons is the development of resistance to the chemotherapy treatment. In particular, cancer stem cells (CSCs), can escape treatment and regenerate the bulk of the tumor. In this article, we describe a comparison between cancer cells resistant to cisplatin and CSCs, both derived from the non-small-cell lung cancer cell lines H460 and A549. Cisplatin-resistant cells were obtained after a single treatment with the drug. CSCs were isolated by culture in defined media, under nonadherent conditions. The isolated CSCs were clonogenic, could be differentiated into adherent cells and were less sensitive to cisplatin than the original cells. Cisplatin resistant and CSCs were able to generate primary tumors and to metastasize when injected into immunodeficient Nu/Nu mice, although they formed smaller tumors with a larger latency than untreated cells. Notably, under appropriated proportions, CSCs synergized with differentiated cells to form larger tumors. CSCs also showed increased capacity to induce angiogenesis in Nu/Nu mice. Conversely, H460 cisplatin-resistant cells showed increased tendency to develop bone metastasis. Gene expression analysis showed that several genes involved in tumor development and metastasis (EGR1, COX2, MALAT1, AKAP12, ADM) were similarly induced in CSC and cisplatin-resistant H460 cells, in agreement with a close similarity between these two cell populations. Cells with the characteristic growth properties of CSCs were also isolated from surgical samples of 18 out of 44 lung cancer patients. A significant correlation (P = 0.028) was found between the absence of CSCs and cisplatin sensitivity. PMID:24961511

  6. CFD of mixing of multi-phase flow in a bioreactor using population balance model.

    Science.gov (United States)

    Sarkar, Jayati; Shekhawat, Lalita Kanwar; Loomba, Varun; Rathore, Anurag S

    2016-05-01

    Mixing in bioreactors is known to be crucial for achieving efficient mass and heat transfer, both of which thereby impact not only growth of cells but also product quality. In a typical bioreactor, the rate of transport of oxygen from air is the limiting factor. While higher impeller speeds can enhance mixing, they can also cause severe cell damage. Hence, it is crucial to understand the hydrodynamics in a bioreactor to achieve optimal performance. This article presents a novel approach involving use of computational fluid dynamics (CFD) to model the hydrodynamics of an aerated stirred bioreactor for production of a monoclonal antibody therapeutic via mammalian cell culture. This is achieved by estimating the volume averaged mass transfer coefficient (kL a) under varying conditions of the process parameters. The process parameters that have been examined include the impeller rotational speed and the flow rate of the incoming gas through the sparger inlet. To undermine the two-phase flow and turbulence, an Eulerian-Eulerian multiphase model and k-ε turbulence model have been used, respectively. These have further been coupled with population balance model to incorporate the various interphase interactions that lead to coalescence and breakage of bubbles. We have successfully demonstrated the utility of CFD as a tool to predict size distribution of bubbles as a function of process parameters and an efficient approach for obtaining optimized mixing conditions in the reactor. The proposed approach is significantly time and resource efficient when compared to the hit and trial, all experimental approach that is presently used. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:613-628, 2016. PMID:26850863

  7. Identification of a novel population of human cord blood cells with hematopoietic and chondrocytic potential

    Institute of Scientific and Technical Information of China (English)

    Karen E JAY; Anne ROULEAU; T Michael UNDERHILL; Mickie BHATIA

    2004-01-01

    With the exception of mature erythrocytes, cells within the human hematopoietic system are characterized by the cell surface expression of the pan-leukocyte receptor CD45. Here, we identify a novel subset among mononuclear cord blood cells depleted of lineage commitment markers (Lin-) that are devoid of CD45 expression. Surprisingly, functional examination of Lin-CD45- cells also lacking cell surface CD34 revealed they were capable of multipotential hematopoietic progenitor capacity. Co-culture with mouse embryonic limb bud cells demonstrated that Lin-CD45-CD34- cells were capable of contributing to cartilage nodules and differentiating into human chondrocytes. BMP-4, a mesodermal factor known to promote chondrogenesis, significantly augmented Lin-CD45-CD34- differentiation into chondrocytes.Moreover, unlike CD34+ human hematopoietic stem cells, Lin-CD45-CD34- cells were unable to proliferate or survive in liquid cultures, whereas single Lin-CD45-CD34- cells were able to chimerize the inner cell mass (ICM) of murine blastocysts and proliferate in this embryonic environment. Our study identifies a novel population of Lin-CD45-CD34-cells capable of commitment into both hematopoietic and chondrocytic lineages, suggesting that human cord blood may provide a more ubiquitous source of tissue with broader developmental potential than previously appreciated.

  8. Combining a weed traits database with a population dynamics model predicts shifts in weed communities

    DEFF Research Database (Denmark)

    Storkey, Jonathan; Holst, Niels; Bøjer, Ole Mission; Bigongiali, Frederica; Bocci, Gionata; Colbach, Nathali; Dorner, Zita; Riemens, Marleen; Satorato, Ivan; Sønderskov, Mette; Verschwele, Arnd

    2015-01-01

    , populated and analysed, initially using data for 19 common European weeds, to begin to consolidate trait data in a single repository. The initial choice of traits was driven by the requirements of empirical models of weed population dynamics to identify correlations between traits and model parameters...

  9. Modelling of population dynamics of red king crab using Bayesian approach

    Directory of Open Access Journals (Sweden)

    Bakanev Sergey ...

    2012-10-01

    Modeling population dynamics based on the Bayesian approach enables to successfully resolve the above issues. The integration of the data from various studies into a unified model based on Bayesian parameter estimation method provides a much more detailed description of the processes occurring in the population.

  10. Population pharmacokinetic modeling of oxcarbazepine active metabolite in Chinese patients with epilepsy.

    Science.gov (United States)

    Yu, Yunli; Zhang, Quanying; Xu, Wenjun; Lv, Chengzhe; Hao, Gang

    2016-08-01

    The aim of the study was to develop a population pharmacokinetic (PPK) model of oxcarbazepine and optimize the treatment of oxcarbazepine in Chinese patients with epilepsy. A total of 108 oxcarbazepine therapeutic drug monitoring samples from 78 patients with epilepsy were collected in this study. The pharmacologically active metabolite 10,11-dihydro-10-hydrocarbamazepine (MHD) was used as the analytical target for monitoring therapy of oxcarbazepine. Patients' clinical data were retrospectively collected. The PPK model for MHD was developed using Phoenix NLME 1.2 with a non-linear mixed-effect model. MHD pharmacokinetics obeys a one-compartment model with first-order absorption and elimination. The effect of age, gender, red blood cell count, red blood cell specific volume, hemoglobin (HGB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatine were analyzed. Bootstrap and data splitting were used simultaneously to validate the final PPK models. The mean values of volume of distribution and clearance of MHD in the patients were 14.2 L and 2.38 L h(-1), respectively. BUN and HGB influenced the MHD volume of distribution according to the following equation: V = tvV × (BUN/4.76)(-0.007) × (HGB/140)(-0.001) × e (ηV) . The MHD clearance was dependent on ALT and gender as follows: CL = tvCL × (ALT/30)(0.181) × (gender) × 1.083 × e (ηCL). The final PPK model was demonstrated to be suitable and effective and it can be used to evaluate the pharmacokinetic parameters of MHD in Chinese patients with epilepsy and to choose an optimal dosage regimen of oxcarbazepine on the basis of these parameters. PMID:25700977

  11. Integrative demographic modeling reveals population level impacts of PCB toxicity to juvenile snapping turtles

    International Nuclear Information System (INIS)

    A significant challenge in ecotoxicology and risk assessment lies in placing observed contaminant effects in a meaningful ecological context. Polychlorinated biphenyls (PCBs) have been shown to affect juvenile snapping turtle survival and growth but the ecological significance of these effects is difficult to discern without a formal, population-level assessment. We used a demographic matrix model to explore the potential population-level effects of PCBs on turtles. Our model showed that effects of PCBs on juvenile survival, growth and size at hatching could translate to negative effects at the population level despite the fact that these life cycle components do not typically contribute strongly to population level processes. This research points to the utility of using integrative demographic modeling approaches to better understand contaminant effects in wildlife. The results indicate that population-level effects are only evident after several years, suggesting that for long-lived species, detecting adverse contaminant effects could prove challenging. -- Highlights: • Previous studies have shown the PCBs can impact juvenile snapping turtles. • We used a demographic model of turtles to evaluate population-level PCB effects. • PCB effects on turtles may translate to negative population responses. • Long-term monitoring is needed to detect contaminant effects on natural turtle populations. • Demographic models can improve our understanding contaminant ecotoxicity. -- A demographic model was used to show that PCB induced effects on young snapping turtles can result in adverse effects at the population level

  12. Tuning stochastic matrix models with hydrologic data to predict the population dynamics of a riverine fish

    Science.gov (United States)

    Sakaris, P.C.; Irwin, E.R.

    2010-01-01

    We developed stochastic matrix models to evaluate the effects of hydrologic alteration and variable mortality on the population dynamics of a lotie fish in a regulated river system. Models were applied to a representative lotic fish species, the flathead catfish (Pylodictis olivaris), for which two populations were examined: a native population from a regulated reach of the Coosa River (Alabama, USA) and an introduced population from an unregulated section of the Ocmulgee River (Georgia, USA). Size-classified matrix models were constructed for both populations, and residuals from catch-curve regressions were used as indices of year class strength (i.e., recruitment). A multiple regression model indicated that recruitment of flathead catfish in the Coosa River was positively related to the frequency of spring pulses between 283 and 566 m3/s. For the Ocmulgee River population, multiple regression models indicated that year class strength was negatively related to mean March discharge and positively related to June low flow. When the Coosa population was modeled to experience five consecutive years of favorable hydrologic conditions during a 50-year projection period, it exhibited a substantial spike in size and increased at an overall 0.2% annual rate. When modeled to experience five years of unfavorable hydrologic conditions, the Coosa population initially exhibited a decrease in size but later stabilized and increased at a 0.4% annual rate following the decline. When the Ocmulgee River population was modeled to experience five years of favorable conditions, it exhibited a substantial spike in size and increased at an overall 0.4% annual rate. After the Ocmulgee population experienced five years of unfavorable conditions, a sharp decline in population size was predicted. However, the population quickly recovered, with population size increasing at a 0.3% annual rate following the decline. In general, stochastic population growth in the Ocmulgee River was more

  13. Melanopsin-expressing ganglion cells on macaque and human retinas form two morphologically distinct populations.

    Science.gov (United States)

    Liao, Hsi-Wen; Ren, Xiaozhi; Peterson, Beth B; Marshak, David W; Yau, King-Wai; Gamlin, Paul D; Dacey, Dennis M

    2016-10-01

    The long-term goal of this research is to understand how retinal ganglion cells that express the photopigment melanopsin, also known as OPN4, contribute to vision in humans and other primates. Here we report the results of anatomical studies using our polyclonal antibody specifically against human melanopsin that confirm and extend previous descriptions of melanopsin cells in primates. In macaque and human retina, two distinct populations of melanopsin cells were identified based on dendritic stratification in either the inner or the outer portion of the inner plexiform layer (IPL). Variation in dendritic field size and cell density with eccentricity was confirmed, and dendritic spines, a new feature of melanopsin cells, were described. The spines were the sites of input from DB6 diffuse bipolar cell axon terminals to the inner stratifying type of melanopsin cells. The outer stratifying melanopsin type received inputs from DB6 bipolar cells via a sparse outer axonal arbor. Outer stratifying melanopsin cells also received inputs from axon terminals of dopaminergic amacrine cells. On the outer stratifying melanopsin cells, ribbon synapses from bipolar cells and conventional synapses from amacrine cells were identified in electron microscopic immunolabeling experiments. Both inner and outer stratifying melanopsin cell types were retrogradely labeled following tracer injection in the lateral geniculate nucleus (LGN). In addition, a method for targeting melanopsin cells for intracellular injection using their intrinsic fluorescence was developed. This technique was used to demonstrate that melanopsin cells were tracer coupled to amacrine cells and would be applicable to electrophysiological experiments in the future. J. Comp. Neurol. 524:2845-2872, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26972791

  14. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets

    OpenAIRE

    Wilm, Andreas; Aw, Pauline Poh Kim; Bertrand, Denis; Yeo, Grace Hui Ting; Ong, Swee Hoe; Wong, Chang Hua; Khor, Chiea Chuen; Petric, Rosemary; Hibberd, Martin Lloyd; Nagarajan, Niranjan

    2012-01-01

    The study of cell-population heterogeneity in a range of biological systems, from viruses to bacterial isolates to tumor samples, has been transformed by recent advances in sequencing throughput. While the high-coverage afforded can be used, in principle, to identify very rare variants in a population, existing ad hoc approaches frequently fail to distinguish true variants from sequencing errors. We report a method (LoFreq) that models sequencing run-specific error rates to accurately call va...

  15. An individual-based model of Zebrafish population dynamics accounting for energy dynamics

    DEFF Research Database (Denmark)

    Beaudouin, Remy; Goussen, Benoit; Piccini, Benjamin;

    2015-01-01

    coupled to an individual based model of zebrafish population dynamics (IBM model). Next, we fitted the DEB model to new experimental data on zebrafish growth and reproduction thus improving existing models. We further analysed the DEB-model and DEB-IBM using a sensitivity analysis. Finally, the...

  16. Coherent population trapping on 87Rb atoms in small-size absorption cells with buffer gas

    Science.gov (United States)

    Ermak, S. V.; Petrenko, M. V.; Semenov, V. V.

    2016-02-01

    Coherent population trapping (CPT) on 87Rb atoms in neon atmosphere has been studied in small-size glass absorption cells under conditions of pumping with narrow-band laser radiation at the D2 line of the main doublet. Parameters of the absorption signal have been measured in 3-mm-diameter cells at buffer gas (Ne) pressures varied within 200-400 Torr, cell temperatures within 65-120°C, and pumping radiation power densities within 30-400 μW/cm2. Optimum values of the buffer gas pressures, cell temperature, and pumping power are determined at which the short-term instability of the resonance line is at minimum. Orientational shifts of the CPT resonance signal in gas-filled cells and small-size cells with antirelaxation coating have been compared.

  17. Z-type control of populations for Lotka-Volterra model with exponential convergence.

    Science.gov (United States)

    Zhang, Yunong; Yan, Xiaogang; Liao, Bolin; Zhang, Yinyan; Ding, Yaqiong

    2016-02-01

    The population control of the Lotka-Volterra model is one of the most important and widely investigated issues in mathematical ecology. In this study, assuming that birth rate is controllable and using the Z-type dynamic method, we develop Z-type control laws to drive the prey population and/or predator population to a desired state to keep species away from extinction and to improve ecosystem stability. A direct controller group is initially designed to control the prey and predator populations simultaneously. Two indirect controllers are then proposed for prey population control and predator population control by exerting exogenous measure on another species. All three control laws possess exponential convergence performances. Finally, the corresponding numerical simulations are performed. Results substantiate the theoretical analysis and effectiveness of such Z-type control laws for the population control of the Lotka-Volterra model. PMID:26644036

  18. Characterization of a Phenotypically Unique Population of CD13+ Dendritic Cells Resident in the Spleen

    OpenAIRE

    Zhuang, Yan; Mwangi, Waithaka; Brown, Wendy C.; Davis, William C.; Hope, Jayne C.; Palmer, Guy H.

    2006-01-01

    Immature dendritic cells (DCs) resident in bovine spleens represent a distinct CD11a+ CD11c+ CD13+ CD172+ CD205+ population compared to those circulating in peripheral blood or trafficking via afferent lymph. Upon cytokine-induced maturation, splenic DCs both efficiently present antigen in the stimulation of allogeneic lymphocyte proliferation and recall antigen-specific responses.

  19. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem cel

  20. Modeling cell behavior: moving beyond intuition

    Directory of Open Access Journals (Sweden)

    Mario Jolicoeur

    2014-04-01

    Full Text Available In the context of the launching of this new journal, we propose a forum to the community of researchers interested and involved in, or even simply questioning the why, what, how, and when of modeling cell or cell culture behavior. To start the discussion, we review some of the usual questions we are routinely asked on the pertinence of modeling cell behavior, and on who might benefit from conducting such work. To draw a global portrait, throughout this text we refer the reader to handbooks introducing the basics of modeling a biosystem, as well as to selected works that can help visualize the broad fields of applications.

  1. Structured modeling of recombinant protein production in batch and fed-batch culture of baculovirus-infected insect cells

    OpenAIRE

    Jang, J. D.; Sanderson, C.S.; Chan, L. C. L.; Barford, J. P.; Reid, S

    2000-01-01

    The infection of insect cells with baculovirus was described in a mathematical model as a part of the structured dynamic model describing whole animal cell metabolism. The model presented here is capable of simulating cell population dynamics, the concentrations of extracellular and intracellularviral components, and the heterologous product titers. The model describes the whole processes of viral infection and theeffect of the infection on the host cell metabolism. Dynamic simulation of the ...

  2. An example of population-level risk assessments for small mammals using individual-based population models

    DEFF Research Database (Denmark)

    Schmitt, Walter; Auteri, Domenica; Bastiansen, Finn; Ebeling, Markus; Lui, Chun; Luttik, Robert; Mastitsky, Sergey; Nacci, Diane; Topping, Christopher John; Wang, Magnus

    2015-01-01

    This article presents a case study demonstrating the application of 3 individual-based, spatially explicit population models (IBMs, also known as agent-based models) in ecological risk assessments to predict long-term effects of a pesticide to populations of small mammals. The 3 IBMs each used a...... structural complexity. The toxicological profile of FungicideX was defined so that the deterministic long-term first tier risk assessment would result in high risk to small mammals, thus providing the opportunity to use the IBMs for risk assessment refinement (i.e., higher tier risk assessment). Despite...... assessments for small mammals, including consistent and transparent direct links to specific protection goals, and the consideration of more realistic scenarios....

  3. An example of population-level risk assessments for small mammals using individual-based population models.

    Science.gov (United States)

    Schmitt, Walter; Auteri, Domenica; Bastiansen, Finn; Ebeling, Markus; Liu, Chun; Luttik, Robert; Mastitsky, Sergey; Nacci, Diane; Topping, Chris; Wang, Magnus

    2016-01-01

    This article presents a case study demonstrating the application of 3 individual-based, spatially explicit population models (IBMs, also known as agent-based models) in ecological risk assessments to predict long-term effects of a pesticide to populations of small mammals. The 3 IBMs each used a hypothetical fungicide (FungicideX) in different scenarios: spraying in cereals (common vole, Microtus arvalis), spraying in orchards (field vole, Microtus agrestis), and cereal seed treatment (wood mouse, Apodemus sylvaticus). Each scenario used existing model landscapes, which differed greatly in size and structural complexity. The toxicological profile of FungicideX was defined so that the deterministic long-term first tier risk assessment would result in high risk to small mammals, thus providing the opportunity to use the IBMs for risk assessment refinement (i.e., higher tier risk assessment). Despite differing internal model design and scenarios, results indicated in all 3 cases low population sensitivity unless FungicideX was applied at very high (×10) rates. Recovery from local population impacts was generally fast. Only when patch extinctions occured in simulations of intentionally high acute toxic effects, recovery periods, then determined by recolonization, were of any concern. Conclusions include recommendations for the most important input considerations, including the selection of exposure levels, duration of simulations, statistically robust number of replicates, and endpoints to report. However, further investigation and agreement are needed to develop recommendations for landscape attributes such as size, structure, and crop rotation to define appropriate regulatory risk assessment scenarios. Overall, the application of IBMs provides multiple advantages to higher tier ecological risk assessments for small mammals, including consistent and transparent direct links to specific protection goals, and the consideration of more realistic scenarios. PMID:25891765

  4. A Bibliometric Analysis on Cancer Population Science with Topic Modeling

    OpenAIRE

    Li, Ding-Cheng; Rastegar-Mojarad, Majid; Okamoto, Janet; Liu, Hongfang; Leichow, Scott

    2015-01-01

    Bibliometric analysis is a research method used in library and information science to evaluate research performance. It applies quantitative and statistical analyses to describe patterns observed in a set of publications and can help identify previous, current, and future research trends or focus. To better guide our institutional strategic plan in cancer population science, we conducted bibliometric analysis on publications of investigators currently funded by either Division of Cancer Preve...

  5. Modelling the effects of climate change on weed population dynamics

    OpenAIRE

    García de León Hernández, David

    2014-01-01

    As the human population continues to increase –it will have surpassed 9 billion people by 2050- food supply must rise in order to sustain people. Climate change represents a threat in the provision of sufficient, secure and nutritious nourishment for everyone. Possible consequences of climate change include a reduction in global agro-ecosystem production, with Spain as one of the most affected countries in Europe. Accordingly, little is known about the possible effects on weed ...

  6. Classifying the expansion kinetics and critical surface dynamics of growing cell populations

    OpenAIRE

    Block, M; Schoell, E.; Drasdo, D.

    2006-01-01

    Based on a cellular automaton model the growth kinetics and the critical surface dynamics of cell monolayers is systematically studied by variation of the cell migration activity, the size of the proliferation zone and the cell cycle time distribution over wide ranges. The model design avoids lattice artifacts and ensures high performance. The monolayer expansion velocity derived from our simulations can be interpreted as a generalization of the velocity relationship for a traveling front in ...

  7. Heuristic modeling of carcinogenesis for the population with dichotomous susceptibility to cancer: a pancreatic cancer example.

    Directory of Open Access Journals (Sweden)

    Tengiz Mdzinarishvili

    Full Text Available At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate from the observed hazard rate in the population (population hazard rate; and (ii modelling of the individual hazard rate by a chosen "up" of the theoretical hazard function describing cancer occurrence in individuals in time (age. The model considers carcinogenesis as a failure of individuals susceptible to cancer to resist cancer occurrence in aging and uses, as the theoretical hazard function, the three-parameter Weibull hazard function, often utilized in a failure analysis. The parameters of this function, providing the best fit of the modeled and observed individual hazard rates (determined from the population hazard rates, are the outcomes of the modeling. The model was applied to the pancreatic cancer data. It was shown that, in the populations stratified by gender, race and the geographic area of living, the modeled and observed population hazard rates of pancreatic cancer occurrence have similar turnovers at old ages. The sizes of the pools of individuals susceptible to this cancer: (i depend on gender, race and the geographic area of living; (ii proportionally influence the corresponding population hazard rates; and (iii do not influence the individual hazard rates. The model should be further tested using data on other types of cancer and for the populations stratified by different categorical variables.

  8. Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population

    Directory of Open Access Journals (Sweden)

    Mariani M

    2006-10-01

    Full Text Available Abstract Background Killer cell immunoglobulin-like receptors (KIRs are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. Methods Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. Results All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. Conclusion The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

  9. B-Cell Activation and Non-Hodgkin Lymphoma Risk in an HIV Positive Population

    OpenAIRE

    Chang, Po-Yin

    2013-01-01

    Background: B-cell non-Hodgkin lymphoma (NHL) in HIV populations (AIDS-NHL) has become the leading cause of AIDS-defining cancers. Studies suggested that genetic or serum markers of B-cell activation are related to AIDS-NHL. However, associations between HIV viral load and AIDS-NHL risk have not been explicitly explored with consideration of B-cell activation markers. Furthermore, associations of hepatitis C virus (HCV) infection to AIDS-NHL risk are inconclusive. Methods: We used two nested ...

  10. Tumor associated antigen specific T-cell populations identified in ex vivo expanded TIL cultures

    DEFF Research Database (Denmark)

    Junker, Niels; Kvistborg, Pia; Køllgaard, Tania;

    2012-01-01

    Ex vivo expanded tumor infiltrating lymphocytes (TILs) from malignant melanoma (MM) and head & neck squamous cell carcinoma (HNSCC) share a similar oligoclonal composition of T effector memory cells, with HLA class I restricted lysis of tumor cell lines. In this study we show that ex vivo expanded...... TILs from MM and HNSCC demonstrate a heterogeneous composition in frequency and magnitude of tumor associated antigen specific populations by Elispot IFN¿ quantitation. TILs from MM and HNSCC shared reactivity towards NY ESO-1, cyclin B1 and Bcl-x derived peptides. Additionally we show that dominating...

  11. Transcriptional and functional differences in stem cell populations isolated from Extraocular and Limb muscles

    DEFF Research Database (Denmark)

    Pacheco-Pinedo, Eugenia Cristina; Budak, Murat T; Zeiger, Ulrike;

    2008-01-01

    and is consistent with a role for their sparing in DMD . We believe the greater numbers of stem cells, their unique transcriptome, the greater proliferative capacity of EOM stem cells and greater number of satellite cells also offers clues for novel cell-based therapeutic strategies. Key words: Side...... capacity. Finally, assays of the committed progenitors or satellite cells performed on myofibers isolated from EOM and limb muscles independently validated increased proliferative capacity of these muscles. We suggest a model wherein unique EOM stem cells contribute to the continual myogenesis noted in EOM...

  12. Differential effects of drugs targeting cancer stem cell (CSC and non-CSC populations on lung primary tumors and metastasis.

    Directory of Open Access Journals (Sweden)

    Leyre Larzabal

    Full Text Available Cancer stem cells (CSCs are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. The aim of this study was to investigate the effect of salinomycin, a selective inhibitor of CSCs, with or without combination with paclitaxel, in a metastatic model. To evaluate the effect of these drugs in metastasis and tumor microenvironment we took advantage of the immunocompetent and highly metastatic LLC mouse model. Aldefluor assays were used to analyze the ALDH+/- populations in murine LLC and human H460 and H1299 lung cancer cells. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the H460 and H1299 cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. In in vivo experiments, paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p<0.05, whereas salinomycin had no effect on primary tumors but reduced lung metastasis (p<0.05. Combination of both drugs did not improve the effect of single therapies. ALDH1A1, SOX2, CXCR4 and SDF-1 mRNA levels were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change when mice were administered with salinomycin. The number of F4/80+ and CD11b+ cells was also reduced upon administration of both drugs, but particularly in metastasis. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. In contrast, paclitaxel (although reducing primary tumor growth promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster

  13. Differential effects of drugs targeting cancer stem cell (CSC) and non-CSC populations on lung primary tumors and metastasis.

    Science.gov (United States)

    Larzabal, Leyre; El-Nikhely, Nefertiti; Redrado, Miriam; Seeger, Werner; Savai, Rajkumar; Calvo, Alfonso

    2013-01-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. The aim of this study was to investigate the effect of salinomycin, a selective inhibitor of CSCs, with or without combination with paclitaxel, in a metastatic model. To evaluate the effect of these drugs in metastasis and tumor microenvironment we took advantage of the immunocompetent and highly metastatic LLC mouse model. Aldefluor assays were used to analyze the ALDH+/- populations in murine LLC and human H460 and H1299 lung cancer cells. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the H460 and H1299 cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. In in vivo experiments, paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p<0.05), whereas salinomycin had no effect on primary tumors but reduced lung metastasis (p<0.05). Combination of both drugs did not improve the effect of single therapies. ALDH1A1, SOX2, CXCR4 and SDF-1 mRNA levels were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change) when mice were administered with salinomycin. The number of F4/80+ and CD11b+ cells was also reduced upon administration of both drugs, but particularly in metastasis. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. In contrast, paclitaxel (although reducing primary tumor growth) promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster metastasis. PMID

  14. Population Evolution Model with the Wealth of the Individual Based on Penna Model

    Science.gov (United States)

    He, Mingfeng; Yu, Binglin; Chen, Liyu; Fang, Jian

    We present a simulation model based on the Penna model to study the population evolution. The wealth of the individual is considered in the model. We define increasing ratio α and decreasing ratio β of the wealth presenting the individual wealth variation, also define minimum wealth PROMO which works when one reproduces. We study the influence of α and β on a species' survival or downfall, and the influence of PROMO on the age distribution of a species. According to the different values of α and β, we find diverse regimes where a species will survive or die out, and even the regime where species' survival or downfall are very sensitive. We study the relation between life expectancy and the wealth of the individual, finding that life expectancy doesn't increase but decrease a little when the wealth of the individual increases.

  15. On a poroviscoelastic model for cell crawling

    KAUST Repository

    Kimpton, L. S.

    2014-02-08

    In this paper a minimal, one-dimensional, two-phase, viscoelastic, reactive, flow model for a crawling cell is presented. Two-phase models are used with a variety of constitutive assumptions in the literature to model cell motility. We use an upper-convected Maxwell model and demonstrate that even the simplest of two-phase, viscoelastic models displays features relevant to cell motility. We also show care must be exercised in choosing parameters for such models as a poor choice can lead to an ill-posed problem. A stability analysis reveals that the initially stationary, spatially uniform strip of cytoplasm starts to crawl in response to a perturbation which breaks the symmetry of the network volume fraction or network stress. We also demonstrate numerically that there is a steady travelling-wave solution in which the crawling velocity has a bell-shaped dependence on adhesion strength, in agreement with biological observation.

  16. Analysis of rare high-DNA cell populations in serous effusions using continuous-motion imaging.

    Science.gov (United States)

    Tucker, J H; Stark, M H; Eason, P; Duvall, E

    1991-07-01

    The rare high-DNA cell sub-populations in a series of serous effusion specimens were analysed to determine whether such measurements could provide a basis for the improved diagnosis of malignancy. Monolayer specimens stained with gallocyanin chrome-alum were scanned with the CERVIFIP continuous-motion image analyser to locate and measure the highest-DNA cells in the sample. Two types of features were obtained for the detected sub-populations; firstly, 'percentile ploidy' values which characterise the ploidy levels above which specified proportions of the total cells are found; and secondly 'percentage abnormal' values which characterise the proportion of the cells diagnosed as malignant during examination by a cytopathologist. The classification accuracy for one or both of these features was then obtained by comparison with the clinical outcome of each patient. The results gave a classification error of 9/44 (20%) using the 0.01% percentile ploidy alone, 6/44 (14%) using the 75% percentage abnormal feature alone, but only 2/44 (5%) from a box discriminant using both features. It was therefore concluded that the analysis of the high-DNA cell population could be of value in the diagnosis of malignancy in serous effusion specimens. PMID:1883747

  17. Hypoxia promotes growth of stem cells in dental follicle cell populations

    OpenAIRE

    Dai, Yuntao; He, Hongzhi; Wise, Gary E.; Yao, Shaomian

    2011-01-01

    Adult stem cells (ASC) have been found in many tissues and are of great therapeutic potential due to their capability of differentiation. However, ASC comprise only a small fraction of the tissues. In order to use ASC for therapeutic purposes, it is important to obtain relatively pure stem cells in large quantities. Current methods for stem cell purification are mainly based on marker-dependent cell sorting techniques, which have various technical difficulties. In this study, we have attempte...

  18. A Population Dynamics Analysis of the Interaction between Adaptive Regulatory T Cells and Antigen Presenting Cells

    OpenAIRE

    Fouchet, David; Regoes, Roland

    2008-01-01

    Background Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks t...

  19. The propagation of uncertainties in stellar population synthesis modeling III: model calibration, comparison, and evaluation

    CERN Document Server

    Conroy, Charlie

    2009-01-01

    Stellar population synthesis (SPS) provides the link between the stellar and dust content of galaxies and their observed spectral energy distributions. In the present work we perform a comprehensive calibration of our own flexible SPS (FSPS) model against a suite of data. Several public SPS models are intercompared, including the models of Bruzual & Charlot (BC03), Maraston (M05) and FSPS. The relative strengths and weaknesses of these models are evaluated, with the following conclusions: 1) The FSPS and BC03 models compare favorably with MC data at all ages, whereas M05 colors are too red and the age-dependence is incorrect; 2) All models yield similar optical and near-IR colors for old metal-poor systems, and yet they all provide poor fits to the integrated J-K and V-K colors of both MW and M31 star clusters; 4) All models predict ugr colors too red, D4000 strengths too strong and Hdelta strengths too weak compared to massive red sequence galaxies, under the assumption that such galaxies are composed so...

  20. Genetic barcode sequencing for screening altered population dynamics of hematopoietic stem cells transduced with lentivirus

    Science.gov (United States)

    Zanatta, Daniela B; Tsujita, Maristela; Borelli, Primavera; Aguiar, Rodrigo B; Ferrari, Daniel G; Strauss, Bryan E

    2014-01-01

    Insertional mutagenesis has been associated with malignant cell transformation in gene therapy protocols, leading to discussions about vector security. Therefore, clonal analysis is important for the assessment of vector safety and its impact on patient health. Here, we report a unique approach to assess dynamic changes in clonality of lentivirus transduced cells upon Sanger sequence analysis of a specially designed genetic barcode. In our approach, changes in the electropherogram peaks are measured and compared between successive time points, revealing alteration in the cell population. After in vitro validation, barcoded lentiviral libraries carrying IL2RG or LMO2 transgenes, or empty vector were used to transduce mouse hematopoietic (ckit+) stem cells, which were subsequently transplanted in recipient mice. We found that neither the empty nor IL2RG encoding vector had an effect on cell dynamics. In sharp contrast, the LMO2 oncogene was associated with altered cell dynamics even though hematologic counts remained unchanged, suggesting that the barcode could reveal changes in cell populations not observed by the frontline clinical assay. We describe a simple and sensitive method for the analysis of clonality, which could be easily used by any laboratory for the assessment of cellular behavior upon lentiviral transduction. PMID:26052520

  1. Multi-dimensional population balance models of crystallization processes

    DEFF Research Database (Denmark)

    Meisler, Kresten Troelstrup; von Solms, Nicolas

    A generic and model-based framework for batch cooling crystallization operations has been extended to incorporate continuous and fed-batch processes. Modules for the framework have been developed, including a module for reactions, allowing the study of reactive crystallization within the framework....... A kinetic model library together with an ontology for knowledge representation has been developed, in which kinetic models and relations from the literature are stored along with the references and data. The model library connects to the generic modelling framework as well, as models can be...... parameters for the simulation can be found in the database. A procedure for parameter estimation has been illustrated based on experimental work. The identifiability of the models has been discussed in relation to parameter estimation using sensitivity analysis. Some important identifiability issues have...

  2. Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a MAFIA-Based Glioma Model

    Directory of Open Access Journals (Sweden)

    Konrad Gabrusiewicz

    2015-04-01

    Full Text Available Monocytes/macrophages are an influential component of the glioma microenvironment. However, understanding their diversity and plasticity constitute one of the most challenging areas of research due to the paucity of models to study these cells' inherent complexity. Herein, we analyzed the role of monocytes/macrophages in glioma growth by using a transgenic model that allows for conditional ablation of this cell population. We modeled glioma using intracranial GL261-bearing CSF-1R–GFP+ macrophage Fas-induced apoptosis (MAFIA transgenic mice. Conditional macrophage ablation was achieved by exposure to the dimerizer AP20187. Double immunofluorescence was used to characterize M1- and M2-like monocytes/macrophages during tumor growth and after conditional ablation. During glioma growth, the monocyte/macrophage population consisted predominantly of M2 macrophages. Conditional temporal depletion of macrophages reduced the number of GFP+ cells, targeting mainly the repopulation of M2-polarized cells, and altered the appearance of M1-like monocytes/macrophages, which suggested a shift in the M1/M2 macrophage balance. Of interest, compared with control-treated mice, macrophage-depleted mice had a lower tumor mitotic index, microvascular density, and reduced tumor growth. These results demonstrated the possibility of studying in vivo the role and phenotype of macrophages in gliomas and suggested that transitory depletion of CSF-1R+ population influences the reconstitutive phenotypic pool of these cells, ultimately suppressing tumor growth. The MAFIA model provides a much needed advance in defining the role of macrophages in gliomas.

  3. Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a MAFIA-Based Glioma Model12

    Science.gov (United States)

    Gabrusiewicz, Konrad; Hossain, Mohammad B.; Cortes-Santiago, Nahir; Fan, Xuejun; Kaminska, Bozena; Marini, Frank C.; Fueyo, Juan; Gomez-Manzano, Candelaria

    2015-01-01

    Monocytes/macrophages are an influential component of the glioma microenvironment. However, understanding their diversity and plasticity constitute one of the most challenging areas of research due to the paucity of models to study these cells' inherent complexity. Herein, we analyzed the role of monocytes/macrophages in glioma growth by using a transgenic model that allows for conditional ablation of this cell population. We modeled glioma using intracranial GL261-bearing CSF-1R–GFP+ macrophage Fas-induced apoptosis (MAFIA) transgenic mice. Conditional macrophage ablation was achieved by exposure to the dimerizer AP20187. Double immunofluorescence was used to characterize M1- and M2-like monocytes/macrophages during tumor growth and after conditional ablation. During glioma growth, the monocyte/macrophage population consisted predominantly of M2 macrophages. Conditional temporal depletion of macrophages reduced the number of GFP+ cells, targeting mainly the repopulation of M2-polarized cells, and altered the appearance of M1-like monocytes/macrophages, which suggested a shift in the M1/M2 macrophage balance. Of interest, compared with control-treated mice, macrophage-depleted mice had a lower tumor mitotic index, microvascular density, and reduced tumor growth. These results demonstrated the possibility of studying in vivo the role and phenotype of macrophages in gliomas and suggested that transitory depletion of CSF-1R+ population influences the reconstitutive phenotypic pool of these cells, ultimately suppressing tumor growth. The MAFIA model provides a much needed advance in defining the role of macrophages in gliomas. PMID:25925380

  4. Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a MAFIA-Based Glioma Model.

    Science.gov (United States)

    Gabrusiewicz, Konrad; Hossain, Mohammad B; Cortes-Santiago, Nahir; Fan, Xuejun; Kaminska, Bozena; Marini, Frank C; Fueyo, Juan; Gomez-Manzano, Candelaria

    2015-04-01

    Monocytes/macrophages are an influential component of the glioma microenvironment. However, understanding their diversity and plasticity constitute one of the most challenging areas of research due to the paucity of models to study these cells' inherent complexity. Herein, we analyzed the role of monocytes/macrophages in glioma growth by using a transgenic model that allows for conditional ablation of this cell population. We modeled glioma using intracranial GL261-bearing CSF-1R-GFP(+) macrophage Fas-induced apoptosis (MAFIA) transgenic mice. Conditional macrophage ablation was achieved by exposure to the dimerizer AP20187. Double immunofluorescence was used to characterize M1- and M2-like monocytes/macrophages during tumor growth and after conditional ablation. During glioma growth, the monocyte/macrophage population consisted predominantly of M2 macrophages. Conditional temporal depletion of macrophages reduced the number of GFP(+) cells, targeting mainly the repopulation of M2-polarized cells, and altered the appearance of M1-like monocytes/macrophages, which suggested a shift in the M1/M2 macrophage balance. Of interest, compared with control-treated mice, macrophage-depleted mice had a lower tumor mitotic index, microvascular density, and reduced tumor growth. These results demonstrated the possibility of studying in vivo the role and phenotype of macrophages in gliomas and suggested that transitory depletion of CSF-1R(+) population influences the reconstitutive phenotypic pool of these cells, ultimately suppressing tumor growth. The MAFIA model provides a much needed advance in defining the role of macrophages in gliomas. PMID:25925380

  5. Quantitative measurement of retinal ganglion cell populations via histology-based random forest classification.

    Science.gov (United States)

    Hedberg-Buenz, Adam; Christopher, Mark A; Lewis, Carly J; Fernandes, Kimberly A; Dutca, Laura M; Wang, Kai; Scheetz, Todd E; Abràmoff, Michael D; Libby, Richard T; Garvin, Mona K; Anderson, Michael G

    2016-05-01

    The inner surface of the retina contains a complex mixture of neurons, glia, and vasculature, including retinal ganglion cells (RGCs), the final output neurons of the retina and primary neurons that are damaged in several blinding diseases. The goal of the current work was two-fold: to assess the feasibility of using computer-assisted detection of nuclei and random forest classification to automate the quantification of RGCs in hematoxylin/eosin (H&E)-stained retinal whole-mounts; and if possible, to use the approach to examine how nuclear size influences disease susceptibility among RGC populations. To achieve this, data from RetFM-J, a semi-automated ImageJ-based module that detects, counts, and collects quantitative data on nuclei of H&E-stained whole-mounted retinas, were used in conjunction with a manually curated set of images to train a random forest classifier. To test performance, computer-derived outputs were compared to previously published features of several well-characterized mouse models of ophthalmic disease and their controls: normal C57BL/6J mice; Jun-sufficient and Jun-deficient mice subjected to controlled optic nerve crush (CONC); and DBA/2J mice with naturally occurring glaucoma. The result of these efforts was development of RetFM-Class, a command-line-based tool that uses data output from RetFM-J to perform random forest classification of cell type. Comparative testing revealed that manual and automated classifications by RetFM-Class correlated well, with 83.2% classification accuracy for RGCs. Automated characterization of C57BL/6J retinas predicted 54,642 RGCs per normal retina, and identified a 48.3% Jun-dependent loss of cells at 35 days post CONC and a 71.2% loss of RGCs among 16-month-old DBA/2J mice with glaucoma. Output from automated analyses was used to compare nuclear area among large numbers of RGCs from DBA/2J mice (n = 127,361). In aged DBA/2J mice with glaucoma, RetFM-Class detected a decrease in median and mean nucleus size

  6. Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003

    Directory of Open Access Journals (Sweden)

    Ooi Eng

    2004-09-01

    Full Text Available Abstract Background The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. Methods We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V, cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L, and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5 arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. Results Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14th October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 × 10-6 nucleotide substitutions per site per day (0.17 mutations per genome per day, or two mutations per human passage (adjusted R-square = 0.4014. Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are

  7. Modeling complex spatial dynamics of two-population interaction in urbanization process

    CERN Document Server

    Chen, Yanguang

    2013-01-01

    This paper is mainly devoted to lay an empirical foundation for further research on complex spatial dynamics of two-population interaction. Based on the US population census data, a rural and urban population interaction model is developed. Subsequently a logistic equation on percentage urban is derived from the urbanization model so that spatial interaction can be connected mathematically with logistic growth. The numerical experiment by using the discretized urban-rural population interaction model of urbanization shows a period-doubling bifurcation and chaotic behavior, which is identical in patterns to those from the simple mathematical models of logistic growth in ecology. This suggests that the complicated dynamics of logistic growth may come from some kind of the nonlinear interaction. The results from this study help to understand urbanization, urban-rural population interaction, chaotic dynamics, and spatial complexity of geographical systems.

  8. Engineered Models of Confined Cell Migration.

    Science.gov (United States)

    Paul, Colin D; Hung, Wei-Chien; Wirtz, Denis; Konstantopoulos, Konstantinos

    2016-07-11

    Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topographies found in the body. Therefore, a number of experimental in vitro models that confine and impose forces on cells in well-defined microenvironments have been engineered. We describe the design and use of microfluidic microchannel devices, grooved substrates, micropatterned lines, vertical confinement devices, patterned hydrogels, and micropipette aspiration assays for studying cell responses to confinement. Use of these devices has enabled the delineation of changes in cytoskeletal reorganization, cell-substrate adhesions, intracellular signaling, nuclear shape, and gene expression that result from physical confinement. These assays and the physiologically relevant signaling pathways that have been elucidated are beginning to have a translational and clinical impact. PMID:27420571

  9. A role for E-cadherin in ensuring cohesive migration of a heterogeneous population of non-epithelial cells

    OpenAIRE

    Campbell, Kyra; Casanova, Jordi

    2015-01-01

    © 2015 Macmillan Publishers Limited. All rights reserved. Collective cell migration is a key process underlying the morphogenesis of many organs as well as tumour invasion, which very often involves heterogeneous cell populations. Here we investigated how such populations can migrate cohesively in the Drosophila posterior midgut, comprised of epithelial and mesenchymal cells and show a novel role for the epithelial adhesion molecule E-cadherin (E-Cad) in mesenchymal cells. Despite a lack of j...

  10. Matching asteroid population characteristics with a model constructed from the YORP-induced rotational fission hypothesis

    CERN Document Server

    Jacobson, Seth Andrew; Rossi, Alessandro; Scheeres, Daniel J

    2016-01-01

    From the results of a comprehensive asteroid population evolution model, we conclude that the YORP-induced rotational fission hypothesis can be consistent with the observed population statistics of small asteroids in the main belt including binaries and contact binaries. The foundation of this model is the asteroid rotation model of Marzari et al. (2011), which incorporates both the YORP effect and collisional evolution. This work adds to that model the rotational fission hypothesis and the binary evolution model of Jacobson & Scheeres (2011). The asteroid population evolution model is highly constrained by these and other previous works, and therefore it has only two significant free parameters: the ratio of low to high mass ratio binaries formed after rotational fission events and the mean strength of the binary YORP (BYORP) effect. We successfully reproduce characteristic statistics of the small asteroid population: the binary fraction, the fast binary fraction, steady-state mass ratio fraction and the...

  11. THE PROPAGATION OF UNCERTAINTIES IN STELLAR POPULATION SYNTHESIS MODELING. III. MODEL CALIBRATION, COMPARISON, AND EVALUATION

    International Nuclear Information System (INIS)

    Stellar population synthesis (SPS) provides the link between the stellar and dust content of galaxies and their observed spectral energy distributions. In the present work, we perform a comprehensive calibration of our own flexible SPS (FSPS) model against a suite of data. These data include ultraviolet, optical, and near-IR photometry, surface brightness fluctuations, and integrated spectra of star clusters in the Magellanic Clouds (MCs), M87, M31, and the Milky Way (MW), and photometry and spectral indices of both quiescent and post-starburst galaxies at z ∼ 0. Several public SPS models are intercompared, including the models of Bruzual and Charlot (BC03), Maraston (M05), and FSPS. The relative strengths and weaknesses of these models are evaluated, with the following conclusions: (1) the FSPS and BC03 models compare favorably with MC data at all ages, whereas M05 colors are too red and the age dependence is incorrect; (2) all models yield similar optical and near-IR colors for old metal-poor systems, and yet they all provide poor fits to the integrated J - K and V - K colors of both MW and M31 star clusters; (3) FSPS is able to fit all of the ultraviolet data because both the post-asymptotic giant branch (post-AGB) and horizontal branch evolutionary phases are handled flexibly, while the BC03 and M05 models fail in the far-UV, and both far- and near-UV, respectively; (4) all models predict ugr colors too red, Dn4000 strengths too strong, and HδA strengths too weak compared to massive red sequence galaxies, under the assumption that such galaxies are composed solely of old metal-rich stars; and (5) FSPS and, to a lesser extent, BC03 can reproduce the optical and near-IR colors of post-starburst galaxies, while M05 cannot. Reasons for these discrepancies are explored. The failure at predicting the ugr colors, Dn4000, and HδA strengths can be explained by some combination of a minority population of metal-poor stars, young stars, blue straggler and/or blue

  12. Application of Moran-Ricker model for analysis of Bupalus piniarius L. population dynamics

    OpenAIRE

    L.V. Nedorezov

    2012-01-01

    Statistical method of analysis of population time series in considered in current publication. This method is based on analysis of dynamics of non-linear ecological model parameter estimations in time, and devoted to investigation of influence of changing of weather conditions on population dynamics. Estimations of model parameters were obtained for all parts (which contains 12 measured values each) of initial sample. For the approximation of sub-samples the well-known Moran - Ricker model (M...

  13. About a dynamic model of interaction of insect population with food plant

    OpenAIRE

    L.V. Nedorezov

    2011-01-01

    In present paper there is the consideration of mathematical model of food plant (resource) - consumer (insect population) - pathogen system dynamics which is constructed as a system of ordinary differential equations. The dynamic regimes of model are analyzed and, in particular, with the help of numerical methods it is shown that trigger regimes (regimes with two stable attractors) can be realized in model under very simple assumptions about ecological and intra-population processes functioni...

  14. Probabilistic models of genetic variation in structured populations applied to global human studies

    OpenAIRE

    Hao, Wei; Song, Minsun; Storey, John D.

    2013-01-01

    Modern population genetics studies typically involve genome-wide genotyping of individuals from a diverse network of ancestries. An important, unsolved problem is how to formulate and estimate probabilistic models of observed genotypes that allow for complex population structure. We formulate two general probabilistic models, and we propose computationally efficient algorithms to estimate them. First, we show how principal component analysis (PCA) can be utilized to estimate a general model t...

  15. A modelling approach to vaccination and contraception programmes for rabies control in fox populations.

    OpenAIRE

    Suppo, C; Naulin, J M; Langlais, M.; Artois, M

    2000-01-01

    In a previous study, three of the authors designed a one-dimensional model to simulate the propagation of rabies within a growing fox population; the influence of various parameters on the epidemic model was studied, including oral-vaccination programmes. In this work, a two-dimensional model of a fox population having either an exponential or a logistic growth pattern was considered. Using numerical simulations, the efficiencies of two prophylactic methods (fox contraception and vaccination ...

  16. Persistence of side population cells with high drug efflux capacity in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To investigate the persistence of side population (SP) cells in pancreatic cancer and their role and mechanism in the drug resistance.METHODS:The presentation of side population cells in pancreatic cancer cell line PANC-1 and its proportion change when cultured with Gemcitabine,was detected by Hoechst 33342 staining and FACS analysis.The expression of ABCB1 and ABCG2 was detected by realtime PCR in either SP cells or non-SP cells.RESULTS:SP cells do exist in PANC-1,with a median of 3.3% and a range of 2.1-8.7%.After cultured with Gemcitabine for 3 d,the proportion of SP cells increased significantly(3.8% ± 1.9%,10.7% ± 3.7%, t = 4.616,P = 0.001 < 0.05).ABCB1 and ABCG2 expressed at higher concentrations in SP as compared with non-SP cells (ABCBI: 1.15 ± 0.72, 5.82 ± 1.16, t = 10.839,P = 0.000 < 0.05; ABCG2:1.16 ± 0.75,5.48 ± 0.94,t = 11.305,P = 0.000 < 0.05),which may contribute to the efflux of fluorescent staining and drug resistance.CONCLUSION:SP cells with inherently high resistance to chemotherapeutic agents do exist in pancreatic cancers,which may be candidate cancer stem cells contributing to the relapse of the tumor.

  17. From invasion to latency: intracellular noise and cell motility as key controls of the competition between resource-limited cellular populations

    KAUST Repository

    Guerrero, Pilar

    2015-04-02

    © 2015, Springer-Verlag Berlin Heidelberg. In this paper we analyse stochastic models of the competition between two resource-limited cell populations which differ in their response to nutrient availability: the resident population exhibits a switch-like response behaviour while the invading population exhibits a bistable response. We investigate how noise in the intracellular regulatory pathways and cell motility influence the fate of the incumbent and invading populations. We focus initially on a spatially homogeneous system and study in detail the role of intracellular noise. We show that in such well-mixed systems, two distinct regimes exist: In the low (intracellular) noise limit, the invader has the ability to invade the resident population, whereas in the high noise regime competition between the two populations is found to be neutral and, in accordance with neutral evolution theory, invasion is a random event. Careful examination of the system dynamics leads us to conclude that (i) even if the invader is unable to invade, the distribution of survival times, PS(t), has a fat-tail behaviour (PS(t)∼t-1) which implies that small colonies of mutants can coexist with the resident population for arbitrarily long times, and (ii) the bistable structure of the invading population increases the stability of the latent population, thus increasing their long-term likelihood of survival, by decreasing the intensity of the noise at the population level. We also examine the effects of spatial inhomogeneity. In the low noise limit we find that cell motility is positively correlated with the aggressiveness of the invader as defined by the time the invader takes to invade the resident population: the faster the invasion, the more aggressive the invader.

  18. Population growth through history and the escape from the Malthusian trap: a homeostatic simulation model.

    Science.gov (United States)

    Artzrouni, M; Komlos, J

    1985-01-01

    "A Malthusian simulation model is proposed to describe the growth of human population from the Neolithic through the Industrial Revolution. The economy is composed of a subsistence sector and a capital-producing sector. Our model captures the 'incessant contest' between population growth and the means of subsistence. When the per capita agricultural output falls below a biological minimum, the growth rate of the population is subject, in a random fashion, to perturbations that can take on disastrous proportions." It is suggested that "the slow accumulation of capital (and the buildup of the population of the capital-producing sector) eventually enables the population to overcome the constraints of the hostile economic environment. Our simulations (complete with confidence intervals) yield numerically realistic estimates of the population that eventually escapes from the Malthusian menace and grows unhindered during the Industrial Revolution." (summary in FRE, ITA) PMID:12280407

  19. Flicker Noise in a Model of Coevolving Biological Populations

    OpenAIRE

    Rikvold, Per Arne; Zia, R. K. P.

    2003-01-01

    We present long Monte Carlo simulations of a simple model of biological macroevolution in which births, deaths, and mutational changes in the genome take place at the level of individual organisms. The model displays punctuated equilibria and flicker noise with a 1/f-like power spectrum, consistent with some current theories of evolutionary dynamics.

  20. Modeling Populations of Thermostatic Loads with Switching Rate Actuation

    DEFF Research Database (Denmark)

    Totu, Luminita Cristiana; Wisniewski, Rafal; Leth, John-Josef

    We model thermostatic devices using a stochastic hybrid description, and introduce an external actuation mechanism that creates random switch events in the discrete dynamics. We then conjecture the form of the Fokker-Planck equation and successfully verify it numerically using Monte Carlo...... simulations. The actuation mechanism and subsequent modeling result are relevant for power system operation....