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Sample records for cellular model mda-mb-468

  1. Optimal Electroporation Condition for Small Interfering RNA Transfection into MDA-MB-468 Cell Line

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    Rita Arabsolghar

    2012-09-01

    Full Text Available Background: Electroporation is a valuable tool for small interfering RNA (siRNA delivery into cells because it efficiently transforms a wide variety of cell types. Since electroporation condition for each cell type must be determined experimentally, this study presents an optimal electroporation strategy to reproducibly and efficiently transfect MDA-MB 468 human breast cancer cell with siRNA. Methods: To identify the best condition, the cells were firstly electroporated without siRNA and cell viability was determined by trypan blue and MTT assays. Then siRNA transfection in the best condition was performed. Western blot analysis was used for monitoring successful siRNA transfection. Results: The best condition for electroporation of this cell line was 220 volt and 975 µF in exponential decay using the Gene Pulser X cell electroporation system. Our data demonstrated that by using proper electroporation condition, DNA methyl transferase mRNA was silenced by 10 nmol DNMT1 siRNA in MDA-MB 468 cells when compared with negative control siRNA electroporation. Analysis of cell viability demonstrated that optimal electroporation condition resulted in 74% and 78% cell viability by trypan blue staining and MTT assay, respectively. Conclusion: Transfection of the MDA-MB-468 breast cancer cell line with siRNA in the obtained electroporation condition was successful and resulted in effective gene silencing and high cellular viability.

  2. CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells

    International Nuclear Information System (INIS)

    Among the different mechanisms proposed to explain the cancer-protecting effect of dietary flavonoids, substrate-like interactions with cytochrome P450 CYP1 enzymes have recently been explored. In the present study, the metabolism of the flavonoids chrysin, baicalein, scutellarein, sinensetin and genkwanin by recombinant CYP1A1, CYP1B1 and CYP1A2 enzymes, as well as their antiproliferative activity in MDA-MB-468 human breast adenocarcinoma and MCF-10A normal breast cell lines, were investigated. Baicalein and 6-hydroxyluteolin were the only conversion products of chrysin and scutellarein metabolism by CYP1 family enzymes, respectively, while baicalein itself was not metabolized further. Sinensetin and genkwanin produced a greater number of metabolites and were shown to inhibit strongly in vitro proliferation of MDA-MB-468 cells at submicromolar and micromolar concentrations, respectively, without essentially affecting the viability of MCF-10A cells. Cotreatment of the CYP1 family inhibitor acacetin reversed the antiproliferative activity noticed for the two flavones in MDA-MB-468 cells to 13 and 14 μM respectively. In contrast chrysin, baicalein and scutellarein inhibited proliferation of MDA-MB-468 cells to a lesser extent than sinensetin and genkwanin. The metabolism of genkwanin to apigenin and of chrysin to baicalein was favored by CYP1B1 and CYP1A1, respectively. Taken together the data suggests that CYP1 family enzymes enhance the antiproliferative activity of dietary flavonoids in breast cancer cells, through bioconversion to more active products.

  3. Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells

    Science.gov (United States)

    MONZAVI-KARBASSI, BEHJATOLAH; HINE, R. JEAN; STANLEY, JOSEPH S.; RAMANI, VISHNU PRAKASH; CARCEL-TRULLOLS, JAIME; WHITEHEAD, TRACY L.; KELLY, THOMAS; SIEGEL, ERIC R.; ARTAUD, CECILE; SHAAF, SAEID; SAHA, RINKU; JOUSHEGHANY, FARIBA; HENRY-TILLMAN, RONDA; KIEBER-EMMONS, THOMAS

    2012-01-01

    Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching β-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional micro-environment of tumor cells may negatively affect the outcome for some breast cancer patients. PMID:20664930

  4. Aryl Hydrocarbon Receptor (AHR)-Active Pharmaceuticals Are Selective AHR Modulators in MDA-MB-468 and BT474 Breast Cancer Cells

    OpenAIRE

    Jin, Un-Ho; Lee, Syng-Ook; Safe, Stephen

    2012-01-01

    Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4-hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as aryl hydrocarbon receptor (AHR) agonists in various cell lines and animal models. In this study, the eight AHR-active pharmaceuticals were investigated in highly aggressive aryl hydrocarbon (Ah)-responsive BT474 and MDA-MB-468 breast cancer cell lines, and their effects on AHR protein, CYP1A1 (protein and mRNA), CYP1B1 (mRNA), and cell migrati...

  5. [Different coexisting genotypes in the breast cancer cell line MDA-MB-468].

    Science.gov (United States)

    Agelopoulos, K; Schmidt, H; Korsching, E; Buerger, H; Brandt, B

    2008-11-01

    Intratumor genetic heterogeneity, a well-known characteristic of numerous cancers, often confounds a precise diagnosis and leads to therapy resistance. This study deals with such chromosomal variability, which may be due to an inherent genetic instability affecting heterogeneity and clonal effects. Subpopulations of the breast cancer cell line MDA-MB-468 were isolated according to epidermal growth factor receptor (EGFR) expression by FACS. Whole genome profiling (CGH; mapping arrays) and determination of egfr gene amplification (fluorescence in situ hybridisation, FISH; qPCR) were done directly after sorting or after several passages of cell culture. Subpopulations differed in the amplification of the egfr-locus 7p11-14 showing egfr gene amplification rates of up to 60-fold in high-level expressing populations and less than 2-fold in low-level expressing populations. However, after several passages the original low-level cells showed a new amplification of the egfr gene, which was as heterogeneous as the original amplification detected in MDA-MB-468. Additional, spontaneously expressed fragile sites could be shown in FISH analyses which may affect cell culture heterogeneity. Understanding the precise chromosomal process would clarify mechanisms in vivo and improve both diagnosis and therapy of corresponding cancers. PMID:18751981

  6. Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells.

    Science.gov (United States)

    Stewart, Teneale A; Azimi, Iman; Brooks, Andrew J; Thompson, Erik W; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2016-07-01

    Epithelial-mesenchymal transition (EMT) is an important process associated with the metastasis of breast cancer cells. Members of the Janus kinases (JAKs) and Src family kinases (SFKs) are implicated in the regulation of an invasive phenotype in various cancer cell types. Using the pharmacological inhibitors JAK Inhibitor I (a pan-JAK inhibitor) and PP2 we investigated the role of the JAKs and SFKs, respectively, in the regulation of EMT markers in the MDA-MB-468 breast cancer cell line model of epidermal growth factor (EGF)-induced EMT. We identified selective inhibition of EGF induction of the mesenchymal marker vimentin by PP2 and JAK Inhibitor I. The effect of JAK Inhibitor I on vimentin protein induction occurred at a concentration lower than that required to significantly inhibit EGF-mediated signal transducer and activator of transcription 3 (STAT3)-phosphorylation, suggesting involvement of a STAT3-independent mechanism of EGF-induced vimentin regulation by JAKs. Despite our identification of a role for the JAK family in EGF-induced vimentin protein expression, siRNA-mediated silencing of each member of the JAK family was unable to phenocopy pharmacological inhibition, indicating potential redundancy among the JAK family members in this pathway. While SFKs and JAKs do not represent global regulators of the EMT phenotype, our findings have identified a role for members of these signaling pathways in the regulation of EGF-induced vimentin expression in the MDA-MB-468 breast cancer cell line. PMID:27163529

  7. Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells.

    Science.gov (United States)

    Jahidin, Aisyah H; Stewart, Teneale A; Thompson, Erik W; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2016-09-01

    Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells. PMID:27353380

  8. YC-1 exerts inhibitory effects on MDA-MB-468 breast cancer cells by targeting EGFR in vitro and in vivo under normoxic condition

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    Huan-Chen Cheng

    2012-05-01

    Full Text Available 3-(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1, the hypoxia-inducible factor-1 alpha (HIF-1α inhibitor, suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic conditions. Our previous studies demonstrated that YC-1 inhibited breast cancer cell proliferation under normoxic conditions. In the current study, we investigated the targets of YC-1 and mechanism of its action in MDA-MB-468 breast cancer cells. In the in vitro experiments, we found that YC-1 significantly inhibited MDA-MB-468 cell proliferation in normoxia and hypoxia. Under normoxic conditions, YC-1 induced apoptosis of MDA-MB-468 cells and blocked cell cycle in the G1 phase, and these effects were possibly related to caspase 8, p21, and p27 expression. RT-PCR and Western blotting results showed that YC-1 primarily inhibited HIF-1α at the mRNA and protein levels under hypoxic conditions, but suppressed the expression of epidermal growth factor receptor(EGFR at the mRNA and protein levels under normoxic conditions. In vivo, YC-1 prolonged survival, increased survival rate, decreased tumor size and metastasis rate, and inhibited tissue EGFR and HIF-1α expression. However, YC-1 exerted no obvious effect on body weight. These results indicate that YC-1 inhibits the proliferation of MDA-MB-468 cells by acting on multiple targets with minimal side effects. Thus, YC-1 is a promising target drug for breast cancer.

  9. Effects of Urtica dioica dichloromethane extract on cell apoptosis and related gene expression in human breast cancer cell line (MDA-MB-468).

    Science.gov (United States)

    Mohammadi, A; Mansoori, B; Goldar, S; Shanehbandi, D; Khaze, V; Mohammadnejad, L; Baghbani, E; Baradaran, B

    2016-01-01

    Breast cancer is the most common cancer among women in worldwide, especially in developing countries. Therefore, a large number of anticancer agents with herbal origins have been reported against this deadly disease. This study is the first to examine the cytotoxic and apoptotic effects of Urtica dioica in MDA-MB-468, human breast adenocarcinoma cells. The 3-(4,5-dimethylethiazol-2 yl)-2,5- diphenyltetrazolium (MTT) reduction and trypan-blue exclusion assay were performed in MDA-MB-468 cells as well as control cell line L929 to analyze the cytotoxic activity of the dichloromethane extract. In addition, Apoptosis induction of Urtica dioica on the MDA-MB-468 cells was assessed using TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) assay and DNA fragmentation analysis and real-time polymerase chain reaction (PCR). The results showed that the extract significantly inhibited cell growth and viability without inducing damage to normal control cells. Nuclei Staining in TUNEL and DNA fragments in DNA fragmentation assay and increase in the mRNA expression levels of caspase-3, caspase-9, decrease in the bcl2 and no significant change in the caspase-8 mRNA expression level, showed that the induction of apoptosis was the main mechanism of cell death that induce by Urtica dioica extract. Our results suggest that urtica dioica dichloromethane extract may contain potential bioactive compound(s) for the treatment of breast adenocarcinoma. PMID:26950453

  10. Co-expression of α9β1 integrin and VEGF-D confers lymphatic metastatic ability to a human breast cancer cell line MDA-MB-468LN.

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    Mousumi Majumder

    Full Text Available INTRODUCTION AND OBJECTIVES: Lymphatic metastasis is a common occurrence in human breast cancer, mechanisms remaining poorly understood. MDA-MB-468LN (468LN, a variant of the MDA-MB-468GFP (468GFP human breast cancer cell line, produces extensive lymphatic metastasis in nude mice. 468LN cells differentially express α9β1 integrin, a receptor for lymphangiogenic factors VEGF-C/-D. We explored whether (1 differential production of VEGF-C/-D by 468LN cells provides an autocrine stimulus for cellular motility by interacting with α9β1 and a paracrine stimulus for lymphangiogenesis in vitro as measured with capillary-like tube formation by human lymphatic endothelial cells (HMVEC-dLy; (2 differential expression of α9 also promotes cellular motility/invasiveness by interacting with macrophage derived factors; (3 stable knock-down of VEGF-D or α9 in 468LN cells abrogates lymphangiogenesis and lymphatic metastasis in vivo in nude mice. RESULTS: A comparison of expression of cyclo-oxygenase (COX-2 (a VEGF-C/-D inducer, VEGF-C/-D and their receptors revealed little COX-2 expression by either cells. However, 468LN cells showed differential VEGF-D and α9β1 expression, VEGF-D secretion, proliferative, migratory/invasive capacities, latter functions being stimulated further with VEGF-D. The requirement of α9β1 for native and VEGF-D-stimulated proliferation, migration and Erk activation was demonstrated by treating with α9β1 blocking antibody or knock-down of α9. An autocrine role of VEGF-D in migration was shown by its impairment by silencing VEGF-D and restoration with VEGF-D. 468LN cells and their soluble products stimulated tube formation, migration/invasiveness of HMVEC-dLy cell in a VEGF-D dependent manner as indicated by the loss of stimulation by silencing VEGF-D in 468LN cells. Furthermore, 468LN cells showed α9-dependent stimulation of migration/invasiveness by macrophage products. Finally, capacity for intra-tumoral lymphangiogenesis and

  11. Anticancer Properties of Novel Rhenium Pentylcarbanato Compounds against MDA-MB-468(HTB-132) Triple Node Negative Human Breast Cancer Cell Lines

    OpenAIRE

    Parson, Carl; SMITH, VALERIE; Krauss, Christopher; Banerjee, Hirendra N.; Reilly, Christopher; Krause, Jeanette A.; Wachira, James M.; Giri, Dipak; Winstead, Angela; Mandal, Santosh K.

    2015-01-01

    Aim To study the efficacy of novel rhenium compounds to treat triple node negative breast cancer. Place and Duration Six (6) novel rhenium pentycarbanato compounds (PC1-6) were synthesized and triple node negative breast cancer cell lines HTB-132 and Balb/c mouse kidney cell lines were treated with each of them for 48 hours. The results were analyzed by a common trypan blue cell death assay system and statistically analyzed. Place and Duration The compounds were synthesized, analyzed and eval...

  12. Modeling and cellular studies

    International Nuclear Information System (INIS)

    Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

  13. Modelling cellular behaviour

    Science.gov (United States)

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  14. Predictive Modelling of Cellular Load

    OpenAIRE

    Carolan, Emmett; McLoone, Seamus; Farrell, Ronan

    2015-01-01

    This work examines the temporal dynamics of cellular load in four Irish regions. Large scale underutilisation of network resources is identified both at the regional level and at the level of individual cells. Cellular load is modeled and prediction intervals are generated. These prediction intervals are used to put an upper bound on usage in a particular cell at a particular time. Opportunities for improvements in network utilization by incorporating these upper bounds on usage are identifie...

  15. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Purcell, James W; Davis, Jefferson; Reddy, Mamatha; Martin, Shamra; Samayoa, Kimberly; Vo, Hung; Thomsen, Karen; Bean, Peter; Kuo, Wen Lin; Ziyad, Safiyyah; Billig, Jessica; Feiler, Heidi S; Gray, Joe W; Wood, Kenneth W; Cases, Sylvaine

    2009-06-10

    Ispinesib (SB-715992) is a potent inhibitor of kinesin spindle protein (KSP), a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. Clinical studies of ispinesib have demonstrated a 9% response rate in patients with locally advanced or metastatic breast cancer, and a favorable safety profile without significant neurotoxicities, gastrointestinal toxicities or hair loss. To better understand the potential of ispinesib in the treatment of breast cancer we explored the activity of ispinesib alone and in combination several therapies approved for the treatment of breast cancer. We measured the ispinesib sensitivity and pharmacodynamic response of breast cancer cell lines representative of various subtypes in vitro and as xenografts in vivo, and tested the ability of ispinesib to enhance the anti-tumor activity of approved therapies. In vitro, ispinesib displayed broad anti-proliferative activity against a panel of 53 breast cell-lines. In vivo, ispinesib produced regressions in each of five breast cancer models, and tumor free survivors in three of these models. The effects of ispinesib treatment on pharmacodynamic markers of mitosis and apoptosis were examined in vitro and in vivo, revealing a greater increase in both mitotic and apoptotic markers in the MDA-MB-468 model than in the less sensitive BT-474 model. In vivo, ispinesib enhanced the anti-tumor activity of trastuzumab, lapatinib, doxorubicin, and capecitabine, and exhibited activity comparable to paclitaxel and ixabepilone. These findings support further clinical exploration of KSP inhibitors for the treatment of breast cancer.

  16. Co-inhibition of epidermal growth factor receptor and insulin-like growth factor receptor 1 enhances radiosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Over-expression of epidermal growth factor receptor (EGFR) or insulin-like growth factor-1 receptor (IGF-1R) have been shown to closely correlate with radioresistance of breast cancer cells. This study aimed to investigate the impact of co-inhibition of EGFR and IGF-1R on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression. The MCF-7 (EGFR +/−, IGF-1R +++) and MDA-MB-468 (EGFR +++, IGF-1R +++) breast cancer cell lines were used. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle distribution were measured by flow cytometry. Phospho-Akt and phospho-Erk1/2 were quantified by western blot. In vivo studies were conducted using MDA-MB-468 cells xenografted in nu/nu mice. In MDA-MB-468 cells, the inhibition of IGF-1R upregulated the p-EGFR expression. Either EGFR (AG1478) or IGF-1R inhibitor (AG1024) radiosensitized MDA-MB-468 cells. In MCF-7 cells, radiosensitivity was enhanced by AG1024, but not by AG1478. Synergistical radiosensitizing effect was observed by co-inhibition of EGFR and IGF-1R only in MDA-MB-468 cells with a DMF10% of 1.90. The co-inhibition plus irradiation significantly induced more apoptosis and arrested the cells at G0/G1 phase in MDA-MB-468 cells. Only co-inhibition of EGFR and IGF-1R synergistically diminished the expression of p-Akt and p-Erk1/2 in MDA-MB-468 cells. In vivo studies further verified the radiosensitizing effects by co-inhibition of both pathways in a MDA-MB-468 xenograft model. Our data suggested that co-inhibition of EGFR and IGF-1R synergistically radiosensitized breast cancer cells with both EGFR and IGF-1R high expression. The approach may have an important therapeutic implication in the treatment of breast cancer patients with high expression of EGFR and IGF-1R

  17. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  18. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

    Science.gov (United States)

    Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

  19. Understanding cisplatin resistance using cellular models.

    OpenAIRE

    STORDAL, BRITTA KRISTINA

    2007-01-01

    PUBLISHED Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 ?g/ml. Cisplatin resistance i...

  20. Understanding cisplatin resistance using cellular models

    OpenAIRE

    Stordal, Britta; Davey, Mary

    2007-01-01

    Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 microg/ml. Cisplatin resistance in these cells correlated...

  1. Animal and cellular models of human disease

    OpenAIRE

    Arends, Mark; White, Eric; Whitelaw, Christopher

    2016-01-01

    In this eighteenth (2016) Annual Review Issue of The Journal of Pathology, we present a collection of 19 invited review articles that cover different aspects of cellular and animal models of disease. These include genetically-engineered models, chemically-induced models, naturally-occurring models, and combinations thereof, with the focus on recent methodological and conceptual developments across a wide range of human diseases.

  2. A Modified Sensitive Driving Cellular Automaton Model

    Institute of Scientific and Technical Information of China (English)

    GE Hong-Xia; DAI Shi-Qiang; DONG Li-Yun; LEI Li

    2005-01-01

    A modified cellular automaton model for traffic flow on highway is proposed with a novel concept about the variable security gap. The concept is first introduced into the original Nagel-Schreckenberg model, which is called the non-sensitive driving cellular automaton model. And then it is incorporated with a sensitive driving NaSch model,in which the randomization brake is arranged before the deterministic deceleration. A parameter related to the variable security gap is determined through simulation. Comparison of the simulation results indicates that the variable security gap has different influence on the two models. The fundamental diagram obtained by simulation with the modified sensitive driving NaSch model shows that the maximumflow are in good agreement with the observed data, indicating that the presented model is more reasonable and realistic.

  3. Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models.

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    Paydar, Mohammadjavad; Kamalidehghan, Behnam; Wong, Yi Li; Wong, Won Fen; Looi, Chung Yeng; Mustafa, Mohd Rais

    2014-01-01

    To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC₅₀ 46.5±3.1 μg/mL) and MDA-MB-468 (48-hour IC₅₀ 50.8±2.7 μg/mL). Boldine had a cytotoxic effect and induced apoptosis in breast cancer cells as indicated by a higher amount of lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase. The anticancer mechanism is associated with disruption of the mitochondrial membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found that boldine could inhibit nuclear factor kappa B activation, a key molecule in tumor progression and metastasis. In addition, protein array and Western blotting analysis showed that treatment with boldine resulted in downregulation of Bcl-2 and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or 100 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that boldine is a potentially useful agent for the treatment of breast cancer. PMID:24944509

  4. Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

    Science.gov (United States)

    Li, Fiona; Cho, Sung Ju; Yu, Lihai; Hudson, Robert H. E.; Luyt, Leonard G.; Pin, Christopher L.; Kovacs, Michael S.; Koropatnick, James; Lee, Ting-Yim

    2016-03-01

    Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated 18F-fluroacetamido-1-hexanoicanilide (18F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using 18F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of 18F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of 18F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with 18F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

  5. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Heravi, Mitra [Department of Human Genetics, McGill University, Montreal (Canada); Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Kumala, Slawomir [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Rachid, Zakaria; Jean-Claude, Bertrand J. [Cancer Drug Research Laboratory, McGill University Health Center, Montreal (Canada); Radzioch, Danuta [Department of Human Genetics, McGill University, Montreal (Canada); Muanza, Thierry M., E-mail: tmuanza@yahoo.com [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada)

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

  6. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    International Nuclear Information System (INIS)

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings

  7. A Mathematical Model for Cisplatin Cellular Pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Ardith W. El-Kareh

    2003-03-01

    Full Text Available A simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls on the time course of extracellular exposure. Cellular pharmacokinetic parameters are derived from uptake data for human ovarian and head and neck cancer cell lines. Survival relative to controls is assumed to depend on the peak concentration of DNA-bound intracellular platinum. Model predictions agree well with published data on cisplatin cytotoxicity for three different cancer cell lines, over a wide range of exposure times. In comparison with previously published mathematical models for anticancer drug pharmacodynamics, the present model provides a better fit to experimental data sets including long exposure times (∼100 hours. The model provides a possible explanation for the fact that cell kill correlates well with area under the extracellular concentration-time curve in some data sets, but not in others. The model may be useful for optimizing delivery schedules and for the dosing of cisplatin for cancer therapy.

  8. Cellular automata modelling of hantarvirus infection

    International Nuclear Information System (INIS)

    Hantaviruses are a group of viruses which have been identified as being responsible for the outbreak of diseases such as the hantavirus pulmonary syndrome. In an effort to understand the characteristics and dynamics of hantavirus infection, mathematical models based on differential equations have been developed and widely studied. However, such models neglect the local characteristics of the spreading process and do not include variable susceptibility of individuals. In this paper, we develop an alternative approach based on cellular automata to analyze and study the spatiotemporal patterns of hantavirus infection.

  9. Cellular automata modelling of hantarvirus infection

    Energy Technology Data Exchange (ETDEWEB)

    Abdul Karim, Mohamad Faisal [School of Distance Education, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: faisal@usm.my; Md Ismail, Ahmad Izani [School of Mathematical Sciences, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: izani@cs.usm.my; Ching, Hoe Bee [School of Mathematical Sciences, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: Bee_Ching_Janice_Hoe@dell.com

    2009-09-15

    Hantaviruses are a group of viruses which have been identified as being responsible for the outbreak of diseases such as the hantavirus pulmonary syndrome. In an effort to understand the characteristics and dynamics of hantavirus infection, mathematical models based on differential equations have been developed and widely studied. However, such models neglect the local characteristics of the spreading process and do not include variable susceptibility of individuals. In this paper, we develop an alternative approach based on cellular automata to analyze and study the spatiotemporal patterns of hantavirus infection.

  10. Spatial game in cellular automaton evacuation model

    Science.gov (United States)

    von Schantz, Anton; Ehtamo, Harri

    2015-11-01

    For numerical simulations of crowd dynamics in an evacuation we need a computationally light environment, such as the cellular automaton model (CA). By choosing the right model parameters, different types of crowd behavior and collective effects can be produced. But the CA does not answer why, when, and how these different behaviors and collective effects occur. In this article, we present a model, where we couple a spatial evacuation game to the CA. In the game, an agent chooses its strategy by observing its neighbors' strategies. The game matrix changes with the distance to the exit as the evacuation conditions develop. In the resulting model, an agent's strategy choice alters the parameters that govern its behavior in the CA. Thus, with our model, we are able to simulate how evacuation conditions affect the behavior of the crowd. Also, we show that some of the collective effects observed in evacuations are a result of the simple game the agents play.

  11. A cellular automata model for ant trails

    Indian Academy of Sciences (India)

    Sibel Gokce; Ozhan Kayacan

    2013-05-01

    In this study, the unidirectional ant traffic flow with U-turn in an ant trail was investigated using one-dimensional cellular automata model. It is known that ants communicate with each other by dropping a chemical, called pheromone, on the substrate. Apart from the studies in the literature, it was considered in the model that (i) ant colony consists of two kinds of ants, goodand poor-smelling ants, (ii) ants might make U-turn for some special reasons. For some values of densities of good- and poor-smelling ants, the flux and mean velocity of the colony were studied as a function of density and evaporation rate of pheromone.

  12. Modeling the topological organization of cellular processes.

    Science.gov (United States)

    Giavitto, Jean-Louis; Michel, Olivier

    2003-07-01

    The cell as a dynamical system presents the characteristics of having a dynamical structure. That is, the exact phase space of the system cannot be fixed before the evolution and integrative cell models must state the evolution of the structure jointly with the evolution of the cell state. This kind of dynamical systems is very challenging to model and simulate. New programming concepts must be developed to ease their modeling and simulation. In this context, the goal of the MGS project is to develop an experimental programming language dedicated to the simulation of this kind of systems. MGS proposes a unified view on several computational mechanisms (CHAM, Lindenmayer systems, Paun systems, cellular automata) enabling the specification of spatially localized computations on heterogeneous entities. The evolution of a dynamical structure is handled through the concept of transformation which relies on the topological organization of the system components. An example based on the modeling of spatially distributed biochemical networks is used to illustrate how these notions can be used to model the spatial and temporal organization of intracellular processes. PMID:12915272

  13. Cellular automata modelling of biomolecular networks dynamics.

    Science.gov (United States)

    Bonchev, D; Thomas, S; Apte, A; Kier, L B

    2010-01-01

    The modelling of biological systems dynamics is traditionally performed by ordinary differential equations (ODEs). When dealing with intracellular networks of genes, proteins and metabolites, however, this approach is hindered by network complexity and the lack of experimental kinetic parameters. This opened the field for other modelling techniques, such as cellular automata (CA) and agent-based modelling (ABM). This article reviews this emerging field of studies on network dynamics in molecular biology. The basics of the CA technique are discussed along with an extensive list of related software and websites. The application of CA to networks of biochemical reactions is exemplified in detail by the case studies of the mitogen-activated protein kinase (MAPK) signalling pathway, the FAS-ligand (FASL)-induced and Bcl-2-related apoptosis. The potential of the CA method to model basic pathways patterns, to identify ways to control pathway dynamics and to help in generating strategies to fight with cancer is demonstrated. The different line of CA applications presented includes the search for the best-performing network motifs, an analysis of importance for effective intracellular signalling and pathway cross-talk. PMID:20373215

  14. Cellular automata modeling of cooperative eutectic growth

    Directory of Open Access Journals (Sweden)

    E. Olejnik

    2010-01-01

    Full Text Available The model and results of the 2D simulation of the cooperative growth of two phases in the lamellar eutectic are presented. The pro-posed model takes into account heat transfer, components diffusion and nonstationary concentration distribution in the liquid and solid phases, non-equlibrium nature of the phase transformation and kinetics of the growth, influence of the surface energy and interface curva-ture on the conditions of the thermodynamic equilibrium. For the determination of the phase interface shape the Cellular Automata tech-nique (CA was used. For the calculation of temperature and concentration distribution the numerical solution of the Fourier equation was used. The partial differential equations were solved by Finite Differences Method (FDM. The spatial position and cell sizes of CA lattice and FDM mesh are equal.Proposed model can predict the steady state growth with a constant interlamellar spacing in the regular plate eutectic, as well as some transient processes that bring to the changes of that parameters. Obtained simulation data show the solid-liquid interface changes result in the termination of lamella and enlargement of interlamellar spacing. Another simulation results illustrate a pocket formation in the center of one phase that forestalls nucleation (or intergrowth of the new lamellae of another phase. The data of the solidification study of the transparent material (CBr4 – 8,4% C2Cl6 obtained in the thin layer demonstrate the qualita-tive agreement of the simulation.

  15. Modeling cellular effects of coal pollutants

    International Nuclear Information System (INIS)

    The goal of this project is to develop and test models for the dose and dose-rate dependence of biological effects of coal pollutants on mammalian cells in tissue culture. Particular attention is given to the interaction of pollutants with the genetic material (deoxyribonucleic acid, or NDA) in the cell. Unlike radiation, which can interact directly with chromatin, chemical pollutants undergo numerous changes before the ultimate carcinogen becomes covalently bound to the DNA. Synthetic vesicles formed from a phospholipid bilayer are being used to investigate chemical transformations that may occur during the transport of pollutants across cellular membranes. The initial damage to DNA is rapidly modified by enzymatic repair systems in most living organisms. A model has been developed for predicting the effects of excision repair on the survival of human cells exposed to chemical carcinogens. In addition to the excision system, normal human cells also have tolerance mechanisms that permit continued growth and division of cells without removal of the damage. We are investigating the biological effect of damage passed to daughter cells by these tolerance mechanisms

  16. Analytical Modeling of Uplink Cellular Networks

    CERN Document Server

    Novlan, Thomas D; Andrews, Jeffrey G

    2012-01-01

    Cellular uplink analysis has typically been undertaken by either a simple approach that lumps all interference into a single deterministic or random parameter in a Wyner-type model, or via complex system level simulations that often do not provide insight into why various trends are observed. This paper proposes a novel middle way that is both accurate and also results in easy-to-evaluate integral expressions based on the Laplace transform of the interference. We assume mobiles and base stations are randomly placed in the network with each mobile pairing up to its closest base station. The model requires two important changes compared to related recent work on the downlink. First, dependence is introduced between the user and base station point processes to make sure each base station serves a single mobile in the given resource block. Second, per-mobile power control is included, which further couples the locations of the mobiles and their receiving base stations. Nevertheless, we succeed in deriving the cov...

  17. Typhoid fever as cellular microbiological model

    OpenAIRE

    Andrade Dahir Ramos de; Andrade Júnior Dahir Ramos de

    2003-01-01

    The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a) Bacterial type III protein secretion system; b) The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein) A, B, C, D and E, which are capable of induce apoptosis in macrophages; c) The function of ...

  18. Site-specific conjugation of HIV-1 tat peptides to IgG: a potential route to construct radioimmunoconjugates for targeting intracellular and nuclear epitopes in cancer

    International Nuclear Information System (INIS)

    Our objective was to study the cellular and nuclear uptake of 123I-mouse IgG (123I-mIgG) linked to peptides [GRKKRRQRRRPPQGYGC] harbouring the membrane-translocating and nuclear import sequences of HIV-1 tat protein. Carbohydrates on mIgG were oxidized by NaIO4, then reacted with a 40-fold excess of peptides. Displacement of binding of anti-mouse IgG (Fab specific; α-mFab) to 123I-mIgG by tat-mIgG or mIgG was compared. Internalization and nuclear translocation of 123I-tat-mIgG in MDA-MB-468, MDA-MB-231 or MCF-7 breast cancer cells were measured. The immunoreactivity of imported tat-mIgG was evaluated by measuring binding of 123I-α-mFab to cell lysate and by displacement of binding of 123I-mIgG to α-mFab by cell lysate. Biodistribution and nuclear uptake of 123I-tat-mIgG, 123I-mIgG and 123I-tat were compared in mice bearing s.c. MDA-MB-468 tumours. There was a 15-fold decrease in affinity of α-mFab for tat-mIgG compared with mIgG. Internalized radioactivity imported into the nucleus for 123I-tat-mIgG in MDA-MB-468, MDA-MB-231 and MCF-7 cells was 61.5±0.6%, 60.3±3.6% and 64.7±1.0%, respectively. The binding of 123I-α-mFab to lysate from MDA-MB-468 cells importing tat-mIgG was 17-fold higher than that for cells not exposed to tat-mIgG. Imported tat-mIgG competed with tat-mIgG for displacement of binding of 123I-mIgG to α-mFab. Conjugation of mIgG to tat peptides did not change tissue distribution. Nuclear localization for 123I-tat-mIgG in MDA-MB-468 tumours was 28.1±5.6%, and for liver, spleen and kidneys it was 41.7±2.7%, 13.8±0.8% and 36.9±3.3%, respectively. (orig.)

  19. Typhoid fever as cellular microbiological model

    Directory of Open Access Journals (Sweden)

    Andrade Dahir Ramos de

    2003-01-01

    Full Text Available The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a Bacterial type III protein secretion system; b The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein A, B, C, D and E, which are capable of induce apoptosis in macrophages; c The function of Toll R2 and Toll R4 receptors present in the macrophage surface (discovered in the Drosophila. The Toll family receptors are critical in the signalizing mediated by LPS in macrophages in association with LBP and CD14; d The lines of immune defense between intestinal lumen and internal organs; e The fundamental role of the endothelial cells in the inflammatory deviation from bloodstream into infected tissues by bacteria. In addition to above subjects, the authors comment the correlation between the clinical features of typhoid fever and the cellular and molecular phenomena of this disease, as well as the therapeutic consequences of this knowledge.

  20. Typhoid fever as cellular microbiological model.

    Science.gov (United States)

    de Andrade, Dahir Ramos; de Andrade Júnior, Dahir Ramos

    2003-01-01

    The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a) Bacterial type III protein secretion system; b) The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein) A, B, C, D and E, which are capable of induce apoptosis in macrophages; c) The function of Toll R2 and Toll R4 receptors present in the macrophage surface (discovered in the Drosophila). The Toll family receptors are critical in the signalizing mediated by LPS in macrophages in association with LBP and CD14; d) The lines of immune defense between intestinal lumen and internal organs; e) The fundamental role of the endothelial cells in the inflammatory deviation from bloodstream into infected tissues by bacteria. In addition to above subjects, the authors comment the correlation between the clinical features of typhoid fever and the cellular and molecular phenomena of this disease, as well as the therapeutic consequences of this knowledge. PMID:14502344

  1. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

    International Nuclear Information System (INIS)

    Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

  2. Modeling In Vitro Cellular Responses to Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    2014-01-01

    Full Text Available Engineered nanoparticles (NPs have been widely demonstrated to induce toxic effects to various cell types. In vitro cell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivo effects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitro measurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitro cellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitro measurements, and provides a “stepping stone” for the development of more advanced in vivo models that will incorporate additional cellular and NP interactions.

  3. TRAFFIC FLOW MODEL BASED ON CELLULAR AUTOMATION WITH ADAPTIVE DECELERATION

    OpenAIRE

    Shinkarev, A. A.

    2016-01-01

    This paper describes continuation of the authors’ work in the field of traffic flow mathematical models based on the cellular automata theory. The refactored representation of the multifactorial traffic flow model based on the cellular automata theory is used for a representation of an adaptive deceleration step implementation. The adaptive deceleration step in the case of a leader deceleration allows slowing down smoothly but not instantly. Concepts of the number of time steps without confli...

  4. Mapping of cellular iron using hyperspectral fluorescence imaging in a cellular model of Parkinson's disease

    Science.gov (United States)

    Oh, Eung Seok; Heo, Chaejeong; Kim, Ji Seon; Lee, Young Hee; Kim, Jong Min

    2013-05-01

    Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss in the substantianigra (SN) and elevated iron levels demonstrated by autopsy and with 7-Tesla magnetic resonance imaging. Direct visualization of iron with live imaging techniques has not yet been successful. The aim of this study is to visualize and quantify the distribution of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in SHSY5Y cells. The cells were exposed to iron by treatment with ferric ammonium citrate (FAC, 100 μM) for up to 6 hours. The hyperspectral fluorescence imaging signal of iron was examined usinga high- resolution dark-field optical microscope system with signal absorption for the visible/ near infrared (VNIR) spectral range. The 6-hour group showed heavy cellular iron deposition compared with the small amount of iron accumulation in the 1-hour group. The cellular iron was dispersed in a small, particulate form, whereas extracellular iron was detected in an aggregated form. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The cellular iron accumulation readily occurred in MPP+-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN in PD. This direct iron imaging methodology could be applied to analyze the physiological role of iron in PD, and its application might be expanded to various neurological disorders involving other metals, such as copper, manganese or zinc.

  5. Cellular automaton for realistic modelling of landslides

    Directory of Open Access Journals (Sweden)

    E. Segre

    1995-01-01

    Full Text Available A numerical model is developed for the simulation of debris flow in landslides over a complex three dimensional topography. The model is then validated by comparing a simulation with reported field data. Our model is in fact a realistic elaboration of simpler "sandpile automata", which have in recent years been studied as supposedly paradigmatic of "self-organized criticality". Statistics and scaling properties of the simulation are examined, and show that the model has an intermittent behaviour.

  6. Body composition analysis: Cellular level modeling of body component ratios

    OpenAIRE

    Z. Wang; Heymsfield, S. B.; PI-SUNYER, F.X.; Gallagher, D.; PIERSON, R.N.

    2008-01-01

    During the past two decades, a major outgrowth of efforts by our research group at St. Luke’s-Roosevelt Hospital is the development of body composition models that include cellular level models, models based on body component ratios, total body potassium models, multi-component models, and resting energy expenditure-body composition models. This review summarizes these models with emphasis on component ratios that we believe are fundamental to understanding human body composition during growt...

  7. QSAR modeling, synthesis and bioassay of diverse leukemia RPMI-8226 cell line active agents.

    Science.gov (United States)

    Katritzky, Alan R; Girgis, Adel S; Slavov, Svetoslav; Tala, Srinivasa R; Stoyanova-Slavova, Iva

    2010-11-01

    A rigorous QSAR modeling procedure employing CODESSA PRO descriptors has been utilized for the prediction of more efficient anti-leukemia agents. Experimental data concerning the effect on leukemia RPMI-8226 cell line tumor growth of 34 compounds (treated at a dose of 10 μM) was related to their chemical structures by a 4-descriptor QSAR model. Four bis(oxy)bis-urea and bis(sulfanediyl)bis-urea derivatives (4a, 4b, 8, 11a) predicted as active by this model, together with 11b predicted to be of low activity, were synthesized and screened for anti-tumor activity utilizing 55 different tumor cell lines. Compounds 8 and 11a showed anti-tumor properties against most of the adopted cell lines with growth inhibition exceeding 50%. The highly promising preliminary anti-tumor properties of compounds 8 and 11a, were screened at serial dilutions (10(-4)-10(-8) μM) for determination of their GI(50) and TGI against the screened human tumor cell lines. Compound 11a (GI(50) = 1.55, TGI = 8.68 μM) is more effective than compound 8 (GI(50)=58.30, TGI = > 100 μM) against the target leukemia RPMI-8226 cell line. Compound 11a also exhibits highly pronounced anti-tumor properties against NCI-H226, NCI-H23 (non-small cell lung cancer), COLO 205 (colon cancer), SNB-75 (CNS cancer), OVCAR-3, SK-OV-3 (ovarian cancer), A498 (renal cancer) MDA-MB-231/ATCC and MDA-MB-468 (breast cancer) cell lines (GI(50) = 1.95, 1.61, 1.38, 1.56, 1.30, 1.98, 1.18, 1.85, 1.08, TGI = 8.35, 6.01, 2.67, 8.59, 4.01, 7.01, 5.62, 6.38, 5.63 μM, respectively). Thus 11a could be a suitable lead towards the design of broad spectrum anti-tumor active agents targeting various human tumor cell lines. PMID:20843586

  8. Modeling cellular deformations using the level set formalism

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2008-07-01

    Full Text Available Abstract Background Many cellular processes involve substantial shape changes. Traditional simulations of these cell shape changes require that grids and boundaries be moved as the cell's shape evolves. Here we demonstrate that accurate cell shape changes can be recreated using level set methods (LSM, in which the cellular shape is defined implicitly, thereby eschewing the need for updating boundaries. Results We obtain a viscoelastic model of Dictyostelium cells using micropipette aspiration and show how this viscoelastic model can be incorporated into LSM simulations to recreate the observed protrusion of cells into the micropipette faithfully. We also demonstrate the use of our techniques by simulating the cell shape changes elicited by the chemotactic response to an external chemoattractant gradient. Conclusion Our results provide a simple but effective means of incorporating cellular deformations into mathematical simulations of cell signaling. Such methods will be useful for simulating important cellular events such as chemotaxis and cytokinesis.

  9. Computational model of cellular metabolic dynamics

    DEFF Research Database (Denmark)

    Li, Yanjun; Solomon, Thomas; Haus, Jacob M;

    2010-01-01

    Identifying the mechanisms by which insulin regulates glucose metabolism in skeletal muscle is critical to understanding the etiology of insulin resistance and type 2 diabetes. Our knowledge of these mechanisms is limited by the difficulty of obtaining in vivo intracellular data. To quantitatively...... cytosol and mitochondria. The model simulated skeletal muscle metabolic responses to insulin corresponding to human hyperinsulinemic-euglycemic clamp studies. Insulin-mediated rate of glucose disposal was the primary model input. For model validation, simulations were compared with experimental data...... type 2 diabetes....

  10. Modeling cellular deformations using the level set formalism

    OpenAIRE

    Yang Liu; Effler Janet C; Kutscher Brett L; Sullivan Sarah E; Robinson Douglas N; Iglesias Pablo A

    2008-01-01

    Abstract Background Many cellular processes involve substantial shape changes. Traditional simulations of these cell shape changes require that grids and boundaries be moved as the cell's shape evolves. Here we demonstrate that accurate cell shape changes can be recreated using level set methods (LSM), in which the cellular shape is defined implicitly, thereby eschewing the need for updating boundaries. Results We obtain a viscoelastic model of Dictyostelium cells using micropipette aspiratio...

  11. Cellular automata modeling of cooperative eutectic growth

    OpenAIRE

    E. Olejnik; E. Fraś; D. Gurgul; A. Burbelko

    2010-01-01

    The model and results of the 2D simulation of the cooperative growth of two phases in the lamellar eutectic are presented. The pro-posed model takes into account heat transfer, components diffusion and nonstationary concentration distribution in the liquid and solid phases, non-equlibrium nature of the phase transformation and kinetics of the growth, influence of the surface energy and interface curva-ture on the conditions of the thermodynamic equilibrium. For the determination of the phase ...

  12. Development and validation of computational models of cellular interaction

    OpenAIRE

    Smallwood, R H; Holcombe, W.M.L.; Walker, D C

    2004-01-01

    In this paper we take the view that computational models of biological systems should satisfy two conditions – they should be able to predict function at a systems biology level, and robust techniques of validation against biological models must be available. A modelling paradigm for developing a predictive computational model of cellular interaction is described, and methods of providing robust validation against biological models are explored, followed by a consideration of soft...

  13. Cellular Automaton Model for Immunology of Tumor Growth

    CERN Document Server

    Voitikova, M

    1998-01-01

    The stochastic discrete space-time model of an immune response on tumor spreading in a two-dimensional square lattice has been developed. The immunity-tumor interactions are described at the cellular level and then transferred into the setting of cellular automata (CA). The multistate CA model for system, in which all statesoflattice sites, composing of both immune and tumor cells populations, are the functions of the states of the 12 nearest neighbors. The CA model incorporates the essential featuresof the immunity-tumor system. Three regimes of neoplastic evolution including metastatic tumor growth and screen effect by inactive immune cells surrounding a tumor have been predicted.

  14. A cellular automata evacuation model considering friction and repulsion

    Institute of Scientific and Technical Information of China (English)

    SONG Weiguo; YU Yanfei; FAN Weicheng; Zhang Heping

    2005-01-01

    There exist interactions among pedestrians and between pedestrian and environment in evacuation. These interactions include attraction, repulsion and friction that play key roles in human evacuation behaviors, speed and efficiency. Most former evacuation models focus on the attraction force, while repulsion and friction are not well modeled. As a kind of multi-particle self-driven model, the social force model introduced in recent years can represent those three forces but with low simulation efficiency because it is a continuous model with complex rules. Discrete models such as the cellular automata model and the lattice gas model have simple rules and high simulation efficiency, but are not quite suitable for interactions' simulation. In this paper, a new cellular automata model based on traditional models is introduced in which repulsion and friction are modeled quantitatively. It is indicated that the model can simulate some basic behaviors, e.g.arching and the "faster-is-slower" phenomenon, in evacuation as multi-particle self-driven models, but with high efficiency as the normal cellular automata model and the lattice gas model.

  15. Modeling diffusion of innovations with probabilistic cellular automata

    OpenAIRE

    Boccara, Nino; Fuks, Henryk

    1997-01-01

    We present a family of one-dimensional cellular automata modeling the diffusion of an innovation in a population. Starting from simple deterministic rules, we construct models parameterized by the interaction range and exhibiting a second-order phase transition. We show that the number of individuals who eventually keep adopting the innovation strongly depends on connectivity between individuals.

  16. Modeling integrated cellular machinery using hybrid Petri-Boolean networks.

    Directory of Open Access Journals (Sweden)

    Natalie Berestovsky

    Full Text Available The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them

  17. Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models

    Directory of Open Access Journals (Sweden)

    Paydar M

    2014-06-01

    Full Text Available Mohammadjavad Paydar,1 Behnam Kamalidehghan,2 Yi Li Wong,1 Won Fen Wong,3 Chung Yeng Looi,1 Mohd Rais Mustafa11Department of Pharmacology, 2Department of Pharmacy, 3Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaAbstract: To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC50 46.5±3.1 µg/mL and MDA-MB-468 (48-hour IC50 50.8±2.7 µg/mL. Boldine had a cytotoxic effect and induced apoptosis in breast cancer cells as indicated by a higher amount of lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase. The anticancer mechanism is associated with disruption of the mitochondrial membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found that boldine could inhibit nuclear factor kappa B activation, a key molecule in tumor progression and metastasis. In addition, protein array and Western blotting analysis showed that treatment with boldine resulted in downregulation of Bcl-2 and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or 100 mg/kg significantly reduced tumor size in an animal model of breast cancer. Our results suggest that boldine is a potentially useful agent for the treatment of breast cancer.Keywords: boldine, breast cancer, caspase cascade, Bcl-2/Bax, heat shock protein 70, nuclear factor kappa B

  18. WWW Business Applications Based on the Cellular Model

    Institute of Scientific and Technical Information of China (English)

    Toshio Kodama; Tosiyasu L. Kunii; Yoichi Seki

    2008-01-01

    A cellular model based on the Incrementally Modular Abstraction Hierarchy (IMAH) is a novel model that can represent the architecture of and changes in cyberworlds, preserving invariants from a general level to a specific one. We have developed a data processing system called the Cellular Data System (CDS). In the development of business applications, you can prevent combinatorial explosion in the process of business design and testing by using CDS. In this paper, we have first designed and implemented wide-use algebra on the presentation level. Next, we have developed and verified the effectiveness of two general business applications using CDS: 1) a customer information management system, and 2) an estimate system.

  19. Lattice gas cellular automata and lattice Boltzmann models an introduction

    CERN Document Server

    Wolf-Gladrow, Dieter A

    2000-01-01

    Lattice-gas cellular automata (LGCA) and lattice Boltzmann models (LBM) are relatively new and promising methods for the numerical solution of nonlinear partial differential equations. The book provides an introduction for graduate students and researchers. Working knowledge of calculus is required and experience in PDEs and fluid dynamics is recommended. Some peculiarities of cellular automata are outlined in Chapter 2. The properties of various LGCA and special coding techniques are discussed in Chapter 3. Concepts from statistical mechanics (Chapter 4) provide the necessary theoretical background for LGCA and LBM. The properties of lattice Boltzmann models and a method for their construction are presented in Chapter 5.

  20. Modeling evolution and immune system by cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Bezzi, M. [Scuola Internazionale Superiore di Studi Avanzati, Trieste (Italy); Istituto Nazionale di Fisica della Materia, Florence (Italy)

    2001-07-01

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section.

  1. Modeling evolution and immune system by cellular automata

    International Nuclear Information System (INIS)

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section

  2. 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

  3. Station Model for Rail Transit System Using Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    XUN Jing; NING Bin; LI Ke-Ping

    2009-01-01

    In this paper, we propose a new cellular automata model to simulate the railway traffic at station.Based on NaSch model, the proposed station model is composed of the main track and the siding track.Two different schemes for trains passing through station are considered.One is the scheme of "pass by the main track, start and stop by the siding track".The other is the scheme of "two tracks play the same role".We simulate the train movement using the proposed model and analyze the traffic flow at station.The simulation results demonstrate that the proposed cellular automata model can be successfully used for the simulations of railway traffic.Some characteristic behaviors of railway traffic flow can be reproduced.Moreover, the simulation values of the minimum headway are close to the theoretical values.This result demonstrates the dependability and availability of the proposed model.

  4. Cellular worlds: a framework for modeling micro - macro dynamics

    OpenAIRE

    H Couclelis

    1985-01-01

    Cellular spaces have recently received a lot of attention in computer science and elsewhere as models capable of bridging the gap between disaggregate and aggregate description. Despite their obvious spatial interpretation, standard cell-space models are too constrained by their background conventions to be useful in realistic geographic applications. In this paper, a generalization of the cell-space principle is presented, based on discrete model theory, and then applied to a hypothetical bu...

  5. A Modified Cellular Automaton Model for Traffic Flow

    Institute of Scientific and Technical Information of China (English)

    葛红霞; 董力耘; 雷丽; 戴世强

    2004-01-01

    A modified cellular automaton model for traffic flow was proposed. A novel concept about the changeable security gap was introduced and a parameter related to the variable security gap was determined. The fundamental diagram obtained by simulation shows that the maximum flow more approaches to the observed data than that of the NaSch model, indicating that the presented model is more reasonable and realistic.

  6. The brittleness model of complex system based on cellular automata

    Institute of Scientific and Technical Information of China (English)

    LIN De-ming; JIN Hong-zhang; LI Qi; WU Hong-mei

    2004-01-01

    Now the research on the complex system is a hot spot. Brittleness is one of the basic characteristics of a complex system. In a complex system, after one of subsystems is struck to be collapsed, the whole system will collapse. Meanwhile, cellular automata is a discrete dynamic system. When the rule is given, the cellular automata could be defined. Then it can imitate the complex action. Cellular automata is used to simulate the brittleness action in this study. Entropy was used to analyze the action and get the rule. Then,three normal brittleness models were given. The result shows that the brittleness of complex system is existent and in addition some important behavior mode of complex system brittleness has been achieved.

  7. Fire Spread Model for Old Towns Based on Cellular Automaton

    Institute of Scientific and Technical Information of China (English)

    GAO Nan; WENG Wenguo; MA Wei; NI Shunjiang; HUANG Quanyi; YUAN Hongyong

    2008-01-01

    Old towns like Lijiang have enormous historic,artistic,and architectural value.The buildings in such old towns are usually made of highly combustible materials,such as wood and grass.If a fire breaks out,it will spread to multiple buildings,so fire spreading and controlling in old towns need to be studied.This paper presents a fire spread model for old towns based on cellular automaton.The cellular automaton rules were set according to historical fire data in empirical formulas.The model also considered the effects of climate.The simulation results were visualized in a geography information system.An example of a fire spread in Lijiang was investigated with the results showing that this model provides a realistic tool for predicting fire spread in old towns.Fire brigades can use this tool to predict when and how a fire spreads to minimize the losses.

  8. An intelligent floor field cellular automata model for pedestrian dynamics

    CERN Document Server

    Kirik, Ekaterina; Krouglov, Dmitriy

    2009-01-01

    A stochastic cellular automata (CA) model for pedestrian dynamics is presented. Our goal is to simulate different types of pedestrian movement, from regular to panic. But here we emphasize regular situations which imply that pedestrians analyze environment and choose their route more carefully. And transition probabilities have to depict such effect. The potentials of floor fields and environment analysis are combined in the model obtained. People patience is included in the model. This makes simulation of pedestrians movement more realistic. Some simulation results are presented and comparison with basic FF-model is made.

  9. A cellular automata model of Ebola virus dynamics

    Science.gov (United States)

    Burkhead, Emily; Hawkins, Jane

    2015-11-01

    We construct a stochastic cellular automaton (SCA) model for the spread of the Ebola virus (EBOV). We make substantial modifications to an existing SCA model used for HIV, introduced by others and studied by the authors. We give a rigorous analysis of the similarities between models due to the spread of virus and the typical immune response to it, and the differences which reflect the drastically different timing of the course of EBOV. We demonstrate output from the model and compare it with clinical data.

  10. Car Deceleration Considering Its Own Velocity in Cellular Automata Model

    Institute of Scientific and Technical Information of China (English)

    LI Ke-Ping

    2006-01-01

    In this paper, we propose a new cellular automaton model, which is based on NaSch traffic model. In our method, when a car has a larger velocity, if the gap between the car and its leading car is not enough large, it will decrease. The aim is that the following car has a buffer space to decrease its velocity at the next time, and then avoid to decelerate too high. The simulation results show that using our model, the car deceleration is realistic, and is closer to thefield measure than that of NaSch model.

  11. Simulations of Living Cell Origins Using a Cellular Automata Model

    Science.gov (United States)

    Ishida, Takeshi

    2014-04-01

    Understanding the generalized mechanisms of cell self-assembly is fundamental for applications in various fields, such as mass producing molecular machines in nanotechnology. Thus, the details of real cellular reaction networks and the necessary conditions for self-organized cells must be elucidated. We constructed a 2-dimensional cellular automata model to investigate the emergence of biological cell formation, which incorporated a looped membrane and a membrane-bound information system (akin to a genetic code and gene expression system). In particular, with an artificial reaction system coupled with a thermal system, the simultaneous formation of a looped membrane and an inner reaction process resulted in a more stable structure. These double structures inspired the primitive biological cell formation process from chemical evolution stage. With a model to simulate cellular self-organization in a 2-dimensional cellular automata model, 3 phenomena could be realized: (1) an inner reaction system developed as an information carrier precursor (akin to DNA); (2) a cell border emerged (akin to a cell membrane); and (3) these cell structures could divide into 2. This double-structured cell was considered to be a primary biological cell. The outer loop evolved toward a lipid bilayer membrane, and inner polymeric particles evolved toward precursor information carriers (evolved toward DNA). This model did not completely clarify all the necessary and sufficient conditions for biological cell self-organization. Further, our virtual cells remained unstable and fragile. However, the "garbage bag model" of Dyson proposed that the first living cells were deficient; thus, it would be reasonable that the earliest cells were more unstable and fragile than the simplest current unicellular organisms.

  12. Mathematical model for flood routing based on cellular automaton

    Directory of Open Access Journals (Sweden)

    Xin CAI

    2014-04-01

    Full Text Available Increasing frequency and severity of flooding have caused tremendous damage in China, requiring more essential countermeasures to alleviate the damage. In this study, the dynamic simulation property of a cellular automaton was used to make further progress in flood routing. In consideration of terrain’s influence on flood routing, we regarded the terrain elevation as an auxiliary attribute of a two-dimensional cellular automaton in path selection for flood routing and developed a mathematical model based on a cellular automaton. A numerical case of propagation of an outburst flood in an area of the lower Yangtze River was analyzed with both the fixed-step and variable-step models. The results show that the flood does not spread simultaneously in all directions, but flows into the lower place first, and that the submerged area grows quickly at the beginning, but slowly later on. The final submerged areas obtained from the two different models are consistent, and the flood volume balance test shows that the flood volume meets the requirement of the total volume balance. The analysis of the case shows that the proposed model can be a valuable tool for flood routing.

  13. Modeling self-organizing traffic lights with elementary cellular automata

    CERN Document Server

    Gershenson, Carlos

    2009-01-01

    There have been several highway traffic models proposed based on cellular automata. The simplest one is elementary cellular automaton rule 184. We extend this model to city traffic with cellular automata coupled at intersections using only rules 184, 252, and 136. The simplicity of the model offers a clear understanding of the main properties of city traffic and its phase transitions. We use the proposed model to compare two methods for coordinating traffic lights: a green-wave method that tries to optimize phases according to expected flows and a self-organizing method that adapts to the current traffic conditions. The self-organizing method delivers considerable improvements over the green-wave method. For low densities, the self-organizing method promotes the formation and coordination of platoons that flow freely in four directions, i.e. with a maximum velocity and no stops. For medium densities, the method allows a constant usage of the intersections, exploiting their maximum flux capacity. For high dens...

  14. A Cellular Model for Screening Neuronal Nitric Oxide Synthase Inhibitors

    OpenAIRE

    Fang, Jianguo; Silverman, Richard B.

    2009-01-01

    Nitric oxide synthase (NOS) inhibitors are potential drug candidates because it has been well demonstrated that excessive production of NO critically contributes to a range of diseases. Most inhibitors have been screened in vitro using recombinant enzymes, leading to the discovery of a variety of potent compounds. To make inhibition studies more physiologically relevant and bridge the gap between the in vitro assay and in vivo studies, we report here a cellular model for screening NOS inhibit...

  15. Cellular-Based Statistical Model for Mobile Dispersion

    OpenAIRE

    Abdulla, Mouhamed; Shayan, Yousef R.

    2013-01-01

    While analyzing mobile systems we often approximate the actual coverage surface and assume an ideal cell shape. In a multi-cellular network, because of its tessellating nature, a hexagon is more preferred than a circular geometry. Despite this reality, perhaps due to the inherent simplicity, only a model for circular based random spreading is available. However, if used, this results an unfair terminal distribution for non-circular contours. Therefore, in this paper we specifically derived an...

  16. Modelling of detonation cellular structure in aluminium suspensions

    Science.gov (United States)

    Briand, A.; Veyssiere, B.; Khasainov, B. A.

    2010-12-01

    Heterogeneous detonations involving aluminium suspensions have been studied for many years for industrial safety policies, and for military and propulsion applications. Owing to their weak detonability and to the lack of available experimental results on the detonation cellular structure, numerical simulations provide a convenient way to improve the knowledge of such detonations. One major difficulty arising in numerical study of heterogeneous detonations involving suspensions of aluminium particles in oxidizing atmospheres is the modelling of aluminium combustion. Our previous two-step model provided results on the effect on the detonation cellular structure of particle diameter and characteristic chemical lengths. In this study, a hybrid model is incorporated in the numerical code EFAE, combining both kinetic and diffusion regimes in parallel. This more realistic model provides good agreement with the previous two-step model and confirms the correlations found between the detonation cell width, and particle diameter and characteristic lengths. Moreover, the linear dependence found between the detonation cell width and the induction length remains valid with the hybrid model.

  17. A cellular automaton model for tumor growth in heterogeneous environment

    Science.gov (United States)

    Jiao, Yang; Torquato, Sal

    2011-03-01

    Cancer is not a single disease: it exhibits heterogeneity on different spatial and temporal scales and strongly interacts with its host environment. Most mathematical modeling of malignant tumor growth has assumed a homogeneous host environment. We have developed a cellular automaton model for tumor growth that explicitly incorporates the structural heterogeneity of the host environment such as tumor stroma. We show that these structural heterogeneities have non-trivial effects on the tumor growth dynamics and prognosis. Y. J. is supported by PSOC, NCI.

  18. Cellular automata model of magnetospheric-ionospheric coupling

    OpenAIRE

    Kozelov, B. V.; Kozelova, T. V.

    2003-01-01

    We propose a cellular automata model (CAM) to describe the substorm activity of the magnetospheric-ionospheric system. The state of each cell in the model is described by two numbers that correspond to the energy content in a region of the current sheet in the magnetospheric tail and to the conductivity of the ionospheric domain that is magnetically connected with this region. The driving force of the system is supposed to be provided by the solar wind that is convected along the two b...

  19. A Realistic Cellular Automaton Model for Synchronized Traffic Flow

    Institute of Scientific and Technical Information of China (English)

    ZHAO Bo-Han; HU Mao-Bin; JIANG Rui; WU Qing-Song

    2009-01-01

    A cellular automaton model is proposed to consider the anticipation effect in drivers' behavior. It is shown that the anticipation effect can be one of the origins of synchronized traffic flow. With anticipation effect, the congested traffic flow simulated by the model exhibits the features of synchronized flow. The spatiotemporal patterns induced by an on-ramp are also consistent with the three-phaee traffic theory. Since the origin of synchronized flow is still controversial, our work can shed some light on the mechanism of synchronized flow.

  20. Cellular automata modelling of phase-change memories

    Institute of Scientific and Technical Information of China (English)

    Wanhua Yu; David Wright

    2008-01-01

    A novel approach to modelling phase-transition processes in phase change materials used for optical and electrical data storage applications is presented. The model is based on a cellular automaton (CA) approach to predict crystallization behaviour that is linked to thermal and electrical simulations to enable the study of the data writing and erasing processes. The CA approach is shown to be able to predict the evolution of the microstructure during the rapid heating and cooling cycles pertinent to data storage technology, and maps crystallization behaviour on the nanoscale. A simple example based on possible future nonvolatile phase-change random access solid-state memory is presented.

  1. Modeling and simulation for train control system using cellular automata

    Institute of Scientific and Technical Information of China (English)

    LI; KePing; GAO; ZiYou; YANG; LiXing

    2007-01-01

    Train control system plays a key role in railway traffic. Its function is to manage and control the train movement on railway networks. In our previous works, based on the cellular automata (CA) model, we proposed several models and algorithms for simulating the train movement under different control system conditions. However, these models are only suitable for some simple traffic conditions. Some basic factors, which are important for train movement, are not considered. In this paper, we extend these models and algorithms and give a unified formula. Using the proposed method, we analyze and discuss the space-time diagram of railway traffic flow and the trajectories of the train movement. The numerical simulation and analytical results demonstrate that the unified CA model is an effective tool for simulating the train control system.

  2. Cellular automaton model considering headway-distance effect

    Science.gov (United States)

    Hu, Shou-Xin; Gao, Kun; Wang, Bing-Hong; Lu, Yu-Feng

    2008-05-01

    This paper presents a cellular automaton model for single-lane traffic flow. On the basis of the Nagel-Schreckenberg (NS) model, it further considers the effect of headway-distance between two successive cars on the randomization of the latter one. In numerical simulations, this model shows the following characteristics. (1) With a simple structure, this model succeeds in reproducing the hysteresis effect, which is absent in the NS model. (2) Compared with the slow-to-start models, this model exhibits a local fundamental diagram which is more consistent to empirical observations. (3) This model has much higher efficiency in dissolving congestions compared with the so-called NS model with velocity-dependent randomization (VDR model). (4) This model is more robust when facing traffic obstructions. It can resist much longer shock times and has much shorter relaxation times on the other hand. To summarize, compared with the existing models, this model is quite simple in structure, but has good characteristics.

  3. Structural modeling of sandwich structures with lightweight cellular cores

    Institute of Scientific and Technical Information of China (English)

    T. Liu; Z. C. Deng; T. J. Lu

    2007-01-01

    An effective single layered finite element (FE) computational model is proposed to predict the structural behavior of lightweight sandwich panels having two dimensional (2D) prismatic or three dimensional (3D) truss cores.Three different types of cellular core topology are considered: pyramidal truss core (3D), Kagome truss core (3D) and corrugated core (2D), representing three kinds of material anisotropy: orthotropic, monoclinic and general anisotropic. A homogenization technique is developed to obtain the homogenized macroscopic stiffness properties of the cellular core. In comparison with the results obtained by using detailed FE model, the single layered computational model cangive acceptable predictions for both the static and dynamic behaviors of orthotropic truss core sandwich panels. However, for non-orthotropic 3D truss cores, the predictions are not so well. For both static and dynamic behaviors of a 2D corrugated core sandwich panel, the predictions derived by the single layered computational model is generally acceptable when the size of the unit cell varies within a certain range, with the predictions for moderately strong or strong corrugated cores more accurate than those for weak cores.

  4. A Fluid Model for Performance Analysis in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Coupechoux Marceau

    2010-01-01

    Full Text Available We propose a new framework to study the performance of cellular networks using a fluid model and we derive from this model analytical formulas for interference, outage probability, and spatial outage probability. The key idea of the fluid model is to consider the discrete base station (BS entities as a continuum of transmitters that are spatially distributed in the network. This model allows us to obtain simple analytical expressions to reveal main characteristics of the network. In this paper, we focus on the downlink other-cell interference factor (OCIF, which is defined for a given user as the ratio of its outer cell received power to its inner cell received power. A closed-form formula of the OCIF is provided in this paper. From this formula, we are able to obtain the global outage probability as well as the spatial outage probability, which depends on the location of a mobile station (MS initiating a new call. Our analytical results are compared to Monte Carlo simulations performed in a traditional hexagonal network. Furthermore, we demonstrate an application of the outage probability related to cell breathing and densification of cellular networks.

  5. Integrating cellular metabolism into a multiscale whole-body model.

    Directory of Open Access Journals (Sweden)

    Markus Krauss

    Full Text Available Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development.

  6. Robustness of a Cellular Automata Model for the HIV Infection

    CERN Document Server

    Figueirêdo, P H; Santos, R M Zorzenon dos

    2008-01-01

    An investigation was conducted to study the robustness of the results obtained from the cellular automata model which describes the spread of the HIV infection within lymphoid tissues [R. M. Zorzenon dos Santos and S. Coutinho, Phys. Rev. Lett. 87, 168102 (2001)]. The analysis focussed on the dynamic behavior of the model when defined in lattices with different symmetries and dimensionalities. The results illustrated that the three-phase dynamics of the planar models suffered minor changes in relation to lattice symmetry variations and, while differences were observed regarding dimensionality changes, qualitative behavior was preserved. A further investigation was conducted into primary infection and sensitiveness of the latency period to variations of the model's stochastic parameters over wide ranging values. The variables characterizing primary infection and the latency period exhibited power-law behavior when the stochastic parameters varied over a few orders of magnitude. The power-law exponents were app...

  7. Fluctuation in option pricing using cellular automata based market models

    Science.gov (United States)

    Gao, Yuying; Beni, Gerardo

    2005-05-01

    A new agent-based Cellular Automaton (CA) computational algorithm for option pricing is proposed. CAs have been extensively used in modeling complex dynamical systems but not in modeling option prices. Compared with traditional tools, which rely on guessing volatilities to calculate option prices, the CA model is directly addressing market mechanisms and simulates price fluctuation from aggregation of actions made by interacting individual market makers in a large population. This paper explores whether CA models can provide reasonable good answers to pricing European options. The Black-Scholes model and the Binomial Tree model are used for comparison. Comparison reveals that CA models perform reasonably well in pricing options, reproducing overall characteristics of random walk based model, while at the same time providing plausible results for the 'fat-tail' phenomenon observed in many markets. We also show that the binomial tree model can be obtained from a CA rule. Thus, CA models are suitable tools to generalize the standard theories of option pricing.

  8. Simulation of root forms using cellular automata model

    International Nuclear Information System (INIS)

    This research aims to produce a simulation program for root forms using cellular automata model. Stephen Wolfram in his book entitled “A New Kind of Science” discusses the formation rules based on the statistical analysis. In accordance with Stephen Wolfram’s investigation, the research will develop a basic idea of computer program using Delphi 7 programming language. To best of our knowledge, there is no previous research developing a simulation describing root forms using the cellular automata model compared to the natural root form with the presence of stone addition as the disturbance. The result shows that (1) the simulation used four rules comparing results of the program towards the natural photographs and each rule had shown different root forms; (2) the stone disturbances prevent the root growth and the multiplication of root forms had been successfully modeled. Therefore, this research had added some stones, which have size of 120 cells placed randomly in the soil. Like in nature, stones cannot be penetrated by plant roots. The result showed that it is very likely to further develop the program of simulating root forms by 50 variations

  9. A hybrid parallel framework for the cellular Potts model simulations

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yi [Los Alamos National Laboratory; He, Kejing [SOUTH CHINA UNIV; Dong, Shoubin [SOUTH CHINA UNIV

    2009-01-01

    The Cellular Potts Model (CPM) has been widely used for biological simulations. However, most current implementations are either sequential or approximated, which can't be used for large scale complex 3D simulation. In this paper we present a hybrid parallel framework for CPM simulations. The time-consuming POE solving, cell division, and cell reaction operation are distributed to clusters using the Message Passing Interface (MPI). The Monte Carlo lattice update is parallelized on shared-memory SMP system using OpenMP. Because the Monte Carlo lattice update is much faster than the POE solving and SMP systems are more and more common, this hybrid approach achieves good performance and high accuracy at the same time. Based on the parallel Cellular Potts Model, we studied the avascular tumor growth using a multiscale model. The application and performance analysis show that the hybrid parallel framework is quite efficient. The hybrid parallel CPM can be used for the large scale simulation ({approx}10{sup 8} sites) of complex collective behavior of numerous cells ({approx}10{sup 6}).

  10. Simulation of root forms using cellular automata model

    Science.gov (United States)

    Winarno, Nanang; Prima, Eka Cahya; Afifah, Ratih Mega Ayu

    2016-02-01

    This research aims to produce a simulation program for root forms using cellular automata model. Stephen Wolfram in his book entitled "A New Kind of Science" discusses the formation rules based on the statistical analysis. In accordance with Stephen Wolfram's investigation, the research will develop a basic idea of computer program using Delphi 7 programming language. To best of our knowledge, there is no previous research developing a simulation describing root forms using the cellular automata model compared to the natural root form with the presence of stone addition as the disturbance. The result shows that (1) the simulation used four rules comparing results of the program towards the natural photographs and each rule had shown different root forms; (2) the stone disturbances prevent the root growth and the multiplication of root forms had been successfully modeled. Therefore, this research had added some stones, which have size of 120 cells placed randomly in the soil. Like in nature, stones cannot be penetrated by plant roots. The result showed that it is very likely to further develop the program of simulating root forms by 50 variations.

  11. Simulation of root forms using cellular automata model

    Energy Technology Data Exchange (ETDEWEB)

    Winarno, Nanang, E-mail: nanang-winarno@upi.edu; Prima, Eka Cahya [International Program on Science Education, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudi no 229, Bandung40154 (Indonesia); Afifah, Ratih Mega Ayu [Department of Physics Education, Post Graduate School, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudi no 229, Bandung40154 (Indonesia)

    2016-02-08

    This research aims to produce a simulation program for root forms using cellular automata model. Stephen Wolfram in his book entitled “A New Kind of Science” discusses the formation rules based on the statistical analysis. In accordance with Stephen Wolfram’s investigation, the research will develop a basic idea of computer program using Delphi 7 programming language. To best of our knowledge, there is no previous research developing a simulation describing root forms using the cellular automata model compared to the natural root form with the presence of stone addition as the disturbance. The result shows that (1) the simulation used four rules comparing results of the program towards the natural photographs and each rule had shown different root forms; (2) the stone disturbances prevent the root growth and the multiplication of root forms had been successfully modeled. Therefore, this research had added some stones, which have size of 120 cells placed randomly in the soil. Like in nature, stones cannot be penetrated by plant roots. The result showed that it is very likely to further develop the program of simulating root forms by 50 variations.

  12. Adeno-associated virus type 2 infection activates caspase dependent and independent apoptosis in multiple breast cancer lines but not in normal mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Tandon Apurva

    2011-08-01

    Full Text Available Abstract Background In normal cells proliferation and apoptosis are tightly regulated, whereas in tumor cells the balance is shifted in favor of increased proliferation and reduced apoptosis. Anticancer agents mediate tumor cell death via targeting multiple pathways of programmed cell death. We have reported that the non-pathogenic, tumor suppressive Adeno-Associated Virus Type 2 (AAV2 induces apoptosis in Human Papillomavirus (HPV positive cervical cancer cells, but not in normal keratinocytes. In the current study, we examined the potential of AAV2 to inhibit proliferation of MCF-7 and MDA-MB-468 (both weakly invasive, as well as MDA-MB-231 (highly invasive human breast cancer derived cell lines. As controls, we used normal human mammary epithelial cells (nHMECs isolated from tissue biopsies of patients undergoing breast reduction surgery. Results AAV2 infected MCF-7 line underwent caspase-independent, and MDA-MB-468 and MDA-MB-231 cell lines underwent caspase-dependent apoptosis. Death of MDA-MB-468 cells was marked by caspase-9 activation, whereas death of MDA-MB-231 cells was marked by activation of both caspase-8 and caspase-9, and resembled a mixture of apoptotic and necrotic cell death. Cellular demise was correlated with the ability of AAV2 to productively infect and differentially express AAV2 non-structural proteins: Rep78, Rep68 and Rep40, dependent on the cell line. Cell death in the MCF-7 and MDA-MB-231 lines coincided with increased S phase entry, whereas the MDA-MB-468 cells increasingly entered into G2. AAV2 infection led to decreased cell viability which correlated with increased expression of proliferation markers c-Myc and Ki-67. In contrast, nHMECs that were infected with AAV2 failed to establish productive infection or undergo apoptosis. Conclusion AAV2 regulated enrichment of cell cycle check-point functions in G1/S, S and G2 phases could create a favorable environment for Rep protein expression. Inherent Rep associated

  13. Cellular toxicity (High-Throughput Cellular Assays for Modeling Toxicity in the Fish Reproductive System)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The purpose of this project is to adapt cellular in vitro assay systems of the rainbow trout pituitary, liver and ovary for high-throughput screening (HTS) of...

  14. Cellular automaton model of cell response to targeted radiation

    International Nuclear Information System (INIS)

    It has been shown that the response of cells to low doses of radiation is not linear and cannot be accurately extrapolated from the high dose response. To investigate possible mechanisms involved in the behaviour of cells under very low doses of radiation, a cellular automaton (CA) model was created. The diffusion and consumption of glucose in the culture dish were computed in parallel to the growth of cells. A new model for calculating survival probability was introduced; the communication between targeted and non-targeted cells was also included. Early results on the response of non-confluent cells to targeted irradiation showed the capability of the model to take account for the non-linear response in the low-dose domain

  15. Cellular automaton model of coupled mass transport and chemical reactions

    International Nuclear Information System (INIS)

    Mass transport, coupled with chemical reactions, is modelled as a cellular automaton in which solute molecules perform a random walk on a lattice and react according to a local probabilistic rule. Assuming molecular chaos and a smooth density function, we obtain the standard reaction-transport equations in the continuum limit. The model is applied to the reactions a + b ↔c and a + b →c, where we observe interesting macroscopic effects resulting from microscopic fluctuations and spatial correlations between molecules. We also simulate autocatalytic reaction schemes displaying spontaneous formation of spatial concentration patterns. Finally, we propose and discuss the limitations of a simple model for mineral-solute interaction. (author) 5 figs., 20 refs

  16. Global Network Model based on Earth Grid and Cellular

    Directory of Open Access Journals (Sweden)

    Dongqi Lu

    2014-06-01

    Full Text Available We aim to understand the current health state of the Earth and find how human activities influence it. Based on the theory of Earth’s Grid and Cellular Automata, we define and test a global network model, analyze the mutual interactions and feedbacks of ecosystem, hydrologic circle and atmosphere. In addition, we consult a lot of data to find a benchmark for the “Earth Health Map”, with the ecosystem distribution on it, which can be helpful for making a strategic decision for policy makers and prediction. Our model can be extended to other similar fields. In the end, we discuss the sensitivity of parameters selection, and the superiorities and weaknesses of our model.

  17. A cellular automata-based mathematical model for thymocyte development.

    Directory of Open Access Journals (Sweden)

    Hallan Souza-e-Silva

    Full Text Available Intrathymic T cell development is an important process necessary for the normal formation of cell-mediated immune responses. Importantly, such a process depends on interactions of developing thymocytes with cellular and extracellular elements of the thymic microenvironment. Additionally, it includes a series of oriented and tunely regulated migration events, ultimately allowing mature cells to cross endothelial barriers and leave the organ. Herein we built a cellular automata-based mathematical model for thymocyte migration and development. The rules comprised in this model take into account the main stages of thymocyte development, two-dimensional sections of the normal thymic microenvironmental network, as well as the chemokines involved in intrathymic cell migration. Parameters of our computer simulations with further adjusted to results derived from previous experimental data using sub-lethally irradiated mice, in which thymus recovery can be evaluated. The model fitted with the increasing numbers of each CD4/CD8-defined thymocyte subset. It was further validated since it fitted with the times of permanence experimentally ascertained in each CD4/CD8-defined differentiation stage. Importantly, correlations using the whole mean volume of young normal adult mice revealed that the numbers of cells generated in silico with the mathematical model fall within the range of total thymocyte numbers seen in these animals. Furthermore, simulations made with a human thymic epithelial network using the same mathematical model generated similar profiles for temporal evolution of thymocyte developmental stages. Lastly, we provided in silico evidence that the thymus architecture is important in the thymocyte development, since changes in the epithelial network result in different theoretical profiles for T cell development/migration. This model likely can be used to predict thymocyte evolution following therapeutic strategies designed for recovery of the

  18. Motor Schema-Based Cellular Automaton Model for Pedestrian Dynamics

    Science.gov (United States)

    Weng, Wenguo; Hasemi, Yuji; Fan, Weicheng

    A new cellular automaton model for pedestrian dynamics based on motor schema is presented. Each pedestrian is treated as an intelligent mobile robot, and motor schemas including move-to-goal, avoid-away and avoid-around drive pedestrians to interact with their environment. We investigate the phenomenon of many pedestrians with different move velocities escaping from a room. The results show that the pedestrian with high velocity have predominance in competitive evacuation, if we only consider repulsion from or avoiding around other pedestrians, and interaction with each other leads to disordered evacuation, i.e., decreased evacuation efficiency. Extensions of the model using learning algorithms for controlling pedestrians, i.e., reinforcement learning, neural network and genetic algorithms, etc. are noted.

  19. Critical Behavior in a Cellular Automata Animal Disease Transmission Model

    CERN Document Server

    Morley, P D; Chang, Julius

    2003-01-01

    Using a cellular automata model, we simulate the British Government Policy (BGP) in the 2001 foot and mouth epidemic in Great Britain. When clinical symptoms of the disease appeared on a farm, there is mandatory slaughter (culling) of all livestock on an infected premise (IP). Those farms that neighbor an IP (contiguous premise, CP), are also culled, aka nearest neighbor interaction. Farms where the disease may be prevalent from animal, human, vehicle or airborne transmission (dangerous contact, DC), are additionally culled, aka next-to-nearest neighbor iteractions and lightning factor. The resulting mathematical model possesses a phase transition, whereupon if the physical disease transmission kernel exceeds a critical value, catastrophic loss of animals ensues. The non-local disease transport probability can be as low as .01% per day and the disease can still be in the high mortality phase. We show that the fundamental equation for sustainable disease transport is the criticality equation for neutron fissio...

  20. Multiscale Model of Colorectal Cancer Using the Cellular Potts Framework

    Science.gov (United States)

    Osborne, James M

    2015-01-01

    Colorectal cancer (CRC) is one of the major causes of death in the developed world and forms a canonical example of tumorigenesis. CRC arises from a string of mutations of individual cells in the colorectal crypt, making it particularly suited for multiscale multicellular modeling, where mutations of individual cells can be clearly represented and their effects readily tracked. In this paper, we present a multicellular model of the onset of colorectal cancer, utilizing the cellular Potts model (CPM). We use the model to investigate how, through the modification of their mechanical properties, mutant cells colonize the crypt. Moreover, we study the influence of mutations on the shape of cells in the crypt, suggesting possible cell- and tissue-level indicators for identifying early-stage cancerous crypts. Crucially, we discuss the effect that the motility parameters of the model (key factors in the behavior of the CPM) have on the distribution of cells within a homeostatic crypt, resulting in an optimal parameter regime that accurately reflects biological assumptions. In summary, the key results of this paper are 1) how to couple the CPM with processes occurring on other spatial scales, using the example of the crypt to motivate suitable motility parameters; 2) modeling mutant cells with the CPM; 3) and investigating how mutations influence the shape of cells in the crypt. PMID:26461973

  1. Computer Modeling of the Earliest Cellular Structures and Functions

    Science.gov (United States)

    Pohorille, Andrew

    2000-03-01

    In the absence of extinct or extant record of protocells (the earliest ancestors of contemporary cells), the most direct way to test ourunderstanding of the origin of cellular life is to construct laboratory models of protocells. Such efforts are currently underway in the NASA Astrobiology Program. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs for molecules that perform protocellular functions. Many of these functions, such as import of nutrients, capture and storage of energy, and response to changes in the environment are carried out by proteins bound to membranes. We will discuss a series of large-scale, molecular-level computer simulations which demonstrate (a) how small proteins (peptides)organize themselves into ordered structures at water-membrane interfaces and insert into membranes, (b) how these peptides aggregate to form membrane-spanning structures (e.g. channels), and (c) by what mechanisms such aggregates perform essential protocellular functions, such as proton transport of protons across cell walls, a key step in cellular bioenergetics. The simulations were performed using the molecular dynamics method, in which Newton's equations of motion for each atom in the system are solved iteratively. The problems of interest required simulations on multi-nanosecond time scales, which corresponded to 10^6-10^8 time steps.

  2. Load-Aware Modeling and Analysis of Heterogeneous Cellular Networks

    CERN Document Server

    Dhillon, Harpreet S; Andrews, Jeffrey G

    2012-01-01

    Random spatial models are attractive for modeling heterogeneous cellular networks (HCNs) due to their realism, tractability, and scalability. A major limitation of such models to date in the context of HCNs is the neglect of network traffic and load: all base stations (BSs) have typically been assumed to always be transmitting. Small cells in particular will have a lighter load than macrocells, and so their contribution to the network interference may be significantly overstated in a fully loaded model. This paper incorporates a flexible notion of BS load by introducing a new idea of conditionally thinning the interference field. For a $K$-tier HCN where BSs across tiers differ in terms of transmit power, supported data rate, deployment density, and now load, we derive the coverage probability for a typical mobile, which connects to the strongest BS signal. Conditioned on this connection, the interfering BSs of the $i^{th}$ tier are assumed to transmit independently with probability $p_i$, which models the lo...

  3. A Computational Model of Cellular Response to Modulated Radiation Fields

    International Nuclear Information System (INIS)

    Purpose: To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies. Materials and Methods: A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields. Results: The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses. Conclusions: The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

  4. A cellular automaton model for neurogenesis in Drosophila

    Science.gov (United States)

    Luthi, Pascal O.; Chopard, Bastien; Preiss, Anette; Ramsden, Jeremy J.

    1998-07-01

    A cellular automaton (CA) is constructed for the formation of the central nervous system of the Drosophila embryo. This is an experimentally well-studied system in which complex interactions between neighbouring cells appear to drive their differentiation into different types. It appears that all the cells initially have the potential to become neuroblasts, and all strive to this end, but those which differentiate first block their as yet undifferentiated neighbours from doing so. The CA makes use of observational evidence for a lateral inhibition mechanism involving signalling products S of the ‘proneural’ or neuralizing genes. The key concept of the model is that cells are continuously producing S, but the production rate is lowered by inhibitory signals received from neighbouring cells which have advanced further along the developmental pathway. Comparison with experimental data shows that it well accounts for the observed proportion of neuroectodermal cells delaminating as neuroblasts.

  5. Cellular automaton model of mass transport with chemical reactions

    International Nuclear Information System (INIS)

    The transport and chemical reactions of solutes are modelled as a cellular automaton in which molecules of different species perform a random walk on a regular lattice and react according to a local probabilistic rule. The model describes advection and diffusion in a simple way, and as no restriction is placed on the number of particles at a lattice site, it is also able to describe a wide variety of chemical reactions. Assuming molecular chaos and a smooth density function, we obtain the standard reaction-transport equations in the continuum limit. Simulations on one-and two-dimensional lattices show that the discrete model can be used to approximate the solutions of the continuum equations. We discuss discrepancies which arise from correlations between molecules and how these discrepancies disappear as the continuum limit is approached. Of particular interest are simulations displaying long-time behaviour which depends on long-wavelength statistical fluctuations not accounted for by the standard equations. The model is applied to the reactions a + b ↔ c and a + b → c with homogeneous and inhomogeneous initial conditions as well as to systems subject to autocatalytic reactions and displaying spontaneous formation of spatial concentration patterns. (author) 9 figs., 34 refs

  6. COMPARATIVE ANALYSIS OF CONGESTION CONTROL MODELS FOR CELLULAR WIRELESS NETWORK

    Directory of Open Access Journals (Sweden)

    Falade A. J

    2015-08-01

    Full Text Available Cellular wireless systems like GSM suffer from congestion resulting in overall system degradation and poor service delivery. When the traffic demand in a geographical area is high, the input traffic rate will exceed thecapacity of the output lines. This work focused on homogenous wireless network (the network traffic and resource dimensioning that are statistically identical such that the network performance evaluation can be reduced to a system with single cell and a single traffic type. Such system can employa queuing model to evaluate the performance metric of a cell in terms of blocking probability. Five congestion control models were compared in the work to ascertain their peculiarities, they are Erlang B, Erlang C, Engset (cleared, Engset (buffered, and Bernoulli. To analyze the system, an aggregate onedimensional Markov chain wasderived, such that it describes a call arrival process under the assumption that it is Poisson distributed. The models were simulated and their results show varying performances, however the Bernoulli model (Pb5 tends to show a situation that allows more users access to the system and the congestion level remain unaffected despite increase in the number of users and the offered traffic into the system.

  7. Cellular automaton model of crowd evacuation inspired by slime mould

    Science.gov (United States)

    Kalogeiton, V. S.; Papadopoulos, D. P.; Georgilas, I. P.; Sirakoulis, G. Ch.; Adamatzky, A. I.

    2015-04-01

    In all the living organisms, the self-preservation behaviour is almost universal. Even the most simple of living organisms, like slime mould, is typically under intense selective pressure to evolve a response to ensure their evolution and safety in the best possible way. On the other hand, evacuation of a place can be easily characterized as one of the most stressful situations for the individuals taking part on it. Taking inspiration from the slime mould behaviour, we are introducing a computational bio-inspired model crowd evacuation model. Cellular Automata (CA) were selected as a fully parallel advanced computation tool able to mimic the Physarum's behaviour. In particular, the proposed CA model takes into account while mimicking the Physarum foraging process, the food diffusion, the organism's growth, the creation of tubes for each organism, the selection of optimum tube for each human in correspondence to the crowd evacuation under study and finally, the movement of all humans at each time step towards near exit. To test the model's efficiency and robustness, several simulation scenarios were proposed both in virtual and real-life indoor environments (namely, the first floor of office building B of the Department of Electrical and Computer Engineering of Democritus University of Thrace). The proposed model is further evaluated in a purely quantitative way by comparing the simulation results with the corresponding ones from the bibliography taken by real data. The examined fundamental diagrams of velocity-density and flow-density are found in full agreement with many of the already published corresponding results proving the adequacy, the fitness and the resulting dynamics of the model. Finally, several real Physarum experiments were conducted in an archetype of the aforementioned real-life environment proving at last that the proposed model succeeded in reproducing sufficiently the Physarum's recorded behaviour derived from observation of the aforementioned

  8. Some properties of the floor field cellular automata evacuation model

    Science.gov (United States)

    Gwizdałła, Tomasz M.

    2015-02-01

    We study the process of evacuation of pedestrians from the room with the given arrangement of doors and obstacles by using the cellular automata technique. The technique which became quite popular is characterized by the discretization of time as well as space. For such a discretized space we use so-called floor field model which generally corresponds to the description of every cell by some monotonic function of distance between this cell and the closest exit. We study several types of effects. We start from some general features of model like the kind of a neighborhood or the factors disrupting the motion. Then we analyze the influence of asymmetry and size on the evacuation time. Finally we show characteristics concerning different arrangements of exits and include a particular approach to the proxemics effects. The scaling analyses help us to distinguish these cases which just reflect the geometry of the system and those which depend also on the simulation properties. All calculations are performed for a wide range of initial densities corresponding to different occupation rates as described by the typical crowd counting techniques.

  9. From equilibrium spin models to probabilistic cellular automata

    International Nuclear Information System (INIS)

    The general equivalence between D-dimensional probabilistic cellular automata (PCA) and (D + 1)-dimensional equilibrium spin models satisfying a disorder condition is first described in a pedagogical way and then used to analyze the phase diagrams, the critical behavior, and the universality classes of some automato. Diagrammatic representations of time-dependent correlation functions PCA are introduced. Two important classes of PCA are singled out for which these correlation functions simplify: (1) Quasi-Hamiltonian automata, which have a current-carrying steady state, and for which some correlation functions are those of a D-dimensional static model PCA satisfying the detailed balance condition appear as a particular case of these rules for which the current vanishes. (2) Linear (and more generally affine) PCA for which the diagrammatics reduces to a random walk problem closely related to (D + 1)-dimensional directed SAWs: both problems display a critical behavior with mean-field exponents in any dimension. The correlation length and effective velocity of propagation of excitations can be calculated for affine PCA, as is shown on an explicit D = 1 example. The authors conclude with some remarks on nonlinear PCA, for which the diagrammatics is related to reaction-diffusion processes, and which belong in some cases to the universality class of Reggeon field theory

  10. Modeling chemical systems using cellular automata a textbook and laboratory manual

    CERN Document Server

    Kier, Lemont B; Cheng, Chao-Kun

    2006-01-01

    Provides a practical introduction to an exciting modeling paradigm for complex systems. This book discusses the nature of scientific inquiry using models and simulations, and describes the nature of cellular automata models. It gives descriptions of how cellular automata models can be used in the study of a variety of phenomena.

  11. Relationship between cellular response models and biochemical mechanisms

    International Nuclear Information System (INIS)

    In most cellular response experiments, survival reflects the kinetics of a variety of damage and repair processes. Unfortunately, biochemical studies of molecular repair deal with mechanisms which cannot be readily correlated with these kinetic observations. The difference in these approaches sometimes leads to confusion over terms such as potentially-lethal and sublethal damage. These terms were introduced with operation definitions, derived from kinetic studies of cell survival, but some researchers have since attempted to associate them with specific biochemical mechanisms. Consequently, the terms are often used in totally different ways be different investigators. The use of carefully constructed models originating either out of assumptions based on mechanisms, or on kinetics, can be used to design experiments to eliminate some alternative kinetic schemes. In turn, some mechanisms may also be eliminated, resulting in a reduction in the number of mechanisms which must be investigated biochemically. One must take advantage of a wide range of specialized radiation procedures in order to accomplish this. Examples of the use of such specialized experimental designs, which have led to a more detailed understanding of the kinetics of both algal and mammalian cell responses, are discussed

  12. Modeling and Performance Analyses of Hybrid Cellular and Broadcasting Networks

    Directory of Open Access Journals (Sweden)

    Peter Unger

    2009-01-01

    Full Text Available Mobile communication services are getting more and more important and, in particular, multimedia services have attracted the interest of the users. Mobile TV is one of the most demanded candidates. Powerful and efficient communication systems are needed, which provide high capacities, especially at the downlink. Furthermore, interactivity is essential for supporting the user needs and to extend the service offering. As one possible solution to meet the mentioned requirements, we consider the combination of the cellular network UMTS and the mobile broadcast network DVB-H, which form a hybrid network. We investigate the performance of hybrid networks and develop a system model, which describes the hybrid network and the load switching between both networks. One of the contributions is the definition of the switching bound concept, which represents an efficient tool to assess the necessity and the feasibility of hybrid networks and the amount of load switching. The performance indicators cell load and grade of service are analyzed by using theoretical and realistic scenarios.

  13. Four Dimensional (4-D BioChemInfoPhysics Models of Cardiac Cellular and Sub-Cellular Vibrations (Oscillations

    Directory of Open Access Journals (Sweden)

    Chang-Hua Zou

    2009-01-01

    Full Text Available Problem statement: Cardiovascular Diseases (CVD continued to be the leading cause of death. Failure or abnormal cardiac cellular or sub-cellular vibrations (oscillations could lead failure or abnormal heart beats that could cause CVD. Understanding the mechanisms of the vibrations (oscillations could help to prevent or to treat the diseases. Scientists have studied the mechanisms for more than 100 years. To our knowledge, the mechanisms are still unclear today. In this investigation, based on published data or results, conservation laws of the momentum as well as the energy, in views of biology, biochemistry, informatics and physics (BioChemInfoPhysics, we proposed our models of cardiac cellular and sub-cellular vibrations (oscillations of biological components, such as free ions in Biological Fluids (BF, Biological Membranes (BM, Ca++H+ (Ca++ and Na+K+ ATPases, Na+Ca++ exchangers (NCX, Ca++ carriers and myosin heads. Approach: Our models were described with 4-D (x, y, z, t or r, ?, z, t momentum transfer equations in mathematical physics. Results: The momentum transfer equations were solved with free and forced, damped, un-damped and over-damped, vibrations (oscillations. The biological components could be modeled as resonators or vibrators (oscillators, such as liquid plasmas, membranes, active springs, passive springs and active swings. Conclusion: We systematically provided new insights of automation (ignition and maintain, transportation, propagation and orientation of the cardiac cellular and sub-cellular vibrations (oscillations and resonances, with our BioChemInfoPhysics models of 4-D momentum transfer equations. Our modeling results implied: Auto-rhythmic cells (Sinoatrial Node Cells (SANC, Atrioventricular Node Cells (AVNC, Purkinje fibers, non-Auto-rhythmic ventricular myocytes and their Sarcoplasmic Reticulums (SR work as Biological Liquid Plasma Resonators (BLPR. The resonators were

  14. Cellular automata model of magnetospheric-ionospheric coupling

    Directory of Open Access Journals (Sweden)

    B. V. Kozelov

    Full Text Available We propose a cellular automata model (CAM to describe the substorm activity of the magnetospheric-ionospheric system. The state of each cell in the model is described by two numbers that correspond to the energy content in a region of the current sheet in the magnetospheric tail and to the conductivity of the ionospheric domain that is magnetically connected with this region. The driving force of the system is supposed to be provided by the solar wind that is convected along the two boundaries of the system. The energy flux inside is ensured by the penetration of the energy from the solar wind into the array of cells (magnetospheric tail with a finite velocity. The third boundary (near to the Earth is closed and the fourth boundary is opened, thereby modeling the flux far away from the tail. The energy dissipation in the system is quite similar to other CAM models, when the energy in a particular cell exceeds some pre-defined threshold, and the part of the energy excess is redistributed between the neighbouring cells. The second number attributed to each cell mimics ionospheric conductivity that can allow for a part of the energy to be shed on field-aligned currents. The feedback between "ionosphere" and "magnetospheric tail" is provided by the change in a part of the energy, which is redistributed in the tail when the threshold is surpassed. The control parameter of the model is the z-component of the interplanetary magnetic field (Bz IMF, "frozen" into the solar wind. To study the internal dynamics of the system at the beginning, this control parameter is taken to be constant. The dynamics of the system undergoes several bifurcations, when the constant varies from - 0.6 to - 6.0. The Bz IMF input results in the periodic transients (activation regions and the inter-transient period decreases with the decrease of Bz. At the same time the onset of activations in the array shifts towards the "Earth". When the modulus of the Bz IMF exceeds some

  15. Millimeter Wave Channel Modeling and Cellular Capacity Evaluation

    OpenAIRE

    Akdeniz, Mustafa Riza; Liu, Yuanpeng; Samimi, Mathew K.; Sun, Shu; Rangan, Sundeep; Rappaport, Theodore S.; Erkip, Elza

    2013-01-01

    With the severe spectrum shortage in conventional cellular bands, millimeter wave (mmW) frequencies between 30 and 300 GHz have been attracting growing attention as a possible candidate for next-generation micro- and picocellular wireless networks. The mmW bands offer orders of magnitude greater spectrum than current cellular allocations and enable very high-dimensional antenna arrays for further gains via beamforming and spatial multiplexing. This paper uses recent real-world measurements at...

  16. A Cellular Automata Model for the Study of Landslides

    Science.gov (United States)

    Liucci, Luisa; Suteanu, Cristian; Melelli, Laura

    2016-04-01

    Power-law scaling has been observed in the frequency distribution of landslide sizes in many regions of the world, for landslides triggered by different factors, and in both multi-temporal and post-event datasets, thus indicating the universal character of this property of landslides and suggesting that the same mechanisms drive the dynamics of mass wasting processes. The reasons for the scaling behavior of landslide sizes are widely debated, since their understanding would improve our knowledge of the spatial and temporal evolution of this phenomenon. Self-Organized Critical (SOC) dynamics and the key role of topography have been suggested as possible explanations. The scaling exponent of the landslide size-frequency distribution defines the probability of landslide magnitudes and it thus represents an important parameter for hazard assessment. Therefore, another - still unanswered - important question concerns the factors on which its value depends. This paper investigates these issues using a Cellular Automata (CA) model. The CA uses a real topographic surface acquired from a Digital Elevation Model to represent the initial state of the system, where the states of cells are defined in terms of altitude. The stability criterion is based on the slope gradient. The system is driven to instability through a temporal decrease of the stability condition of cells, which may be thought of as representing the temporal weakening of soil caused by factors like rainfall. A transition rule defines the way in which instabilities lead to discharge from unstable cells to the neighboring cells, deciding upon the landslide direction and the quantity of mass involved. Both the direction and the transferred mass depend on the local topographic features. The scaling properties of the area-frequency distributions of the resulting landslide series are investigated for several rates of weakening and for different time windows, in order to explore the response of the system to model

  17. Cellular Automata Models Applied to the Study of Landslide Dynamics

    Science.gov (United States)

    Liucci, Luisa; Melelli, Laura; Suteanu, Cristian

    2015-04-01

    Landslides are caused by complex processes controlled by the interaction of numerous factors. Increasing efforts are being made to understand the spatial and temporal evolution of this phenomenon, and the use of remote sensing data is making significant contributions in improving forecast. This paper studies landslides seen as complex dynamic systems, in order to investigate their potential Self Organized Critical (SOC) behavior, and in particular, scale-invariant aspects of processes governing the spatial development of landslides and their temporal evolution, as well as the mechanisms involved in driving the system and keeping it in a critical state. For this purpose, we build Cellular Automata Models, which have been shown to be capable of reproducing the complexity of real world features using a small number of variables and simple rules, thus allowing for the reduction of the number of input parameters commonly used in the study of processes governing landslide evolution, such as those linked to the geomechanical properties of soils. This type of models has already been successfully applied in studying the dynamics of other natural hazards, such as earthquakes and forest fires. The basic structure of the model is composed of three modules: (i) An initialization module, which defines the topographic surface at time zero as a grid of square cells, each described by an altitude value; the surface is acquired from real Digital Elevation Models (DEMs). (ii) A transition function, which defines the rules used by the model to update the state of the system at each iteration. The rules use a stability criterion based on the slope angle and introduce a variable describing the weakening of the material over time, caused for example by rainfall. The weakening brings some sites of the system out of equilibrium thus causing the triggering of landslides, which propagate within the system through local interactions between neighboring cells. By using different rates of

  18. Genetic Algorithm Calibration of Probabilistic Cellular Automata for Modeling Mining Permit Activity

    Science.gov (United States)

    Louis, S.J.; Raines, G.L.

    2003-01-01

    We use a genetic algorithm to calibrate a spatially and temporally resolved cellular automata to model mining activity on public land in Idaho and western Montana. The genetic algorithm searches through a space of transition rule parameters of a two dimensional cellular automata model to find rule parameters that fit observed mining activity data. Previous work by one of the authors in calibrating the cellular automaton took weeks - the genetic algorithm takes a day and produces rules leading to about the same (or better) fit to observed data. These preliminary results indicate that genetic algorithms are a viable tool in calibrating cellular automata for this application. Experience gained during the calibration of this cellular automata suggests that mineral resource information is a critical factor in the quality of the results. With automated calibration, further refinements of how the mineral-resource information is provided to the cellular automaton will probably improve our model.

  19. The similia principle: results obtained in a cellular model system.

    Science.gov (United States)

    Wiegant, Fred; Van Wijk, Roeland

    2010-01-01

    This paper describes the results of a research program focused on the beneficial effect of low dose stress conditions that were applied according to the similia principle to cells previously disturbed by more severe stress conditions. In first instance, we discuss criteria for research on the similia principle at the cellular level. Then, the homologous ('isopathic') approach is reviewed, in which the initial (high dose) stress used to disturb cellular physiology and the subsequent (low dose) stress are identical. Beneficial effects of low dose stress are described in terms of increased cellular survival capacity and at the molecular level as an increase in the synthesis of heat shock proteins (hsps). Both phenomena reflect a stimulation of the endogenous cellular self-recovery capacity. Low dose stress conditions applied in a homologous approach stimulate the synthesis of hsps and enhance survival in comparison with stressed cells that were incubated in the absence of low dose stress conditions. Thirdly, the specificity of the low dose stress condition is described where the initial (high dose) stress is different in nature from the subsequently applied (low dose) stress; the heterologous or 'heteropathic' approach. The results support the similia principle at the cellular level and add to understanding of how low dose stress conditions influence the regulatory processes underlying self-recovery. In addition, the phenomenon of 'symptom aggravation' which is also observed at the cellular level, is discussed in the context of self-recovery. Finally, the difference in efficiency between the homologous and the heterologous approach is discussed; a perspective is indicated for further research; and the relationship between studies on the similia principle and the recently introduced concept of 'postconditioning hormesis' is emphasized. PMID:20129172

  20. Cellular-automata model of the dwarf shrubs populations and communities dynamics

    OpenAIRE

    A. S. Komarov; E. V. Zubkova; P. V. Frolov

    2015-01-01

    The probabilistic cellular-automata model of development and long-time dynamics of dwarf shrub populations and communities is developed. It is based on the concept of discrete description of the plant ontogenesis and joint model approaches in terms of probabilistic cellular automata and L-systems by Lindenmayer. Short representation of the basic model allows evaluation of the approach and software implementation. The main variables of the model are a number of partial bushes in clones or area...

  1. Stochastic Models of Vesicular Sorting in Cellular Organelles

    CERN Document Server

    Vagne, Quentin

    2016-01-01

    The proper sorting of membrane components by regulated exchange between cellular organelles is crucial to intra-cellular organization. This process relies on the budding and fusion of transport vesicles, and should be strongly influenced by stochastic fluctuations considering the relatively small size of many organelles. We identify the perfect sorting of two membrane components initially mixed in a single compartment as a first passage process, and we show that the mean sorting time exhibits two distinct regimes as a function of the ratio of vesicle fusion to budding rates. Low ratio values leads to fast sorting, but results in a broad size distribution of sorted compartments dominated by small entities. High ratio values result in two well defined sorted compartments but is exponentially slow. Our results suggests an optimal balance between vesicle budding and fusion for the rapid and efficient sorting of membrane components, and highlight the importance of stochastic effects for the steady-state organizati...

  2. Mathematical models and multiscale simulations of cellular secretion processes

    OpenAIRE

    González-Vélez, Virginia

    2011-01-01

    Exocytosis is the cellular process whereby a product such as a hormone or a neurotransmitter is released as a response to stimulation. There are a lot of exocytotic cells in mammals, and each cell type has their specific subcellular mechanisms, needed to achieve the final substance release. Therefore, unveiling the role of subcellular mechanisms in secretion processes is highly relevant to understand disease evolution and possible therapies. The efficiency of the coupling between stimulus...

  3. A Large Deformation Model for the Elastic Moduli of Two-dimensional Cellular Materials

    Institute of Scientific and Technical Information of China (English)

    HU Guoming; WAN Hui; ZHANG Youlin; BAO Wujun

    2006-01-01

    We developed a large deformation model for predicting the elastic moduli of two-dimensional cellular materials. This large deformation model was based on the large deflection of the inclined members of the cells of cellular materials. The deflection of the inclined member, the strain of the representative structure and the elastic moduli of two-dimensional cellular materials were expressed using incomplete elliptic integrals. The experimental results show that these elastic moduli are no longer constant at large deformation, but vary significantly with the strain. A comparison was made between this large deformation model and the small deformation model proposed by Gibson and Ashby.

  4. A mathematical model of amphibian skin epithelium with two types of transporting cellular units

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Rasmussen, B E

    1985-01-01

    A computer model of ion transport across amphibian skin epithelium containing two types of cellular units, their relative number and sizes, and a paracellular pathway has been developed. The two cellular units are, a large Na+ transporting compartment representing the major epithelium from stratum...

  5. Predictive model to describe water migration in cellular solid foods during storage

    NARCIS (Netherlands)

    Voogt, J.A.; Hirte, A.; Meinders, M.B.J.

    2011-01-01

    BACKGROUND: Water migration in cellular solid foods during storage causes loss of crispness. To improve crispness retention, physical understanding of this process is needed. Mathematical models are suitable tools to gain this physical knowledge. RESULTS: Water migration in cellular solid foods invo

  6. Excellent approach to modeling urban expansion by fuzzy cellular automata: agent base model

    Science.gov (United States)

    Khajavigodellou, Yousef; Alesheikh, Ali A.; Mohammed, Abdulrazak A. S.; Chapi, Kamran

    2014-09-01

    Recently, the interaction between humans and their environment is the one of important challenges in the world. Landuse/ cover change (LUCC) is a complex process that includes actors and factors at different social and spatial levels. The complexity and dynamics of urban systems make the applicable practice of urban modeling very difficult. With the increased computational power and the greater availability of spatial data, micro-simulation such as the agent based and cellular automata simulation methods, has been developed by geographers, planners, and scholars, and it has shown great potential for representing and simulating the complexity of the dynamic processes involved in urban growth and land use change. This paper presents Fuzzy Cellular Automata in Geospatial Information System and remote Sensing to simulated and predicted urban expansion pattern. These FCA-based dynamic spatial urban models provide an improved ability to forecast and assess future urban growth and to create planning scenarios, allowing us to explore the potential impacts of simulations that correspond to urban planning and management policies. A fuzzy inference guided cellular automata approach. Semantic or linguistic knowledge on Land use change is expressed as fuzzy rules, based on which fuzzy inference is applied to determine the urban development potential for each pixel. The model integrates an ABM (agent-based model) and FCA (Fuzzy Cellular Automata) to investigate a complex decision-making process and future urban dynamic processes. Based on this model rapid development and green land protection under the influences of the behaviors and decision modes of regional authority agents, real estate developer agents, resident agents and non- resident agents and their interactions have been applied to predict the future development patterns of the Erbil metropolitan region.

  7. Dynamic modeling of cellular response to DNA damage based on p53 stress response networks

    Institute of Scientific and Technical Information of China (English)

    Jinpeng Qi; Yongsheng Ding; Shihuang Shao

    2009-01-01

    Under acute perturbations from the outside, cells can trigger self-defensive mechanisms to fight against genome stress. To investigate the cellular response to continuous ion radiation (IR), a dynamic model for p53 stress response networks at the cellular level is proposed. The model can successfully be used to simulate the dynamic processes of double-strand breaks (DSBs) generation and their repair, switch-like ataxia telangiectasia mutated (ATM) activation, oscillations occurring in the p53-MDM2 feedback loop, as well as toxins elimination triggered by p53 stress response networks. Especially, the model can predict the plausible outcomes of cellular response under different IR dose regimes.

  8. Modeling and Analysis of Cellular Networks using Stochastic Geometry: A Tutorial

    KAUST Repository

    ElSawy, Hesham

    2016-03-22

    This paper presents a tutorial on stochastic geometry (SG) based analysis for cellular networks. This tutorial is distinguished by its depth with respect to wireless communication details and its focus on cellular networks. The paper starts by modeling and analyzing the baseband interference in a basic cellular network model. Then, it characterizes signal-tointerference- plus-noise-ratio (SINR) and its related performance metrics. In particular, a unified approach to conduct error probability, outage probability, and rate analysis is presented. Although the main focus of the paper is on cellular networks, the presented unified approach applies for other types of wireless networks that impose interference protection around receivers. The paper then extends the baseline unified approach to capture cellular network characteristics (e.g., frequency reuse, multiple antenna, power control, etc.). It also presents numerical examples associated with demonstrations and discussions. Finally, we point out future research directions.

  9. Cellular Automation Model of Traffic Flow Based on the Car-Following Model

    Institute of Scientific and Technical Information of China (English)

    LI Ke-Ping; GAO Zi-You

    2004-01-01

    @@ We propose a new cellular automation (CA) traffic model that is based on the car-following model. A class of driving strategies is used in the car-following model instead of the acceleration in the NaSch traffic model. In our model, some realistic driver behaviour and detailed vehicle characteristics have been taken into account, such as distance-headway and safe distance, etc. The simulation results show that our model can exhibit some traffic flow states that have been observed in the real traffic, and both of the maximum flux and the critical density are very close to the real measurement. Moreover, it is easy to extend our method to multi-lane traffic.

  10. Linking Cellular and Mechanical Processes in Articular Cartilage Lesion Formation: A Mathematical Model

    OpenAIRE

    Kapitanov, Georgi I.; Wang, Xiayi; Ayati, Bruce P; Brouillette, Marc J.; Martin, James A.

    2016-01-01

    A severe application of stress on articular cartilage can initiate a cascade of biochemical reactions that can lead to the development of osteoarthritis. We constructed a multiscale mathematical model of the process with three components: cellular, chemical, and mechanical. The cellular component describes the different chondrocyte states according to the chemicals these cells release. The chemical component models the change in concentrations of those chemicals. The mechanical component cont...

  11. Simulation Modeling by Classification of Problems: A Case of Cellular Manufacturing

    Science.gov (United States)

    Afiqah, K. N.; Mahayuddin, Z. R.

    2016-02-01

    Cellular manufacturing provides good solution approach to manufacturing area by applying Group Technology concept. The evolution of cellular manufacturing can enhance performance of the cell and to increase the quality of the product manufactured but it triggers other problem. Generally, this paper highlights factors and problems which emerge commonly in cellular manufacturing. The aim of the research is to develop a thorough understanding of common problems in cellular manufacturing. A part from that, in order to find a solution to the problems exist using simulation technique, this classification framework is very useful to be adapted during model building. Biology evolution tool was used in the research in order to classify the problems emerge. The result reveals 22 problems and 25 factors using cladistic technique. In this research, the expected result is the cladogram established based on the problems in cellular manufacturing gathered.

  12. Cellular cardiac electrophysiology modeling with Chaste and CellML

    OpenAIRE

    Cooper, Jonathan; Spiteri, Raymond J.; Mirams, Gary R

    2014-01-01

    Chaste is an open-source C++ library for computational biology that has well-developed cardiac electrophysiology tissue simulation support. In this paper, we introduce the features available for performing cardiac electrophysiology action potential simulations using a wide range of models from the Physiome repository. The mathematics of the models are described in CellML, with units for all quantities. The primary idea is that the model is defined in one place (the CellML file), and all model...

  13. Modelling lava flows by Cellular Nonlinear Networks (CNN: preliminary results

    Directory of Open Access Journals (Sweden)

    C. Del Negro

    2005-01-01

    Full Text Available The forecasting of lava flow paths is a complex problem in which temperature, rheology and flux-rate all vary with space and time. The problem is more difficult to solve when lava runs down a real topography, considering that the relations between characteristic parameters of flow are typically nonlinear. An alternative approach to this problem that does not use standard differential equation methods is Cellular Nonlinear Networks (CNNs. The CNN paradigm is a natural and flexible framework for describing locally interconnected, simple, dynamic systems that have a lattice-like structure. They consist of arrays of essentially simple, nonlinearly coupled dynamic circuits containing linear and non-linear elements able to process large amounts of information in real time. Two different approaches have been implemented in simulating some lava flows. Firstly, a typical technique of the CNNs to analyze spatio-temporal phenomena (as Autowaves in 2-D and in 3-D has been utilized. Secondly, the CNNs have been used as solvers of partial differential equations of the Navier-Stokes treatment of Newtonian flow.

  14. Study of phase separation using liquid-gas model of lattice-gas cellular automata

    International Nuclear Information System (INIS)

    This report describes the study of phase separation by the liquid gas model of lattice gas cellular automata. The lattice gas cellular automaton is one model for simulating fluid phenomena which was proposed by Frisch, Hasslacher and Pomeau in 1986. In 1990, Appert and Zaleski added a new long-range interaction to lattice gas cellular automata to construct a model, the liquid-gas model, which could simulate phase separation using lattice-gas cellular automata. Gerits et al formulated the liquid-gas model mathematically using the theory of statistical dynamics in 1993 and explained the mechanism of phase separation in the liquid-gas model using the equation of state. At first this report explains the FHP model of lattice gas cellular automata and derives fluid dynamics equations such as the equation of continuity and the Navier-Stokes equation. Then the equation of state for the liquid-gas model which was derived by Gerits et al is modified by adding the interactions which were proposed by Appert but not considered by Gerits et al. The modified equation of state is verified by the computer simulation using the liquid gas model. The relation between phase separation and the equation of state is discussed. (author)

  15. Modified cellular automaton model for modeling of microstructure and microsegregation in solidification of ternary alloys

    Institute of Scientific and Technical Information of China (English)

    ZHU Ming-fang; CAO Wei-sheng; CHEN Shuang-lin; XIE Fan-you; HONG Chunpyo; CHANG Y. Austin

    2006-01-01

    A modified cellular automaton (MCA) model has been extended to the ternary alloy system by coupling thermodynamic and phase equilibrium calculation engine PanEngine. In the present model the dendrite growth is driven by the difference between the local equilibrium liquidus temperature and local actual temperature, incorporating the effect of curvature. The local equilibrium liquidus temperature is calculated with PanEngine according to the local liquid concentrations of two solutes, which are determined by numerically solving the species transport equation in the domain. Model validation was carried out through the comparison of the simulated values to the prediction of the Scheil model for solute profiles in the primary dendrites. The simulated data with zero solid diffusivity and limited liquid diffusivity were increasingly close to the Scheil profiles as the solidification rate decreased. The simulated microstructure and microsegregation in an Al-Cu-Mg ternary alloy were compared with those obtained experimentally.

  16. Jeans type instability for a chemotactic model of cellular aggregation

    CERN Document Server

    Chavanis, Pierre-Henri

    2008-01-01

    We consider an inertial model of chemotactic aggregation generalizing the Keller-Segel model and we study the linear dynamical stability of an infinite and homogeneous distribution of cells (bacteria, amoebae, endothelial cells,...) when inertial effects are accounted for. These inertial terms model cells directional persistance. We determine the condition of instability and the growth rate of the perturbation as a function of the cell density and the wavelength of the perturbation. We discuss the differences between overdamped (Keller-Segel) and inertial models. Finally, we show the analogy between the instability criterion for biological populations and the Jeans instability criterion in astrophysics.

  17. From cellular to tissue scales by asymptotic limits of thermostatted kinetic models

    Science.gov (United States)

    Bianca, Carlo; Dogbe, Christian; Lemarchand, Annie

    2016-02-01

    Tumor growth strictly depends on the interactions occurring at the cellular scale. In order to obtain the linking between the dynamics described at tissue and cellular scales, asymptotic methods have been employed, consisting in deriving tissue equations by suitable limits of mesoscopic models. In this paper, the evolution at the cellular scale is described by thermostatted kinetic theory that include conservative, nonconservative (proliferation, destruction and mutations), stochastic terms, and the role of external agents. The dynamics at the tissue scale (cell-density evolution) is obtained by performing a low-field scaling and considering the related convergence of the rescaled framework when the scaling parameter goes to zero.

  18. Cellular cardiac electrophysiology modeling with Chaste and CellML.

    Science.gov (United States)

    Cooper, Jonathan; Spiteri, Raymond J; Mirams, Gary R

    2014-01-01

    Chaste is an open-source C++ library for computational biology that has well-developed cardiac electrophysiology tissue simulation support. In this paper, we introduce the features available for performing cardiac electrophysiology action potential simulations using a wide range of models from the Physiome repository. The mathematics of the models are described in CellML, with units for all quantities. The primary idea is that the model is defined in one place (the CellML file), and all model code is auto-generated at compile or run time; it never has to be manually edited. We use ontological annotation to identify model variables describing certain biological quantities (membrane voltage, capacitance, etc.) to allow us to import any relevant CellML models into the Chaste framework in consistent units and to interact with them via consistent interfaces. This approach provides a great deal of flexibility for analysing different models of the same system. Chaste provides a wide choice of numerical methods for solving the ordinary differential equations that describe the models. Fixed-timestep explicit and implicit solvers are provided, as discussed in previous work. Here we introduce the Rush-Larsen and Generalized Rush-Larsen integration techniques, made available via symbolic manipulation of the model equations, which are automatically rearranged into the forms required by these approaches. We have also integrated the CVODE solvers, a 'gold standard' for stiff systems, and we have developed support for symbolic computation of the Jacobian matrix, yielding further increases in the performance and accuracy of CVODE. We discuss some of the technical details of this work and compare the performance of the available numerical methods. Finally, we discuss how this is generalized in our functional curation framework, which uses a domain-specific language for defining complex experiments as a basis for comparison of model behavior. PMID:25610400

  19. A study of a main-road cellular automata traffic flow model

    Institute of Scientific and Technical Information of China (English)

    黄乒花; 孔令江; 刘慕仁

    2002-01-01

    A main-road cellular automata traffic flow model on two dimensions is presented based on the Biham-Middleton-Levine traffic model. Its evolution equations are given and the self-organization and organization cooperation phenomenain this model are also studied by using computer simulation.

  20. Propagation Path Loss Models for 5G Urban Micro- and Macro-Cellular Scenarios

    DEFF Research Database (Denmark)

    Sun, Shu; Rappaport, Theodore S.; Rangan, Sundeep;

    2016-01-01

    This paper presents and compares two candidate large-scale propagation path loss models, the alpha-beta-gamma (ABG) model and the close-in (CI) free space reference distance model, for the design of fifth generation (5G) wireless communication systems in urban micro- and macro-cellular scenarios...

  1. Integration of logistic regression, Markov chain and cellular automata models to simulate urban expansion

    NARCIS (Netherlands)

    Jokar Arsanjani, J.; Helbich, M.; Kainz, W.; Boloorani, A.

    2013-01-01

    This research analyses the suburban expansion in the metropolitan area of Tehran, Iran. A hybrid model consisting of logistic regression model, Markov chain (MC), and cellular automata (CA) was designed to improve the performance of the standard logistic regression model. Environmental and socio-eco

  2. On Modeling Coverage and Rate of Random Cellular Networks under Generic Channel Fading

    OpenAIRE

    Al-Hourani, Akram; Kandeepan, Sithamparanathan

    2016-01-01

    In this paper we provide an analytic framework for computing the expected downlink coverage probability, and the associated data rate of cellular networks, where base stations are distributed in a random manner. The provided expressions are in computable integral forms that accommodate generic channel fading conditions. We develop these expressions by modelling the cellular interference using stochastic geometry analysis, then we employ them for comparing the coverage resulting from various c...

  3. A cellular network model with Ginibre configured base stations

    OpenAIRE

    Miyoshi, Naoto; Shirai, Tomoyuki

    2014-01-01

    Stochastic geometry models for wireless communication networks have recently attracted much attention. This is because the performance of such networks critically depends on the spatial configuration of wireless nodes and the irregularity of the node configuration in a real network can be captured by a spatial point process. However, most analysis of such stochastic geometry models for wireless networks assumes, owing to its tractability, that the wireless nodes are deployed...

  4. A cellular automata model for simulating fed-batch penicillin fermentation process

    Institute of Scientific and Technical Information of China (English)

    Yu Naigong; Ruan Xiaogang

    2006-01-01

    A cellular automata model to simulate penicillin fed-batch fermentation process(CAPFM)was established in this study,based on a morphologically structured dynamic penicillin production model,that is in turn based on the growth mechanism of penicillin producing microorganisms and the characteristics of penicillin fed-batch fermentation.CAPFM uses the three-dimensional cellular automata as a growth space,and a Moore-type neighborhood as the cellular neighborhood.The transition roles of CAPFM are designed based on mechanical and structural kinetic models of penicillin batch-fed fermentation processes.Every cell of CAPFM represents a single or specific number of penicillin producing microorganisms,and has various state.The simulation experimental results show that CAPFM replicates the evolutionary behavior of penicillin batch-fed fermentation processes described by the structured penicillin production kinetic model accordingly.

  5. Mathematical Modeling Predicts How Proteins Affect Cellular Communication

    OpenAIRE

    Lee Ethan; Salic Adrian; Krüger Roland; Heinrich Reinhart; Kirschner Marc W

    2003-01-01

    Wnt signaling plays an important role in both oncogenesis and development. Activation of the Wnt pathway results in stabilization of the transcriptional coactivator beta-catenin. Recent studies have demonstrated that axin, which coordinates beta-catenin degradation, is itself degraded. Although the key molecules required for transducing a Wnt signal have been identified, a quantitative understanding of this pathway has been lacking. We have developed a mathematical model for the canonical Wnt...

  6. Cellular automata cell structure for modeling heterogeneous traffic

    OpenAIRE

    Pal, Dibyendu; C.Mallikarjuna

    2010-01-01

    Gap maintaining behavior significantly affects the traffic flow modeling under heterogeneous traffic conditions. The clearance between two adjacent moving vehicles varies depending on several traffic conditions. From the data collected on the gap maintaining behavior it has been observed that vehicles maintain different gaps when travelling under different traffic conditions and this is also influenced by lateral position of the vehicle. Mallikarjuna (2007) has found that this variable gap ma...

  7. Cellular models and therapies for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    David L. Forest

    2015-05-01

    Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

  8. Equal Distribution Model of Epidemic Drugs Based on a Cellular Automata Model

    Directory of Open Access Journals (Sweden)

    Huang Xinyi

    2015-01-01

    Full Text Available The epidemic spreading of infectious disease is a process of evolution over time. Based on the cellular automata model[1], this paper analyzes the epidemic spreading rules, and establishes an efficient equal distribution model of drugs in a broad sense. For multiple regions, in case of demand of drugs exceeding supply, the drugs shall be distributed according to the proportion of a total number of people in each region, the number of patients, the number of the isolated, and the number of deaths. It is necessary to simulate based on these four schemes to obtain simulation results. The results show that, when the drugs are distributed by the proportion of the number of deaths, it is optimal for controlling over epidemic situations.

  9. Stochastic Model of Maturation and Vesicular Exchange in Cellular Organelles

    CERN Document Server

    Vagne, Quentin

    2016-01-01

    The dynamical organization of membrane-bound organelles along intracellular transport pathways relies on vesicular exchange between organelles and on biochemical maturation of the organelle content by specific enzymes. The relative importance of each mechanism in controlling organelle dynamics remains controversial, in particular for transport through the Golgi apparatus. Using a stochastic model, we show that full maturation of membrane-bound compartments can be seen as the stochastic escape from a steady-state in which export is dominated by vesicular exchange. We show that full maturation can contribute a significant fraction of the total out-flux for small organelles such as endosomes and Golgi cisternae.

  10. Designing and implementing a regional urban modeling system using the SLEUTH cellular urban model

    Science.gov (United States)

    Jantz, C.A.; Goetz, S.J.; Donato, D.; Claggett, P.

    2010-01-01

    This paper presents a fine-scale (30 meter resolution) regional land cover modeling system, based on the SLEUTH cellular automata model, that was developed for a 257000 km2 area comprising the Chesapeake Bay drainage basin in the eastern United States. As part of this effort, we developed a new version of the SLEUTH model (SLEUTH-3r), which introduces new functionality and fit metrics that substantially increase the performance and applicability of the model. In addition, we developed methods that expand the capability of SLEUTH to incorporate economic, cultural and policy information, opening up new avenues for the integration of SLEUTH with other land-change models. SLEUTH-3r is also more computationally efficient (by a factor of 5) and uses less memory (reduced 65%) than the original software. With the new version of SLEUTH, we were able to achieve high accuracies at both the aggregate level of 15 sub-regional modeling units and at finer scales. We present forecasts to 2030 of urban development under a current trends scenario across the entire Chesapeake Bay drainage basin, and three alternative scenarios for a sub-region within the Chesapeake Bay watershed to illustrate the new ability of SLEUTH-3r to generate forecasts across a broad range of conditions. ?? 2009 Elsevier Ltd.

  11. Modelling Cellular Processes using Membrane Systems with Peripheral and Integral Proteins

    OpenAIRE

    Cavaliere, Matteo; Sedwards, Sean

    2006-01-01

    Membrane systems were introduced as models of computation inspired by the structure and functioning of biological cells. Recently, membrane systems have also been shown to be suitable to model cellular processes. We introduce a new model called Membrane Systems with Peripheral and Integral Proteins. The model has compartments enclosed by membranes, floating objects, objects associated to the internal and external surfaces of the membranes and also objects integral to the membranes. The floati...

  12. Evaluation of BACE1 Silencing in Cellular Models

    Directory of Open Access Journals (Sweden)

    Barbara Nawrot

    2009-01-01

    Full Text Available Beta-secretase (BACE1 is the major enzyme participating in generation of toxic amyloid-beta (Aβ peptides, identified in amyloid plaques of Alzheimer's disease (AD brains. Its downregulation results in decreasing secretion of Aβ. Thus, BACE1 silencing by RNAi represents possible strategy for antiamyloid therapy in the treatment of AD. In this study, a series of newly designed sequences of synthetic and vector-encoded siRNAs (pSilencer, pcPURhU6, and lentivirus were tested against overexpressed and endogenous BACE1 in several cell lines and in adult neural progenitor cells, derived from rat hippocampus. SiRNAs active in human, mouse, and rat cell models were shown to diminish the level of BACE1. In HCN A94 cells, two BACE1-specific siRNAs did not alter the expression of genes of BACE2 and several selected genes involved in neurogenesis (Synapsin I, βIII-Tubulin, Calbidin, NeuroD1, GluR2, CREB, MeCP2, PKR, however, remarkable lowering of SCG10 mRNA, coding protein of stathmin family, important in the development of nervous system, was observed.

  13. Tools and Models for Integrating Multiple Cellular Networks

    Energy Technology Data Exchange (ETDEWEB)

    Gerstein, Mark [Yale Univ., New Haven, CT (United States). Gerstein Lab.

    2015-11-06

    CRIT for correlation analysis in systems biology [5]. For Aim 3, we have further investigated the scaling relationship that the number of Transcription Factors (TFs) in a genome is proportional to the square of the total number of genes. We have extended the analysis from transcription factors to various classes of functional categories, and from individual categories to joint distribution [6]. By introducing a new analytical framework, we have generalized the original toolbox model to take into account of metabolic network with arbitrary network topology [7].

  14. Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running

    Directory of Open Access Journals (Sweden)

    Mondry Adrian

    2004-08-01

    Full Text Available Abstract Background Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. Methods We have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG. Results We demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given. Conclusions Quantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods

  15. A robust cellular associative memory for pattern recognitions using composite trigonometric chaotic neuron models

    Directory of Open Access Journals (Sweden)

    Wimol San-Um

    2015-12-01

    Full Text Available This paper presents a robust cellular associative memory for pattern recognitions using composite trigonometric chaotic neuron models. Robust chaotic neurons are designed through a scan of positive Lyapunov Exponent (LE bifurcation structures, which indicate the quantitative measure of chaoticity for one-dimensional discrete-time dynamical systems. The proposed chaotic neuron model is a composite of sine and cosine chaotic maps, which are independent from the output activation function. Dynamics behaviors are demonstrated through bifurcation diagrams and LE-based bifurcation structures. An application to associative memories of binary patterns in Cellular Neural Networks (CNN topology is demonstrated using a signum output activation function. Examples of English alphabets are stored using symmetric auto-associative matrix of n-binary patterns. Simulation results have demonstrated that the cellular neural network can quickly and effectively restore the distorted pattern to expected information.

  16. Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model

    Science.gov (United States)

    Moglianetti, Mauro; de Luca, Elisa; Pedone, Deborah; Marotta, Roberto; Catelani, Tiziano; Sartori, Barbara; Amenitsch, Heinz; Retta, Saverio Francesco; Pompa, Pier Paolo

    2016-02-01

    In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide

  17. Simulation of evacuation processes using a bionics-inspired cellular automaton model for pedestrian dynamics

    OpenAIRE

    Kirchner, Ansgar; Schadschneider, Andreas

    2002-01-01

    We present simulations of evacuation processes using a recently introduced cellular automaton model for pedestrian dynamics. This model applies a bionics approach to describe the interaction between the pedestrians using ideas from chemotaxis. Here we study a rather simple situation, namely the evacuation from a large room with one or two doors. It is shown that the variation of the model parameters allows to describe different types of behaviour, from regular to panic. We find a non-monotoni...

  18. Color Graphs: An Efficient Model For Two-Dimensional Cellular Automata Linear Rules

    CERN Document Server

    Nayak, Birendra Kumar; Rout, Sushant Kumar

    2008-01-01

    Two-dimensional nine neighbor hood rectangular Cellular Automata rules can be modeled using many different techniques like Rule matrices, State Transition Diagrams, Boolean functions, Algebraic Normal Form etc. In this paper, a new model is introduced using color graphs to model all the 512 linear rules. The graph theoretic properties therefore studied in this paper simplifies the analysis of all linear rules in comparison with other ways of its study.

  19. A Modified Cellular Automaton Approach for Mixed Bicycle Traffic Flow Modeling

    OpenAIRE

    Xiaonian Shan; Zhibin Li; Xiaohong Chen; Jianhong Ye

    2015-01-01

    Several previous studies have used the Cellular Automaton (CA) for the modeling of bicycle traffic flow. However, previous CA models have several limitations, resulting in differences between the simulated and the observed traffic flow features. The primary objective of this study is to propose a modified CA model for simulating the characteristics of mixed bicycle traffic flow. Field data were collected on physically separated bicycle path in Shanghai, China, and were used to calibrate the C...

  20. Lattice gas cellular automata model for rippling and aggregation in myxobacteria

    OpenAIRE

    Alber, Mark S.; Jiang, Yi; Kiskowski, Maria A.

    2004-01-01

    A lattice-gas cellular automaton (LGCA) model is used to simulate rippling and aggregation in myxobacteria. An efficient way of representing cells of different cell size, shape and orientation is presented that may be easily extended to model later stages of fruiting body formation. This LGCA model is designed to investigate whether a refractory period, a minimum response time, a maximum oscillation period and non-linear dependence of reversals of cells on C-factor are necessary assumptions f...

  1. PHANTOM MODEL OF HUMAN BRAIN TISSUE FOR CELLULAR PHONE FREQUENCIES IN ELECTROMAGNETIC FIELD RADIATION ABSORPTION STUDIES

    OpenAIRE

    Özen, Şükrü; Köylü, Halis

    2010-01-01

    ABSTRACTThere is a necessity of tissue equivalent (phantom) models in research of electromagnetic (EM) effects in biologic tissues. Recently, many kinds of tissue models depend on the different aim were proposed. So many studies were carried on the interaction of human-head and cellular phone. The most of them are related to numerical models. Owing to difficulty of study on human body, simulation of human tissues is required. In this study two different, for 900MHz and for 1800MHz, brain equi...

  2. Embryonic stem cells as an ectodermal cellular model of human p63-related dysplasia syndromes.

    NARCIS (Netherlands)

    Rostagno, P.; Wolchinsky, Z.; Vigano, A.M.; Shivtiel, S.; Zhou, H.; Bokhoven, J.H.L.M. van; Ferone, G.; Missero, C.; Mantovani, R.; Aberdam, D.; Virolle, T.

    2010-01-01

    Heterozygous mutations in the TP63 transcription factor underlie the molecular basis of several similar autosomal dominant ectodermal dysplasia (ED) syndromes. Here we provide a novel cellular model derived from embryonic stem (ES) cells that recapitulates in vitro the main steps of embryonic skin d

  3. An agent-based model of cellular dynamics and circadian variability in human endotoxemia.

    Directory of Open Access Journals (Sweden)

    Tung T Nguyen

    Full Text Available As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.

  4. A material optimization model to approximate energy bounds for cellular materials under multiload conditions

    DEFF Research Database (Denmark)

    Guedes, J.M.; Rodrigues, H.C.; Bendsøe, Martin P.

    2003-01-01

    This paper describes a computational model, based on inverse homogenization and topology design, for approximating energy bounds for two-phase composites under multiple load cases. The approach allows for the identification of possible single-scale cellular materials that give rise to the optimal...

  5. Model Perubahan Penggunaan Lahan Menggunakan Cellular Automata-Markov Chain di Kawasan Mamminasata

    OpenAIRE

    Vera Damayanti Peruge, Tiur

    2012-01-01

    Telah dilakukan penelitian tentang perubahan penggunaan lahan di kawasan Mamminasata menggunakan model Cellular Automata-Markov Chain. Tujuan dari penelitian ini adalah menganalisis perubahan penggunaan lahan melalui peta penggunaan lahan kawasan Mamminasata tahun 2004 dan 2009 untuk memperoleh penggunaan lahan tahun 2012 berbasis Markov Chain dengan analisis probabilitas transisi Markov. Hasil analisis yang diperoleh dilakukan validasi dengan validasi Kappa m...

  6. Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

    Science.gov (United States)

    Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

    2016-04-01

    Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes

  7. Computational Modelling of the Structural Integrity following Mass-Loss in Polymeric Charred Cellular Solids

    Directory of Open Access Journals (Sweden)

    J. P. M. Whitty

    2014-01-01

    Full Text Available A novel computational technique is presented for embedding mass-loss due to burning into the ANSYS finite element modelling code. The approaches employ a range of computational modelling methods in order to provide more complete theoretical treatment of thermoelasticity absent from the literature for over six decades. Techniques are employed to evaluate structural integrity (namely, elastic moduli, Poisson’s ratios, and compressive brittle strength of honeycomb systems known to approximate three-dimensional cellular chars. That is, reducing the mass of diagonal ribs and both diagonal-plus-vertical ribs simultaneously show rapid decreases in the structural integrity of both conventional and reentrant (auxetic, i.e., possessing a negative Poisson’s ratio honeycombs. On the other hand, reducing only the vertical ribs shows initially modest reductions in such properties, followed by catastrophic failure of the material system. Calculations of thermal stress distributions indicate that in all cases the total stress is reduced in reentrant (auxetic cellular solids. This indicates that conventional cellular solids are expected to fail before their auxetic counterparts. Furthermore, both analytical and FE modelling predictions of the brittle crush strength of both auxteic and conventional cellular solids show a relationship with structural stiffness.

  8. Modeling of solidification grain structure for Ti-45%Al alloy ingot by cellular automaton

    Institute of Scientific and Technical Information of China (English)

    WU Shi-ping; LIU Dong-rong; GUO Jing-jie; FU Heng-zhi

    2005-01-01

    A cellular automaton model for simulating grain structure formation during solidification processes of Ti45%Al(mole fraction) alloy ingot was developed, based on finite differential method for macroscopic modeling of heat transfer and a cellular automaton technique for microscopic modeling of nucleation, growth, solute redistribution and solute diffusion. The relation between the growth velocity of a dendrite tip and the local undercooling,which consists of constitutional, thermal, curvature and attachment kinetics undercooling is calculated according to the Kurz-Giovanola-Trivedi model. The effect of solidification contraction is taken into consideration. The influence of process variables upon the resultant grain structures was investigated. Special moving allocation technique was designed to minimize the computation time and memory size associated with a large number of cells. The predicted grain structures are in good agreement with the experimental results.

  9. Parallel Genetic Algorithms for calibrating Cellular Automata models: Application to lava flows

    International Nuclear Information System (INIS)

    Cellular Automata are highly nonlinear dynamical systems which are suitable far simulating natural phenomena whose behaviour may be specified in terms of local interactions. The Cellular Automata model SCIARA, developed far the simulation of lava flows, demonstrated to be able to reproduce the behaviour of Etnean events. However, in order to apply the model far the prediction of future scenarios, a thorough calibrating phase is required. This work presents the application of Genetic Algorithms, general-purpose search algorithms inspired to natural selection and genetics, far the parameters optimisation of the model SCIARA. Difficulties due to the elevated computational time suggested the adoption a Master-Slave Parallel Genetic Algorithm far the calibration of the model with respect to the 2001 Mt. Etna eruption. Results demonstrated the usefulness of the approach, both in terms of computing time and quality of performed simulations

  10. Preparation of oligodeoxynucleotide encapsulated cationic liposomes and release study with models of cellular membranes

    OpenAIRE

    Tamaddon AM.; Hosseini-Shirazi F.; Moghimi HR

    2007-01-01

    Cationic liposomes are used for cellular delivery of antisense oligodeoxynucleotide (AsODN), where release of encapsulated AsODN is mainly controlled by endocytosis and fusion mechanisms. In this investigation, it was tried to model such a release process that is difficult to evaluate in cell culture. For this purpose, an AsODN model (against protein kinase C-α) was encapsulated in a DODAP-containing cationic liposome and evaluated for size, zeta-potential, encapsulation and ODN stab...

  11. Modeling of aluminum-silicon irregular eutectic growth by cellular automaton model

    Directory of Open Access Journals (Sweden)

    Rui Chen

    2016-03-01

    Full Text Available Due to the extensive application of Al-Si alloys in the automotive and aerospace industries as structural components, an understanding of their microstructural formation, such as dendrite and (Al+Si eutectic, is of great importance to control the desirable microstructure, so as to modify the performance of castings. Since previous major themes of microstructural simulation are dendrite and regular eutectic growth, few efforts have been paid to simulate the irregular eutectic growth. Therefore, a multiphase cellular automaton (CA model is developed and applied to simulate the time-dependent Al-Si irregular eutectic growth. Prior to model establishment, related experiments were carried out to investigate the influence of cooling rate and Sr modification on the growth of eutectic Si. This CA model incorporates several aspects, including growth algorithms and nucleation criterion, to achieve the competitive and cooperative growth mechanism for nonfaceted-faceted Al-Si irregular eutectic. The growth kinetics considers thermal undercooling, constitutional undercooling, and curvature undercooling, as well as the anisotropic characteristic of eutectic Si growth. The capturing rule takes into account the effects of modification on the silicon growth behaviors. The simulated results indicate that for unmodified alloy, the higher eutectic undercooling results in the higher eutectic growth velocity, and a more refined eutectic microstructure as well as narrower eutectic lamellar spacing. For modified alloy, the eutectic silicon tends to be obvious fibrous morphology and the morphology of eutectic Si is determined by both chemical modifier and cooling rate. The predicted microstructure of Al-7Si alloy under different solidification conditions shows that this proposed model can successfully reproduce both dendrite and eutectic microstructures.

  12. GIM3E: Condition-specific Models of Cellular Metabolism Developed from Metabolomics and Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Brian; Ebrahim, Ali; Metz, Thomas O.; Adkins, Joshua N.; Palsson, Bernard O.; Hyduke, Daniel R.

    2013-11-15

    Motivation: Genome-scale metabolic models have been used extensively to investigate alterations in cellular metabolism. The accuracy of these models to represent cellular metabolism in specific conditions has been improved by constraining the model with omics data sources. However, few practical methods for integrating metabolomics data with other omics data sources into genome-scale models of metabolism have been reported. Results: GIMMME (Gene Inactivation Moderated by Metabolism, Metabolomics, and Expression) is an algorithm that enables the development of condition-specific models based on an objective function, transcriptomics, and intracellular metabolomics data. GIMMME establishes metabolite utilization requirements with metabolomics data, uses model-paired transcriptomics data to find experimentally supported solutions, and also provides calculations of the turnover (production / consumption) flux of metabolites. GIMMME was employed to investigate the effects of integrating additional omics datasets to create increasingly constrained solution spaces of Salmonella Typhimurium metabolism during growth in both rich and virulence media. This integration proved to be informative and resulted in a requirement of additional active reactions (12 in each case) or metabolites (26 or 29, respectively). The addition of constraints from transcriptomics also impacted the allowed solution space, and the cellular metabolites with turnover fluxes that were necessarily altered by the change in conditions increased from 118 to 271 of 1397. Availability: GIMMME has been implemented in Python and requires a COBRApy 0.2.x. The algorithm and sample data described here are freely available at: http://opencobra.sourceforge.net/

  13. Magneto-optical cellular chip model for intracellular orientational-dynamic-activity detection

    Science.gov (United States)

    Miyashita, Y.; Iwasaka, M.; Kurita, S.; Owada, N.

    2012-04-01

    In the present study, a magneto-optical cellular chip model (MoCCM) was developed to detect intracellular dynamics in macromolecules by using magneto-optical effects. For the purpose of cell-measurement under strong static magnetic fields of up to 10 T, we constructed a cellular chip model, which was a thin glass plate with a well for a cell culture. A cell line of osteoblast MC3T3-E1 was incubated in the glass well, and the well, 0.3 mm in depth, was sealed by a cover glass when the MoCCM was set in a fiber optic system. An initial intensity change of the polarized light transmission, which dispersed perpendicular to the cell's attaching surface, was collected for 10 to 60 min, and then magnetic fields were applied parallel and perpendicular to the surface and light direction, respectively. The magnetic birefringence signals that originated from the magnetic orientation of intracellular molecules such as cytoskeletons apparently appeared when the magnetic fields were constant at 10 T. A statistical analysis with 15 experiments confirmed that the cellular components under 10 T magnetic fields caused a stronger alignment, which was transferred into polarizing light intensity that increased more than the case before exposure. Cellular conditions such as generation and cell density affected the magnetic birefringence signals.

  14. Modeling of time-dose-LET effects in the cellular response to radiation

    International Nuclear Information System (INIS)

    This work is dedicated to the elucidation of time-dose- and if applicable linear energy transfer (LET) effects in the cellular response to ion or photon radiation. In particular, the common concept of the Local Effect Model (LEM) and the Giant Loop Binary Lesion (GLOBLE) model, which explains cell survival probabilities on the hand of clustering of double-strand breaks (DSB) in micrometer-sized sub-structural units of the DNA, was investigated with regard to temporal aspects. In previous studies with the LEM and GLOBLE model, it has been demonstrated that the definition of two lesion classes, characterized by single or multiple DSB in a DNA giant loop, with two repair fidelities is adequate to comprehensively describe the dose dependence of the cellular response to instantaneous photon irradiation or ion irradiation with varying LET. Furthermore, with the GLOBLE model for photon radiation, it has been shown that the assignment of two repair time scales to the two lesion classes allows to adequately reproduce time-dose effects after photon irradiation with an arbitrary constant dose-rate. In this work, the results of four projects that strengthen the mechanistic consistency and the practical applicability of the LEM and GLOBLE model will be presented. First, it was found that the GLOBLE model is applicable to describe time-dose effects in the cellular response to two split photon doses and in the occurrence of deterministic radiation effects. Second, in a comparison of ten models for the temporal course of DSB rejoining, it was revealed that a bi-exponential approach, as suggested by the LEM and GLOBLE model, finds a relatively large support by 61 experimental data sets. Third, in a comparison of four kinetic photon cell survival models that was based on fits to 13 dose-rate experiments, it was shown that the GLOBLE model performs well with respect to e.g. accuracy, parsimony, reliability and other factors that characterize a good approach. Last but not least, the

  15. Modeling of time-dose-LET effects in the cellular response to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Herr, Lisa Antje

    2015-07-20

    This work is dedicated to the elucidation of time-dose- and if applicable linear energy transfer (LET) effects in the cellular response to ion or photon radiation. In particular, the common concept of the Local Effect Model (LEM) and the Giant Loop Binary Lesion (GLOBLE) model, which explains cell survival probabilities on the hand of clustering of double-strand breaks (DSB) in micrometer-sized sub-structural units of the DNA, was investigated with regard to temporal aspects. In previous studies with the LEM and GLOBLE model, it has been demonstrated that the definition of two lesion classes, characterized by single or multiple DSB in a DNA giant loop, with two repair fidelities is adequate to comprehensively describe the dose dependence of the cellular response to instantaneous photon irradiation or ion irradiation with varying LET. Furthermore, with the GLOBLE model for photon radiation, it has been shown that the assignment of two repair time scales to the two lesion classes allows to adequately reproduce time-dose effects after photon irradiation with an arbitrary constant dose-rate. In this work, the results of four projects that strengthen the mechanistic consistency and the practical applicability of the LEM and GLOBLE model will be presented. First, it was found that the GLOBLE model is applicable to describe time-dose effects in the cellular response to two split photon doses and in the occurrence of deterministic radiation effects. Second, in a comparison of ten models for the temporal course of DSB rejoining, it was revealed that a bi-exponential approach, as suggested by the LEM and GLOBLE model, finds a relatively large support by 61 experimental data sets. Third, in a comparison of four kinetic photon cell survival models that was based on fits to 13 dose-rate experiments, it was shown that the GLOBLE model performs well with respect to e.g. accuracy, parsimony, reliability and other factors that characterize a good approach. Last but not least, the

  16. A Cellular Automaton Model for Tumor Dormancy: Emergence of a Proliferative Switch

    CERN Document Server

    Chen, Duyu; Torquato, Salvatore

    2014-01-01

    Malignant cancers that lead to fatal outcomes for patients may remain dormant for very long periods of time. Although individual mechanisms such as cellular dormancy, angiogenic dormancy and immunosurveillance have been proposed, a comprehensive understanding of cancer dormancy and the "switch" from a dormant to a proliferative state still needs to be strengthened from both a basic and clinical point of view. Computational modeling enables one to explore a variety of scenarios for possible but realistic microscopic dormancy mechanisms and their predicted outcomes. The aim of this paper is to devise such a predictive computational model of dormancy with an emergent "switch" behavior. Specifically, we generalize a previous cellular automaton (CA) model for proliferative growth of solid tumor that now incorporates a variety of cell-level tumor-host interactions and different mechanisms for tumor dormancy, for example the effects of the immune system. Our new CA rules induce a natural "competition" between the tu...

  17. A cellular automata traffic flow model considering the heterogeneity of acceleration and delay probability

    Science.gov (United States)

    Li, Qi-Lang; Wong, S. C.; Min, Jie; Tian, Shuo; Wang, Bing-Hong

    2016-08-01

    This study examines the cellular automata traffic flow model, which considers the heterogeneity of vehicle acceleration and the delay probability of vehicles. Computer simulations are used to identify three typical phases in the model: free-flow, synchronized flow, and wide moving traffic jam. In the synchronized flow region of the fundamental diagram, the low and high velocity vehicles compete with each other and play an important role in the evolution of the system. The analysis shows that there are two types of bistable phases. However, in the original Nagel and Schreckenberg cellular automata traffic model, there are only two kinds of traffic conditions, namely, free-flow and traffic jams. The synchronized flow phase and bistable phase have not been found.

  18. An Extended Cellular Automaton Model for Train Traffic Flow on the Dedicated Passenger Lines

    Directory of Open Access Journals (Sweden)

    Wenbo Zhao

    2014-01-01

    Full Text Available As one of the key components for the railway transportation system, the Train Operation Diagram can be greatly influenced by many extrinsic and intrinsic factors. Therefore, the railway train flow has shown the strong nonlinear characteristics, which makes it quite difficult to take further relative studies. Fortunately, the cellular automaton model has its own advantages in solving nonlinear problems and traffic flow simulation. Considering the mixed features of multispeed running trains on the passenger dedicated lines, this paper presents a new train model under the moving block system with different types of trains running with the cellular automaton idea. By analyzing such key factors as the maintenance skylight, the proportion of the multispeed running trains, and the distance between adjacent stations and departure intervals, the corresponding running rules for the cellular automaton model are reestablished herewith. By means of this CA model, the program of train running system is designed to analyze the potential impact on railway carrying capacity by various factors; the model can also be implemented to simulate the actual train running process and to draw the train operation diagram by computers. Basically the theory can be applied to organize the train operation on the dedicated passenger lines.

  19. A generalized cellular automata approach to modeling first order enzyme kinetics

    Indian Academy of Sciences (India)

    Abhishek Dutta; Saurajyoti Kar; Advait Apte; Ingmar Nopens; Denis Constales

    2015-04-01

    Biochemical processes occur through intermediate steps which are associated with the formation of reaction complexes. These enzyme-catalyzed biochemical reactions are inhibited in a number of ways such as inhibitors competing for the binding site directly, inhibitors deforming the allosteric site or inhibitors changing the structure of active substrate. Using an in silico approach, the concentration of various reaction agents can be monitored at every single time step, which are otherwise difficult to analyze experimentally. Cell-based models with discrete state variables, such as Cellular Automata (CA) provide an understanding of the organizational principles of interacting cellular systems to link the individual cell (microscopic) dynamics wit a particular collective (macroscopic) phenomenon. In this study, a CA model representing a first order enzyme kinetics with inhibitor activity is formulated. The framework of enzyme reaction rules described in this study is probabilistic. An extended von Neumann neighborhood with periodic boundary condition is implemented on a two-dimensional (2D) lattice framework. The effect of lattice-size variation is studied followed by a sensitivity analysis of the model output to the probabilistic parameters which represent various kinetic reaction constants in the enzyme kinetic model. This provides a deeper insight into the sensitivity of the CA model to these parameters. It is observed that cellular automata can capture the essential features of a discrete real system, consisting of space, time and state, structured with simple local rules without making complex implementations but resulting in complex but explainable patterns.

  20. In Silico Modeling of the Immune System: Cellular and Molecular Scale Approaches

    Directory of Open Access Journals (Sweden)

    Mariagrazia Belfiore

    2014-01-01

    Full Text Available The revolutions in biotechnology and information technology have produced clinical data, which complement biological data. These data enable detailed descriptions of various healthy and diseased states and responses to therapies. For the investigation of the physiology and pathology of the immune responses, computer and mathematical models have been used in the last decades, enabling the representation of biological processes. In this modeling effort, a major issue is represented by the communication between models that work at cellular and molecular level, that is, multiscale representation. Here we sketch some attempts to model immune system dynamics at both levels.

  1. A Stochastic Cellular Automaton Model of Non-linear Diffusion and Diffusion with Reaction

    Science.gov (United States)

    Brieger, Leesa M.; Bonomi, Ernesto

    1991-06-01

    This article presents a stochastic cellular automaton model of diffusion and diffusion with reaction. The master equations for the model are examined, and we assess the difference between the implementation in which a single particle at a time moves (asynchronous dynamics) and one implementation in which all particles move simultaneously (synchronous dynamics). Biasing locally each particle's random walk, we alter the diffusion coefficients of the system. By appropriately choosing the biasing function, we can impose a desired non-linear diffusive behaviour in the model. We present an application of this model, adapted to include two diffusing species, two static species, and a chemical reaction in a prototypical simulation of carbonation in concrete.

  2. 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

  3. A Geometrical-Based Model for Cochannel Interference Analysis and Capacity Estimation of CDMA Cellular Systems

    Directory of Open Access Journals (Sweden)

    Konstantinos B. Baltzis

    2008-10-01

    Full Text Available A common assumption in cellular communications is the circular-cell approximation. In this paper, an alternative analysis based on the hexagonal shape of the cells is presented. A geometrical-based stochastic model is proposed to describe the angle of arrival of the interfering signals in the reverse link of a cellular system. Explicit closed form expressions are derived, and simulations performed exhibit the characteristics and validate the accuracy of the proposed model. Applications in the capacity estimation of WCDMA cellular networks are presented. Dependence of system capacity of the sectorization of the cells and the base station antenna radiation pattern is explored. Comparisons with data in literature validate the accuracy of the proposed model. The degree of error of the hexagonal and the circular-cell approaches has been investigated indicating the validity of the proposed model. Results have also shown that, in many cases, the two approaches give similar results when the radius of the circle equals to the hexagon inradius. A brief discussion on how the proposed technique may be applied to broadband access networks is finally made.

  4. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    Directory of Open Access Journals (Sweden)

    Hui Guo

    2016-07-01

    Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

  5. Analysis on Traffic Conflicts of Two-lane Highway Based on Improved Cellular Automation Model

    Directory of Open Access Journals (Sweden)

    Xiru Tang

    2013-06-01

    Full Text Available Based on microscopic traffic characteristics of two-lane highway and different driving characteristics for drivers, the characteristics of drivers and vehicle structure are introduced into Cellular Automation model for establishing new Cellular Automation model of two-lane highway. Through computer simulation, the paper analyzes the effect of the promotion of different vehicles, drivers and arrival rates on traffic conflicts of two-lane highway, which gets the relationship between the parameters such as road traffic and velocity variance and collision. The results indicate that the frequency of traffic conflicts has close relationship with the product of traffic flow and velocity variation. When the traffic flow and velocity variation are great, the frequency of the conflict is the greatest, and when the traffic flow and velocity variation are little, the frequency of the conflict is the least.

  6. Bit-Vectorized GPU Implementation of a Stochastic Cellular Automaton Model for Surface Growth

    CERN Document Server

    Kelling, Jeffrey; Gemming, Sibylle

    2016-01-01

    Stochastic surface growth models aid in studying properties of universality classes like the Kardar--Paris--Zhang class. High precision results obtained from large scale computational studies can be transferred to many physical systems. Many properties, such as roughening and some two-time functions can be studied using stochastic cellular automaton (SCA) variants of stochastic models. Here we present a highly efficient SCA implementation of a surface growth model capable of simulating billions of lattice sites on a single GPU. We also provide insight into cases requiring arbitrary random probabilities which are not accessible through bit-vectorization.

  7. Transfer-matrix DMRG for stochastic models: The Domany-Kinzel cellular automaton

    OpenAIRE

    Kemper, A.; Schadschneider, A.; Zittartz, J.

    2001-01-01

    We apply the transfer-matrix DMRG (TMRG) to a stochastic model, the Domany-Kinzel cellular automaton, which exhibits a non-equilibrium phase transition in the directed percolation universality class. Estimates for the stochastic time evolution, phase boundaries and critical exponents can be obtained with high precision. This is possible using only modest numerical effort since the thermodynamic limit can be taken analytically in our approach. We also point out further advantages of the TMRG o...

  8. An Exact Path-Loss Density Model for Mobiles in a Cellular System

    OpenAIRE

    Abdulla, Mouhamed; Shayan, Yousef R.

    2013-01-01

    In trying to emulate the spatial position of wireless nodes for purpose of analysis, we rely on stochastic simulation. And, it is customary, for mobile systems, to consider a base-station radiation coverage by an ideal cell shape. For cellular analysis, a hexagon contour is always preferred mainly because of its tessellating nature. Despite this fact, largely due to its intrinsic simplicity, in literature only random dispersion model for a circular shape is known. However, if considered, this...

  9. A Novel Mathematical Model Describing Adaptive Cellular Drug Metabolism and Toxicity in the Chemoimmune System

    OpenAIRE

    Tóth, Attila; Brózik, Anna; Szakács, Gergely; Sarkadi, Balázs; Hegedüs, Tamás

    2015-01-01

    Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This “chemoimmune system” consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC) membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on d...

  10. Embedding reach-scale fluvial dynamics within the CAESAR cellular automaton landscape evolution model

    Science.gov (United States)

    Van De Wiel, Marco J.; Coulthard, Tom J.; Macklin, Mark G.; Lewin, John

    2007-10-01

    We introduce a new computational model designed to simulate and investigate reach-scale alluvial dynamics within a landscape evolution model. The model is based on the cellular automaton concept, whereby the continued iteration of a series of local process 'rules' governs the behaviour of the entire system. The model is a modified version of the CAESAR landscape evolution model, which applies a suite of physically based rules to simulate the entrainment, transport and deposition of sediments. The CAESAR model has been altered to improve the representation of hydraulic and geomorphic processes in an alluvial environment. In-channel and overbank flow, sediment entrainment and deposition, suspended load and bed load transport, lateral erosion and bank failure have all been represented as local cellular automaton rules. Although these rules are relatively simple and straightforward, their combined and repeatedly iterated effect is such that complex, non-linear geomorphological response can be simulated within the model. Examples of such larger-scale, emergent responses include channel incision and aggradation, terrace formation, channel migration and river meandering, formation of meander cutoffs, and transitions between braided and single-thread channel patterns. In the current study, the model is illustrated on a reach of the River Teifi, near Lampeter, Wales, UK.

  11. Developing land use scenario dynamics model by the integration of system dynamics model and cellular automata model

    Institute of Scientific and Technical Information of China (English)

    HE; Chunyang; SHI; Peijun; CHEN; Jin; Li; Xiaobing; PAN; Ya

    2005-01-01

    Modeling land use scenario changes and its potential impacts on the structure and function of the ecosystem in the typical regions are helpful to understanding the interactive mechanism between land use system and ecological system. A Land Use Scenario Dynamics (LUSD) model by the integration of System Dynamics (SD) model and Cellular Automata (CA) model is developed with land use scenario changes in northern China in the next 20 years simulated in this paper. The basic idea of LUSD model is to simulate the land use scenario demands by using SD model at first, then allocate the land use scenario patterns at the local scale with the considerations of land use suitability, inheritance ability and neighborhood effect by using CA model to satisfy the balance between land use scenario demands and supply. The application of LUSD model in northern China suggests that the model has the ability to reflect the complex behavior of land use system at different scales to some extent and is a useful tool for assessing the potential impacts of land use system on ecological system. In addition, the simulated results also indicate that obvious land use changes will take place in the farming-pastoral zone of northern China in the next 20 years with cultivated land and urban land being the most active land use types.

  12. Modeling of trophospheric ozone concentrations using genetically trained multi-level cellular neural networks

    Science.gov (United States)

    Ozcan, H. Kurtulus; Bilgili, Erdem; Sahin, Ulku; Ucan, O. Nuri; Bayat, Cuma

    2007-09-01

    Tropospheric ozone concentrations, which are an important air pollutant, are modeled by the use of an artificial intelligence structure. Data obtained from air pollution measurement stations in the city of Istanbul are utilized in constituting the model. A supervised algorithm for the evaluation of ozone concentration using a genetically trained multi-level cellular neural network (ML-CNN) is introduced, developed, and applied to real data. A genetic algorithm is used in the optimization of CNN templates. The model results and the actual measurement results are compared and statistically evaluated. It is observed that seasonal changes in ozone concentrations are reflected effectively by the concentrations estimated by the multilevel-CNN model structure, with a correlation value of 0.57 ascertained between actual and model results. It is shown that the multilevel-CNN modeling technique is as satisfactory as other modeling techniques in associating the data in a complex medium in air pollution applications.

  13. Modeling of Trophospheric Ozone Concentrations Using Genetically Trained Multi-Level Cellular Neural Networks

    Institute of Scientific and Technical Information of China (English)

    H. Kurtulus OZCAN; Erdem BILGILI; Ulku SAHIN; O. Nuri UCAN; Cuma BAYAT

    2007-01-01

    Tropospheric ozone concentrations, which are an important air pollutant, are modeled by the use of an artificial intelligence structure. Data obtained from air pollution measurement stations in the city of Istanbul are utilized in constituting the model. A supervised algorithm for the evaluation of ozone concentration using a genetically trained multi-level cellular neural network (ML-CNN) is introduced, developed, and applied to real data. A genetic algorithm is used in the optimization of CNN templates. The model results and the actual measurement results are compared and statistically evaluated. It is observed that seasonal changes in ozone concentrations are reflected effectively by the concentrations estimated by the multilevel-CNN model structure, with a correlation value of 0.57 ascertained between actual and model results. It is shown that the multilevel-CNN modeling technique is as satisfactory as other modeling techniques in associating the data in a complex medium in air pollution applications.

  14. CDH1 and IL1-beta expression dictates FAK and MAPKK-dependent cross-talk between cancer cells and human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Al-toub, Mashael; Vishnubalaji, Radhakrishnan; Hamam, Rimi;

    2015-01-01

    : (MCF7, BT-20, BT-474, MDA-MB-468, T-47D, SK-BR-3, MDA-MB-231, PC-3, HT-29, MDA-MB-435s, and FaDu) and changes in their morphology were assessed using fluorescent microscopy. For cellular tracking, cells were labeled with Vybrant DiO, DiL, and DiD lipophilic dyes. Time-lapse microscopy was conducted...... signaling pathways related to bone formation, FAK and MAPKK signaling. Co-culturing hMSCs with MCF7 cells increased their growth evidenced by increase in Ki67 and PCNA staining in tumor cells in direct contact with hMSCs niche. On the other hand, co-culturing hMSCs with FaDu, HT-29 or MDA-MB-231 cells led...

  15. An improved multi-value cellular automata model for heterogeneous bicycle traffic flow

    International Nuclear Information System (INIS)

    This letter develops an improved multi-value cellular automata model for heterogeneous bicycle traffic flow taking the higher maximum speed of electric bicycles into consideration. The update rules of both regular and electric bicycles are improved, with maximum speeds of two and three cells per second respectively. Numerical simulation results for deterministic and stochastic cases are obtained. The fundamental diagrams and multiple states effects under different model parameters are analyzed and discussed. Field observations were made to calibrate the slowdown probabilities. The results imply that the improved extended Burgers cellular automata (IEBCA) model is more consistent with the field observations than previous models and greatly enhances the realism of the bicycle traffic model. - Highlights: • We proposed an improved multi-value CA model with higher maximum speed. • Update rules are introduced for heterogeneous bicycle traffic with maximum speed 2 and 3 cells/s. • Simulation results of the proposed model are consistent with field bicycle data. • Slowdown probabilities of both regular and electric bicycles are calibrated

  16. An improved multi-value cellular automata model for heterogeneous bicycle traffic flow

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Sheng [College of Civil Engineering and Architecture, Zhejiang University, Hangzhou, 310058 China (China); Qu, Xiaobo [Griffith School of Engineering, Griffith University, Gold Coast, 4222 Australia (Australia); Xu, Cheng [Department of Transportation Management Engineering, Zhejiang Police College, Hangzhou, 310053 China (China); College of Transportation, Jilin University, Changchun, 130022 China (China); Ma, Dongfang, E-mail: mdf2004@zju.edu.cn [Ocean College, Zhejiang University, Hangzhou, 310058 China (China); Wang, Dianhai [College of Civil Engineering and Architecture, Zhejiang University, Hangzhou, 310058 China (China)

    2015-10-16

    This letter develops an improved multi-value cellular automata model for heterogeneous bicycle traffic flow taking the higher maximum speed of electric bicycles into consideration. The update rules of both regular and electric bicycles are improved, with maximum speeds of two and three cells per second respectively. Numerical simulation results for deterministic and stochastic cases are obtained. The fundamental diagrams and multiple states effects under different model parameters are analyzed and discussed. Field observations were made to calibrate the slowdown probabilities. The results imply that the improved extended Burgers cellular automata (IEBCA) model is more consistent with the field observations than previous models and greatly enhances the realism of the bicycle traffic model. - Highlights: • We proposed an improved multi-value CA model with higher maximum speed. • Update rules are introduced for heterogeneous bicycle traffic with maximum speed 2 and 3 cells/s. • Simulation results of the proposed model are consistent with field bicycle data. • Slowdown probabilities of both regular and electric bicycles are calibrated.

  17. Modelling land-use effects of future urbanization using cellular automata

    DEFF Research Database (Denmark)

    Fuglsang, Morten; Münier, B.; Hansen, H.S.

    2013-01-01

    The modelling of land use change is a way to analyse future scenarios by modelling different pathways. Application of spatial data of different scales coupled with socio-economic data makes it possible to explore and test the understanding of land use change relations. In the EU-FP7 research...... project PASHMINA (Paradigm Shift modelling and innovative approaches), three storylines of future transportation paradigm shifts towards 2040 are created. These storylines are translated into spatial planning strategies and modelled using the cellular automata model LUCIA. For the modelling, an Eastern...... Danish case area was selected, comprising of the Copenhagen metropolitan area and its hinterland. The different scenarios are described using a range of different descriptive GIS datasets. These include mapping of accessibility based on public and private transportation, urban density and structure, and...

  18. Guided Inquiry and Consensus-Building Used to Construct Cellular Models

    Directory of Open Access Journals (Sweden)

    Joel I. Cohen

    2015-02-01

    Full Text Available Using models helps students learn from a “whole systems” perspective when studying the cell. This paper describes a model that employs guided inquiry and requires consensus building among students for its completion. The model is interactive, meaning that it expands upon a static model which, once completed, cannot be altered and additionally relates various levels of biological organization (molecular, organelle, and cellular to define cell and organelle function and interaction. Learning goals are assessed using data summed from final grades and from images of the student’s final cell model (plant, bacteria, and yeast taken from diverse seventh grade classes. Instructional figures showing consensus-building pathways and seating arrangements are discussed. Results suggest that the model leads to a high rate of participation, facilitates guided inquiry, and fosters group and individual exploration by challenging student understanding of the living cell.

  19. CELLULAR AUTOMATA MODELLING OF GRAIN COARSENING DURING REIHEATING AND VALIDATION WITH THE EXPERIMENTAL RESULTS

    Institute of Scientific and Technical Information of China (English)

    W.H. Yu; E.J. Palmiere; S.P. Banks; J.T. Han

    2005-01-01

    A novel 2D cellular automata (CA) model has been developed for description of normal grain coarsening and abnormal grain coarsening process. The program reflects the grain coarsening quite well even through the average grain size becomes very large. Follow results have been obtained: (a) The model reflect the normal grain growth kinetics gradually increase with probability and grain growth speed can be controlled. Based on this result, temperature can be coupled in the model. (b) Abnormal grain growth is modelled successfully. (c) Methodology has been put forward to find the relationship between the experiment results and modelling results. The experimental work on the grain coarsening has been carried out. Graphical output matched the realistic microstructure in every detail. Because many physical parameters can be taken into account in the CA programme, this CA model could not only qualitatively demonstrate the grain growth process, but also quantitatively predict and analyse the grain coarsening process.

  20. Random walk theory of jamming in a cellular automaton model for traffic flow

    Science.gov (United States)

    Barlovic, Robert; Schadschneider, Andreas; Schreckenberg, Michael

    2001-05-01

    The jamming behavior of a single lane traffic model based on a cellular automaton approach is studied. Our investigations concentrate on the so-called VDR model which is a simple generalization of the well-known Nagel-Schreckenberg model. In the VDR model one finds a separation between a free flow phase and jammed vehicles. This phase separation allows to use random walk like arguments to predict the resolving probabilities and lifetimes of jam clusters or disturbances. These predictions are in good agreement with the results of computer simulations and even become exact for a special case of the model. Our findings allow a deeper insight into the dynamics of wide jams occuring in the model.

  1. Predictive modeling of multicellular structure formation by using Cellular Particle Dynamics simulations

    Science.gov (United States)

    McCune, Matthew; Shafiee, Ashkan; Forgacs, Gabor; Kosztin, Ioan

    2014-03-01

    Cellular Particle Dynamics (CPD) is an effective computational method for describing and predicting the time evolution of biomechanical relaxation processes of multicellular systems. A typical example is the fusion of spheroidal bioink particles during post bioprinting structure formation. In CPD cells are modeled as an ensemble of cellular particles (CPs) that interact via short-range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through integration of their equations of motion. CPD was successfully applied to describe and predict the fusion of 3D tissue construct involving identical spherical aggregates. Here, we demonstrate that CPD can also predict tissue formation involving uneven spherical aggregates whose volumes decrease during the fusion process. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

  2. Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid

    Directory of Open Access Journals (Sweden)

    Keith L. Black

    2012-09-01

    Full Text Available Doxorubicin (DOX is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β-L-malic acid (PMLA. DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.

  3. A Cellular Automaton Model for Heterogeneous and Incosistent Driver Behavior in Urban Traffic

    Science.gov (United States)

    Liu, Ming-Zhe; Zhao, Shi-Bo; Wang, Rui-Li

    2012-11-01

    In this paper a cellular automaton model is proposed to describe driver behavior at a single-lane urban roundabout. Driver behavior has been considered as heterogeneous and inconsistent. Most traffic papers in the literature just discussed heterogeneous driver behavior, to our best knowledge. Two truncated Gaussian distributions are used to model heterogeneous and inconsistent driver behavior, respectively. The physical meanings of two truncated distributions are indicated. This method may help enhance a better understanding of driver behavior at roundabout traffic, and even possibly provide references for roundabout design and management.

  4. Two-dimensional cellular automaton model for simulating structural evolution of binary alloys during solidification

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lin; ZHANG Cai-bei

    2006-01-01

    Two-dimensional cellular automaton(CA) simulations of phase transformations of binary alloys during solidification were reported. The modelling incorporates local concentration and heat changes into a nucleation or growth function, which is utilized by the automaton in a probabilistic fashion. These simulations may provide an efficient method of discovering how the physical processes involved in solidification processes dynamically progress and how they interact with each other during solidification. The simulated results show that the final morphology during solidification is related with the cooling conditions. The established model can be used to evaluate the phase transformation of binary alloys during solidification.

  5. A Cellular Automaton Model for Heterogeneous and Incosistent Driver Behavior in Urban Traffic

    Institute of Scientific and Technical Information of China (English)

    LIUMing-Zhe; ZHAO Shi-Bo; WANG Rui-Li

    2012-01-01

    In this paper a cellular automaton model is proposed to describe driver behavior at a single-lane urban roundabout. Driver behavior has been considered as heterogeneous and inconsistent. Most traffic papers in the literature just discussed heterogeneous driver behavior, to our best knowledge. Two truncated Caussian distributions are used to model heterogeneous and inconsistent driver behavior, respectively. The physical meanings of two truncated distributions are indicated. This method may help enhance a better understanding of driver behavior at roundabout traffic, and even possibly provide references for roundabout design and management.

  6. Modeling Mixed Bicycle Traffic Flow: A Comparative Study on the Cellular Automata Approach

    Directory of Open Access Journals (Sweden)

    Dan Zhou

    2015-01-01

    Full Text Available Simulation, as a powerful tool for evaluating transportation systems, has been widely used in transportation planning, management, and operations. Most of the simulation models are focused on motorized vehicles, and the modeling of nonmotorized vehicles is ignored. The cellular automata (CA model is a very important simulation approach and is widely used for motorized vehicle traffic. The Nagel-Schreckenberg (NS CA model and the multivalue CA (M-CA model are two categories of CA model that have been used in previous studies on bicycle traffic flow. This paper improves on these two CA models and also compares their characteristics. It introduces a two-lane NS CA model and M-CA model for both regular bicycles (RBs and electric bicycles (EBs. In the research for this paper, many cases, featuring different values for the slowing down probability, lane-changing probability, and proportion of EBs, were simulated, while the fundamental diagrams and capacities of the proposed models were analyzed and compared between the two models. Field data were collected for the evaluation of the two models. The results show that the M-CA model exhibits more stable performance than the two-lane NS model and provides results that are closer to real bicycle traffic.

  7. 2D cellular automaton model for the evolution of active region coronal plasmas

    CERN Document Server

    Fuentes, Marcelo López

    2016-01-01

    We study a 2D cellular automaton (CA) model for the evolution of coronal loop plasmas. The model is based on the idea that coronal loops are made of elementary magnetic strands that are tangled and stressed by the displacement of their footpoints by photospheric motions. The magnetic stress accumulated between neighbor strands is released in sudden reconnection events or nanoflares that heat the plasma. We combine the CA model with the Enthalpy Based Thermal Evolution of Loops (EBTEL) model to compute the response of the plasma to the heating events. Using the known response of the XRT telescope on board Hinode we also obtain synthetic data. The model obeys easy to understand scaling laws relating the output (nanoflare energy, temperature, density, intensity) to the input parameters (field strength, strand length, critical misalignment angle). The nanoflares have a power-law distribution with a universal slope of -2.5, independent of the input parameters. The repetition frequency of nanoflares, expressed in t...

  8. Numerical study on photoresist etching processes based on a cellular automata model

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    For the three-dimensional (3-D) numerical study of photoresist etching processes, the 2-D dynamic cellular automata (CA) model has been successfully extended to a 3-D dynamic CA model. Only the boundary cells will be processed in the 3-D dy-namic CA model and the structure of “if-else” description in the simulation pro-gram is avoided to speed up the simulation. The 3-D dynamic CA model has found to be stable, fast and accurate for the numerical study of photoresist etching processes. The exposure simulation, post-exposure bake (PEB) simulation and etching simulation are integrated together to further investigate the performances of the CA model. Simulation results have been compared with the available ex-perimental results and the simulations show good agreement with the available experiments.

  9. Numerical study on photoresist etching processes based on a cellular automata model

    Institute of Scientific and Technical Information of China (English)

    ZHOU ZaiFa; HUANG QingAn; LI WeiHua; LU Wei

    2007-01-01

    For the three-dimensional (3-D) numerical study of photoresist etching processes, the 2-D dynamic cellular automata (CA) model has been successfully extended to a 3-D dynamic CA model. Only the boundary cells will be processed in the 3-D dynamic CA model and the structure of "if-else" description in the simulation program is avoided to speed up the simulation. The 3-D dynamic CA model has found to be stable, fast and accurate for the numerical study of photoresist etching processes. The exposure simulation, post-exposure bake (PEB) simulation and etching simulation are integrated together to further investigate the performances of the CA model. Simulation results have been compared with the available experimental results and the simulations show good agreement with the available experiments.

  10. A traffic flow cellular automaton model to considering drivers' learning and forgetting behaviour

    Institute of Scientific and Technical Information of China (English)

    Ding Jian-Xun; Huang Hai-Jun; Tian Qiong

    2011-01-01

    It is known that the commonly used NaSch cellular automaton (CA) model and its modifications can help explain the internal causes of the macro phenomena of traffic flow. However, the randomization probability of vehicle velocity used in these models is assumed to be an exogenous constant or a conditional constant, which cannot reflect the learning and forgetting behaviour of drivers with historical experiences. This paper further modifies the NaSch model by enabling the randomization probability to be adjusted on the bases of drivers' memory. The Markov properties of this modified model are discussed. Analytical and simulation results show that the traffic fundamental diagrams can be indeed improved when considering drivers' intelligent behaviour. Some new features of traffic are revealed by differently combining the model parameters representing learning and forgetting behaviour.

  11. A novel mathematical model describing adaptive cellular drug metabolism and toxicity in the chemoimmune system.

    Directory of Open Access Journals (Sweden)

    Attila Tóth

    Full Text Available Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This "chemoimmune system" consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on differential equations describing Phase 0-III participants and regulatory elements, and characterized cellular fitness to evaluate toxicity. In spite of the simplifications, the model recapitulates changes associated with acquired drug resistance and allows toxicity predictions under variable protein expression and xenobiotic exposure conditions. Our simulations suggest that multidrug ABC transporters at Phase 0 significantly facilitate the defense function of successive network members by lowering intracellular drug concentrations. The model was extended with a novel toxicity framework which opened the possibility of performing in silico cytotoxicity assays. The alterations of the in silico cytotoxicity curves show good agreement with in vitro cell killing experiments. The behavior of the simplified kinetic model suggests that it can serve as a basis for more complex models to efficiently predict xenobiotic and drug metabolism for human medical applications.

  12. Calibrating Cellular Automata of Land Use/cover Change Models Using a Genetic Algorithm

    Science.gov (United States)

    Mas, J. F.; Soares-Filho, B.; Rodrigues, H.

    2015-08-01

    Spatially explicit land use / land cover (LUCC) models aim at simulating the patterns of change on the landscape. In order to simulate landscape structure, the simulation procedures of most computational LUCC models use a cellular automata to replicate the land use / cover patches. Generally, model evaluation is based on assessing the location of the simulated changes in comparison to the true locations but landscapes metrics can also be used to assess landscape structure. As model complexity increases, the need to improve calibration and assessment techniques also increases. In this study, we applied a genetic algorithm tool to optimize cellular automata's parameters to simulate deforestation in a region of the Brazilian Amazon. We found that the genetic algorithm was able to calibrate the model to simulate more realistic landscape in term of connectivity. Results show also that more realistic simulated landscapes are often obtained at the expense of the location coincidence. However, when considering processes such as the fragmentation impacts on biodiversity, the simulation of more realistic landscape structure should be preferred to spatial coincidence performance.

  13. A general allometric and life-history model for cellular differentiation in the transition to multicellularity.

    Science.gov (United States)

    Solari, Cristian A; Kessler, John O; Goldstein, Raymond E

    2013-03-01

    The transition from unicellular, to colonial, to larger multicellular organisms has benefits, costs, and requirements. Here we present a model inspired by the volvocine green algae that explains the dynamics involved in the unicellular-multicellular transition using life-history theory and allometry. We model the two fitness components (fecundity and viability) and compare the fitness of hypothetical colonies of different sizes with varying degrees of cellular differentiation to understand the general principles that underlie the evolution of multicellularity. We argue that germ-soma separation may have evolved to counteract the increasing costs and requirements of larger multicellular colonies. The model shows that the cost of investing in soma decreases with size. For lineages such as the Volvocales, as reproduction costs increase with size for undifferentiated colonies, soma specialization benefits the colony indirectly by decreasing such costs and directly by helping reproductive cells acquire resources for their metabolic needs. Germ specialization is favored once soma evolves and takes care of vegetative functions. To illustrate the model, we use some allometric relationships measured in Volvocales. Our analysis shows that the cost of reproducing an increasingly larger group has likely played an important role in the transition to multicellularity and cellular differentiation. PMID:23448886

  14. Simulation of emotional contagion using modified SIR model: A cellular automaton approach

    Science.gov (United States)

    Fu, Libi; Song, Weiguo; Lv, Wei; Lo, Siuming

    2014-07-01

    Emotion plays an important role in the decision-making of individuals in some emergency situations. The contagion of emotion may induce either normal or abnormal consolidated crowd behavior. This paper aims to simulate the dynamics of emotional contagion among crowds by modifying the epidemiological SIR model to a cellular automaton approach. This new cellular automaton model, entitled the “CA-SIRS model”, captures the dynamic process ‘susceptible-infected-recovered-susceptible', which is based on SIRS contagion in epidemiological theory. Moreover, in this new model, the process is integrated with individual movement. The simulation results of this model show that multiple waves and dynamical stability around a mean value will appear during emotion spreading. It was found that the proportion of initial infected individuals had little influence on the final stable proportion of infected population in a given system, and that infection frequency increased with an increase in the average crowd density. Our results further suggest that individual movement accelerates the spread speed of emotion and increases the stable proportion of infected population. Furthermore, decreasing the duration of an infection and the probability of reinfection can markedly reduce the number of infected individuals. It is hoped that this study will be helpful in crowd management and evacuation organization.

  15. Non-linearity and spatial resolution in a cellular automaton model of a small upland basin

    Directory of Open Access Journals (Sweden)

    T. J. Coulthard

    1998-01-01

    Full Text Available The continuing development of computational fluid dynamics is allowing the high resolution study of hydraulic and sediment transport processes but, due to computational complexities, these are rarely applied to areas larger than a reach. Existing approaches, based upon linked cross sections, can give a quasi two-dimensional view, effectively simulating sediment transport for a single river reach. However, a basin represents a whole discrete dynamic system within which channel, floodplain and slope processes operate over a wide range of space and time scales. Here, a cellular automaton (CA approach has been used to overcome some of these difficulties, in which the landscape is represented as a series of fixed size cells. For every model iteration, each cell acts only in relation to the influence of its immediate neighbours in accordance with appropriate rules. The model presented here takes approximations of existing flow and sediment transport equations, and integrates them, together with slope and floodplain approximations, within a cellular automaton framework. This method has been applied to the basin of Cam Gill Beck (4.2 km2 above Starbotton, upper Wharfedale, a tributary of the River Wharfe, North Yorkshire, UK. This approach provides, for the first time, a workable model of the whole basin at a 1 m resolution. Preliminary results show the evolution of bars, braids, terraces and alluvial fans which are similar to those observed in the field, and examples of large and small scale non-linear behaviour which may have considerable implications for future models.

  16. Advanced spatial metrics analysis in cellular automata land use and cover change modeling

    International Nuclear Information System (INIS)

    This paper proposes an approach for a more effective definition of cellular automata transition rules for landscape change modeling using an advanced spatial metrics analysis. This approach considers a four-stage methodology based on: (i) the search for the appropriate spatial metrics with minimal correlations; (ii) the selection of the appropriate neighborhood size; (iii) the selection of the appropriate technique for spatial metrics application; and (iv) the analysis of the contribution level of each spatial metric for joint use. The case study uses an initial set of 7 spatial metrics of which 4 are selected for modeling. Results show a better model performance when compared to modeling without any spatial metrics or with the initial set of 7 metrics.

  17. Empirical results for pedestrian dynamics and their implications for cellular automata models

    CERN Document Server

    Schadschneider, Andreas

    2010-01-01

    A large number of models for pedestrian dynamics have been developed over the years. However, so far not much attention has been paid to their quantitative validation. Usually the focus is on the reproduction of empirically observed collective phenomena, as lane formation in counterflow. This can give an indication for the realism of the model, but practical applications, e.g. in safety analysis, require quantitative predictions. We discuss the current experimental situation, especially for the fundamental diagram which is the most important quantity needed for calibration. In addition we consider the implications for the modelling based on cellular automata. As specific example the floor field model is introduced. Apart from the properties of its fundamental diagram we discuss the implications of an egress experiment for the relevance of conflicts and friction effects.

  18. A new three-step cellular automaton model considering a realistic driving decision

    International Nuclear Information System (INIS)

    Most cellular automaton (CA) traffic flow models include four steps and take the velocity as the driver’s main concern. To better understand traffic behaviors, a new three-step CA model is studied, in which a realistic driving decision is divided into three stages: decision-making, action and result. The new model is novel in using the acceleration as a decision variable. It considers the deceleration limitation and proposes the maximum deceleration to be 2 cells per time step, based on real experimental data. Simulation results show that the model can reproduce the synchronized flow effectively and describe the phase transition well. Moreover, it can exhibit metastability and hysteresis if the slow-to-start effect is involved. Finally, a realistic application to systematic flow optimization is analyzed and an interesting result is obtained that a restriction of the inflow can lead to an improvement of the total flow through a bottleneck. (paper)

  19. Modelling of Eutectic Saturation Influence on Microstructure in Thin Wall Ductile Iron Casting Using Cellular Automata

    Directory of Open Access Journals (Sweden)

    M. Górny

    2012-12-01

    Full Text Available The mathematical model of the globular eutectic solidification in 2D was designed. Proposed model is based on the Cellular AutomatonFinite Differences (CA-FD calculation method. Model has been used for studies of the primary austenite and of globular eutectic grainsgrowth during the ductile iron solidification in the thin wall casting. Model takes into account, among other things, non-uniformtemperature distribution in the casting wall cross-section, kinetics of the austenite and graphite grains nucleation, and non-equilibriumnature of the interphase boundary migration. Calculation of eutectic saturation influence (Sc = 0.9 - 1.1 on microstructure (austenite and graphite fraction, density of austenite and graphite grains and temperature curves in 2 mm wall ductile iron casting has been done.

  20. Cellular-automata model of the dwarf shrubs populations and communities dynamics

    Directory of Open Access Journals (Sweden)

    A. S. Komarov

    2015-06-01

    Full Text Available The probabilistic cellular-automata model of development and long-time dynamics of dwarf shrub populations and communities is developed. It is based on the concept of discrete description of the plant ontogenesis and joint model approaches in terms of probabilistic cellular automata and L-systems by Lindenmayer. Short representation of the basic model allows evaluation of the approach and software implementation. The main variables of the model are a number of partial bushes in clones or area projective cover. The model allows us to investigate the conditions of self-maintenance and sustainability population under different environmental conditions (inaccessibility of the territory for settlement, mosaic moisture conditions of soil and wealth. The model provides a forecast of the total biomass dynamics shrubs and their fractions (stems, leaves, roots, fine roots, fruits on the basis of the data obtained in the discrete description of ontogenesis and further information on the productivity of the plant fractions. The inclusion of the joint dynamics of biomass of shrubs and soil in EFIMOD models cycle of carbon and nitrogen to evaluate the role of shrubs in these circulations, especially at high impact, such as forest fires and clear cutting, allow forecasting of the dynamics of populations and ecosystem functions of shrubs (regulation of biogeochemical cycles maintaining biodiversity, participation in the creation of non-wood products with changing climatic conditions and strong damaging effects (logging, fires; and application of the models developed to investigate the stability and productivity of shrubs and their participation in the cycle of carbon and nitrogen in different climatic and edaphic conditions.

  1. Cellular automata model based on GIS and urban sprawl dynamics simulation

    Science.gov (United States)

    Mu, Fengyun; Zhang, Zengxiang

    2005-10-01

    The simulation of land use change process needs the support of Geographical Information System (GIS) and other relative technologies. While the present commercial GIS lack capabilities of distribution, prediction, and simulation of spatial-temporal data. Cellular automata (CA) provide dynamically modeling "from bottom-to-top" framework and posses the capability of modeling spatial-temporal evolvement process of a complicated geographical system, which is composed of a fourfold: cells, states, neighbors and rules. The simplicity and flexibility make CA have the ability to simulate a variety of behaviors of complex systems. One of the most potentially useful applications of cellular automata from the point of view of spatial planning is their use in simulations of urban sprawl at local and regional level. The paper firstly introduces the principles and characters of the cellular automata, and then discusses three methods of the integration of CA and GIS. The paper analyses from a practical point of view the factors that effect urban activities in the science of spatial decision-making. The status of using CA to dynamic simulates of urban expansion at home and abroad is analyzed. Finally, the problems and tendencies that exist in the application of CA model are detailed discussed, such as the quality of the data that the CA needs, the self-organization of the CA roots in the mutual function among the elements of the system, the partition of the space scale, the time calibration of the CA and the integration of the CA with other modular such as artificial nerve net modular and population modular etc.

  2. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    Science.gov (United States)

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle. PMID:27087101

  3. In situ sensing and modeling of molecular events at the cellular level

    Science.gov (United States)

    Yang, Ruiguo

    We developed the Atomic Force Microscopy (AFM) based nanorobot in combination with other nanomechanical sensors for the investigation of cell signaling pathways. The AFM nanorobotics hinge on the superior spatial resolution of AFM in imaging and extends it into the measurement of biological processes and manipulation of biological matters. A multiple input single output control system was designed and implemented to solve the issues of nanomanipulation of biological materials, feedback, response frequency and nonlinearity. The AFM nanorobotic system therefore provide the human-directed position, velocity and force control with high frequency feedback, and more importantly it can feed the operator with the real-time imaging of manipulation result from the fast-imaging based local scanning. The use of the system has taken the study of cellular process at the molecular scale into a new level. The cellular response to the physiological conditions can be significantly manifested in cellular mechanics. Dynamic mechanical property has been regarded as biomarkers, sometimes even regulators of the signaling and physiological processes, thus the name mechanobiology. We sought to characterize the relationship between the structural dynamics and the molecular dynamics and the role of them in the regulation of cell behavior. We used the AFM nanorobotics to investigate the mechanical properties in real-time of cells that are stimulated by different chemical species. These reagents could result in similar ion channel responses but distinctive mechanical behaviors. We applied these measurement results to establish a model that describes the cellular stimulation and the mechanical property change, a "two-hit" model that comprises the loss of cell adhesion and the initiation of cell apoptosis. The first hit was verified by functional experiments: depletion of Calcium and nanosurgery to disrupt the cellular adhesion. The second hit was tested by a labeling of apoptotic markers that

  4. Cellular Automata

    OpenAIRE

    Bagnoli, Franco

    1998-01-01

    An introduction to cellular automata (both deterministic and probabilistic) with examples. Definition of deterministic automata, dynamical properties, damage spreading and Lyapunov exponents; probabilistic automata and Markov processes, nonequilibrium phase transitions, directed percolation, diffusion; simulation techniques, mean field. Investigation themes: life, epidemics, forest fires, percolation, modeling of ecosystems and speciation. They represent my notes for the school "Dynamical Mod...

  5. A novel model for studies of blood-mediated long-term responses to cellular transplants

    OpenAIRE

    Hårdstedt, Maria; Lindblom, Susanne; Hong, Jaan; Nilsson, Bo; Korsgren, Olle; Ronquist, Gunnar

    2015-01-01

    Aims Interaction between blood and bio-surfaces is important in many medical fields. With the aim of studying blood-mediated reactions to cellular transplants, we developed a whole-blood model for incubation of small volumes for up to 48 h. Methods Heparinized polyvinyl chloride tubing was cut in suitable lengths and sealed to create small bags. Multiple bags, with fresh venous blood, were incubated attached to a rotating wheel at 37°C. Physiological variables in blood were monitored: glucose...

  6. Case Study of Phase Transition in Cellular Models of Pedestrian Flow

    Czech Academy of Sciences Publication Activity Database

    Bukáček, M.; Hrabák, Pavel

    Cham : Springer, 2014 - (Was, J.; Sirakoulis, G.; Bandini, S.), s. 508-517 ISBN 978-3-319-11519-1. ISSN 0302-9743. - (Lecture Notes in Computer Science. 8751). [ACRI 2014. International Conference on Cellular Automata for Research and Industry /11./. Krakov (PL), 22.09.2014-25.09.2014] R&D Projects: GA ČR GA13-13502S Institutional support: RVO:67985556 Keywords : Floor field model * phase transition * travel time * bounds principle * asynchronous update Subject RIV: IN - Informatics, Computer Science http://library.utia.cas.cz/separaty/2014/AS/hrabak-0432244.pdf

  7. Metabolically active portion of fat-free mass: a cellular body composition level modeling analysis

    OpenAIRE

    Wang, ZiMian; Heshka, Stanley; Wang, Jack; Gallagher, Dympna; Deurenberg, Paul; Chen, Zhao; Heymsfield, Steven B

    2006-01-01

    The proportion of fat-free mass (FFM) as body cell mass (BCM) is highly related to whole body resting energy expenditure. However, the magnitude of BCM/FFM may have been underestimated in previous studies. This is because Moore’s equation [BCM (kg) =0.00833 × total body potassium (in mmol)], which was used to predict BCM, underestimates BCM by ~ %. The aims of the present study were to develop a theoretical BCM/FFM model at the cellular level and to explore the influences of sex, age, and adi...

  8. Driver’s Awareness and Lane Changing Maneuver in Traffic Flow based on Cellular Automaton Model

    OpenAIRE

    Kohei Arai; Steven Ray Sentinuwo

    2015-01-01

    Effect of driver’s awareness (e.g., to estimate the speed and arrival time of another vehicle) on the lane changing maneuver is discussed. “Scope awareness” is defined as the visibility which is required for the driver to make a visual perception about road condition and the speed of vehicle that appears in the target lane for lane changing in the road. Cellular automaton based simulation model is created and applied to simulation studies for driver awareness behavior. This study clarifies re...

  9. A novel chaotic based image encryption using a hybrid model of deoxyribonucleic acid and cellular automata

    Science.gov (United States)

    Enayatifar, Rasul; Sadaei, Hossein Javedani; Abdullah, Abdul Hanan; Lee, Malrey; Isnin, Ismail Fauzi

    2015-08-01

    Currently, there are many studies have conducted on developing security of the digital image in order to protect such data while they are sending on the internet. This work aims to propose a new approach based on a hybrid model of the Tinkerbell chaotic map, deoxyribonucleic acid (DNA) and cellular automata (CA). DNA rules, DNA sequence XOR operator and CA rules are used simultaneously to encrypt the plain-image pixels. To determine rule number in DNA sequence and also CA, a 2-dimension Tinkerbell chaotic map is employed. Experimental results and computer simulations, both confirm that the proposed scheme not only demonstrates outstanding encryption, but also resists various typical attacks.

  10. Transition between immune and disease states in a cellular automaton model of clonal immune response

    CERN Document Server

    Bezzi, M; Ruffo, S; Seiden, P E; Bezzi, Michele; Celada, Franco; Ruffo, Stefano; Seiden, Philip E.

    1997-01-01

    In this paper we extend the Celada-Seiden (CS) model of the humoral immune response to include infectious virus and cytotoxic T lymphocytes (cellular response). The response of the system to virus involves a competition between the ability of the virus to kill the host cells and the host's ability to eliminate the virus. We find two basins of attraction in the dynamics of this system, one is identified with disease and the other with the immune state. There is also an oscillating state that exists on the border of these two stable states. Fluctuations in the population of virus or antibody can end the oscillation and drive the system into one of the stable states. The introduction of mechanisms of cross-regulation between the two responses can bias the system towards one of them. We also study a mean field model, based on coupled maps, to investigate virus-like infections. This simple model reproduces the attractors for average populations observed in the cellular automaton. All the dynamical behavior connect...

  11. An implementation of cellular automaton model for single-line train working diagram

    Institute of Scientific and Technical Information of China (English)

    Hua Wei; Liu Jun

    2006-01-01

    According to the railway transportation system's characteristics,a new cellular automaton model for the singleline railway system is presented in this paper.Based on this model,several simulations were done to imitate the train operation under three working diagrams.From a different angle the results show how the organization of train operation impacts on the railway carrying capacity.By using the non-parallel train working diagram the influence of fast-train on slow-train is found to be the strongest.Many slow-trains have to wait in-between neighbouring stations to let the fast-train(s) pass through first.So the slow-train will advance like a wave propagating from the departure station to the arrival station.This also resembles the situation of a highway jammed traffic flow.Furthermore,the nonuniformity of travel times between the sections also greatly limits the railway carrying capacity.After converting the nonuniform sections into the sections with uniform travel times while the total travel time is kept unchanged,all three carrying capacities are improved greatly as shown by simulation.It also shows that the cellular automaton model is an effective and feasible way to investigate the railway transDortation system.

  12. Modeling of the competition life cycle using the software complex of cellular automata PyCAlab

    Science.gov (United States)

    Berg, D. B.; Beklemishev, K. A.; Medvedev, A. N.; Medvedeva, M. A.

    2015-11-01

    The aim of the work is to develop a numerical model of the life cycle of competition on the basis of software complex cellular automata PyCAlab. The model is based on the general patterns of growth of various systems in resource-limited settings. At examples it is shown that the period of transition from an unlimited growth of the market agents to the stage of competitive growth takes quite a long time and may be characterized as monotonic. During this period two main strategies of competitive selection coexist: 1) capture of maximum market space with any reasonable costs; 2) saving by reducing costs. The obtained results allow concluding that the competitive strategies of companies must combine two mentioned types of behavior, and this issue needs to be given adequate attention in the academic literature on management. The created numerical model may be used for market research when developing of the strategies for promotion of new goods and services.

  13. A Two-Lane Cellular Automata Model with Influence of Next-Nearest Neighbor Vehicle

    International Nuclear Information System (INIS)

    In this paper, we propose a new two-lane cellular automata model in which the influence of the next-nearest neighbor vehicle is considered. The attributes of the traffic system composed of fast-lane and slow-lane are investigated by the new traffic model. The simulation results show that the proposed two-lane traffic model can reproduce some traffic phenomena observed in real traffic, and that maximum flux and critical density are close to the field measurements. Moreover, the initial density distribution of the fast-lane and slow-lane has much influence on the traffic flow states. With the ratio between the densities of slow lane and fast lane increasing the lane changing frequency increases, but maximum flux decreases. Finally, the influence of the sensitivity coefficients is discussed.

  14. Designing a mathematical model for integrating dynamic cellular manufacturing into supply chain system

    Science.gov (United States)

    Aalaei, Amin; Davoudpour, Hamid

    2012-11-01

    This article presents designing a new mathematical model for integrating dynamic cellular manufacturing into supply chain system with an extensive coverage of important manufacturing features consideration of multiple plants location, multi-markets allocation, multi-period planning horizons with demand and part mix variation, machine capacity, and the main constraints are demand of markets satisfaction in each period, machine availability, machine time-capacity, worker assignment, available time of worker, production volume for each plant and the amounts allocated to each market. The aim of the proposed model is to minimize holding and outsourcing costs, inter-cell material handling cost, external transportation cost, procurement & maintenance and overhead cost of machines, setup cost, reconfiguration cost of machines installation and removal, hiring, firing and salary worker costs. Aimed to prove the potential benefits of such a design, presented an example is shown using a proposed model.

  15. Heterogeneous cellular automata model for straight-through bicycle traffic at signalized intersection

    Science.gov (United States)

    Ren, Gang; Jiang, Hang; Chen, Jingxu; Huang, Zhengfeng; Lu, Lili

    2016-06-01

    This paper presents a cellular automata (CA) model to elucidate the straight-through movements of the heterogeneous bicycle traffic at signalized intersection. The CA model, via simulation, particularly exposits the dispersion phenomenon existing in the straight-through bicycle traffic. The nonlane-based cycling behavior and diverse bicycle properties are also incorporated in the CA model. A series of simulations are conducted to reveal the travel process, bicycles interaction and influence of the dispersion phenomenon. The simulation results show that the dispersion phenomenon significantly results in more bicycles interactions in terms of spilling maneuvers and overtaking maneuvers during the straight-through movements. Meanwhile, the dispersion phenomenon could contribute to the efficiency of the bicycle traffic, and straight-through bicycles need less time to depart the intersection under the circumstance of dispersion phenomenon. The simulation results are able to provide specific guideline for reasonably utilizing the dispersion phenomenon to improve the operational efficiency of straight-through bicycle traffic.

  16. A mathematical model in cellular manufacturing system considering subcontracting approach under constraints

    Directory of Open Access Journals (Sweden)

    Kamran Forghani

    2012-10-01

    Full Text Available In this paper, a new mathematical model in cellular manufacturing systems (CMSs has been presented. In order to increase the performance of manufacturing system, the production quantity of parts has been considered as a decision variable, i.e. each part can be produced and outsourced, simultaneously. This extension would be minimized the unused capacity of machines. The exceptional elements (EEs are taken into account and would be totally outsourced to the external supplier in order to remove intercellular material handling cost. The problem has been formulated as a mixed-integer programming to minimize the sum of manufacturing variable costs under budget, machines capacity and demand constraints. Also, to evaluate advantages of the model, several illustrative numerical examples have been provided to compare the performance of the proposed model with the available classical approaches in the literature.

  17. Steady state speed distribution analysis for a combined cellular automaton traffic model

    Institute of Scientific and Technical Information of China (English)

    Wang Jun-Feng; Chen Gui-Sheng; Liu Jin

    2008-01-01

    Cellular Automaton (CA) baaed traffic flow models have been extensively studied due to their effectiveness and simplicity in recent years. This paper develops a discrete time Markov chain (DTMC) analytical framework for a Nagel-Schreckenberg and Fukui-Ishibashi combined CA model (W2H traffic flow model) from microscopic point of view to capture the macroscopic steady state speed distributions. The inter-vehicle spacing Markov chain and the steady state speed Markov chain are proved to be irreducible and ergodie. The theoretical speed probability distributions depending on the traffic density and stochastic delay probability are in good accordance with numerical simulations. The derived fundamental diagram of the average speed from theoretical speed distributions is equivalent to the results in the previous work.

  18. Problems, pitfalls, perspectives and potentials of quantitative theoretical models for cellular radiation action

    International Nuclear Information System (INIS)

    The problem of quantitative mathematical models in cellular radiation biology is discussed in a general way. It is emphasized that there are a number of stages, starting from the spatial pattern of energy deposition and ending with repair/misrepair processes which all need to be incorporated. Since different types of radiation commonly yield very similar dose-response curves a model which is only valid for one special case cannot claim general applicability. Interaction experiments with ultraviolet and ionizing radiation are discussed in this context. Also the role of different experimental systems (microorganisms versus mammalian cells) has to be taken into account. A number of current model approaches are discussed within this context, and it is shown that most of them do not satisfy the criterion of universal applicability and can therefore not claim to give a 'true' picture of biological reality. Shouldered survival curves are taken as an example to illustrate these points in a more specific way

  19. A computable cellular stress network model for non-diseased pulmonary and cardiovascular tissue

    Directory of Open Access Journals (Sweden)

    Drubin David

    2011-10-01

    Full Text Available Abstract Background Humans and other organisms are equipped with a set of responses that can prevent damage from exposure to a multitude of endogenous and environmental stressors. If these stress responses are overwhelmed, this can result in pathogenesis of diseases, which is reflected by an increased development of, e.g., pulmonary and cardiac diseases in humans exposed to chronic levels of environmental stress, including inhaled cigarette smoke (CS. Systems biology data sets (e.g., transcriptomics, phosphoproteomics, metabolomics could enable comprehensive investigation of the biological impact of these stressors. However, detailed mechanistic networks are needed to determine which specific pathways are activated in response to different stressors and to drive the qualitative and eventually quantitative assessment of these data. A current limiting step in this process is the availability of detailed mechanistic networks that can be used as an analytical substrate. Results We have built a detailed network model that captures the biology underlying the physiological cellular response to endogenous and exogenous stressors in non-diseased mammalian pulmonary and cardiovascular cells. The contents of the network model reflect several diverse areas of signaling, including oxidative stress, hypoxia, shear stress, endoplasmic reticulum stress, and xenobiotic stress, that are elicited in response to common pulmonary and cardiovascular stressors. We then tested the ability of the network model to identify the mechanisms that are activated in response to CS, a broad inducer of cellular stress. Using transcriptomic data from the lungs of mice exposed to CS, the network model identified a robust increase in the oxidative stress response, largely mediated by the anti-oxidant NRF2 pathways, consistent with previous reports on the impact of CS exposure in the mammalian lung. Conclusions The results presented here describe the construction of a cellular stress

  20. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  1. A Vector-based Cellular Automata Model for Simulating Urban Land Use Change

    Institute of Scientific and Technical Information of China (English)

    LU Yi; CAO Min; ZHANG Lei

    2015-01-01

    Cellular Automata (CA) is widely used for the simulation of land use changes.This study applied a vector-based CA model to simulate land use change in order to minimize or eliminate the scale sensitivity in traditional raster-based CA model.The cells of vector-based CA model are presented according to the shapes and attributes of geographic entities,and the transition rules of vector-based CA model are improved by taking spatial variables of the study area into consideration.The vector-based CA model is applied to simulate land use changes in downtown of Qidong City,Jiangsu Province,China and its validation is confirmed by the methods of visual assessment and spatial accuracy.The simulation result of vector-based CA model reveals that nearly 75% of newly increased urban cells are located in the northwest and southwest parts of the study area from 2002 to 2007,which is in consistent with real land use map.In addition,the simulation results of the vector-based and raster-based CA models are compared to real land use data and their spatial accuracies are found to be 84.0% and 81.9%,respectively.In conclusion,results from this study indicate that the vector-based CA model is a practical and applicable method for the simulation of urbanization processes.

  2. Geographic Spatiotemporal Dynamic Model using Cellular Automata and Data Mining Techniques

    Directory of Open Access Journals (Sweden)

    Ahmad Zuhdi

    2011-05-01

    Full Text Available Geospatial data and information availability has been increasing rapidly and has provided users with knowledge on entities change and movement in a system. Cellular Geography model applies Cellular Automata on Geographic data by defining transition rules to the data grid. This paper presents the techniques for extracting transition rule(s from time series data grids, using multiple linear regression analysis. Clustering technique is applied to minimize the number of transition rules, which can be offered and chosen to change a new unknown grid. Each centroid of a cluster is associated with a transition rule and a grid of data. The chosen transition rule is associated with grid that has a minimum distance to the new data grid to be simulated. Validation of the model can be provided either quantitatively through an error measurement or qualitatively by visualizing the result of the simulation process. The visualization can also be more informative by adding the error information. Increasing number of cluster may give possibility to improve the simulation accuracy.

  3. The mechanics of cellular compartmentalization as a model for tumor spreading

    Science.gov (United States)

    Fritsch, Anatol; Pawlizak, Steve; Zink, Mareike; Kaes, Josef A.

    2012-02-01

    Based on a recently developed surgical method of Michael H"ockel, which makes use of cellular confinement to compartments in the human body, we study the mechanics of the process of cell segregation. Compartmentalization is a fundamental process of cellular organization and occurs during embryonic development. A simple model system can demonstrate the process of compartmentalization: When two populations of suspended cells are mixed, this mixture will eventually segregate into two phases, whereas mixtures of the same cell type will not. In the 1960s, Malcolm S. Steinberg formulated the so-called differential adhesion hypothesis which explains the segregation in the model system and the process of compartmentalization by differences in surface tension and adhesiveness of the interacting cells. We are interested in to which extend the same physical principles affect tumor growth and spreading between compartments. For our studies, we use healthy and cancerous breast cell lines of different malignancy as well as primary cells from human cervix carcinoma. We apply a set of techniques to study their mechanical properties and interactions. The Optical Stretcher is used for whole cell rheology, while Cell-cell-adhesion forces are directly measured with a modified AFM. In combination with 3D segregation experiments in droplet cultures we try to clarify the role of surface tension in tumor spreading.

  4. Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model.

    Science.gov (United States)

    Achour, Imène; Arel-Dubeau, Anne-Marie; Renaud, Justine; Legrand, Manon; Attard, Everaldo; Germain, Marc; Martinoli, Maria-Grazia

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE's ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model. PMID:27517912

  5. Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model

    Directory of Open Access Journals (Sweden)

    Imène Achour

    2016-08-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE, the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA. We also investigated OLE’s ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.

  6. Quantum chemical modelling of reactivity and selectivity of 1,2-dithiolanes towards retroviral and cellular zinc fingers

    Science.gov (United States)

    Topol, Igor A.; Nemukhin, Alexander V.; Burt, Stanley K.

    Interactions of 1,2-dithiolane species with zinc-containing sites, which mimic the zinc finger domains of retroviral and the cellular zinc finger proteins, have been investigated by quantum chemistry tools. According to the calculations, the immediate domains of zinc binding sites in the cellular and retroviral zinc fingers interact differently with such agents of the disulphide family. Thus, when approaching the model cellular-type domains, the molecules of 1,2-dithiolanes experience considerable potential barriers along the reaction path. However, these species react practically barrier-less with the model retroviral-type domains at the correlated DFT level. The results of the quantum chemical modelling provide firm support to the selectivity of 1,2-dithiolanes towards retroviral and cellular zinc fingers. This can be of great practical importance for the design of therapeutics that accomplish functional inactivation of the zinc fingers of the human immunodeficiency virus (HIV-1) retroviral type nucleocapsid protein NCp7.

  7. Dynamic computational model suggests that cellular citizenship is fundamental for selective tumor apoptosis.

    Directory of Open Access Journals (Sweden)

    Megan Olsen

    Full Text Available Computational models in the field of cancer research have focused primarily on estimates of biological events based on laboratory generated data. We introduce a novel in-silico technology that takes us to the next level of prediction models and facilitates innovative solutions through the mathematical system. The model's building blocks are cells defined phenotypically as normal or tumor, with biological processes translated into equations describing the life protocols of the cells in a quantitative and stochastic manner. The essentials of communication in a society composed of normal and tumor cells are explored to reveal "protocols" for selective tumor eradication. Results consistently identify "citizenship properties" among cells that are essential for the induction of healing processes in a healthy system invaded by cancer. These properties act via inter-cellular communication protocols that can be optimized to induce tumor eradication along with system recovery. Within the computational systems, the protocols universally succeed in removing a wide variety of tumors defined by proliferation rates, initial volumes, and apoptosis resistant phenotypes; they show high adaptability for biological details and allow incorporation of population heterogeneity. These protocols work as long as at least 32% of cells obey extra-cellular commands and at least 28% of cancer cells report their deaths. This low percentage implies that the protocols are resilient to the suboptimal situations often seen in biological systems. We conclude that our in-silico model is a powerful tool to investigate, to propose, and to exercise logical anti-cancer solutions. Functional results should be confirmed in a biological system and molecular findings should be loaded into the computational model for the next level of directed experiments.

  8. A Modified Cellular Automaton Approach for Mixed Bicycle Traffic Flow Modeling

    Directory of Open Access Journals (Sweden)

    Xiaonian Shan

    2015-01-01

    Full Text Available Several previous studies have used the Cellular Automaton (CA for the modeling of bicycle traffic flow. However, previous CA models have several limitations, resulting in differences between the simulated and the observed traffic flow features. The primary objective of this study is to propose a modified CA model for simulating the characteristics of mixed bicycle traffic flow. Field data were collected on physically separated bicycle path in Shanghai, China, and were used to calibrate the CA model using the genetic algorithm. Traffic flow features between simulations of several CA models and field observations were compared. The results showed that our modified CA model produced more accurate simulation for the fundamental diagram and the passing events in mixed bicycle traffic flow. Based on our model, the bicycle traffic flow features, including the fundamental diagram, the number of passing events, and the number of lane changes, were analyzed. We also analyzed the traffic flow features with different traffic densities, traffic components on different travel lanes. Results of the study can provide important information for understanding and simulating the operations of mixed bicycle traffic flow.

  9. Idealized Mesoscale Model Simulations of Open Cellular Convection Over the Sea

    DEFF Research Database (Denmark)

    Vincent, Claire Louise; Hahmann, Andrea N.; Kelly, Mark C.

    2012-01-01

    important terms in the budgets were buoyancy, pressure balance and inter-scale transfer to subgrid scales. Cells were also composited to calculate the average cell-scale flow and each of the budget terms on two-dimensional cross-sections through the cells, parallel and perpendicular to the mean wind......The atmospheric conditions during an observed case of open cellular convection over the North Sea were simulated using the Weather Research and Forecasting (WRF) numerical model. Wind, temperature and water vapour mixing ratio profiles from the WRF simulation were used to initialize an idealized...... version of the model, which excluded the effects of topography, surface inhomogeneities and large-scale weather forcing. Cells with an average diameter of 17.4 km developed. Simulations both with and without a capping inversion were made, and the cell-scale kinetic energy budget was calculated for each...

  10. Modeling and Simulation for Urban Rail Traffic Problem Based on Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    许琰; 曹成铉; 李明华; 罗金龙

    2012-01-01

    Based on the Nagel-Schreckenberg model, we propose a new cellular automata model to simulate the urban rail traffic flow under moving block system and present a new minimum instantaneous distance formula under pure moving block. We also analyze the characteristics of the urban rail traffic flow under the influence of train density, station dwell times, the length of train, and the train velocity. Train delays can be decreased effectively through flexible departure intervals according to the preceding train type before its departure. The results demonstrate that a suitable adjustment of the current train velocity based on the following train velocity can greatly shorten the minimum departure intervals and then increase the capacity of rail transit.

  11. Decellularized extracellular matrix microparticles as a vehicle for cellular delivery in a model of anastomosis healing.

    Science.gov (United States)

    Hoganson, David M; Owens, Gwen E; Meppelink, Amanda M; Bassett, Erik K; Bowley, Chris M; Hinkel, Cameron J; Finkelstein, Eric B; Goldman, Scott M; Vacanti, Joseph P

    2016-07-01

    Extracellular matrix (ECM) materials from animal and human sources have become important materials for soft tissue repair. Microparticles of ECM materials have increased surface area and exposed binding sites compared to sheet materials. Decellularized porcine peritoneum was mechanically dissociated into 200 µm microparticles, seeded with fibroblasts and cultured in a low gravity rotating bioreactor. The cells avidly attached and maintained excellent viability on the microparticles. When the seeded microparticles were placed in a collagen gel, the cells quickly migrated off the microparticles and through the gel. Cells from seeded microparticles migrated to and across an in vitro anastomosis model, increasing the tensile strength of the model. Cell seeded microparticles of ECM material have potential for paracrine and cellular delivery therapies when delivered in a gel carrier. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1728-1735, 2016. PMID:26946064

  12. Driver’s Awareness and Lane Changing Maneuver in Traffic Flow based on Cellular Automaton Model

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2015-08-01

    Full Text Available Effect of driver’s awareness (e.g., to estimate the speed and arrival time of another vehicle on the lane changing maneuver is discussed. “Scope awareness” is defined as the visibility which is required for the driver to make a visual perception about road condition and the speed of vehicle that appears in the target lane for lane changing in the road. Cellular automaton based simulation model is created and applied to simulation studies for driver awareness behavior. This study clarifies relations between the lane changing behavior and the scope awareness parameter that reflects driver behavior. Simulation results show that the proposed model is valid for investigation of the important features of lane changing maneuver.

  13. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  14. An improved cellular automaton model considering the effect of traffic lights and driving behaviour

    Science.gov (United States)

    He, Hong-Di; Lu, Wei-Zhen; Dong, Li-Yun

    2011-04-01

    This paper proposes an improved cellular automaton model to describe the urban traffic flow with the consideration of traffic light and driving behaviour effects. Based on the model, the characteristics of the urban traffic flow on a single-lane road are investigated under three different control strategies, i.e., the synchronized, the green wave and the random strategies. The fundamental diagrams and time-space patterns of the traffic flows are provided for these strategies respectively. It finds that the dynamical transition to the congested flow appears when the vehicle density is higher than a critical level. The saturated flow is less dependent on the cycle time and the strategies of the traffic light control, while the critical vehicle density varies with the cycle time and the strategies. Simulated results indicate that the green wave strategy is proven to be the most effective one among the above three control strategies.

  15. The Aldous-Shields model revisited (with application to cellular ageing)

    CERN Document Server

    Best, Katharina

    2010-01-01

    In Aldous and Shields (1988), a model for a rooted, growing random binary tree was presented. For some c>0, an external vertex splits at rate c^(-i) (and becomes internal) if its distance from the root (depth) is i. For c>1, we reanalyse the tree profile, i.e. the numbers of external vertices in depth i=1,2,.... Our main result are concrete formulas for the expectation and covariance-structure of the profile. In addition, we present the application of the model to cellular ageing. Here, we assume that nodes in depth h+1 are senescent, i.e. do not split. We obtain a limit result for the proportion of non-senescent vertices for large h.

  16. A cellular automation model for the change of public attitude regarding nuclear energy

    International Nuclear Information System (INIS)

    A cellular automation model was constructed to investigate how public opinion on nuclear energy in Japan depends upon the information environment and personal communication between people. From simulation with this model, the following become clear; (i) society is a highly non-linear system with a self-organizing potential: (ii) in a society composed of one type of constituent member with homogeneous characteristics, the trend of public opinion is substantially changed only when the effort to ameliorate public acceptance over a long period of time, by means such as education, persuasion and advertisement, exceeds a certain threshold, and (iii) in the case when the amount of information on nuclear risk released from the newsmedia is reduced continuously from now on, the acceptability of nuclear energy is significantly improved so far as the extent of the reduction exceeds a certain threshold. (author)

  17. A nanoflare based cellular automaton model and the observed properties of the coronal plasma

    CERN Document Server

    Fuentes, Marcelo López

    2016-01-01

    We use the cellular automaton model described in L\\'opez Fuentes \\& Klimchuk (2015, ApJ, 799, 128) to study the evolution of coronal loop plasmas. The model, based on the idea of a critical misalignment angle in tangled magnetic fields, produces nanoflares of varying frequency with respect to the plasma cooling time. We compare the results of the model with active region (AR) observations obtained with the Hinode/XRT and SDO/AIA instruments. The comparison is based on the statistical properties of synthetic and observed loop lightcurves. Our results show that the model reproduces the main observational characteristics of the evolution of the plasma in AR coronal loops. The typical intensity fluctuations have an amplitude of 10 to 15\\% both for the model and the observations. The sign of the skewness of the intensity distributions indicates the presence of cooling plasma in the loops. We also study the emission measure (EM) distribution predicted by the model and obtain slopes in log(EM) versus log(T) betw...

  18. CellLab-CTS 2015: continuous-time stochastic cellular automaton modeling using Landlab

    Science.gov (United States)

    Tucker, Gregory E.; Hobley, Daniel E. J.; Hutton, Eric; Gasparini, Nicole M.; Istanbulluoglu, Erkan; Adams, Jordan M.; Siddartha Nudurupati, Sai

    2016-02-01

    CellLab-CTS 2015 is a Python-language software library for creating two-dimensional, continuous-time stochastic (CTS) cellular automaton models. The model domain consists of a set of grid nodes, with each node assigned an integer state code that represents its condition or composition. Adjacent pairs of nodes may undergo transitions to different states, according to a user-defined average transition rate. A model is created by writing a Python code that defines the possible states, the transitions, and the rates of those transitions. The code instantiates, initializes, and runs one of four object classes that represent different types of CTS models. CellLab-CTS provides the option of using either square or hexagonal grid cells. The software provides the ability to treat particular grid-node states as moving particles, and to track their position over time. Grid nodes may also be assigned user-defined properties, which the user can update after each transition through the use of a callback function. As a component of the Landlab modeling framework, CellLab-CTS models take advantage of a suite of Landlab's tools and capabilities, such as support for standardized input and output.

  19. Modelling urban growth in the Indo-Gangetic plain using nighttime OLS data and cellular automata

    Science.gov (United States)

    Roy Chowdhury, P. K.; Maithani, Sandeep

    2014-12-01

    The present study demonstrates the applicability of the Operational Linescan System (OLS) sensor in modelling urban growth at regional level. The nighttime OLS data provides an easy, inexpensive way to map urban areas at a regional scale, requiring a very small volume of data. A cellular automata (CA) model was developed for simulating urban growth in the Indo-Gangetic plain; using OLS data derived maps as input. In the proposed CA model, urban growth was expressed in terms of causative factors like economy, topography, accessibility and urban infrastructure. The model was calibrated and validated based on OLS data of year 2003 and 2008 respectively using spatial metrics measures and subsequently the urban growth was predicted for the year 2020. The model predicted high urban growth in North Western part of the study area, in south eastern part growth would be concentrated around two cities, Kolkata and Howrah. While in the middle portion of the study area, i.e., Jharkhand, Bihar and Eastern Uttar Pradesh, urban growth has been predicted in form of clusters, mostly around the present big cities. These results will not only provide an input to urban planning but can also be utilized in hydrological and ecological modelling which require an estimate of future built up areas especially at regional level.

  20. Open boundaries in a cellular automaton model for traffic flow with metastable states

    Science.gov (United States)

    Barlovic, Robert; Huisinga, Torsten; Schadschneider, Andreas; Schreckenberg, Michael

    2002-10-01

    The effects of open boundaries in the velocity-dependent randomization (VDR) model, a modified version of the well-known Nagel-Schreckenberg (NaSch) cellular automaton model for traffic flow, are investigated. In contrast to the NaSch model, the VDR model exhibits metastable states and phase separation in a certain density regime. A proper insertion strategy allows us to investigate the whole spectrum of possible system states and the structure of the phase diagram by Monte Carlo simulations. We observe an interesting microscopic structure of the jammed phases, which is different from the one of the NaSch model. For finite systems, the existence of high flow states in a certain parameter regime leads to a special structure of the fundamental diagram measured in the open system. Apart from that, the results are in agreement with an extremal principle for the flow, which has been introduced for models with a unique flow-density relation. Finally, we discuss the application of our findings for a systematic flow optimization. Here some surprising results are obtained, e.g., a restriction of the inflow can lead to an improvement of the total flow through a bottleneck.

  1. Two-Photon Enzymatic Probes Visualizing Sub-cellular/Deep-brain Caspase Activities in Neurodegenerative Models.

    Science.gov (United States)

    Qian, Linghui; Zhang, Cheng-Wu; Mao, Yanli; Li, Lin; Gao, Nengyue; Lim, Kah-Leong; Xu, Qing-Hua; Yao, Shao Q

    2016-01-01

    Caspases work as a double-edged sword in maintaining cell homeostasis. Highly regulated caspase activities are essential during animal development, but dysregulation might lead to different diseases, e.g. extreme caspase activation is known to promote neurodegeneration. At present, visualization of caspase activation has mostly remained at the cellular level, in part due to a lack of cell-permeable imaging probes capable of direct, real-time investigations of endogenous caspase activities in deep tissues. Herein, we report a suite of two-photon, small molecule/peptide probes which enable sensitive and dynamic imaging of individual caspase activities in neurodegenerative models under physiological conditions. With no apparent toxicity and the ability of imaging endogenous caspases both in different subcellular organelles of mammalian cells and in brain tissues, these probes serve as complementary tools to conventional histological analysis. They should facilitate future explorations of caspases at molecular, cellular and organism levels and inspire development of novel two-photon probes against other enzymes. PMID:27210613

  2. Distinctive behavioral and cellular responses to fluoxetine in the mouse model for Fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Marko eUutela

    2014-05-01

    Full Text Available Fluoxetine is used as a therapeutic agent for autism spectrum disorder (ASD, including Fragile X syndrome (FXS. The treatment often associates with disruptive behaviors such as agitation and disinhibited behaviors in FXS. To identify mechanisms that increase the risk to poor treatment outcome, we investigated the behavioral and cellular effects of fluoxetine on adult Fmr1 knockout (KO mice, a mouse model for FXS. We found that fluoxetine reduced anxiety-like behavior of both wild type and Fmr1 KO mice seen as shortened latency to enter the center area in the open field test. In Fmr1 KO mice, fluoxetine normalized locomotor hyperactivity but abnormally increased exploratory activity. Reduced Brain-derived neurotrophic factor (BDNF and increased TrkB receptor expression levels in the hippocampus of Fmr1 KO mice associated with inappropriate coping responses under stressful condition and abolished antidepressant activity of fluoxetine. Fluoxetine response in the cell proliferation was also missing in the hippocampus of Fmr1 KO mice when compared with wild type controls. The postnatal expression of serotonin transporter was reduced in the thalamic nuclei of Fmr1 KO mice during the time of transient innervation of somatosensory neurons suggesting that developmental changes of serotonin transporter (SERT expression were involved in the differential cellular and behavioral responses to fluoxetine in wild type and Fmr1 mice. The results indicate that changes of BDNF/TrkB signaling contribute to differential behavioral responses to fluoxetine among individuals with ASD.

  3. Cognitive and Energy Harvesting-Based D2D Communication in Cellular Networks: Stochastic Geometry Modeling and Analysis

    OpenAIRE

    Sakr, Ahmed Hamdi; Hossain, Ekram

    2014-01-01

    While cognitive radio enables spectrum-efficient wireless communication, radio frequency (RF) energy harvesting from ambient interference is an enabler for energy-efficient wireless communication. In this paper, we model and analyze cognitive and energy harvesting-based D2D communication in cellular networks. The cognitive D2D transmitters harvest energy from ambient interference and use one of the channels allocated to cellular users (in uplink or downlink), which is referred to as the D2D c...

  4. Multi-Scale Continuum Modeling of Biological Processes: From Molecular Electro-Diffusion to Sub-Cellular Signaling Transduction

    OpenAIRE

    Cheng, Y; Kekenes-Huskey, P; Hake, JE; Holst, MJ; McCammon, JA; Michailova, AP

    2012-01-01

    This article provides a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally-validated estimates ...

  5. Developing an Abaqus *HYPERFOAM Model for M9747 (4003047) Cellular Silicone Foam

    Energy Technology Data Exchange (ETDEWEB)

    Siranosian, Antranik A. [Los Alamos National Laboratory; Stevens, R. Robert [Los Alamos National Laboratory

    2012-04-26

    This report documents work done to develop an Abaqus *HYPERFOAM hyperelastic model for M9747 (4003047) cellular silicone foam for use in quasi-static analyses at ambient temperature. Experimental data, from acceptance tests for 'Pad A' conducted at the Kansas City Plant (KCP), was used to calibrate the model. The data includes gap (relative displacement) and load measurements from three locations on the pad. Thirteen sets of data, from pads with different serial numbers, were provided. The thirty-nine gap-load curves were extracted from the thirteen supplied Excel spreadsheets and analyzed, and from those thirty-nine one set of data, representing a qualitative mean, was chosen to calibrate the model. The data was converted from gap and load to nominal (engineering) strain and nominal stress in order to implement it in Abaqus. Strain computations required initial pad thickness estimates. An Abaqus model of a right-circular cylinder was used to evaluate and calibrate the *HYPERFOAM model.

  6. Scaling, phase transitions, and nonuniversality in a self-organized critical cellular-automaton model

    International Nuclear Information System (INIS)

    We present a two-dimensional continuous cellular automaton that is equivalent to a driven spring-block model. Both the conservation and the anisotropy in the model are controllable quantities. Above a critical level of conservation, the model exhibits self-organized criticality. The self-organization of this system and hence the critical exponents depend on the conservation and the boundary conditions. In the critical isotropic nonconservative phase, the exponents change continuously as a function of conservation. Furthermore, the exponents vary continuously when changing the boundary conditions smoothly. Consequently, there is no universality of the critical exponents. We discuss the relevance of this for earthquakes. Introducing anisotropy changes the scaling of the distribution function, but not the power-law exponent. We explore the phase diagram of this model. We find that at low conservation levels a localization transition occurs. We see two additional phase transitions. The first is seen when moving from the conservative into the nonconservative model. The second appears when passing from the anisotropic two-dimensional system to the purely one-dimensional system

  7. Derivation of Solar Flare Cellular Automata Models from a Subset of the Magnetohydrodynamic Equations

    Science.gov (United States)

    Vassiliadis, D.; Anastasiadis, A.; Georgoulis, M.; Vlahos, L.

    1998-12-01

    Cellular automata (CA) models account for the power-law distributions found for solar flare hard X-ray observations, but their physics has been unclear. We examine four of these models and show that their criteria and magnetic field distribution rules can be derived by discretizing the MHD diffusion equation as obtained from a simplified Ohm's law. Identifying the discrete MHD with the CA models leads to an expression for the resistivity as a function of the current on the flux tube boundary, as may be expected from current-driven instabilities. Anisotropic CA models correspond to a nonlinear resistivity η(J), while isotropic ones are associated with hyperresistivity η(▽2J). The discrete equations satisfy the necessary conditions for self-organized criticality (Lu): there is local conservation of a field (magnetic flux), while the nonlinear resistivity provides a rapid dissipation and relaxation mechanism. The approach justifies many features of the CA models that were originally based on intuition.

  8. A multi-objective model for designing a group layout of a dynamic cellular manufacturing system

    Science.gov (United States)

    Kia, Reza; Shirazi, Hossein; Javadian, Nikbakhsh; Tavakkoli-Moghaddam, Reza

    2013-04-01

    This paper presents a multi-objective mixed-integer nonlinear programming model to design a group layout of a cellular manufacturing system in a dynamic environment, in which the number of cells to be formed is variable. Cell formation (CF) and group layout (GL) are concurrently made in a dynamic environment by the integrated model, which incorporates with an extensive coverage of important manufacturing features used in the design of CMSs. Additionally, there are some features that make the presented model different from the previous studies. These features include the following: (1) the variable number of cells, (2) the integrated CF and GL decisions in a dynamic environment by a multi-objective mathematical model, and (3) two conflicting objectives that minimize the total costs (i.e., costs of intra and inter-cell material handling, machine relocation, purchasing new machines, machine overhead, machine processing, and forming cells) and minimize the imbalance of workload among cells. Furthermore, the presented model considers some limitations, such as machine capability, machine capacity, part demands satisfaction, cell size, material flow conservation, and location assignment. Four numerical examples are solved by the GAMS software to illustrate the promising results obtained by the incorporated features.

  9. Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number.

    Directory of Open Access Journals (Sweden)

    Joseph Andrews

    Full Text Available BACKGROUND: We have previously identified genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. These complex epigenetic changes that we observed, along with concurrent karyotype analyses, have led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy are superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes observed in breast cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We undertook simultaneous high-resolution, whole-genome analyses of MDA-MB-468GFP and MDA-MB-468GFP-LN human breast cancer cell lines (an isogenic, paired lymphatic metastasis cell line model using Affymetrix gene expression (U133, promoter (1.0R, and SNP/CNV (SNP 6.0 microarray platforms to correlate data from gene expression, epigenetic (DNA methylation, and combination copy number variant/single nucleotide polymorphism microarrays. Using Partek Software and Ingenuity Pathway Analysis we integrated datasets from these three platforms and detected multiple hypomethylation and hypermethylation events. Many of these epigenetic alterations correlated with gene expression changes. In addition, gene dosage events correlated with the karyotypic differences observed between the cell lines and were reflected in specific promoter methylation patterns. Gene subsets were identified that correlated hyper (and hypo methylation with the loss (or gain of gene expression and in parallel, with gene dosage losses and gains, respectively. Individual gene targets from these subsets were also validated for their methylation, expression and copy number status, and susceptible gene pathways were identified that may indicate how selective advantage drives the processes of tumourigenesis and metastasis. CONCLUSIONS/SIGNIFICANCE: Our approach allows more precisely profiling of functionally relevant epigenetic signatures that are associated with cancer

  10. Maximiscin Induces DNA Damage, Activates DNA Damage Response Pathways, and Has Selective Cytotoxic Activity against a Subtype of Triple-Negative Breast Cancer.

    Science.gov (United States)

    Robles, Andrew J; Du, Lin; Cichewicz, Robert H; Mooberry, Susan L

    2016-07-22

    Triple-negative breast cancers are highly aggressive, and patients with these types of tumors have poor long-term survival. These breast cancers do not express estrogen or progesterone receptors and do not have gene amplification of human epidermal growth factor receptor 2; therefore, they do not respond to available targeted therapies. The lack of targeted therapies for triple-negative breast cancers stems from their heterogeneous nature and lack of a clear definition of driver defects. Studies have recently identified triple-negative breast cancer molecular subtypes based on gene expression profiling and representative cell lines, allowing for the identification of subtype-specific drug leads and molecular targets. We previously reported the identification of a new fungal metabolite named maximiscin (1) identified through a crowdsourcing program. New results show that 1 has selective cytotoxic efficacy against basal-like 1 MDA-MB-468 cells compared to cell lines modeling other triple-negative breast cancer molecular subtypes. This compound also exhibited antitumor efficacy in a xenograft mouse model. The mechanisms of action of 1 in MDA-MB-468 cells were investigated to identify potential molecular targets and affected pathways. Compound 1 caused accumulation of cells in the G1 phase of the cell cycle, suggesting induction of DNA damage. Indeed, treatment with 1 caused DNA double-strand breaks with concomitant activation of the DNA damage response pathways, indicated by phosphorylation of p53, Chk1, and Chk2. Collectively, these results suggest basal-like triple-negative breast cancer may be inherently sensitive to DNA-damaging agents relative to other triple-negative breast cancer subtypes. These results also demonstrate the potential of our citizen crowdsourcing program to identify new lead molecules for treating the subtypes of triple-negative breast cancer. PMID:27310425

  11. Molecular modeling of the conformational dynamics of the cellular prion protein

    Science.gov (United States)

    Nguyen, Charles; Colling, Ian; Bartz, Jason; Soto, Patricia

    2014-03-01

    Prions are infectious agents responsible for transmissible spongiform encephalopathies (TSEs), a type of fatal neurodegenerative disease in mammals. Prions propagate biological information by conversion of the non-pathological version of the prion protein to the infectious conformation, PrPSc. A wealth of knowledge has shed light on the nature and mechanism of prion protein conversion. In spite of the significance of this problem, we are far from fully understanding the conformational dynamics of the cellular isoform. To remedy this situation we employ multiple biomolecular modeling techniques such as docking and molecular dynamics simulations to map the free energy landscape and determine what specific regions of the prion protein are most conductive to binding. The overall goal is to characterize the conformational dynamics of the cell form of the prion protein, PrPc, to gain insight into inhibition pathways against misfolding. NE EPSCoR FIRST Award to Patricia Soto.

  12. Emergent Behavior from A Cellular Automaton Model for Invasive Tumor Growth in Heterogeneous Microenvironments

    CERN Document Server

    Jiao, Yang

    2011-01-01

    Understanding tumor invasion and metastasis is of crucial importance for both fundamental cancer research and clinical practice. In vitro experiments have established that the invasive growth of malignant tumors is characterized by the dendritic invasive branches composed of chains of tumor cells emanating from the primary tumor mass. The preponderance of previous tumor simulations focused on non-invasive (or proliferative) growth. The formation of the invasive cell chains and their interactions with the primary tumor mass and host microenvironment are not well understood. Here, we present a novel cellular automaton (CA) model that enables one to efficiently simulate invasive tumor growth in a heterogeneous host microenvironment. By taking into account a variety of microscopic-scale tumor-host interactions, including the short-range mechanical interactions between tumor cells and tumor stroma, degradation of extracellular matrix by the invasive cells and oxygen/nutrient gradient driven cell motions, our CA mo...

  13. Fatigue design of a cellular phone folder using regression model-based multi-objective optimization

    Science.gov (United States)

    Kim, Young Gyun; Lee, Jongsoo

    2016-08-01

    In a folding cellular phone, the folding device is repeatedly opened and closed by the user, which eventually results in fatigue damage, particularly to the front of the folder. Hence, it is important to improve the safety and endurance of the folder while also reducing its weight. This article presents an optimal design for the folder front that maximizes its fatigue endurance while minimizing its thickness. Design data for analysis and optimization were obtained experimentally using a test jig. Multi-objective optimization was carried out using a nonlinear regression model. Three regression methods were employed: back-propagation neural networks, logistic regression and support vector machines. The AdaBoost ensemble technique was also used to improve the approximation. Two-objective Pareto-optimal solutions were identified using the non-dominated sorting genetic algorithm (NSGA-II). Finally, a numerically optimized solution was validated against experimental product data, in terms of both fatigue endurance and thickness index.

  14. Phase transition in the economically modeled growth of a cellular nervous system

    CERN Document Server

    Nicosia, Vincenzo; Schafer, William R; Latora, Vito; Bullmore, Edward T; 10.1073/pnas.1300753110

    2013-01-01

    Spatially-embedded complex networks, such as nervous systems, the Internet and transportation networks, generally have non-trivial topological patterns of connections combined with nearly minimal wiring costs. However the growth rules shaping these economical trade-offs between cost and topology are not well understood. Here we study the cellular nervous system of the nematode worm C. elegans, together with information on the birth times of neurons and on their spatial locations. We find that the growth of this network undergoes a transition from an accelerated to a constant increase in the number of links (synaptic connections) as a function of the number of nodes (neurons). The time of this phase transition coincides closely with the observed moment of hatching, when development switches metamorphically from oval to larval stages. We use graph analysis and generative modelling to show that the transition between different growth regimes, as well as its coincidence with the moment of hatching, can be explain...

  15. Phase transitions in a cellular automaton model of a highway on-ramp

    Science.gov (United States)

    Belitsky, Vladimir; Maric, Nevena; Schütz, Gunter M.

    2007-09-01

    We introduce a lattice gas model for the merging of two single-lane automobile highways. The merging rules for traffic on the two lanes are deterministic, but the inflow on both lanes is stochastic. Analysing the stationary distribution of this stochastic cellular automaton, we find a discontinuous phase transition from a free-flow phase which depends on the initial state of the road to a jammed phase where all memory of the initial state is lost. Inside the jammed phase we identify dynamical phase transitions in the approach to stationarity. Each dynamical phase is characterized by a fixed number of relaxation cycles which is decreasing as one moves deeper into the jammed phase. In each cycle step, the number of 'desperate' drivers who force their way onto the main road when they reach the end of the on-ramp increases until stationarity.

  16. Phase transitions in a cellular automaton model of a highway on-ramp

    International Nuclear Information System (INIS)

    We introduce a lattice gas model for the merging of two single-lane automobile highways. The merging rules for traffic on the two lanes are deterministic, but the inflow on both lanes is stochastic. Analysing the stationary distribution of this stochastic cellular automaton, we find a discontinuous phase transition from a free-flow phase which depends on the initial state of the road to a jammed phase where all memory of the initial state is lost. Inside the jammed phase we identify dynamical phase transitions in the approach to stationarity. Each dynamical phase is characterized by a fixed number of relaxation cycles which is decreasing as one moves deeper into the jammed phase. In each cycle step, the number of 'desperate' drivers who force their way onto the main road when they reach the end of the on-ramp increases until stationarity

  17. Cellular and circuit models of increased resting-state network gamma activity in schizophrenia.

    Science.gov (United States)

    White, R S; Siegel, S J

    2016-05-01

    Schizophrenia (SCZ) is a disorder characterized by positive symptoms (hallucinations, delusions), negative symptoms (blunted affect, alogia, reduced sociability, and anhedonia), as well as persistent cognitive deficits (memory, concentration, and learning). While the biology underlying subjective experiences is difficult to study, abnormalities in electroencephalographic (EEG) measures offer a means to dissect potential circuit and cellular changes in brain function. EEG is indispensable for studying cerebral information processing due to the introduction of techniques for the decomposition of event-related activity into its frequency components. Specifically, brain activity in the gamma frequency range (30-80Hz) is thought to underlie cognitive function and may be used as an endophenotype to aid in diagnosis and treatment of SCZ. In this review we address evidence indicating that there is increased resting-state gamma power in SCZ. We address how modeling this aspect of the illness in animals may help treatment development as well as providing insights into the etiology of SCZ. PMID:26577758

  18. A Discrete/continuous Coupled Approach for Modeling Impacts on Cellular Geostructures

    Science.gov (United States)

    Breugnot, A.; Lambert, S.; Villard, P.; Gotteland, P.

    2016-05-01

    This article presents a numerical model coupling the finite difference method and discrete element methods (FDM, DEM) for simulating the response of cellular geostructures to impacts. DEM is used in the vicinity of the impacted area while FDM is used far away. The continuity between the DEM and FDM domains is insured using the edge-to-edge method. The numerical parameters are calibrated based on compression and impact experiments conducted on elementary cells. Numerical simulations at the structure scale are compared with real-scale experimental data. The response of the structure is addressed varying the impact conditions. The projectile shape and the position of the impact point appear to be the most influential parameters.

  19. Cellular Automata Models of Traffic Behavior in Presence of Speed Breaking Structures

    International Nuclear Information System (INIS)

    In this article, we study traffic flow in the presence of speed breaking structures. The speed breakers are typically used to reduce the local speed of vehicles near certain institutions such as schools and hospitals. Through a cellular automata model we study the impact of such structures on global traffic characteristics. The simulation results indicate that the presence of speed breakers could reduce the global flow under moderate global densities. However, under low and high global density traffic regime the presence of speed breakers does not have an impact on the global flow. Further the speed limit enforced by the speed breaker creates a phase distinction. For a given global density and slowdown probability, as the speed limit enforced by the speed breaker increases, the traffic moves from the reduced flow phase to maximum flow phase. This underlines the importance of proper design of these structures to avoid undesired flow restrictions. (general)

  20. Computer simulation of a cellular automata model for the immune response in a retrovirus system

    International Nuclear Information System (INIS)

    Immune response in a retrovirus system is modeled by a network of three binary cell elements to take into account some of the main functional features of T4 cells, T8 cells, and viruses. Two different intercell interactions are introduced, one of which leads to three fixed points while the other yields bistable fixed points oscillating between a healthy state and a sick state in a mean field treatment. Evolution of these cells is studied for quenched and annealed random interactions on a simple cubic lattice with a nearest neighbor interaction using inhomogenous cellular automata. Populations of T4 cells and viral cells oscillate together with damping (with constant amplitude) for annealed (quenched) interaction on increasing the value of mixing probability B from zero to a characteristic value Bca (Bcq). For higher B, the average number of T4 cells increases while that of the viral infected cells decreases monotonically on increasing B, suggesting a phase transition at Bca (Bcq)

  1. Preparation of oligodeoxynucleotide encapsulated cationic liposomes and release study with models of cellular membranes

    Directory of Open Access Journals (Sweden)

    Tamaddon AM.

    2007-05-01

    Full Text Available Cationic liposomes are used for cellular delivery of antisense oligodeoxynucleotide (AsODN, where release of encapsulated AsODN is mainly controlled by endocytosis and fusion mechanisms. In this investigation, it was tried to model such a release process that is difficult to evaluate in cell culture. For this purpose, an AsODN model (against protein kinase C-α was encapsulated in a DODAP-containing cationic liposome and evaluated for size, zeta-potential, encapsulation and ODN stability. Vesicular models of outer layer and total plasma membranes and early and late endosomal membranes were developed, based on lipid content and pH, using ether injection method. ODN release was determined by the fluorescence dequenching of encapsulated FITC-ODN. Zeta potential, size and ODN encapsulation efficiency of the prepared liposomes were -2.49 ± 7.15 mV, 108.4 nm and 73% respectively. ODN protection was 3-4 times more than that of conventional liposome/ODN complexation method. There was a correlation between model concentration and percent of ODN release. At 7.5 µM, the percent of released ODN was 76% for the cholesterol-free model of the late endosome and 16% for the early endosomal membrane; while the release was less than 11% for the models of plasma membrane. ODN release increased with temperature in the range of 4-37◦C for the late endosomal model, but not for others, possibly due to their high cholesterol contents or acidic pH. The interaction was fast and completed within 5 minutes and didn’t change in the range of 5-60 minutes. Our data are in agreement with published cell culture studies and reveal that cell-liposomes interaction can be modeled by lamellar membranes.

  2. Immediate in vivo target-specific cancer cell death after near infrared photoimmunotherapy

    Directory of Open Access Journals (Sweden)

    Mitsunaga Makoto

    2012-08-01

    Full Text Available Abstract Background Near infrared (NIR photoimmunotherapy (PIT is a new type of cancer treatment based on a monoclonal antibody (mAb-NIR phthalocyanine dye, (IR700 conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult. Methods A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI was performed before and after PIT. Results Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2, however, in mice receiving lower intensity NIR (50 J/cm2, tumors recurred with gradually increasing BLI signal. Conclusion PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.

  3. Immediate in vivo target-specific cancer cell death after near infrared photoimmunotherapy

    International Nuclear Information System (INIS)

    Near infrared (NIR) photoimmunotherapy (PIT) is a new type of cancer treatment based on a monoclonal antibody (mAb)-NIR phthalocyanine dye, (IR700) conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult. A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells) was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI) was performed before and after PIT. Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2), however, in mice receiving lower intensity NIR (50 J/cm2), tumors recurred with gradually increasing BLI signal. PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo

  4. Characterization of Bizzy Nut extracts in estrogen-responsive MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Kola acuminate, also known as Bizzy Nut or Kola Nut, is a natural product that contains bioactive chemicals that possess hormonal properties. The purpose of this study was to characterize the putative phytoestrogenic compounds present in Bizzy Nut for estrogenic-like activity. As an initial step, five extracts (E1 - hexane, E2 - ether, E3 - acetone, E4 - methanol and E5 - water) were sequentially generated using solid-liquid phase extraction and their bioactivity was examined in MCF-7, MDA-MB-468 and LNCaP cancer cell models. MTT cell viability, dye exclusion, caspase activity and microscopic assessment of apoptotic cells demonstrated that extracts of Bizzy were cytotoxic to MCF-7, MDA-MB 468 and LNCaP cells. In MCF-7 cells, the acetone extract (E3) at 100 ppm elicited a potent cytotoxic response with a growth-inhibitory concentration (GI50) of 67 ppm. In contrast, E3 stimulated growth in LNCaP cells. The ether extract (E2) showed a dose-dependent cytotoxic response with a GI50 of 13 ppm in the LNCaP cell line. Examination of the apoptotic response induced by E2 and E3 paralleled the level of cell cytotoxicity observed in both cell lines. The methanol extract (E4) was the only extract that showed a time-, dose-, and estrogen-receptor-dependent stimulation of pS2 gene expression. On the other hand, the acetone extract (E3), which showed the highest degree of cytotoxicity, showed no transcription stimulation of pS2 in MCF-7 cells. Altogether, these data indicate that Bizzy contains unique active hormonal compounds that have specific biological properties that are cell line-dependent

  5. Neuroprotective effects of protocatechuic aldehyde against neurotoxin-induced cellular and animal models of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Xin Zhao

    Full Text Available Protocatechuic aldehyde (PAL has been reported to bind to DJ-1, a key protein involved in Parkinson's disease (PD, and exerts potential neuroprotective effects via DJ-1 in SH-SY5Y cells. In this study, we investigated the neuroprotective pharmacological effects of PAL against neurotoxin-induced cell and animal models of PD. In cellular models of PD, PAL markedly increased cell viability rates, mitochondrial oxidation-reduction activity and mitochondrial membrane potential, and reduced intracellular ROS levels to prevent neurotoxicity in PC12 cells. In animal models of PD, PAL reduced the apomorphine injection, caused turning in 6-OHDA treated rats, and increased the motor coordination and stride decreases in MPTP treated mice. Meanwhile, in an MPTP mouse model, PAL prevented a decrease of the contents of dopamine (DA and its metabolites in the striatum and TH-positive dopaminergic neuron loss in the substantia nigra (SN. In addition, PAL increased the protein expression of DJ-1 and reduced the level of α-synuclein in the SN of MPTP lesioned mice. PAL also increased the spine density in hippocampal CA1 neurons. The current study demonstrates that PAL can efficiently protect dopaminergic neurons against neurotoxin injury in vitro and in vivo, and that the potential mechanisms may be related to its effects in increasing DJ-1, decreasing α-synuclein and its growth-promoting effect on spine density.

  6. Lattice gas cellular automation model for rippling and aggregation in myxobacteria

    Science.gov (United States)

    Alber, Mark S.; Jiang, Yi; Kiskowski, Maria A.

    2004-05-01

    A lattice gas cellular automation (LGCA) model is used to simulate rippling and aggregation in myxobacteria. An efficient way of representing cells of different cell size, shape and orientation is presented that may be easily extended to model later stages of fruiting body formation. This LGCA model is designed to investigate whether a refractory period, a minimum response time, a maximum oscillation period and non-linear dependence of reversals of cells on C-factor are necessary assumptions for rippling. It is shown that a refractory period of 2-3 min, a minimum response time of up to 1 min and no maximum oscillation period best reproduce rippling in the experiments of Myxococcus xanthus. Non-linear dependence of reversals on C-factor is critical at high cell density. Quantitative simulations demonstrate that the increase in wavelength of ripples when a culture is diluted with non-signaling cells can be explained entirely by the decreased density of C-signaling cells. This result further supports the hypothesis that levels of C-signaling quantitatively depend on and modulate cell density. Analysis of the interpenetrating high density waves shows the presence of a phase shift analogous to the phase shift of interpenetrating solitons. Finally, a model for swarming, aggregation and early fruiting body formation is presented.

  7. Cellular replication limits in the Luria-Delbrück mutation model

    Science.gov (United States)

    Rodriguez-Brenes, Ignacio A.; Wodarz, Dominik; Komarova, Natalia L.

    2016-08-01

    Originally developed to elucidate the mechanisms of natural selection in bacteria, the Luria-Delbrück model assumed that cells are intrinsically capable of dividing an unlimited number of times. This assumption however, is not true for human somatic cells which undergo replicative senescence. Replicative senescence is thought to act as a mechanism to protect against cancer and the escape from it is a rate-limiting step in cancer progression. Here we introduce a Luria-Delbrück model that explicitly takes into account cellular replication limits in the wild type cell population and models the emergence of mutants that escape replicative senescence. We present results on the mean, variance, distribution, and asymptotic behavior of the mutant population in terms of three classical formulations of the problem. More broadly the paper introduces the concept of incorporating replicative limits as part of the Luria-Delbrück mutational framework. Guidelines to extend the theory to include other types of mutations and possible applications to the modeling of telomere crisis and fluctuation analysis are also discussed.

  8. Stability Analysis of a Hybrid Cellular Automaton Model of Cell Colony Growth

    CERN Document Server

    Gerlee, P

    2007-01-01

    Cell colonies of bacteria, tumour cells and fungi, under nutrient limited growth conditions, exhibit complex branched growth patterns. In order to investigate this phenomenon we present a simple hybrid cellular automaton model of cell colony growth. In the model the growth of the colony is limited by a nutrient that is consumed by the cells and which inhibits cell division if it falls below a certain threshold. Using this model we have investigated how the nutrient consumption rate of the cells affects the growth dynamics of the colony. We found that for low consumption rates the colony takes on a Eden-like morphology, while for higher consumption rates the morphology of the colony is branched with a fractal geometry. These findings are in agreement with previous results, but the simplicity of the model presented here allows for a linear stability analysis of the system. By observing that the local growth of the colony is proportional to the flux of the nutrient we derive an approximate dispersion relation fo...

  9. A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Qin; Ya-Nan Wang

    2012-01-01

    A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper.The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model.Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model),but also predict the realtime development pattern of BMC and BFE,as well as the dynamics of osteoblasts (OBA),osteoclasts (OCA),nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme,which can hardly be monitored through experiment.In conclusion,the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass.More importantly,this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated.The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies.Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

  10. Large-scale parallel lattice Boltzmann-cellular automaton model of two-dimensional dendritic growth

    Science.gov (United States)

    Jelinek, Bohumir; Eshraghi, Mohsen; Felicelli, Sergio; Peters, John F.

    2014-03-01

    An extremely scalable lattice Boltzmann (LB)-cellular automaton (CA) model for simulations of two-dimensional (2D) dendritic solidification under forced convection is presented. The model incorporates effects of phase change, solute diffusion, melt convection, and heat transport. The LB model represents the diffusion, convection, and heat transfer phenomena. The dendrite growth is driven by a difference between actual and equilibrium liquid composition at the solid-liquid interface. The CA technique is deployed to track the new interface cells. The computer program was parallelized using the Message Passing Interface (MPI) technique. Parallel scaling of the algorithm was studied and major scalability bottlenecks were identified. Efficiency loss attributable to the high memory bandwidth requirement of the algorithm was observed when using multiple cores per processor. Parallel writing of the output variables of interest was implemented in the binary Hierarchical Data Format 5 (HDF5) to improve the output performance, and to simplify visualization. Calculations were carried out in single precision arithmetic without significant loss in accuracy, resulting in 50% reduction of memory and computational time requirements. The presented solidification model shows a very good scalability up to centimeter size domains, including more than ten million of dendrites. Catalogue identifier: AEQZ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEQZ_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, UK Licensing provisions: Standard CPC license, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 29,767 No. of bytes in distributed program, including test data, etc.: 3131,367 Distribution format: tar.gz Programming language: Fortran 90. Computer: Linux PC and clusters. Operating system: Linux. Has the code been vectorized or parallelized?: Yes. Program is parallelized using MPI

  11. A trans-well-based cellular model for the rapid pre-evaluation of tympanic membrane repair materials.

    Science.gov (United States)

    Hung, Shih-Han; Su, Chin-Hui; Tseng, How

    2016-08-01

    It is important to have a standardized tympanic membrane (TM) perforation platform to evaluate the various myringoplasty materials that have been studied and developed extensively during recent years. However, currently there are no cellular models specifically designed for this purpose, and animal models remain unsatisfactory. The purpose of this study is to propose an inexpensive, readily available, well-controlled, and easy-to-create cellular model as a substitute for use in the evaluation of TM repairing materials. A trans-well model was created using a cell culture insert with a round hole created at the center of the polycarbonate membrane. HaCaT cells were cultured on the fenestrated culture insert, and the desired myringoplasty graft was placed at the center of the window for one week and observed by fluorescent microscopy under vital staining. Under this cellular model, there was notable migration of HaCaT cells onto the positive control graft (rabbit fascia), while only a few cell clusters were observed on the negative control graft (paper). Model validation showed that the cell migration ratio for the PLLA + 1% hyaluronic acid (HA) graft is significantly higher than using myringoplasty paper, poly L-lactide (PLLA), or PLLA + 0.5% HA (p < 0.05). This trans-well-based cellular model might be a useful pre-evaluation platform for the evaluation of TM repairing materials. The model is inexpensive, readily available, easy to create, and standardized for use. PMID:26335291

  12. Development of novel cellular model for affinity studies of histamine H(4) receptor ligands.

    Science.gov (United States)

    Karcz, Tadeusz; Kieć-Kononowicz, Katarzyna

    2013-01-01

    The G protein-coupled histamine H4 receptor (H4R) is the last member of histamine receptors family discovered so far. Its expression pattern, together with postulated involvement in a wide variety of immunological and inflammatory processes make histamine H4 receptor an interesting target for drug development. Potential H4R ligands may provide an innovative therapies for different immuno-based diseases, including allergy, asthma, pruritus associated with allergy or autoimmune skin conditions, rheumatoid arthritis and pain. However, none of successfully developed selective and potent histamine H4 receptor ligands have been introduced to the market up to date. For that reason there is still a strong demand for pharmacological models to be used in studies on potent H4R ligands. In current work we present the development of novel mammalian cell line, stably expressing human histamine H4 receptor, with use of retroviral transduction approach. Obtained cell line was pharmacologically characterized in radioligand binding studies and its utility for affinity testing of potent receptor ligands was confirmed in comparative studies with the use of relevant insect cells expression model. Obtained results allow for statement that developed cellular model may be successfully employed in search for new compounds active at histamine H4 receptor. PMID:24432340

  13. Effect of Driver Scope Awareness in the Lane Changing Maneuvers Using Cellular Automaton Model

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-07-01

    Full Text Available This paper investigated the effect of drivers’ visibility and their perception (e.g., to estimate the speed and arrival time of another vehicle on the lane changing maneuver. The term of scope awareness was used to describe the visibility required by the driver to make a perception about road condition and the speed of vehicle that exist in that road. A computer simulation model was conducted to show this driver awareness behavior. This studying attempt to precisely catching the lane changing behavior and illustrate the scope awareness parameter that reflects driver behavior. This paper proposes a simple cellular automata model for studying driver visibility effects of lane changing maneuver and driver perception of estimated speed. Different values of scope awareness were examined to capture its effect on the traffic flow. Simulation results show the ability of this model to capture the important features of lane changing maneuver and revealed the appearance of the short-thin solid line jam and the wide solid line jam in the traffic flow as the consequences of lane changing maneuver.

  14. Simulation of estrogen transport and behavior in laboratory soil columns using a cellular automata model

    Science.gov (United States)

    Chen, Qingcai; Shi, Jianghong; Liu, Xiaowei; Wu, Wei; Liu, Bo; Zhang, Hui

    2013-03-01

    A cellular automata model (CA model) was used to simulate the soil column leaching process of estrogens during the processes of migration and transformation. The results of the simulated leaching experiment showed that the first-order degradation rates of 17α-ethynylestradiol (EE2), 17β-estradiol (E2) and estrone (E1) were 0.131 h- 1 for E2, 0.099 h- 1 for E1 and 0.064 h- 1 for EE2 in the EE2 and E2 leaching process, and the first-order sorption rates were 5.94 h- 1 for E2, 5.63 h- 1 for EE2, 3.125 h- 1 for E1. Their sorption rates were positively correlated with the n-octanol/water partition coefficients. When the diffusion rate was low, its impact on the simulation results was insignificant. The increase in sorption and degradation rates caused the decrease in the total estrogens that leached. In addition, increasing the sorption rate could delay the emerging time of the maximum concentration of estrogen that leached, whereas increasing the degradation rate could shorten the emerging time of the maximum concentration of estrogen that leached. The comparison made between the experimental data and the simulation results of the CA model and the HYDRUS-1D software showed that the establishment of one-component and multi-component CA models could simulate EE2 and E2 soil column leaching processes, and the CA models achieve an intuitive, dynamic, and visual simulation.

  15. Load-aware modeling for uplink cellular networks in a multi-channel environment

    KAUST Repository

    Alammouri, Ahmad Mohammad Abdel-Karim

    2014-09-01

    We exploit tools from stochastic geometry to develop a tractable analytical approach for modeling uplink cellular networks. The developed model is load aware and accounts for per-user power control as well as the limited transmit power constraint for the users\\' equipment (UEs). The proposed analytical paradigm is based on a simple per-user power control scheme in which each user inverts his path-loss such that the signal is received at his serving base station (BS) with a certain power threshold ρ Due to the limited transmit power of the UEs, users that cannot invert their path-loss to their serving BSs are allowed to transmit with their maximum transmit power. We show that the proposed power control scheme not only provides a balanced cell center and cell edge user performance, it also facilitates the analysis when compared to the state-of-the-art approaches in the literature. To this end, we discuss how to manipulate the design variable ρ in response to the network parameters to optimize one or more of the performance metrics such as the outage probability, the network capacity, and the energy efficiency.

  16. Cellular responses to disruption of the permeability barrier in a three-dimensional organotypic epidermal model

    International Nuclear Information System (INIS)

    Repeated injury to the stratum corneum of mammalian skin (caused by friction, soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening. Functionally, these changes serve to restore the cutaneous barrier and protect the organism. To better understand the molecular and cellular basis of this response, we have engineered an in vitro model of acetone-induced injury using organotypic epidermal cultures. Rat epidermal keratinocytes (REKs), grown on a collagen raft in the absence of any feeder fibroblasts, developed all the hallmarks of a true epidermis including a well-formed cornified layer. To induce barrier injury, REK cultures were treated with intermittent 30-s exposures to acetone then were fixed and paraffin-sectioned. After two exposures, increased proliferation (Ki67 and BrdU staining) was observed in basal and suprabasal layers. After three exposures, proliferation became confined to localized buds in the basal layer and increased terminal differentiation was observed (compact hyperkeratosis of the stratum corneum, elevated levels of K10 and filaggrin, and heightened transglutaminase activity). Thus, barrier disruption causes epidermal hyperplasia and/or enhances differentiation, depending upon the extent and duration of injury. Given that no fibroblasts are present in the model, the ability to mount a hyperplastic response to barrier injury is an inherent property of keratinocytes

  17. Theoretical models and simulation codes to investigate bystander effects and cellular communication at low doses

    Science.gov (United States)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Mairani, A.; Nano, R.; Ottolenghi, A.

    Astronauts in space are continuously exposed to low doses of ionizing radiation from Galactic Cosmic Rays During the last ten years the effects of low radiation doses have been widely re-discussed following a large number of observations on the so-called non targeted effects in particular bystander effects The latter consist of induction of cytogenetic damage in cells not directly traversed by radiation most likely as a response to molecular messengers released by directly irradiated cells Bystander effects which are observed both for lethal endpoints e g clonogenic inactivation and apoptosis and for non-lethal ones e g mutations and neoplastic transformation tend to show non-linear dose responses This might have significant consequences in terms of low-dose risk which is generally calculated on the basis of the Linear No Threshold hypothesis Although the mechanisms underlying bystander effects are still largely unknown it is now clear that two types of cellular communication i e via gap junctions and or release of molecular messengers into the extracellular environment play a fundamental role Theoretical models and simulation codes can be of help in elucidating such mechanisms In the present paper we will review different available modelling approaches including one that is being developed at the University of Pavia The focus will be on the different assumptions adopted by the various authors and on the implications of such assumptions in terms of non-targeted radiobiological damage and more generally low-dose

  18. Detection and Projection of Forest Changes by Using the Markov Chain Model and Cellular Automata

    Directory of Open Access Journals (Sweden)

    Griselda Vázquez-Quintero

    2016-03-01

    Full Text Available The spatio-temporal analysis of land use changes could provide basic information for managing the protection, conservation and production of forestlands, which promotes a sustainable resource use of temperate ecosystems. In this study we modeled and analyzed the spatial and temporal dynamics of land use of a temperate forests in the region of Pueblo Nuevo, Durango, Mexico. Data from the Landsat images Multispectral Scanner (MSS 1973, Thematic Mapper (TM 1990, and Operational Land Imager (OLI 2014 were used. Supervised classification methods were then applied to generate the land use for these years. To validate the land use classifications on the images, the Kappa coefficient was used. The resulting Kappa coefficients were 91%, 92% and 90% for 1973, 1990 and 2014, respectively. The analysis of the change dynamics was assessed with Markov Chains and Cellular Automata (CA, which are based on probabilistic modeling techniques. The Markov Chains and CA show constant changes in land use. The class most affected by these changes is the pine forest. Changes in the extent of temperate forest of the study area were further projected until 2028, indicating that the area of pine forest could be continuously reduced. The results of this study could provide quantitative information, which represents a base for assessing the sustainability in the management of these temperate forest ecosystems and for taking actions to mitigate their degradation.

  19. Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

    KAUST Repository

    Li, YZ

    2014-08-01

    Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

  20. Tectonic modeling of Konya-Beysehir Region (Turkey using cellular neural networks

    Directory of Open Access Journals (Sweden)

    D. Aydogan

    2007-06-01

    Full Text Available In this paper, to separate regional-residual anomaly maps and to detect borders of buried geological bodies, we applied the Cellular Neural Network (CNN approach to gravity and magnetic anomaly maps. CNN is a stochastic image processing technique, based optimization of templates, which imply relationships of neighborhood pixels in 2-Dimensional (2D potential anomalies. Here, CNN performance in geophysics, tested by various synthetic examples and the results are compared to classical methods such as boundary analysis and second vertical derivatives. After we obtained satisfactory results in synthetic models, we applied CNN to Bouguer anomaly map of Konya-Beysehir Region, which has complex tectonic structure with various fault combinations. We evaluated CNN outputs and 2D/3D models, which are constructed using forward and inversion methods. Then we presented a new tectonic structure of Konya-Beysehir Region. We have denoted (F1, F2, …, F7 and (Konya1, Konya2 faults according to our evaluations of CNN outputs. Thus, we have concluded that CNN is a compromising stochastic image processing technique in geophysics.

  1. Renal Contrast-Enhanced Sonography Findings in a Model of Acute Cellular Allograft Rejection.

    Science.gov (United States)

    Grabner, A; Kentrup, D; Pawelski, H; Mühlmeister, M; Biermann, C; Edemir, B; Heitplatz, B; Van Marck, V; Bettinger, T; Pavenstädt, H; Schlatter, E; Stypmann, J; Tiemann, K; Reuter, S

    2016-05-01

    Noninvasive methods to diagnose and differentiate acute cellular rejection from acute tubular necrosis or acute calcineurin inhibitor toxicity are still missing. Because T lymphocytes play a decisive role in early states of rejection, we investigated the suitability and feasibility of antibody-mediated contrast-enhanced ultrasound by using microbubbles targeted to CD3(+) , CD4(+) , or CD8(+) T cells in different models of renal disease. In an established rat renal transplantation model, CD3-mediated ultrasound allows the detection of acute rejection as early as on postoperative day 2. Ultrasound signal intensities increased with the severity of inflammation. Further, an early response to therapy could be monitored by using contrast-enhanced sonography. Notably, acute tubular necrosis occurring after ischemia-reperfusion injury as well as acute calcineurin inhibitor toxicity could easily be differentiated. Finally, the quantified ultrasound signal correlated significantly with the number of infiltrating T cells obtained by histology and with CD3 mRNA levels, as well as with chemokine CXCL9, CXCL11, and CCL19 mRNA but not with KIM-1 mRNA expression, thereby representing the severity of graft inflammation but not the degree of kidney injury. In summary, we demonstrate that antibody-mediated contrast-enhanced ultrasound targeting T lymphocytes could be a promising tool for an easy and reproducible assessment of acute rejection after renal transplantation. PMID:26613381

  2. Model of Handover and Traffic Based on Cellular Geometry with Smart Antenna

    OpenAIRE

    Zufan Zhang; Jie Zhang; Shaohui Sun

    2014-01-01

    Based on the application of smart antennas in cellular mobile communications, this paper introduces the impact of the width of the antenna beams playing on the dwell time probability density function in cellular geometry with smart antenna. The research results indicate that the smart cell structure can improve the dwell time of users within the cell and improve the traffic system performance.

  3. Simulating debris flows through a hexagonal cellular automata model: SCIDDICA S3–hex

    Directory of Open Access Journals (Sweden)

    D. D’Ambrosio

    2003-01-01

    Full Text Available Cellular Automata (CA represent a formal frame for dynamical systems, which evolve on the base of local interactions. Some types of landslide, such as debris flows, match well this requirement. The latest hexagonal release (S3–hex of the deterministic model SCIDDICA, specifically developed for simulating debris flows, is described. For CA simulation purposes, landslides can be viewed as a dynamical system, subdivided into elementary parts, whose state evolves exclusively as a consequence of local interactions within a spatial and temporal discretum. Space is the world of the CA, here constituted by hexagonal cells. The attributes of each cell ("substates" describe physical characteristics. For computational reasons, the natural phenomenon is "decomposed" into a number of elementary processes, whose proper composition makes up the "transition function" of the CA. By simultaneously applying this function to all the cells, the evolution of the phenomenon can be simulated in terms of modifications of the substates. SCIDDICA S3–hex exhibits a great flexibility in modelling debris flows. With respect to the previous releases of the model, the mechanism of progressive erosion of the soil cover has been added to the transition function. Considered substates are: altitude; thickness and energy of landslide debris; depth of erodable soil cover; debris outflows. Considered elementary processes are: mobilisation triggering and effect (T1, debris outflows (I1, update of landslide debris thickness and energy (I2, and energy loss (T2.  Simulations of real debris flows, occurred in Campania (Southern Italy in May 1998 (Sarno and December 1999 (San Martino V.C. and Cervinara, have been performed for model calibration purposes; some examples of analysis are briefly described. Possible applications of the method are: risk mapping, also based on a statistical approach; evaluating the effects of mitigation actions (e.g. stream deviations, topographic

  4. Evolving Transport Networks With Cellular Automata Models Inspired by Slime Mould.

    Science.gov (United States)

    Tsompanas, Michail-Antisthenis I; Sirakoulis, Georgios Ch; Adamatzky, Andrew I

    2015-09-01

    Man-made transport networks and their design are closely related to the shortest path problem and considered amongst the most debated problems of computational intelligence. Apart from using conventional or bio-inspired computer algorithms, many researchers tried to solve this kind of problem using biological computing substrates, gas-discharge solvers, prototypes of a mobile droplet, and hot ice computers. In this aspect, another example of biological computer is the plasmodium of acellular slime mould Physarum polycephalum (P. polycephalum), which is a large single cell visible by an unaided eye and has been proven as a reliable living substrate for implementing biological computing devices for computational geometry, graph-theoretical problems, and optimization and imitation of transport networks. Although P. polycephalum is easy to experiment with, computing devices built with the living slime mould are extremely slow; it takes slime mould days to execute a computation. Consequently, mapping key computing mechanisms of the slime mould onto silicon would allow us to produce efficient bio-inspired computing devices to tackle with hard to solve computational intelligence problems like the aforementioned. Toward this direction, a cellular automaton (CA)-based, Physarum-inspired, network designing model is proposed. This novel CA-based model is inspired by the propagating strategy, the formation of tubular networks, and the computing abilities of the plasmodium of P. polycephalum. The results delivered by the CA model demonstrate a good match with several previously published results of experimental laboratory studies on imitation of man-made transport networks with P. polycephalum. Consequently, the proposed CA model can be used as a virtual, easy-to-access, and biomimicking laboratory emulator that will economize large time periods needed for biological experiments while producing networks almost identical to the tubular networks of the real-slime mould. PMID

  5. fA cellular automaton model of crystalline cellulose hydrolysis by cellulases

    Directory of Open Access Journals (Sweden)

    Little Bryce A

    2011-10-01

    Full Text Available Abstract Background Cellulose from plant biomass is an abundant, renewable material which could be a major feedstock for low emissions transport fuels such as cellulosic ethanol. Cellulase enzymes that break down cellulose into fermentable sugars are composed of different types - cellobiohydrolases I and II, endoglucanase and β-glucosidase - with separate functions. They form a complex interacting network between themselves, soluble hydrolysis product molecules, solution and solid phase substrates and inhibitors. There have been many models proposed for enzymatic saccharification however none have yet employed a cellular automaton approach, which allows important phenomena, such as enzyme crowding on the surface of solid substrates, denaturation and substrate inhibition, to be considered in the model. Results The Cellulase 4D model was developed de novo taking into account the size and composition of the substrate and surface-acting enzymes were ascribed behaviors based on their movements, catalytic activities and rates, affinity for, and potential for crowding of, the cellulose surface, substrates and inhibitors, and denaturation rates. A basic case modeled on literature-derived parameters obtained from Trichoderma reesei cellulases resulted in cellulose hydrolysis curves that closely matched curves obtained from published experimental data. Scenarios were tested in the model, which included variation of enzyme loadings, adsorption strengths of surface acting enzymes and reaction periods, and the effect on saccharide production over time was assessed. The model simulations indicated an optimal enzyme loading of between 0.5 and 2 of the base case concentrations where a balance was obtained between enzyme crowding on the cellulose crystal, and that the affinities of enzymes for the cellulose surface had a large effect on cellulose hydrolysis. In addition, improvements to the cellobiohydrolase I activity period substantially improved overall

  6. Computer Experiment on the Complex Behavior of a Two-Dimensional Cellular Automaton as a Phenomenological Model for an Ecosystem

    Science.gov (United States)

    Satoh, Kazuhiro

    1989-10-01

    Numerical studies are made on the complex behavior of a cellular automaton which serves as a phenomenological model for an ecosystem. The ecosystem is assumed to contain only three populations, i.e., a population of plants, of herbivores, and of carnivores. A two-dimensional region where organisms live is divided into square cells and the population density in each cell is regarded as a discrete variable. The influence of the physical environment and the interactions between organisms are reduced to a simple rule of cellular automaton evolution. It is found that the time dependent spatial distribution of organisms is, in general, very random and complex. However, under certain conditions, the self-organization of ordered patterns such as rotating spirals or concentric circles takes place. The relevance of the cellular automaton as a model for the ecosystem is discussed.

  7. Analyzing the Influence of Mobile Phone Use of Drivers on Traffic Flow Based on an Improved Cellular Automaton Model

    OpenAIRE

    Yao Xiao; Jing Shi

    2015-01-01

    This paper aimed to analyze the influence of drivers’ behavior of phone use while driving on traffic flow, including both traffic efficiency and traffic safety. An improved cellular automaton model was proposed to simulate traffic flow with distracted drivers based on the Nagel-Schreckenberg model. The driving characters of drivers using a phone were first discussed and a value representing the probability to use a phone while driving was put into the CA model. Simulation results showed that ...

  8. A cellular automata model for population expansion of Spartina alterniflora at Jiuduansha Shoals, Shanghai, China

    Science.gov (United States)

    Huang, Hua-mei; Zhang, Li-quan; Guan, Yu-juan; Wang, Dong-hui

    2008-03-01

    Biological invasion has received considerable attention recently because of increasing impacts on local ecosystems. Expansion of Spartina alterniflora, a non-native species, on the intertidal mudflats of Jiuduansha Shoals at the Yangtze River Estuary is a prime example of a spatially-structured invasion in a relatively simple habitat, for which strategic control efforts can be modeled and applied. Here, we developed a Cellular Automata (CA) model, in conjunction with Remote Sensing and Geographical Information Systems, to simulate the expanding process of S. alterniflora for a period of 8 years after being introduced to the new shoals, and to study the interactions between spatial pattern and ecosystem processes for the saltmarsh vegetation. The results showed that the CA model could simulate the population dynamics of S. alterniflora and Phragmites australis on the Jiuduansha Shoals successfully. The results strongly support the hypothesis of space pre-emption as well as range expansion with simple advancing wave fronts for these two species. In the Yangtze River Estuary, the native species P. australis shares the same niche with the exotic species S. alterniflora. However, the range expansion rate of P. australis was much slower than that of S. alterniflora. With the accretion of the Jiuduansha Shoals due to the large quantity of sediments deposited by the Yangtze River, a rapid range expansion of S. alterniflora is predicted to last for a long period into future. This study indicated the potential for this approach to provide valuable insights into population and community ecology of invasive species, which could be very important for wetland biodiversity conservation and resource management in the Yangtze River Estuary and other such impacted areas.

  9. Modeling and Simulation of Polarization in Internet Group Opinions Based on Cellular Automata

    Directory of Open Access Journals (Sweden)

    Yaofeng Zhang

    2015-01-01

    Full Text Available Hot events on Internet always attract many people who usually form one or several opinion camps through discussion. For the problem of polarization in Internet group opinions, we propose a new model based on Cellular Automata by considering neighbors, opinion leaders, and external influences. Simulation results show the following: (1 It is easy to form the polarization for both continuous opinions and discrete opinions when we only consider neighbors influence, and continuous opinions are more effective in speeding the polarization of group. (2 Coevolution mechanism takes more time to make the system stable, and the global coupling mechanism leads the system to consensus. (3 Opinion leaders play an important role in the development of consensus in Internet group opinions. However, both taking the opinion leaders as zealots and taking some randomly selected individuals as zealots are not conductive to the consensus. (4 Double opinion leaders with consistent opinions will accelerate the formation of group consensus, but the opposite opinions will lead to group polarization. (5 Only small external influences can change the evolutionary direction of Internet group opinions.

  10. In silico analyses of dystrophin Dp40 cellular distribution, nuclear export signals and structure modeling

    Directory of Open Access Journals (Sweden)

    Alejandro Martínez-Herrera

    2015-09-01

    Full Text Available Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids 93LEQEHNNLV101 and 168LLLHDSIQI176 could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here are related to the research article entitled “EF-hand domains are involved in the differential cellular distribution of dystrophin Dp40” (J. Aragón et al. Neurosci. Lett. 600 (2015 115–120 [1].

  11. Optimized parallel computing for cellular automaton–finite element modeling of solidification grain structures

    International Nuclear Information System (INIS)

    A numerical implementation of a three-dimensional (3D) cellular automaton (CA)–finite element (FE) model has been developed for the prediction of solidification grain structures. For the first time, it relies on optimized parallel computation to solve industrial-scale problems (centimeter to meter long) while using a sufficiently small CA grid size to predict representative structures. Several algorithm modifications and strategies to maximize parallel efficiency are introduced. Improvements on a real case simulation are measured and discussed. The CA–FE implementation here is demonstrated using 32 computing units to predict grain structure in a 2.08 m × 0.382 m × 0.382 m ingot involving 4.9 billion cells and 1.6 million grains. These numerical improvements permit tracking of local changes in texture and grain size over real-cast parts while integrating interactions with macrosegregation, heat flow and fluid flow. Full 3D is essential in all these analyses, and can be dealt with successfully using the implementation presented here. (paper)

  12. Modeling mechanical behaviors of composites with various ratios of matrixeinclusion properties using movable cellular automaton method

    Institute of Scientific and Technical Information of China (English)

    A.Yu. SMOLIN; E.V. SHILKO; S.V. ASTAFUROV; I.S. KONOVALENKO; S.P. BUYAKOVA; S.G. PSAKHIE

    2015-01-01

    Two classes of composite materials are considered: classical metaleceramic composites with reinforcing hard inclusions as well as hard ceramics matrix with soft gel inclusions. Movable cellular automaton method is used for modeling the mechanical behaviors of such different heterogeneous materials. The method is based on particle approach and may be considered as a kind of discrete element method. The main feature of the method is the use of many-body forces of inter-element interaction within the formalism of simply deformable element approximation. It was shown that the strength of reinforcing particles and the width of particle-binder interphase boundaries had determining influence on the service characteristics of metaleceramic composite. In particular, the increasing of strength of carbide inclusions may lead to significant increase in the strength and ultimate strain of composite material. On the example of porous zirconia ceramics it was shown that the change in the mechanical properties of pore surface leads to the corresponding change in effective elastic modulus and strength limit of the ceramic sample. The less is the pore size, the more is this effect. The increase in the elastic properties of pore surface of ceramics may reduce its fracture energy.

  13. Computer simulation of a cellular automata model for the immune response in a retrovirus system

    Science.gov (United States)

    Pandey, R. B.

    1989-02-01

    Immune response in a retrovirus system is modeled by a network of three binary cell elements to take into account some of the main functional features of T4 cells, T8 cells, and viruses. Two different intercell interactions are introduced, one of which leads to three fixed points while the other yields bistable fixed points oscillating between a healthy state and a sick state in a mean field treatment. Evolution of these cells is studied for quenched and annealed random interactions on a simple cubic lattice with a nearest neighbor interaction using inhomogenous cellular automata. Populations of T4 cells and viral cells oscillate together with damping (with constant amplitude) for annealed (quenched) interaction on increasing the value of mixing probability B from zero to a characteristic value B ca ( B cq). For higher B, the average number of T4 cells increases while that of the viral infected cells decreases monotonically on increasing B, suggesting a phase transition at B ca ( B cq).

  14. Lateral Drift Behavior Analysis in Mixed Bicycle Traffic: A Cellular Automaton Model Approach

    Directory of Open Access Journals (Sweden)

    Xue Feng

    2016-01-01

    Full Text Available Bicycle movements are always associated with lateral drifts. However, the impacts of lateral drift behavior, as well as variable lateral clearance maintaining behavior due to the variation of drift intensity, on mixed bicycle flow are not clear. This paper establishes a new cellular automata model to study typical characteristics of mixed bicycle traffic induced by lateral drift and its accompanying behavior. Based on derived positive correlation between passing speed and drift speed through survey, the occurrence probability of lateral drift and the degree of maintained lateral clearance are both introduced in accordance with the variance of passing speed. Then, in whole density region, firm conformity between simulation results and actual survey data is reached, which has seldom been achieved in previous studies. It is further verified that speed distortions in intermediate and high density region induced by assumption of constant lateral clearance requirements can be revised by introducing its variability characteristics. In addition, two contrastive impacts of lateral drift behavior are observed. That is, it causes speed fluctuation in low density while alleviating the speed fluctuation in relatively high density. These results are expected to be helpful to improve the simulation performance of mixed bicycle flow as well as depict more realistic vehicle-bicycle conflicts and so on.

  15. Path Loss, Shadow Fading, and Line-Of-Sight Probability Models for 5G Urban Macro-Cellular Scenarios

    DEFF Research Database (Denmark)

    Sun, Shu; Thomas, Timothy; Rappaport, Theodore S.;

    2015-01-01

    This paper presents key parameters including the line-of-sight (LOS) probability, large-scale path loss, and shadow fading models for the design of future fifth generation (5G) wireless communication systems in urban macro-cellular (UMa) scenarios, using the data obtained from propagation...

  16. Modeling kinematic hardening in a dispersion strengthened aluminum alloy using a stochastic cellular automation

    International Nuclear Information System (INIS)

    Full text: The Bauschinger effect refers to an observed asymmetry in the forward and reverse loading curves of a metal or an alloy. Typically, the absolute value of the yield stress in reverse loading is lower than the maximum stress imposed on the initial, forward loading. This difference arises from either the presence of a back stress or from the greater strength of obstacles opposing dislocation motion in the forward than in the reverse direction. Thus, the Bauschinger effect contributes to the phenomena referred to as kinematic hardening. In particular dispersion hardened systems, containing strong, non-shearable particles that offer obstacles to dislocation motion, will often exhibit a large kinematic hardening component. When a material is described as a group of parallel elements (a composite) having variable yield stresses and or Young's moduli, kinematic hardening of type KI, is observed when the first element to yield on forward loading is the first element to yield on reverse loading. Kinematic hardening types KII and KIII result when the order of relaxation of the elements is different from the order of their initial yielding. The reverse loading curves for types KII and KIII hardening generally exhibit inflection points at the initiation of yielding on reverse loading. In previous work, a micromechanics model, with a detailed description of the microstructure, was employed to model the effects of plastic inhomogeneity and duplicate the loading and unloading trends observed experimentally. Trends predicted by the model corresponded well to some of the expectations derived from observation, e.g. the effects related to the inclusions of different phases, however in some cases the correlation depended on the assignment of unrealistic properties to microstructural constituents. In the current work, the material is modeled as an array of coupled elements with varying stiffnesses and strengths. A stochastic cellular automaton is then used to simulate the

  17. Recurrence time statistics of landslide events simulated by a cellular automaton model

    Science.gov (United States)

    Piegari, Ester; Di Maio, Rosa; Avella, Adolfo

    2014-05-01

    The recurrence time statistics of a cellular automaton modelling landslide events is analyzed by performing a numerical analysis in the parameter space and estimating Fano factor behaviors. The model is an extended version of the OFC model, which is a paradigm for SOC in non-conserved systems, but it works differently from the original OFC model as a finite value of the driving rate is applied. By driving the system to instability with different rates, the model exhibits a smooth transition from a correlated to an uncorrelated regime as the effect of a change in predominant mechanisms to propagate instability. If the rate at which instability is approached is small, chain processes dominate the landslide dynamics, and power laws govern probability distributions. However, the power-law regime typical of SOC-like systems is found in a range of return intervals that becomes shorter and shorter by increasing the values of the driving rates. Indeed, if the rates at which instability is approached are large, domino processes are no longer active in propagating instability, and large events simply occur because a large number of cells simultaneously reach instability. Such a gradual loss of the effectiveness of the chain propagation mechanism causes the system gradually enter to an uncorrelated regime where recurrence time distributions are characterized by Weibull behaviors. Simulation results are qualitatively compared with those from a recent analysis performed by Witt et al.(Earth Surf. Process. Landforms, 35, 1138, 2010) for the first complete databases of landslide occurrences over a period as large as fifty years. From the comparison with the extensive landslide data set, the numerical analysis suggests that statistics of such landslide data seem to be described by a crossover region between a correlated regime and an uncorrelated regime, where recurrence time distributions are characterized by power-law and Weibull behaviors for short and long return times

  18. Model of Handover and Traffic Based on Cellular Geometry with Smart Antenna

    Directory of Open Access Journals (Sweden)

    Zufan Zhang

    2014-01-01

    Full Text Available Based on the application of smart antennas in cellular mobile communications, this paper introduces the impact of the width of the antenna beams playing on the dwell time probability density function in cellular geometry with smart antenna. The research results indicate that the smart cell structure can improve the dwell time of users within the cell and improve the traffic system performance.

  19. Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia.

    Directory of Open Access Journals (Sweden)

    Nathalie Boone

    Full Text Available BACKGROUND: Familial dysautonomia (FD is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells. METHODOLOGY/PRINCIPAL FINDINGS: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion:MU (exon 20 skipping ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation. CONCLUSIONS/SIGNIFICANCE: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better

  20. The Use of Amnion-Derived Cellular Cytokine Solution to Improve Healing in Acute and Chronic Wound Models

    OpenAIRE

    Franz, Michael G.; Payne, Wyatt G.; Xing, Liyu; Naidu, D. K; Salas, R. E; Marshall, Vivienne S.; Trumpower, C. J; Smith, Charlotte A; Steed, David L.; Robson, M. C.

    2008-01-01

    Objective: Growth factors demonstrate mixed results improving wound healing. Amnion-derived multipotent cells release physiologic levels of growth factors and tissue inhibitors of metalloproteinases. This solution was tested in models of acute and chronic wound healing. Methods: Acute model: Sprague-Dawley rats underwent laparotomy incisions. The midline fascia was primed with phosphate-buffered saline, unconditioned media, or amnion-derived cellular cytokine suspension prior to incision. Bre...

  1. Secure D2D Communication in Large-Scale Cognitive Cellular Networks: A Wireless Power Transfer Model

    OpenAIRE

    Liu, Yuanwei; Wang, Lifeng; Zaidi, Syed Ali Raza; Elkashlan, Maged; Duong, Trung Q.

    2015-01-01

    In this paper, we investigate secure device-to-device (D2D) communication in energy harvesting large-scale cognitive cellular networks. The energy constrained D2D transmitter harvests energy from multiantenna equipped power beacons (PBs), and communicates with the corresponding receiver using the spectrum of the primary base stations (BSs). We introduce a power transfer model and an information signal model to enable wireless energy harvesting and secure information transmission. In the power...

  2. Effect of preoperative immunonutrition and other nutrition models on cellular immune parameters

    Institute of Scientific and Technical Information of China (English)

    Yusuf Gunerhan; Neset Koksal; Umit Yasar Sahin; Mehmet Ali Uzun; Emel Ek(s)ioglu-Demiralp

    2009-01-01

    AIM: To evaluate the effects of preoperative immunonutrition and other nutrition models on the cellular immunity parameters of patients with gastrointestinal tumors before surgical intervention. In addition, effects on postoperative complications were examined.METHODS: Patients with gastrointestinal tumors were randomized into 3 groups. The immunonutrition group received a combination of arginine, fatty acids and nucleotides. The second and third group received normal nutrition and standard enteral nutrition,respectively. Nutrition protocols were administered for 7 d prior to the operation. Nutritional parameters,in particular prealbumin levels and lymphocyte subpopulations (CD4+, CD8+, CD16+/56+, and CD69 cells) were evaluated before and after the nutrition protocols. Groups were compared in terms of postoperative complications and duration of hospital stay.RESULTS: Of the 42 patients who completed the study, 16 received immunonutrition, 13 received normal nutrition and 13 received standard enteral nutrition.prealbumin values were low in every group, but this parameter was improved after the nutritional protocol only in the immunonutrition group (13.64 ± 8.83vs 15.98 ± 8.66, P = 0.037). Groups were similar in terms of CD4+, CD16+/56, and CD69+ prior to the nutritional protocol; whereas CD8+ was higher in the standard nutrition group compared to the immunonutrition group. After nutritional protocols,none of the groups had an increase in their lymphocyte subpopulations. Also, groups did not differ in terms of postoperative complications and postoperative durations of hospital stay.CONCLUSION: Preoperative immunonutrition provided a significant increase in prealbumin levels,while it did not significantly alter T lymphocyte subpopulation counts, the rate of postoperative complications and the duration of hospital stay.

  3. On stochastic geometry modeling of cellular uplink transmission with truncated channel inversion power control

    KAUST Repository

    Elsawy, Hesham

    2014-08-01

    Using stochastic geometry, we develop a tractable uplink modeling paradigm for outage probability and spectral efficiency in both single and multi-tier cellular wireless networks. The analysis accounts for per user equipment (UE) power control as well as the maximum power limitations for UEs. More specifically, for interference mitigation and robust uplink communication, each UE is required to control its transmit power such that the average received signal power at its serving base station (BS) is equal to a certain threshold ρo. Due to the limited transmit power, the UEs employ a truncated channel inversion power control policy with a cutoff threshold of ρo. We show that there exists a transfer point in the uplink system performance that depends on the following tuple: BS intensity λ, maximum transmit power of UEs Pu, and ρo. That is, when Pu is a tight operational constraint with respect to (w.r.t.) λ and ρo, the uplink outage probability and spectral efficiency highly depend on the values of λ and ρo. In this case, there exists an optimal cutoff threshold ρ*o, which depends on the system parameters, that minimizes the outage probability. On the other hand, when Pu is not a binding operational constraint w.r.t. λ and ρo, the uplink outage probability and spectral efficiency become independent of λ and ρo. We obtain approximate yet accurate simple expressions for outage probability and spectral efficiency, which reduce to closed forms in some special cases. © 2002-2012 IEEE.

  4. A computational model of cellular mechanisms of temporal coding in the medial geniculate body (MGB.

    Directory of Open Access Journals (Sweden)

    Cal F Rabang

    Full Text Available Acoustic stimuli are often represented in the early auditory pathway as patterns of neural activity synchronized to time-varying features. This phase-locking predominates until the level of the medial geniculate body (MGB, where previous studies have identified two main, largely segregated response types: Stimulus-synchronized responses faithfully preserve the temporal coding from its afferent inputs, and Non-synchronized responses, which are not phase locked to the inputs, represent changes in temporal modulation by a rate code. The cellular mechanisms underlying this transformation from phase-locked to rate code are not well understood. We use a computational model of a MGB thalamocortical neuron to test the hypothesis that these response classes arise from inferior colliculus (IC excitatory afferents with divergent properties similar to those observed in brain slice studies. Large-conductance inputs exhibiting synaptic depression preserved input synchrony as short as 12.5 ms interclick intervals, while maintaining low firing rates and low-pass filtering responses. By contrast, small-conductance inputs with Mixed plasticity (depression of AMPA-receptor component and facilitation of NMDA-receptor component desynchronized afferent inputs, generated a click-rate dependent increase in firing rate, and high-pass filtered the inputs. Synaptic inputs with facilitation often permitted band-pass synchrony along with band-pass rate tuning. These responses could be tuned by changes in membrane potential, strength of the NMDA component, and characteristics of synaptic plasticity. These results demonstrate how the same synchronized input spike trains from the inferior colliculus can be transformed into different representations of temporal modulation by divergent synaptic properties.

  5. Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available Dysregulation of Ras and Rho family small GTPases drives the invasion and metastasis of multiple cancers. For their biological functions, these GTPases require proper subcellular localization to cellular membranes, which is regulated by a series of post-translational modifications that result in either farnesylation or geranylgeranylation of the C-terminal CAAX motif. This concept provided the rationale for targeting farnesyltransferase (FTase and geranylgeranyltransferases (GGTase for cancer treatment. However, the resulting prenyl transferase inhibitors have not performed well in the clinic due to issues with alternative prenylation and toxicity. As an alternative, we have developed a unique class of potential anti-cancer therapeutics called Prenyl Function Inhibitors (PFIs, which are farnesol or geranyl-geraniol analogs that act as alternate substrates for FTase or GGTase. Here, we test the ability of our lead PFIs, anilinogeraniol (AGOH and anilinofarnesol (AFOH, to block the invasion of breast cancer cells. We found that AGOH treatment effectively decreased invasion of MDA-MB-231 cells in a two-dimensional (2D invasion assay at 100 µM while it blocked invasive growth in three-dimensional (3D culture model at as little as 20 µM. Notably, the effect of AGOH on 3D invasive growth was phenocopied by electroporation of cells with C3 exotransferase. To determine if RhoA and RhoC were direct targets of AGOH, we performed Rho activity assays in MDA-MB-231 and MDA-MB-468 cells and found that AGOH blocked RhoA and RhoC activation in response to LPA and EGF stimulation. Notably, the geranylgeraniol analog AFOH was more potent than AGOH in inhibiting RhoA and RhoC activation and invasive growth. Interestingly, neither AGOH nor AFOH impacted 3D growth of MCF10A cells. Collectively, this study demonstrates that AGOH and AFOH dramatically inhibit breast cancer invasion, at least in part by blocking Rho function, thus, suggesting that targeting

  6. The principles of Katz's cellular track structure radiobiological model

    International Nuclear Information System (INIS)

    The cellular track structure theory (TST), introduced by Katz in 1968, applies the concept of action cross section as the probability of targets in the radiation detector being activated to elicit the observed endpoint (e.g. cell killing). The ion beam radiation field is specified by the charge Z, speed β (or energy), fluence and linear energy transfer (LET) of the ion, rather than by its total absorbed dose or dose-averaged LET. The detector is represented by radiosensitive elements of size a0 and radiosensitivity D0, its gamma-ray response being represented by c-hit or multi-target expressions rather than by the linear-quadratic formula. Key to TST is the Dδ(r) formula describing the radial distribution of delta-ray dose (RDD) around the ion path. This formula, when folded with the dose response of the detector and radially integrated, yields the 'point target' action cross section value, sPT. The averaged value of the cross section, σ, is obtained by radially integrating the a0-averaged RDD. In the 'track width' regime which may occur at the distal end of the ion's path, the value of s may considerably exceed its geometrical value, πa20. Several scaling principles are applied in TST, resulting in its simple analytic formulation. Multi-target detectors, such as cells, are represented in TST by m, D0, σ0 (the 'saturation value' of the cross section which replaces a0) and k (a 'detector saturation index'), as the fourth model parameter. With increasing LET of the ion, the two-component formulation of TST allows for successive transition from shouldered survival curves at low LET values to exponential ones at radiobiological effectiveness (RBE) maximum, followed by 'thin-down' at the end of the ion track. For a given cell line, having best-fitted the four model parameters (m, D0, σ0 and k) to an available data set of measured survival curves, TST is able to quantitatively predict cell survival and RBE for

  7. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    OpenAIRE

    Hui Guo; Dongmei Liu; Bin Gao; Xiaohui Zhang; Minli You; Hui Ren; Hongbo Zhang; Santos, Hélder A.; Feng Xu

    2016-01-01

    Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT i...

  8. Strength analysis and modeling of cellular lattice structures manufactured using selective laser melting for tooling applications

    DEFF Research Database (Denmark)

    Mahshid, Rasoul; Hansen, Hans Nørgaard; Loft Højbjerre, Klaus

    2016-01-01

    Additive manufacturing is rapidly developing and gaining popularity for direct metal fabrication systems like selective laser melting (SLM). The technology has shown significant improvement for high-quality fabrication of lightweight design-efficient structures such as conformal cooling channels in...... injection molding tools and lattice structures. This research examines the effect of cellular lattice structures on the strength of workpieces additively manufactured from ultra high-strength steel powder. Two commercial SLM machines are used to fabricate cellular samples based on four architectures— solid...

  9. Multi-scale continuum modeling of biological processes: from molecular electro-diffusion to sub-cellular signaling transduction

    Science.gov (United States)

    Cheng, Y.; Kekenes-Huskey, P.; Hake, J. E.; Holst, M. J.; McCammon, J. A.; Michailova, A. P.

    2012-01-01

    This paper presents a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of the time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times, with increasing ionic strength, and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a nonlinear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally derived rodent ventricular myocyte geometries. Results reveal the important role of mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate sub-cellular Ca2+ signals. The model predicts that reduced off-rate in the whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for the integration of molecular-scale information into simulations of cellular-scale systems.

  10. Multi-scale continuum modeling of biological processes: from molecular electro-diffusion to sub-cellular signaling transduction

    International Nuclear Information System (INIS)

    This paper presents a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of the time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times, with increasing ionic strength, and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a nonlinear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally derived rodent ventricular myocyte geometries. Results reveal the important role of mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate sub-cellular Ca2+ signals. The model predicts that reduced off-rate in the whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for the integration of molecular-scale information into simulations of cellular-scale systems.

  11. Mechanical models of the cellular cytoskeletal network for the analysis of intracellular mechanical properties and force distributions: a review.

    Science.gov (United States)

    Chen, Ting-Jung; Wu, Chia-Ching; Su, Fong-Chin

    2012-12-01

    The cytoskeleton, which is the major mechanical component of cells, supports the cell body and regulates the cellular motility to assist the cell in performing its biological functions. Several cytoskeletal network models have been proposed to investigate the mechanical properties of cells. This review paper summarizes these models with a focus on the prestressed cable network, the semi-flexible chain network, the open-cell foam, the tensegrity, and the granular models. The components, material parameters, types of connection joints, tension conditions, and the advantages and disadvantages of each model are evaluated from a structural and biological point of view. The underlying mechanisms that are associated with the morphological changes of spreading cells are expected to be simulated using a cytoskeletal model; however, it is still paid less attention most likely due to the lack of a suitable cytoskeletal model that can accurately model the spreading process. In this review article, the established cytoskeletal models are hoped to provide useful information for the development of future cytoskeletal models with different degrees of cell attachment for the study of the mechanical mechanisms underlying the cellular behaviors in response to external stimulations. PMID:23062682

  12. Precipitation and cloud cellular structures in marine stratocumulus over the southeast pacific: model simulations

    Directory of Open Access Journals (Sweden)

    H. Wang

    2010-03-01

    Full Text Available Microphysical and meteorological controls on the formation of open and closed cellular structures in the Southeast Pacific are explored using model simulations based on aircraft observations during the VAMOS Ocean-Cloud-Atmosphere-Land Study Regional Experiment (VOCALS-REx. The effectiveness of factors such as boundary-layer moisture and temperature perturbations, surface heat and moisture fluxes, large-scale vertical motion and solar heating in promoting drizzle and open cell formation for prescribed aerosol number concentrations is explored. For the case considered, drizzle and subsequent open cell formation over a broad region are more sensitive to the observed boundary-layer moisture and temperature perturbations (=0.9 g kg−1; −1 K than to a five-fold decrease in aerosol number concentrations (150 vs. 30 mg−1. When embedding the perturbations in closed cells, local drizzle and pockets of open cells (POCs formation respond faster to the aerosol reduction than to the moisture increase, but the latter generate stronger and more persistent drizzle. The local negative perturbation in temperature drives a mesoscale circulation that prevents local drizzle formation but promotes it in a remote area where lower-level horizontal transport of moisture is blocked and converges to enhance liquid water path. This represents a potential mechanism for POC formation in the Southeast Pacific stratocumulus region whereby the circulation is triggered by strong precipitation in adjacent broad regions of open cells. A simulation that attempts to mimic the influence of a coastally induced upsidence wave results in an increase in cloud water but this alone is insufficient to initiate drizzle. An increase of surface sensible heat flux is also effective in triggering local drizzle and POC formation. Both open and closed cells simulated with observed initial conditions exhibit distinct diurnal variations in cloud properties. A stratocumulus

  13. Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues.

    Science.gov (United States)

    Calì, Corrado; Baghabra, Jumana; Boges, Daniya J; Holst, Glendon R; Kreshuk, Anna; Hamprecht, Fred A; Srinivasan, Madhusudhanan; Lehväslaiho, Heikki; Magistretti, Pierre J

    2016-01-01

    Advances in the application of electron microscopy (EM) to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow us to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions. From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room in which we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of EM preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to the observation of a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. PMID:26179415

  14. Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

    Science.gov (United States)

    Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

    2015-11-01

    Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

  15. Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues

    KAUST Repository

    Cali, Corrado

    2015-07-14

    Advances for application of electron microscopy to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions (3D). From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here, we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room where we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of electron microscopy (EM) preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to observe a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. This article is protected by copyright. All rights reserved.

  16. Modelling and analyzing the watershed dynamics using Cellular Automata (CA)-Markov model - A geo-information based approach

    Science.gov (United States)

    Behera, Mukunda D.; Borate, Santosh N.; Panda, Sudhindra N.; Behera, Priti R.; Roy, Partha S.

    2012-08-01

    Improper practices of land use and land cover (LULC) including deforestation, expansion of agriculture and infrastructure development are deteriorating watershed conditions. Here, we have utilized remote sensing and GIS tools to study LULC dynamics using Cellular Automata (CA)-Markov model and predicted the future LULC scenario, in terms of magnitude and direction, based on past trend in a hydrological unit, Choudwar watershed, India. By analyzing the LULC pattern during 1972, 1990, 1999 and 2005 using satellite-derived maps, we observed that the biophysical and socio-economic drivers including residential/industrial development, road-rail and settlement proximity have influenced the spatial pattern of the watershed LULC, leading to an accretive linear growth of agricultural and settlement areas. The annual rate of increase from 1972 to 2004 in agriculture land, settlement was observed to be 181.96, 9.89 ha/year, respectively, while decrease in forest, wetland and marshy land were 91.22, 27.56 and 39.52 ha/year, respectively. Transition probability and transition area matrix derived using inputs of (i) residential/industrial development and (ii) proximity to transportation network as the major causes. The predicted LULC scenario for the year 2014, with reasonably good accuracy would provide useful inputs to the LULC planners for effective management of the watershed. The study is a maiden attempt that revealed agricultural expansion is the main driving force for loss of forest, wetland and marshy land in the Choudwar watershed and has the potential to continue in future. The forest in lower slopes has been converted to agricultural land and may soon take a call on forests occurring on higher slopes. Our study utilizes three time period changes to better account for the trend and the modelling exercise; thereby advocates for better agricultural practices with additional energy subsidy to arrest further forest loss and LULC alternations.

  17. Tractable Model for Rate in Self-Backhauled Millimeter Wave Cellular Networks

    OpenAIRE

    Singh, Sarabjot; Kulkarni, Mandar N.; Ghosh, Amitava; Andrews, Jeffrey G.

    2014-01-01

    Millimeter wave (mmW) cellular systems will require high gain directional antennas and dense base station (BS) deployments to overcome high near field path loss and poor diffraction. As a desirable side effect, high gain antennas provide interference isolation, providing an opportunity to incorporate self-backhauling--BSs backhauling among themselves in a mesh architecture without significant loss in throughput--to enable the requisite large BS densities. The use of directional antennas and r...

  18. Multi-Scale Modeling of Respiration: Linking External to Cellular Respiration during Exercise

    OpenAIRE

    Zhou, Haiying; Lai, Nicola; Saidel, Gerald M.; Cabrera, Marco E.

    2009-01-01

    In human studies investigating factors that control cellular respiration in working skeletal muscle, pulmonary VO2 dynamics (VO2p) measured at the mouth by indirect calorimetry is typically used to represent muscle O2 consumption (UO2m). Furthermore, measurement of muscle oxygenation using near-infrared spectroscopy has provided information on the dynamic balance between oxygen delivery and oxygen consumption at the microvascular level. To relate these measurements and gain quantitative under...

  19. Phase transition in the economically modeled growth of a cellular nervous system

    OpenAIRE

    Nicosia V.; Vertes P.E.; Schafer W.R.; Latora V.; Bullmore E.T.

    2013-01-01

    Spatially embedded complex networks, such as nervous systems, the Internet, and transportation networks, generally have nontrivial topological patterns of connections combined with nearly minimal wiring costs. However, the growth rules shaping these economical tradeoffs between cost and topology are not well understood. Here, we study the cellular nervous system of the nematode worm Caenorhabditis elegans, together with information on the birth times of neurons and on their spatial locations....

  20. Tectonic modeling of Konya-Beysehir Region (Turkey) using cellular neural networks

    OpenAIRE

    D. Aydogan; O. Nuri Uçan; A. Muhittin ALBORA

    2007-01-01

    In this paper, to separate regional-residual anomaly maps and to detect borders of buried geological bodies, we applied the Cellular Neural Network (CNN) approach to gravity and magnetic anomaly maps. CNN is a stochastic image processing technique, based optimization of templates, which imply relationships of neighborhood pixels in 2-Dimensional (2D) potential anomalies. Here, CNN performance in geophysics, tested by various synthetic examples and the results are compared ...

  1. An integrated cellular model to evaluate cytotoxic effects in mammalian cell lines.

    Science.gov (United States)

    Fernández Freire, P; Peropadre, A; Pérez Martín, J M; Herrero, O; Hazen, M J

    2009-12-01

    The ever growing anthropogenic pressure to the environment has lead in 2007 to the revision of the existing legislation and the approval of the new European law regarding the production and importation of chemicals, known as REACH. This new legal framework supports the development of alternative methods to animal experimentation encouraging the improvement and/or design of new methodological strategies for the toxicological evaluation of chemical compounds. Even though cytotoxicity studies are a reductionist approach to acute toxicity in vivo, they offer the best agreement between obtaining relevant information about the mechanism of toxic action and the use of alternative methods. Following this trend, this work presents an integrated cellular strategy in order to know the toxicity and mechanism of action of chemical compounds, using simple and reproducible in vitro systems. The experimental procedures are performed in two steps. The first one involves the systematic analysis of the main cellular targets using proliferation, viability and morphological probes. The second step relies upon the results obtained in the first step, including specific assays that focus on the mechanism of toxic action and the cellular response. The benefits of this strategy are exemplified with two real cases: pentachlorophenol and rotenone. PMID:19540333

  2. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  3. Relating the dynamics of road traffic in a stochastic cellular automaton to a macroscopic first-order model

    CERN Document Server

    Maerivoet, S; Immers, B; De Moor, B; Maerivoet, Sven; Logghe, Steven; Immers, Ben; Moor, Bart De

    2005-01-01

    In this paper, we describe a relation between a microscopic traffic cellular automaton (TCA) model (i.e., the stochastic TCA model of Nagel and Schreckenberg) and the macroscopic first-order hydrodynamic model of Lighthill, Whitham, and Richards (LWR). The innovative aspect of our approach, is that we explicitly derive the LWR's fundamental diagram directly from the STCA's rule set, by assuming a stationarity condition that converts the STCA's rules into a set of linear inequalities. In turn, these constraints define the shape of the fundamental diagram, which is then specified to the LWR model. Application of our methodology to a simulation case study, allows us to compare the tempo-spatial behavior of both models. Our results indicate that, in the presence of noise, the capacity flows in the derived fundamental diagram are overestimations of those of the STCA model. Directly specifying the STCA's capacity flows to the LWR fundamental diagram, effectively remedies most of the mismatches between both approach...

  4. On Modeling Large-Scale Multi-Agent Systems with Parallel, Sequential and Genuinely Asynchronous Cellular Automata

    International Nuclear Information System (INIS)

    We study certain types of Cellular Automata (CA) viewed as an abstraction of large-scale Multi-Agent Systems (MAS). We argue that the classical CA model needs to be modified in several important respects, in order to become a relevant and sufficiently general model for the large-scale MAS, and so that thus generalized model can capture many important MAS properties at the level of agent ensembles and their long-term collective behavior patterns. We specifically focus on the issue of inter-agent communication in CA, and propose sequential cellular automata (SCA) as the first step, and genuinely Asynchronous Cellular Automata (ACA) as the ultimate deterministic CA-based abstract models for large-scale MAS made of simple reactive agents. We first formulate deterministic and nondeterministic versions of sequential CA, and then summarize some interesting configuration space properties (i.e., possible behaviors) of a restricted class of sequential CA. In particular, we compare and contrast those properties of sequential CA with the corresponding properties of the classical (that is, parallel and perfectly synchronous) CA with the same restricted class of update rules. We analytically demonstrate failure of the studied sequential CA models to simulate all possible behaviors of perfectly synchronous parallel CA, even for a very restricted class of non-linear totalistic node update rules. The lesson learned is that the interleaving semantics of concurrency, when applied to sequential CA, is not refined enough to adequately capture the perfect synchrony of parallel CA updates. Last but not least, we outline what would be an appropriate CA-like abstraction for large-scale distributed computing insofar as the inter-agent communication model is concerned, and in that context we propose genuinely asynchronous CA. (author)

  5. Gain in cellular organization of inflammatory breast cancer: A 3D in vitro model that mimics the in vivo metastasis

    Directory of Open Access Journals (Sweden)

    Alpaugh Mary L

    2009-12-01

    Full Text Available Abstract Background The initial step of metastasis in carcinomas, often referred to as the epithelial-mesenchymal transition (EMT, occurs via the loss of adherens junctions (e.g. cadherins by the tumor embolus. This leads to a subsequent loss of cell polarity and cellular differentiation and organization, enabling cells of the embolus to become motile and invasive. However highly malignant inflammatory breast cancer (IBC over-expresses E-cadherin. The human xenograft model of IBC (MARY-X, like IBC, displays the signature phenotype of an exaggerated degree of lymphovascular invasion (LVI in situ by tumor emboli. An intact E-cadherin/α, β-catenin axis mediates the tight, compact clump of cells found both in vitro and in vivo as spheroids and tumor emboli, respectively. Methods Using electron microscopy and focused ion beam milling to acquire in situ sections, we performed ultrastructural analysis of both an IBC and non-IBC, E-cadherin positive cell line to determine if retention of this adhesion molecule contributed to cellular organization. Results Here we report through ultrastructural analysis that IBC exhibits a high degree of cellular organization with polar elements such as apical/lateral positioning of E-cadherin, apical surface microvilli, and tortuous lumen-like (canalis structures. In contrast, agarose-induced spheroids of MCF-7, a weakly invasive E-cadherin positive breast carcinoma cell line, do not exhibit ultrastructural polar features. Conclusions This study has determined that the highly metastatic IBC with an exaggerated malignant phenotype challenges conventional wisdom in that instead of displaying a loss of cellular organization, IBC acquires a highly structured architecture. These findings suggest that the metastatic efficiency might be linked to the formation and maintenance of these architectural features. The comparative architectural features of both the spheroid and embolus of MARY-X provide an in vitro model with

  6. Water Extract of Dolichos lablab Attenuates Hepatic Lipid Accumulation in a Cellular Nonalcoholic Fatty Liver Disease Model.

    Science.gov (United States)

    Im, A-Rang; Kim, Yun Hee; Lee, Hye Won; Song, Kwang Hoon

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rising in prevalence worldwide. Therapeutic strategies for patients with NAFLD are limited by a lack of effective drugs. In this report, we show that Dolichos lablab water extract (DLL-Ex) protects against free fatty acid (FFA)-induced lipid accumulation and attenuates expression of genes involved in lipid droplet accumulation in cellular NAFLD models. The hepatoprotective effects and underlying mechanism of DLL-Ex were assessed using an in vitro cellular model in which NAFLD was simulated by inducing excessive FFA influx into hepatocytes. HepG2 cells were treated with DLL-Ex and FFAs for 24 h, after which intracellular lipid content was observed by using Nile Red and Oil Red O staining. Quantitative real-time polymerase chain reaction was used to measure expression levels of genes related to FFA-mediated cellular energy depletion. Western blotting was used to measure protein levels of phosphorylated c-Jun N-terminal kinase, AMP-activated protein kinase alpha (AMPKα), and peroxisome proliferator-activated receptor γ coactivator 1 alpha. In HepG2 cells, DLL-Ex inhibited expression of CD36, which regulates fatty acid uptake, as well as BODIPY-labeled fatty acid uptake. Additionally, DLL-Ex significantly attenuated FFA-mediated cellular energy depletion and mitochondrial membrane depolarization. Furthermore, DLL-Ex enhanced phosphorylation of AMPK, indicating that AMPK is a critical regulator of DLL-Ex-mediated inhibition of hepatic lipid accumulation, possibly through its antioxidative effect. These results demonstrate that DLL-Ex exerts potent anti-NAFLD activity, suggesting that it could be a potential adjuvant treatment for patients with NAFLD. PMID:27152979

  7. Gain in cellular organization of inflammatory breast cancer: A 3D in vitro model that mimics the in vivo metastasis

    International Nuclear Information System (INIS)

    The initial step of metastasis in carcinomas, often referred to as the epithelial-mesenchymal transition (EMT), occurs via the loss of adherens junctions (e.g. cadherins) by the tumor embolus. This leads to a subsequent loss of cell polarity and cellular differentiation and organization, enabling cells of the embolus to become motile and invasive. However highly malignant inflammatory breast cancer (IBC) over-expresses E-cadherin. The human xenograft model of IBC (MARY-X), like IBC, displays the signature phenotype of an exaggerated degree of lymphovascular invasion (LVI) in situ by tumor emboli. An intact E-cadherin/α, β-catenin axis mediates the tight, compact clump of cells found both in vitro and in vivo as spheroids and tumor emboli, respectively. Using electron microscopy and focused ion beam milling to acquire in situ sections, we performed ultrastructural analysis of both an IBC and non-IBC, E-cadherin positive cell line to determine if retention of this adhesion molecule contributed to cellular organization. Here we report through ultrastructural analysis that IBC exhibits a high degree of cellular organization with polar elements such as apical/lateral positioning of E-cadherin, apical surface microvilli, and tortuous lumen-like (canalis) structures. In contrast, agarose-induced spheroids of MCF-7, a weakly invasive E-cadherin positive breast carcinoma cell line, do not exhibit ultrastructural polar features. This study has determined that the highly metastatic IBC with an exaggerated malignant phenotype challenges conventional wisdom in that instead of displaying a loss of cellular organization, IBC acquires a highly structured architecture. These findings suggest that the metastatic efficiency might be linked to the formation and maintenance of these architectural features. The comparative architectural features of both the spheroid and embolus of MARY-X provide an in vitro model with tractable in vivo applications

  8. Development and Evaluation of a Cellular Automata Model for Simulating Tillage Erosion in the Presence of Obstacles

    Science.gov (United States)

    Vanwalleghem, T.; Jiménez-Hornero, F. J.; Giráldez, J. V.; Laguna, A.

    2009-04-01

    The process of tillage translocation is well studied and can be described adequately by different existing models. Nevertheless, in complex environments such as olive orchards, characterized by numerous obstacles, application of such conventional tillage erosion models is not straightforward. However, these obstacles have important effects on the spatial pattern of soil redistribution and on resulting soil properties. In this kind of environment, cellular automata could provide a valuable alternative. This study aims at developing a cellular automata model for tillage translocation (CATT) that can take into account such obstacles and at exploring its possibilities and limitations. A simple model was developed, which main parameters are tillage direction, speed and depth. Firstly, the modeĺs outcome was tested against existing 137Cs inventories for a study site in the Belgian loam belt. The observed spatial soil redistribution patterns could be adequately represented by the CATT model. Secondly, a sensitivity analysis was performed to explore the effect of input uncertainty on several selected model outputs. The variance-based extended FAST method was used to determine first and total order sensitivity indices. Tillage depth was identified as the input parameter that determined most of the output variance, followed respectively by tillage direction and speed. The difference between the total and first-order sensitivity indices, between 0.8 and 2, indicated that, in spite of the simple model structure, the model behaves non-linearly with respect to some of the model output variables. Higher-order interactions were especially important for determining the proportion of eroding and deposition cells. Finally, simulations were performed to analyse the model behaviour in complex landscapes, applying it to a field with protruding obstacles (e.g. olive trees). The model adequately represented some morphological features observed in the olive orchards, such as mounds around

  9. Phase-Type Models of Channel-Holding Times in Cellular Communication Systems

    DEFF Research Database (Denmark)

    Christensen, Thomas Kaare; Nielsen, Bo Friis; Iversen, Villy Bæk

    2004-01-01

    In this paper, we derive the distribution of the channel-holding time when both cell-residence and call-holding times are phase-type distributed. Furthermore, the distribution of the number of handovers, the conditional channel-holding time distributions, and the channel-holding time when cell re...... residence times are correlated are derived. All distributions are of phase type, making them very general and flexible. The channel-holding times are of importance in performance evaluation and simulation of cellular mobile communication systems....

  10. Mechanistic model of radon-induced lung cancer risk at low exposure levels based on cellular alpha particle hits

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Hofmann; Hatim, Fakir [Salzburg Univ., Div. of Physics and Biophysics, Dept. of Material Science (Austria); Lucia-Adina, Truta-Popa [Babes-Bolyai Univ., Faculty of Physics (Romania)

    2006-07-01

    To explore the role of the multiplicity of cellular hits by radon progeny alpha particles for lung cancer incidence, the number of single and multiple alpha particle hits were computed for basal and secretory cells in the bronchial epithelium of human airway bifurcations employing Monte Carlo methods. Hot spots of alpha particle hits were observed at the branching points of bronchial airway bifurcations, suggesting that multiple alpha particle hits may occur primarily at carinal ridges. Random alpha particle intersections of bronchial cells during a given exposure period, selected from a Poisson distribution, were simulated by an initiation-promotion model, based on experimentally observed cellular transformation and survival functions. To consider potential bystander effects, which have been observed in cellular in vitro studies, alpha particle interactions were also simulated for larger sensitive target volumes in bronchial epithelium, consisting of a collection of cells. Lung cancer risk simulations indicated that cancer induction for continuous exposures is related to the cycle time of an irradiated cell, thus exhibiting a distinct dose-rate effect. While the dominant role of single hits leads to a linear dose-response relationship at low radon exposure levels, predicted lung cancer risk for a collection of interacting cells exhibits a linear-quadratic response, suggesting that bystander effects, if operating at all under in vivo irradiations, may be restricted to a small number of adjacent cells. (author)

  11. Mechanistic model of radon-induced lung cancer risk at low exposure levels based on cellular alpha particle hits

    International Nuclear Information System (INIS)

    To explore the role of the multiplicity of cellular hits by radon progeny alpha particles for lung cancer incidence, the number of single and multiple alpha particle hits were computed for basal and secretory cells in the bronchial epithelium of human airway bifurcations employing Monte Carlo methods. Hot spots of alpha particle hits were observed at the branching points of bronchial airway bifurcations, suggesting that multiple alpha particle hits may occur primarily at carinal ridges. Random alpha particle intersections of bronchial cells during a given exposure period, selected from a Poisson distribution, were simulated by an initiation-promotion model, based on experimentally observed cellular transformation and survival functions. To consider potential bystander effects, which have been observed in cellular in vitro studies, alpha particle interactions were also simulated for larger sensitive target volumes in bronchial epithelium, consisting of a collection of cells. Lung cancer risk simulations indicated that cancer induction for continuous exposures is related to the cycle time of an irradiated cell, thus exhibiting a distinct dose-rate effect. While the dominant role of single hits leads to a linear dose-response relationship at low radon exposure levels, predicted lung cancer risk for a collection of interacting cells exhibits a linear-quadratic response, suggesting that bystander effects, if operating at all under in vivo irradiations, may be restricted to a small number of adjacent cells. (author)

  12. Mobile Robot Motion Using Cellular Automaton Model to Avoid Transient Obstacles

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-10-01

    Full Text Available The obstacle avoidance is currently treated by methods that fall into two broad categories: global and local approach. This paper considers the obstacles whose velocity and direction cannot be easily predicted. Such obstacle is called transient obstacle. To avoid such kind of obstacle, we introduce a local path planning method for a robotics by using cellular automaton approach. The cellular automaton was combined with Dijkstra shortest path algorithm as global path planning to obtain a path for mobile robot to be able to avoid transient obstacle along the path. Using the proposed method, a scene in a typical corridor has been created. Moreover, this paper also evaluated two kinds of obstacle avoidance motion. First, the robot uses the “stop and go” method, which is the robot decreases its speed while encounter a transient obstacle. The second one is detour method, in which the robot makes a detour motion to avoid a transient obstacle. To coupe the drawbacks of local path planning, this paper also propose the enhancement of detour method. The simulation results show that in dynamic environment with transient obstacles, the “stop and go” method produces minimal collision with shortest-distance path. While, using the detour method generates minimal collision with time-minimal navigation path.

  13. Developing an effective 2-D urban flood inundation model for city emergency management based on cellular automata

    Directory of Open Access Journals (Sweden)

    L. Liu

    2014-09-01

    Full Text Available Flash floods have occurred frequently and severely in the urban areas of South China. An effective process-oriented urban flood inundation model becomes an urgent demand for urban storm water and emergency management. This study develops an effective and flexible cellular automaton (CA model to simulate storm water runoff and the flood inundation process during extreme storm events. The process of infiltration, inlets discharge and flow dynamic can be simulated only with little pre-processing on commonly available basic urban geographic data. In this model, a set of gravitational diverging rules are implemented in a cellular automation (CA model to govern the water flow in a 3 x 3 cell template of a raster layer. The model is calibrated by one storm event and validated by another in a small urban catchment in Guangzhou of Southern China. The depth of accumulated water at the catchment outlet is interpreted from street monitoring sensors and verified by on-site survey. A good level of agreement between the simulated process and the reality is reached for both storm events. The model reproduces the changing extent and depth of flooded areas at the catchment outlet with an accuracy of 4 cm in water depth. Comparisons with a physically-based 2-D model (FloodMap results show that the model have the capability of simulating flow dynamics. The high computational efficiency of CA model can satisfy the demand of city emergency management. The encouraging results of the simulations demonstrate that the CA-based approach is capable of effectively representing the key processes associated with a storm event and reproducing the process of water accumulation at the catchment outlet for making process-considered city emergency management decisions.

  14. Cell damage from radiation-induced bystander effects for different cell densities simulated by a mathematical model via cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Meireles, Sincler P. de; Santos, Adriano M.; Grynberg, Suely Epsztein, E-mail: spm@cdtn.b, E-mail: amsantos@cdtn.b, E-mail: seg@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Nunes, Maria Eugenia S., E-mail: mariaeugenia@iceb.ufop.b [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

    2011-07-01

    During recent years, there has been a shift from an approach focused entirely on DNA as the main target of ionizing radiation to a vision that considers complex signaling pathways in cells and among cells within tissues. Several newly recognized responses were classified as the so-called non-target responses in which the biological effects are not directly related to the amount of energy deposited in the DNA of cells that were traversed by radiation. In 1992 the bystander effect was described referring to a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. In this work, we have developed a mathematical model via cellular automata, to quantify cell death induced by the bystander effect. The model is based on experiments with irradiated cells conditioned medium which suggests that irradiated cells secrete molecules in the medium that are capable of damaging other cells. The computational model consists of two-dimensional cellular automata which is able to simulate the transmission of bystander signals via extrinsic route and via Gap junctions. The model has been validated by experimental results in the literature. The time evolution of the effect and the dose-response curves were obtained in good accordance to them. Simulations were conducted for different values of bystander and irradiated cell densities with constant dose. From this work, we have obtained a relationship between cell density and effect. (author)

  15. Cell damage from radiation-induced bystander effects for different cell densities simulated by a mathematical model via cellular automata

    International Nuclear Information System (INIS)

    During recent years, there has been a shift from an approach focused entirely on DNA as the main target of ionizing radiation to a vision that considers complex signaling pathways in cells and among cells within tissues. Several newly recognized responses were classified as the so-called non-target responses in which the biological effects are not directly related to the amount of energy deposited in the DNA of cells that were traversed by radiation. In 1992 the bystander effect was described referring to a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. In this work, we have developed a mathematical model via cellular automata, to quantify cell death induced by the bystander effect. The model is based on experiments with irradiated cells conditioned medium which suggests that irradiated cells secrete molecules in the medium that are capable of damaging other cells. The computational model consists of two-dimensional cellular automata which is able to simulate the transmission of bystander signals via extrinsic route and via Gap junctions. The model has been validated by experimental results in the literature. The time evolution of the effect and the dose-response curves were obtained in good accordance to them. Simulations were conducted for different values of bystander and irradiated cell densities with constant dose. From this work, we have obtained a relationship between cell density and effect. (author)

  16. Transfer-matrix density-matrix renormalization group for stochastic models: the Domany-Kinzel cellular automaton

    Energy Technology Data Exchange (ETDEWEB)

    Kemper, A. [Institut fuer Theoretische Physik, Universitaet zu Koeln, Cologne (Germany). E-mail: kemper@thp.uni-koeln.de; Schadschneider, A. [Institut fuer Theoretische Physik, Universitaet zu Koeln, Cologne (Germany). E-mail: as@thp.uni-koeln.de; Zittartz, J. [Institut fuer Theoretische Physik, Universitaet zu Koeln, Cologne (Germany)

    2001-05-18

    We apply the transfer-matrix density-matrix renormalization group (TMRG) to a stochastic model, the Domany-Kinzel cellular automaton, which exhibits a non-equilibrium phase transition in the directed percolation universality class. Estimates for the stochastic time evolution, phase boundaries and critical exponents can be obtained with high precision. This is possible using only modest numerical effort since the thermodynamic limit can be taken analytically in our approach. We also point out further advantages of the TMRG over other numerical approaches, such as classical DMRG or Monte Carlo simulations. (author). Letter-to-the-editor.

  17. Transfer-matrix density-matrix renormalization group for stochastic models: the Domany-Kinzel cellular automaton

    International Nuclear Information System (INIS)

    We apply the transfer-matrix density-matrix renormalization group (TMRG) to a stochastic model, the Domany-Kinzel cellular automaton, which exhibits a non-equilibrium phase transition in the directed percolation universality class. Estimates for the stochastic time evolution, phase boundaries and critical exponents can be obtained with high precision. This is possible using only modest numerical effort since the thermodynamic limit can be taken analytically in our approach. We also point out further advantages of the TMRG over other numerical approaches, such as classical DMRG or Monte Carlo simulations. (author). Letter-to-the-editor

  18. 3D hierarchical computational model of wood as a cellular material with fibril reinforced, heterogeneous multiple layers

    DEFF Research Database (Denmark)

    Qing, Hai; Mishnaevsky, Leon

    2009-01-01

    A 3D hierarchical computational model of deformation and stiffness of wood, which takes into account the structures of wood at several scale levels (cellularity, multilayered nature of cell walls, composite-like structures of the wall layers) is developed. At the mesoscale, the softwood cell is...... presented as a 3D hexagon-shape-tube with multilayered walls. The layers in the softwood cell are considered as considered as composite reinforced by microfibrils (celluloses). The elastic properties of the layers are determined with Halpin–Tsai equations, and introduced into mesoscale finite element...

  19. Stylized Facts Generated Through Cellular Automata Models. Case of Study: The Game of Life

    CERN Document Server

    Coronel-Brizio, H F; Rodriguez-Achach, M E; Stevens-Ramirez, G A

    2007-01-01

    In the present work, a geometrical method to generate a two dimensional random walk by means of a bidimensional Cellular Automaton is presented. We illustrate it by means of Conway's Game of Life with periodical borders, with a large lattice of 3000 x 3000 cells. The obtained random walk is of character anomalous, and its projection to a one dimensional random walk is analyzed, showing that it presents some statistical properties similar to the so-called stylized facts observed in financial time series. We consider that the procedure presented here is important not only because of its simplicity, but also because it could help us to understand and shed light on the stylized facts formation mechanism.

  20. Modelling the role of nucleation on recrystallization kinetics: A cellular automata approach

    Science.gov (United States)

    Tripathy, Haraprasanna; Rai, Arun Kumar; Hajra, Raj Narayan; Raju, Subramanian; Saibaba, Saroja

    2016-05-01

    In present study, a two dimensional cellular automata (CA) simulation has been carried out to study the effect of nucleation mode on the kinetics of recrystallization and microstructure evolution in an austenitic stainless steel. Two different nucleation modes i.e. site saturation and continuous nucleation with interface control growth mechanism has been considered in this modified CA algorithm. The observed Avrami exponent for both nucleation modes shows a better agreement with the theoretical predicted values. The site saturated nucleation mode shows a nearly consistent value of Avrami exponent, whereas in the case of continuous nucleation the exponent shows a little variation during transformation. The simulations in the present work can be applied for the optimization of microstructure and properties in austenitic steels.

  1. Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters.

    Science.gov (United States)

    Dimastrogiovanni, Giorgio; Córdoba, Marlon; Navarro, Isabel; Jáuregui, Olga; Porte, Cinta

    2015-08-01

    This work investigates the suitability of the rainbow trout liver cell line (RTL-W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL-W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish. PMID:26143618

  2. Linear programming embedded particle swarm optimization for solving an extended model of dynamic virtual cellular manufacturing systems

    Directory of Open Access Journals (Sweden)

    H. Rezazadeh

    2009-04-01

    Full Text Available The concept of virtual cellular manufacturing system (VCMS is finding acceptance among researchers as an extension to grouptechnology. In fact, in order to realize benefits of cellular manufacturing system in the functional layout, the VCMS createsprovisional groups of resources (machines, parts and workers in the production planning and control system. This paperdevelops a mathematical model to design the VCMS under a dynamic environment with a more integrated approach whereproduction planning, system reconfiguration and workforce requirements decisions are incorporated. The advantages of theproposed model are as follows: considering the operations sequence, alternative process plans for part types, machine timecapacity,worker time‐capacity, cross‐training, lot splitting, maximal cell size, balanced workload for cells and workers. Anefficient linear programming embedded particle swarm optimization algorithm is used to solve the proposed model. Thealgorithm searches over the 0‐1 integer variables and for each 0‐1 integer solution visited; corresponding values of integervariables are determined by solving a linear programming sub‐problem using the simplex algorithm. Numerical examples showthat the proposed method is efficient and effective in searching for near optimal solutions.

  3. BioJazz: in silico evolution of cellular networks with unbounded complexity using rule-based modeling.

    Science.gov (United States)

    Feng, Song; Ollivier, Julien F; Swain, Peter S; Soyer, Orkun S

    2015-10-30

    Systems biologists aim to decipher the structure and dynamics of signaling and regulatory networks underpinning cellular responses; synthetic biologists can use this insight to alter existing networks or engineer de novo ones. Both tasks will benefit from an understanding of which structural and dynamic features of networks can emerge from evolutionary processes, through which intermediary steps these arise, and whether they embody general design principles. As natural evolution at the level of network dynamics is difficult to study, in silico evolution of network models can provide important insights. However, current tools used for in silico evolution of network dynamics are limited to ad hoc computer simulations and models. Here we introduce BioJazz, an extendable, user-friendly tool for simulating the evolution of dynamic biochemical networks. Unlike previous tools for in silico evolution, BioJazz allows for the evolution of cellular networks with unbounded complexity by combining rule-based modeling with an encoding of networks that is akin to a genome. We show that BioJazz can be used to implement biologically realistic selective pressures and allows exploration of the space of network architectures and dynamics that implement prescribed physiological functions. BioJazz is provided as an open-source tool to facilitate its further development and use. Source code and user manuals are available at: http://oss-lab.github.io/biojazz and http://osslab.lifesci.warwick.ac.uk/BioJazz.aspx. PMID:26101250

  4. Targeted metabolomic analyses of cellular models of pelizaeus-merzbacher disease reveal plasmalogen and myo-inositol solute carrier dysfunction

    Directory of Open Access Journals (Sweden)

    Pelzer Lindsay

    2011-06-01

    Full Text Available Abstract Background Leukodystrophies are devastating diseases characterized by dys- and hypo-myelination. While there are a number of histological and imaging studies of these disorders, there are limited biochemical data available. We undertook targeted lipidomic analyses of Pelizaeus-Merzbacher disease (PMD fibroblasts, PMD lymphocytes, and 158JP oligodendrocytes, a murine model of PMD, to define the lipid changes in these cell models. Further targeted metabolomics analyses were conducted to obtain a preliminary evaluation of the metabolic consequences of lipid changes and gene mutations in these cell models. Results In both PMD fibroblasts and lymphocytes, and 158JP oligodendrocytes, ethanolamine plasmalogens were significantly decreased. Labeling studies with 158JP oligodendrocytes further demonstrated a decreased rate of lipid remodeling at sn-2. Targeted metabolomics analyses of these cells revealed dramatic increases in cellular levels of myo-inositol. Further uptake studies demonstrated increased rates of myo-inositol uptake by PMD lymphocytes. Conclusions Our data demonstrating PlsEtn decrements, support previous studies indicating leukodystrophy cells possess significant peroxisomal deficits. Our data for the first time also demonstrate that decrements in peroxisomal function coupled with the PLP1 gene defects of PMD, result in changes in the function of membrane myo-inositol solute carriers resulting in dramatic increases in cellular myo-inositol levels.

  5. Analytical Models for Dimensioning of OFDMA-based Cellular Networks Carrying VoIP and Best-Effort Traffic

    Directory of Open Access Journals (Sweden)

    Bruno Baynat

    2012-10-01

    Full Text Available The last years have seen an exponentially growing interest for mobile telecommunication services. As a consequence, a great diversity of applications is expected to be supported by cellular networks. To answer this ever increasing demand, the ITU-R defined the requirements that the fourth generation (4G of mobile standards must fulfill. Today, two especially promising candidates for 4G stand out: WiMAX and LTE. However, 4G cellular networks are still far from being implemented, and the high deployment costs render over-provisioning out of question. We thus propose in this paper accurate and convenient analytical models well-suited for the complex dimensioning of these promising access networks. Our main interest is WiMAX, yet, we show how our models can be easily used to consider LTE cells since both technologies are based on OFDMA. Generic Markovian models are developed specifically for three service classes defined in the WiMAX standard: UGS, ertPS and BE, respectively corresponding to VoIP, VoIP with silence suppression and best-effort traffic. First, we consider cells carrying either UGS, ertPS or BE traffic. Three methods to combine the previous models are then proposed to assume both UGS and BE traffic in the studied cell. Finally, we provide a way to easily integrate the ertPS traffic and obtain a UGS/ertPS/BE model able to account for multiple traffic profiles in each service class while keeping an instantaneous resolution. The proposed models are compared in depth with realistic simulations that show their accuracy. Lastly, we demonstrate through different examples how our models can be used to answer dimensioning issues which would be intractable with simulations.

  6. Study of cellular retention of HMPAO and ECD in a model simulating the blood-brain barrier

    International Nuclear Information System (INIS)

    The HMPAO and ECD are two technetium-labelled lipophilic agents clinically used in the imagery of cerebral perfusion. These molecules cross the membranes and are retained inside the cell after being converted to a hydrophilic form. The aim of this study is to establish the distribution of this retention at the level of blood-brain barrier (BBB) and nerve cells. The incorporation of HMPAO or ECD was studied on a model of co-culture simulating the BBB by means of a T84 single-cell layer of tight junction separated from another layer of U373 astrocyte cells. The cell quality and tight junction permeability were evaluated by the cellular retention of 111-indium chloride and by para-cellular diffusion of 14C mannitol,d-1. The values reported below were obtained at 180 minutes when the radiotracers were added near the 'T84 layer'. The cell quality is validated by the low cellular retention of the indium chloride(2.3±0.3 μg-1 for the T84 cells and 8.2±5.8 μg-1 for the U373 cells). The activity of 14C mannitol,d-1 diminishes by 23 ± 5 % in the added compartment. The retention of ECD by the U373 cells is significantly higher (20.7 ±4.5 g-1) than that of T84 cells (2.9 ± 0.2 μg-1). For HMPAO a non-significant tendency could be observed (49 ± 34 μg-1 for the U373 cells and 38 ± 25 μg-1 for the T84 cells)> The results of cellular retention of indium by HMPAO or ECD when added near 'U373 layer' are not significantly different.In conclusion, independently of the side exposed to the radiotracers, one observes an enhanced incorporation of the U373 cells. The ensemble of these results represent additional arguments in favour of a specific cellular incorporation of the radiotracers, independent of the BBB permittivity

  7. 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...

  8. Modelling for near-surface interaction of lithium ceramics and sweep-gas by use of cellular automation

    International Nuclear Information System (INIS)

    Tritium release from the lithium ceramics as a fusion reactor breeder material is strongly affected by the composition of the sweep-gas as result of its influences with the material's surface. The typical surface processes which play important roles are adsorption, desorption and interaction between vacancy site and the constituents of the sweep-gas. Among a large number of studies and models, yet it seems to be difficult to model the overall behaviour of those processes due to its complex time-transient nature. In the present work the coarse grained atomic simulation based on the Cellular Automaton (CA) is used to model the dynamics of near-surface interaction between Li2O surface and sweep-gas that is consisting of a noble gas, hydrogen gas and water vapour. (author)

  9. Analyzing the Influence of Mobile Phone Use of Drivers on Traffic Flow Based on an Improved Cellular Automaton Model

    Directory of Open Access Journals (Sweden)

    Yao Xiao

    2015-01-01

    Full Text Available This paper aimed to analyze the influence of drivers’ behavior of phone use while driving on traffic flow, including both traffic efficiency and traffic safety. An improved cellular automaton model was proposed to simulate traffic flow with distracted drivers based on the Nagel-Schreckenberg model. The driving characters of drivers using a phone were first discussed and a value representing the probability to use a phone while driving was put into the CA model. Simulation results showed that traffic flow rate was significantly reduced if some drivers used a phone compared to no phone use. The flow rate and velocity decreased as the proportion of drivers using a phone increased. While, under low density, the risk of traffic decreased first and then increased as the distracted drivers increased, the distracted behavior of drivers, like using a phone, could reduce the flow rate by 5 percent according to the simulation.

  10. Self-organized criticality in a spherically closed cellular automaton: Modeling soft gamma repeater bursts driven by magnetic reconnection

    CERN Document Server

    Nakazato, Ken'ichiro

    2014-01-01

    A new cellular automaton (CA) model is presented for the self-organized criticality (SOC) in recurrent bursts of soft gamma repeaters (SGRs), which are interpreted as avalanches of reconnection in the magnetosphere of neutron stars. The nodes of a regular dodecahedron and a truncated icosahedron are adopted as spherically closed grids enclosing a neutron star. It is found that the system enters the SOC state if there are sites where the expectation value of the added perturbation is nonzero. The energy distributions of SOC avalanches in CA simulations are described by a power law with a cutoff, which is consistent with the observations of SGR 1806-20 and SGR 1900+14. The power-law index is not universal and depends on the amplitude of the perturbation. This result shows that the SOC of SGRs can be illustrated not only by the crust quake model but also by the magnetic reconnection model.

  11. Cellular High-energy Cavitation Trauma - description of a novel in vitro trauma model in three different cell types.

    Directory of Open Access Journals (Sweden)

    Yuli eCao

    2016-02-01

    Full Text Available The mechanisms involved in traumatic brain injury (TBI have yet to be fully characterized. One mechanism that, especially in high energy trauma, could be of importance is cavitation. Cavitation can be described as a process of vaporization, bubble generation and bubble implosion as a result of a decrease and subsequent increase in pressure. Cavitation as an injury mechanism is difficult to visualize and model due to its short duration and limited spatial distribution. One strategy to analyze the cellular response of cavitation is to employ suitable in vitro models. The flyer plate is an in vitro high energy trauma model that includes cavitation as a trauma mechanism. A copper fragment is accelerated by means of a laser, hits the bottom of a cell culture well causing cavitation and shock waves inside the well and cell medium. We have found the flyer plate model to be efficient, reproducible and easy to control. In this study we have used the model to analyze the cellular response to microcavitation in SH-SY5Y neuroblastoma, Caco-2, and C6 glioma cell lines. Mitotic activity in neuroblastoma and glioma was investigated with BrdU staining, and cell numbers were calculated using automated time-lapse imaging. We found variations between cell types and between different zones surrounding the lesion with these methods. It was also shown that the injured cell cultures released S-100B in a dose dependent manner. Using gene expression microarray a number of gene families of potential interest were found to be strongly, but differently regulated in neuroblastoma and glioma at 24 hr post trauma. The data from the gene expression arrays may be used to identify new candidates for biomarkers in cavitation trauma. We conclude that our model is useful for studies of trauma in vitro and that it could be applied in future treatment studies.

  12. Structural-mechanical model of wax crystal networks—a mesoscale cellular solid approach

    International Nuclear Information System (INIS)

    Mineral waxes are widely used materials in industrial applications; however, the relationship between structure and mechanical properties is poorly understood. In this work, mineral wax-oil networks were characterized as closed-cell cellular solids, and differences in their mechanical response predicted from structural data. The systems studied included straight-chain paraffin wax (SW)-oil mixtures and polyethylene wax (PW)-oil mixtures. Analysis of cryogenic-SEM images of wax-oil networks allowed for the determination of the length (l) and thickness (t) of the wax cell walls as a function of wax mass fraction (Φ). A linear relationship between t/l and Φ (t/l ∼ Φ 0.89) suggested that wax-oil networks were cellular solids of the closed-cell type. However, the scaling behavior of the elastic modulus with the volume fraction of solids did not agree with theoretical predictions, yielding the same scaling exponent, μ = 0.84, for both waxes. This scaling exponent obtained from mechanical measurements could be predicted from the scaling behavior of the effective wax cell size as a function of wax mass fraction in oil obtained by cryogenic scanning electron microscopy. Microscopy studies allowed us to propose that wax-oil networks are structured as an ensemble of close-packed spherical cells filled with oil, and that it is the links between cells that yield under simple uniaxial compression. Thus, the Young’s moduli for the links between cells in SW and PW wax systems could be estimated as E L(SW) = 2.76 × 109 Pa and E L(PW) = 1.64 × 109 Pa, respectively. The structural parameter responsible for the observed differences in the mechanical strength between the two wax-oil systems is the size of the cells. Polyethylene wax has much smaller cell sizes than the straight chain wax and thus displays a higher Young’s modulus and yield stress. (papers)

  13. Developing an effective 2-D urban flood inundation model for city emergency management based on cellular automata

    Science.gov (United States)

    Liu, L.; Liu, Y.; Wang, X.; Yu, D.; Liu, K.; Huang, H.; Hu, G.

    2015-03-01

    Flash floods have occurred frequently in the urban areas of southern China. An effective process-oriented urban flood inundation model is urgently needed for urban storm-water and emergency management. This study develops an efficient and flexible cellular automaton (CA) model to simulate storm-water runoff and the flood inundation process during extreme storm events. The process of infiltration, inlets discharge and flow dynamics can be simulated with little preprocessing on commonly available basic urban geographic data. In this model, a set of gravitational diverging rules are implemented to govern the water flow in a rectangular template of three cells by three cells of a raster layer. The model is calibrated by one storm event and validated by another in a small urban catchment in Guangzhou of southern China. The depth of accumulated water at the catchment outlet is interpreted from street-monitoring closed-circuit television (CCTV) videos and verified by on-site survey. A good level of agreement between the simulated process and the reality is reached for both storm events. The model reproduces the changing extent and depth of flooded areas at the catchment outlet with an accuracy of 4 cm in water depth. Comparisons with a physically based 2-D model (FloodMap) show that the model is capable of effectively simulating flow dynamics. The high computational efficiency of the CA model can meet the needs of city emergency management.

  14. Fuzzy Case-Based Reasoning in Product Style Acquisition Incorporating Valence-Arousal-Based Emotional Cellular Model

    Directory of Open Access Journals (Sweden)

    Fuqian Shi

    2012-01-01

    Full Text Available Emotional cellular (EC, proposed in our previous works, is a kind of semantic cell that contains kernel and shell and the kernel is formalized by a triple- L = , where P denotes a typical set of positive examples relative to word-L, d is a pseudodistance measure on emotional two-dimensional space: valence-arousal, and δ is a probability density function on positive real number field. The basic idea of EC model is to assume that the neighborhood radius of each semantic concept is uncertain, and this uncertainty will be measured by one-dimensional density function δ. In this paper, product form features were evaluated by using ECs and to establish the product style database, fuzzy case based reasoning (FCBR model under a defined similarity measurement based on fuzzy nearest neighbors (FNN incorporating EC was applied to extract product styles. A mathematical formalized inference system for product style was also proposed, and it also includes uncertainty measurement tool emotional cellular. A case study of style acquisition of mobile phones illustrated the effectiveness of the proposed methodology.

  15. A modified size-dependent core-shell model and its application in the wave propagation of square cellular networks

    Science.gov (United States)

    Xu, Xiao-Jian; Wang, Ya-Chuan; Wang, Bo; Zhang, Kai

    2016-06-01

    We propose a modified core-shell model to depict the size-dependent elastic properties of materials with several different cross-sections. By using the Young-Laplace equation, a modified Euler-Bernoulli equation, which has taken a power-law relation between the bulk and surface moduli into account, is derived. A finite element method of the modified Euler-Bernoulli equation is formulated, and assembled to investigate the dispersion relations of the infinite two-dimensional periodic square cellular networks. The effectiveness of the proposed core-shell model is verified by comparing with results of the experiments and the molecular dynamics simulations available in the literature. Numerical results show that surface effects play an important role on the cellular networks with small diameters, large aspect ratios and high wave frequencies. Meanwhile, the analytical expressions for the size-dependent elastic modulus may be useful for the study of the size-dependent elasticity of materials and structures at small length scales.

  16. Reconstructing the emergence of cellular life through the synthesis of model protocells.

    Science.gov (United States)

    Mansy, S S; Szostak, J W

    2009-01-01

    The complexity of modern biological life has long made it difficult to understand how life could emerge spontaneously from the chemistry of the early earth. The key to resolving this mystery lies in the simplicity of the earliest living cells, together with the ability of the appropriate molecular building blocks to spontaneously self-assemble into larger structures. In our view, the two key components of a primitive cell are not only self-assembling, but also self-replicating, structures: the nucleic acid genome and the cell membrane. Here, we summarize recent experimental progress toward the synthesis of efficient self-replicating nucleic acid and membrane vesicle systems and discuss some of the issues that arise during efforts to integrate these two subsystems into a coherent whole. We have shown that spontaneous nucleic-acid-copying chemistry can take place within membrane vesicles, using externally supplied activated nucleotides as substrates. Thus, membranes need not be a barrier to the uptake of environmentally supplied nutrients. We examine some of the remaining obstacles that must be overcome to enable the synthesis of a complete self-replicating protocell, and we discuss the implications of these experiments for our understanding of the emergence of Darwinian evolution and the origin and early evolution of cellular life. PMID:19734203

  17. Sub-cellular modeling of platelet transport in blood flow through microchannels with constriction.

    Science.gov (United States)

    Yazdani, Alireza; Karniadakis, George Em

    2016-05-11

    Platelet transport through arterial constrictions is one of the controlling processes influencing their adhesive functions and the formation of thrombi. We perform high-fidelity mesoscopic simulations of blood flow in microchannels with constriction, resembling arterial stenoses. The wall shear rates inside the constrictions reach levels as high as ≈8000 s(-1), similar to those encountered in moderate atherosclerotic plaques. Both red blood cells and platelets are resolved at sub-cellular resolution using the Dissipative Particle Dynamics (DPD) method. We perform a systematic study on the red blood cell and platelet transport by considering different levels of constriction, blood hematocrit and flow rates. We find that higher levels of constriction and wall shear rates lead to significantly enhanced margination of platelets, which may explain the experimental observations of enhanced post-stenosis platelet aggregation. We also observe similar margination effects for stiff particles of spherical shapes such as leukocytes. To our knowledge, such numerical simulations of dense blood through complex geometries have not been performed before, and our quantitative findings could shed new light on the associated physiological processes such as ATP release, plasma skimming, and thrombus formation. PMID:27087267

  18. Modelling chronotaxicity of cellular energy metabolism to facilitate the identification of altered metabolic states

    Science.gov (United States)

    Lancaster, Gemma; Suprunenko, Yevhen F.; Jenkins, Kirsten; Stefanovska, Aneta

    2016-01-01

    Altered cellular energy metabolism is a hallmark of many diseases, one notable example being cancer. Here, we focus on the identification of the transition from healthy to abnormal metabolic states. To do this, we study the dynamics of energy production in a cell. Due to the thermodynamic openness of a living cell, the inability to instantaneously match fluctuating supply and demand in energy metabolism results in nonautonomous time-varying oscillatory dynamics. However, such oscillatory dynamics is often neglected and treated as stochastic. Based on experimental evidence of metabolic oscillations, we show that changes in metabolic state can be described robustly by alterations in the chronotaxicity of the corresponding metabolic oscillations, i.e. the ability of an oscillator to resist external perturbations. We also present a method for the identification of chronotaxicity, applicable to general oscillatory signals and, importantly, apply this to real experimental data. Evidence of chronotaxicity was found in glycolytic oscillations in real yeast cells, verifying that chronotaxicity could be used to study transitions between metabolic states. PMID:27483987

  19. Development of an elementary climate model: two-layer cellular case

    CERN Document Server

    Schmidt, L E; Knox, R S; Schmidt, Laura E.; Knox, Robert S.

    2003-01-01

    A qualitative understanding of the greenhouse effect has long been available through models based on globally- and time-averaged quantities. We examine here a simple 864-cell climatological model that emphasizes vertical radiative energy transport within each cell. It reproduces yearly average temperatures obtained earlier from one of these global models and predicts a locally distributed non-radiative flux when observed temperatures are employed as input data. Vertical and lateral transport of latent heat do not appear explicitly in this model. They are apparently handled well by one non-radiative flux variable, SNR, which shows a strong latitude dependence. Only the Sahara desert and Saudi Arabian regions appear to be complex. For those interested in climatology and construction of climate models, our model provides constraints upon specifying averaged non-radiative energy transport. The model is a useful simplification for learning about radiative energy transfer into and out of Earth?s atmosphere and for ...

  20. Modelling extracellular electrical stimulation: IV. Effect of the cellular composition of neural tissue on its spatio-temporal filtering properties

    Science.gov (United States)

    Tahayori, Bahman; Meffin, Hamish; Sergeev, Evgeni N.; Mareels, Iven M. Y.; Burkitt, Anthony N.; Grayden, David B.

    2014-12-01

    Objective. The objective of this paper is to present a concrete application of the cellular composite model for calculating the membrane potential, described in an accompanying paper. Approach. A composite model that is used to determine the membrane potential for both longitudinal and transverse modes of stimulation is demonstrated. Main results. Two extreme limits of the model, near-field and far-field for an electrode close to or distant from a neuron, respectively, are derived in this paper. Results for typical neural tissue are compared using the composite, near-field and far-field models as well as the standard isotropic volume conductor model. The self-consistency of the composite model, its spatial profile response and the extracellular potential time behaviour are presented. The magnitudes of the longitudinal and transverse components for different values of electrode-neurite separations are compared. Significance. The unique features of the composite model and its simplified versions can be used to accurately estimate the spatio-temporal response of neural tissue to extracellular electrical stimulation.

  1. Cellular intrinsic mechanism affecting the outcome of AML treated with Ara-C in a syngeneic mouse model.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhao

    Full Text Available The mechanisms underlying acute myeloid leukemia (AML treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C.

  2. Self Organized Criticality in a two dimensional Cellular Automaton model of a magnetic flux tube with background flow

    CERN Document Server

    Danila, Bogdan; Mocanu, Gabriela

    2015-01-01

    We investigate the transition to Self Organized Criticality in a two-dimensional model of a flux tube with a background flow. The magnetic induction equation, represented by a partial differential equation with a stochastic source term, is discretized and implemented on a two dimensional cellular automaton. The energy released by the automaton during one relaxation event is the magnetic energy. As a result of the simulations we obtain the time evolution of the energy release, of the system control parameter, of the event lifetime distribution and of the event size distribution, respectively, and we establish that a Self Organized Critical state is indeed reached by the system. Moreover, energetic initial impulses in the magnetohydrodynamic flow can lead to one dimensional signatures in the magnetic two dimensional system, once the Self Organized Critical regime is established. The applications of the model for the study of Gamma Ray Bursts is briefly considered, and it is shown that some astrophysical paramet...

  3. A new model for anaerobic processes of up-flow anaerobic sludge blanket reactors based on cellular automata

    DEFF Research Database (Denmark)

    Skiadas, Ioannis V.; Ahring, Birgitte Kiær

    2002-01-01

    characteristics and lead to different reactor behaviour. A dynamic mathematical model has been developed for the anaerobic digestion of a glucose based synthetic wastewater in UASB reactors. Cellular automata (CA) theory has been applied to simulate the granule development process. The model takes......The advantageous performance of the UASB reactors is due to the immobilisation of the active biomass, since bacteria coagulate forming aggregates usually called granules. Changes in organic loading rate, hydraulic loading rate or influent substrate composition usually result in changes in granule...... into consideration that granule diameter and granule microbial composition are functions of the reactor operational parameters and is capable of predicting the UASB performance and the layer structure of the granules....

  4. Dynamic Computational Model Suggests That Cellular Citizenship Is Fundamental for Selective Tumor Apoptosis

    OpenAIRE

    Olsen, Megan; Siegelmann-Danieli, Nava; Siegelmann, Hava T.

    2010-01-01

    Computational models in the field of cancer research have focused primarily on estimates of biological events based on laboratory generated data. We introduce a novel in-silico technology that takes us to the next level of prediction models and facilitates innovative solutions through the mathematical system. The model's building blocks are cells defined phenotypically as normal or tumor, with biological processes translated into equations describing the life protocols of the cells in a quant...

  5. Dengue encephalitis-associated immunopathology in the mouse model: Implications for vaccine developers and antigens inducer of cellular immune response.

    Science.gov (United States)

    Marcos, Ernesto; Lazo, Laura; Gil, Lázaro; Izquierdo, Alienys; Suzarte, Edith; Valdés, Iris; Blanco, Aracelys; Ancizar, Julio; Alba, José Suárez; Pérez, Yusleydis de la C; Cobas, Karen; Romero, Yaremis; Guillén, Gerardo; Guzmán, María G; Hermida, Lisset

    2016-08-01

    Despite the many efforts made by the scientific community in the development of vaccine candidates against dengue virus (DENV), no vaccine has been licensed up to date. Although the immunopathogenesis associated to the disease is a key factor to take into account by vaccine developers, the lack of animal models that reproduce the clinical signs of the disease has hampered the vaccine progress. Non-human primates support viral replication, but they are very expensive and do not show signs of disease. Immunocompromised mice develop viremia and some signs of the disease; however, they are not valuable for vaccine testing. Nowadays, immunocompetent mice are the most used model to evaluate the immunogenicity of vaccine candidates. These animals are resistant to DENV infection; therefore, the intracranial inoculation with neuroadapted virus, which provokes viral encephalitis, represents an alternative to evaluate the protective capacity of vaccine candidates. Previous results have demonstrated the crucial role of cellular immune response in the protection induced by the virus and vaccine candidates in this mouse encephalitis model. However, in the present work we are proposing that the magnitude of the cell-mediated immunity and the inflammatory response generated by the vaccine can modulate the survival rate after viral challenge. We observed that the intracranial challenge of naïve mice with DENV-2 induces the recruitment of immune cells that contribute to the reduction of viral load, but does not increase the survival rate. On the contrary, animals treated with cyclophosphamide, an immunosuppressive drug that affects proliferating lymphocytes, had a higher viral load but a better survival rate than untreated animals. These results suggest that the immune system is playing an immunopathogenic role in this model and the survival rate may not be a suitable endpoint in the evaluation of vaccine candidates based on antigens that induce a strong cellular immune response

  6. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    International Nuclear Information System (INIS)

    Highlights: • Astrocytes exhibit characteristic changes in [Ca2+]i under OGD. • Astrocytic [Ca2+]i increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca2+]i) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca2+]i oscillations followed by larger and sustained [Ca2+]i increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca2+]i increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca2+]i increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca2+]i increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage during the acute phase of ischemia

  7. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo, E-mail: mnuriya@z2.keio.jp

    2014-02-07

    Highlights: • Astrocytes exhibit characteristic changes in [Ca{sup 2+}]{sub i} under OGD. • Astrocytic [Ca{sup 2+}]{sub i} increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca{sup 2+}]{sub i} oscillations followed by larger and sustained [Ca{sup 2+}]{sub i} increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca{sup 2+}]{sub i} increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca{sup 2+}]{sub i} increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca{sup 2+}]{sub i} increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage

  8. CellLab-CTS 2015: a Python library for continuous-time stochastic cellular automaton modeling using Landlab

    Science.gov (United States)

    Tucker, G. E.; Hobley, D. E. J.; Hutton, E.; Gasparini, N. M.; Istanbulluoglu, E.; Adams, J. M.; Nudurupati, S. S.

    2015-11-01

    CellLab-CTS 2015 is a Python-language software library for creating two-dimensional, continuous-time stochastic (CTS) cellular automaton models. The model domain consists of a set of grid nodes, with each node assigned an integer state-code that represents its condition or composition. Adjacent pairs of nodes may undergo transitions to different states, according to a user-defined average transition rate. A model is created by writing a Python code that defines the possible states, the transitions, and the rates of those transitions. The code instantiates, initializes, and runs one of four object classes that represent different types of CTS model. CellLab-CTS provides the option of using either square or hexagonal grid cells. The software provides the ability to treat particular grid-node states as moving particles, and to track their position over time. Grid nodes may also be assigned user-defined properties, which the user can update after each transition through the use of a callback function. As a component of the Landlab modeling framework, CellLab-CTS models take advantage of a suite of Landlab's tools and capabilities, such as support for standardized input and output.

  9. Drosophila embryos as model to assess cellular and developmental toxicity of multi-walled carbon nanotubes (MWCNT in living organisms.

    Directory of Open Access Journals (Sweden)

    Boyin Liu

    Full Text Available Different toxicity tests for carbon nanotubes (CNT have been developed to assess their impact on human health and on aquatic and terrestrial animal and plant life. We present a new model, the fruit fly Drosophila embryo offering the opportunity for rapid, inexpensive and detailed analysis of CNTs toxicity during embryonic development. We show that injected DiI labelled multi-walled carbon nanotubes (MWCNTs become incorporated into cells in early Drosophila embryos, allowing the study of the consequences of cellular uptake of CNTs on cell communication, tissue and organ formation in living embryos. Fluorescently labelled subcellular structures showed that MWCNTs remained cytoplasmic and were excluded from the nucleus. Analysis of developing ectodermal and neural stem cells in MWCNTs injected embryos revealed normal division patterns and differentiation capacity. However, an increase in cell death of ectodermal but not of neural stem cells was observed, indicating stem cell-specific vulnerability to MWCNT exposure. The ease of CNT embryo injections, the possibility of detailed morphological and genomic analysis and the low costs make Drosophila embryos a system of choice to assess potential developmental and cellular effects of CNTs and test their use in future CNT based new therapies including drug delivery.

  10. Animal models of human disease. Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes.

    OpenAIRE

    Pattengale, P K; Stewart, T A; Leder, A; Sinn, E; Muller, W.; Tepler, I; Schmidt, E.; Leder, P

    1989-01-01

    This present review focuses on spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes. The historical development of transgenic mice as in vivo disease models is briefly traced, followed by a brief description of the actual technology in such systems. Additional emphasis is placed on the concept of targeting activated cellular oncogenes to specific tissues in transgenic mice. Cumulative experience with activated (Vmyc, ras, and neu (erb-B2] onc...

  11. Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke

    OpenAIRE

    Yan, Tao; Chopp, Michael; Chen, Jieli

    2015-01-01

    Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand nove...

  12. ACCESS TO INFORMATION IN WORD OF MOUTH MARKETING WITHIN A CELLULAR AUTOMATA MODEL

    OpenAIRE

    AGNIESZKA KOWALSKA-STYCZEŃ; KATARZYNA SZNAJD-WERON

    2012-01-01

    We propose a simple microscopic model of consumer behavior in which decisions are made solely on the basis of person to person communication. Within our model we determine which factors are important in word of mouth marketing. We provide both Monte Carlo simulations, as well as mean-field analytical calculations and show that both the average decision time and uncertainty of decision grow nonlinearly with the amount of information up to a certain threshold value.

  13. Cellular automaton model with dynamical 2D speed-gap relation reproduces empirical and experimental features of traffic flow

    CERN Document Server

    Tian, Junfang; Ma, Shoufeng; Zhu, Chenqiang; Jiang, Rui; Ding, YaoXian

    2015-01-01

    This paper proposes an improved cellular automaton traffic flow model based on the brake light model, which takes into account that the desired time gap of vehicles is remarkably larger than one second. Although the hypothetical steady state of vehicles in the deterministic limit corresponds to a unique relationship between speeds and gaps in the proposed model, the traffic states of vehicles dynamically span a two-dimensional region in the plane of speed versus gap, due to the various randomizations. It is shown that the model is able to well reproduce (i) the free flow, synchronized flow, jam as well as the transitions among the three phases; (ii) the evolution features of disturbances and the spatiotemporal patterns in a car-following platoon; (iii) the empirical time series of traffic speed obtained from NGSIM data. Therefore, we argue that a model can potentially reproduce the empirical and experimental features of traffic flow, provided that the traffic states are able to dynamically span a 2D speed-gap...

  14. A limit cycle oscillator model for cycling mood variations of bipolar disorder patients derived from cellular biochemical reaction equations

    Science.gov (United States)

    Frank, T. D.

    2013-08-01

    We derive a nonlinear limit cycle model for oscillatory mood variations as observed in patients with cycling bipolar disorder. To this end, we consider two signaling pathways leading to the activation of two enzymes that play a key role for cellular and neural processes. We model pathway cross-talk in terms of an inhibitory impact of the first pathway on the second and an excitatory impact of the second on the first. The model also involves a negative feedback loop (inhibitory self-regulation) for the first pathway and a positive feedback loop (excitatory self-regulation) for the second pathway. We demonstrate that due to the cross-talk the biochemical dynamics is described by an oscillator equation. Under disease-free conditions the oscillatory system exhibits a stable fixed point. The breakdown of the self-inhibition of the first pathway at higher concentration levels is studied by means of a scalar control parameter ξ, where ξ equal to zero refers to intact self-inhibition at all concentration levels. Under certain conditions, stable limit cycle solutions emerge at critical parameter values of ξ larger than zero. These oscillations mimic pathological cycling mood variations that emerge due to a disease-induced bifurcation. Consequently, our modeling analysis supports the notion of bipolar disorder as a dynamical disease. In addition, our study establishes a connection between mechanistic biochemical modeling of bipolar disorder and phenomenological nonlinear oscillator approaches to bipolar disorder suggested in the literature.

  15. Cell-centred model for the simulation of curved cellular monolayers

    Science.gov (United States)

    Mosaffa, Payman; Asadipour, Nina; Millán, Daniel; Rodríguez-Ferran, Antonio; J Muñoz, Jose

    2015-12-01

    This paper presents a cell-centred model for the simulation of planar and curved multicellular soft tissues. We propose a computational model that includes stress relaxation due to cell reorganisation (intercellular connectivity changes) and cytoskeleton remodelling (intracellular changes). Cells are represented by their cell centres, and their mechanical interaction is modelled through active non-linear elastic laws with a dynamically changing resting length. Special attention is paid to the handling of connectivity changes between cells, and the relaxation that the tissues exhibit under these topological changes. Cell-cell connectivity is computed by resorting to a Delaunay triangulation, which is combined with a mapping technique in order to obtain triangulations on curved manifolds. Our numerical results show that even a linear elastic cell-cell interaction model may induce a global non-linear response due to the reorganisation of the cell connectivity. This plastic-like behaviour is combined with a non-linear rheological law where the resting length depends on the elastic strain, mimicking the global visco-elastic response of tissues. The model is applied to simulate the elongation of planar and curved monolayers.

  16. In vivo whole brain, cellular and molecular imaging in nonhuman primate models of neuropathology.

    Science.gov (United States)

    Huang, Lieven; Merson, Tobias D; Bourne, James A

    2016-07-01

    Rodents have been the principal model to study brain anatomy and function due to their well-mapped brain architecture, rapid reproduction and amenability to genetic modification. However, there are clear limitations, for example their simpler neocortex, necessitating the need to adopt a model that is closer to humans in order to understand human cognition and brain conditions. Nonhuman primates (NHPs) are ideally suited as they are our closest relatives in the animal kingdom but in vivo imaging technologies to study brain structure and function in these species can be challenging. With the surge in NHP research in recent years, scientists have begun adapting imaging technologies, such as two-photon microscopy, for these species. Here we review the various NHP models that exist as well as their use in advanced microscopic and mesoscopic studies. We discuss the challenges in the field and investigate the opportunities that lie ahead. PMID:27151822

  17. The simulation of the two-dimensional Ising model on the Creutz cellular automaton for the fractals obtained by using the model of diffusion-limited aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Merdan, Ziya [Dept. of Physics, Kirikkale Univ. (Turkey); Bayirli, Mehmet [Dept. of Physics, Balikesir Univ. (Turkey); Ozturk, Mustafa Kemal [Dept. of Mineral Analysis and Technology, MTA, Ankara (Turkey)

    2010-08-15

    The fractals are obtained by using the model of diffusion-limited aggregation (DLA) for the lattice with L = 80, 120, and 160. The values of the fractal dimensions are compared with the results of former studies. As increasing the linear dimensions they are in good agreement with those. The fractals obtained by using the model of DLA are simulated on the Creutz cellular automaton by using a two-bit demon. The values computed for the critical temperature and the static critical exponents within the framework of the finite-size scaling theory are in agreement with the results of other simulations and theoretical values. (orig.)

  18. Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities.

    Science.gov (United States)

    Banno, Kimihiko; Omori, Sayaka; Hirata, Katsuya; Nawa, Nobutoshi; Nakagawa, Natsuki; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakuma, Tetsushi; Yamamoto, Takashi; Toki, Tsutomu; Ito, Etsuro; Yamamoto, Toshiyuki; Kokubu, Chikara; Takeda, Junji; Taniguchi, Hidetoshi; Arahori, Hitomi; Wada, Kazuko; Kitabatake, Yasuji; Ozono, Keiichi

    2016-05-10

    Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis. PMID:27134169

  19. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    International Nuclear Information System (INIS)

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution

  20. "A Cellular Encounter": Constructing the Cell as a Whole System Using Illustrative Models

    Science.gov (United States)

    Cohen, Joel I.

    2014-01-01

    A standard part of biology curricula is a project-based assessment of cell structure and function. However, these are often individual assignments that promote little problem-solving or group learning and avoid the subject of organelle chemical interactions. I evaluate a model-based cell project designed to foster group and individual guided…

  1. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

    Directory of Open Access Journals (Sweden)

    Christopher S. Anderson

    2016-01-01

    Full Text Available Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.

  2. Cloud computing models and their application in LTE based cellular systems

    NARCIS (Netherlands)

    Staring, A.J.; Karagiannis, G.

    2013-01-01

    As cloud computing emerges as the next novel concept in computer science, it becomes clear that the model applied in large data storage systems used to resolve issues coming forth from an increasing demand, could also be used to resolve the very high bandwidth requirements on access network, core ne

  3. A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen.

    Science.gov (United States)

    Michaut, Anaïs; Le Guillou, Dounia; Moreau, Caroline; Bucher, Simon; McGill, Mitchell R; Martinais, Sophie; Gicquel, Thomas; Morel, Isabelle; Robin, Marie-Anne; Jaeschke, Hartmut; Fromenty, Bernard

    2016-02-01

    Obesity and nonalcoholic fatty liver disease (NAFLD) can increase susceptibility to hepatotoxicity induced by some xenobiotics including drugs, but the involved mechanisms are poorly understood. For acetaminophen (APAP), a role of hepatic cytochrome P450 2E1 (CYP2E1) is suspected since the activity of this enzyme is consistently enhanced during NAFLD. The first aim of our study was to set up a cellular model of NAFLD characterized not only by triglyceride accumulation but also by higher CYP2E1 activity. To this end, human HepaRG cells were incubated for one week with stearic acid or oleic acid, in the presence of different concentrations of insulin. Although cellular triglycerides and the expression of lipid-responsive genes were similar with both fatty acids, CYP2E1 activity was significantly increased only by stearic acid. CYP2E1 activity was reduced by insulin and this effect was reproduced in cultured primary human hepatocytes. Next, APAP cytotoxicity was assessed in HepaRG cells with or without lipid accretion and CYP2E1 induction. Experiments with a large range of APAP concentrations showed that the loss of ATP and glutathione was almost always greater in the presence of stearic acid. In cells pretreated with the CYP2E1 inhibitor chlormethiazole, recovery of ATP was significantly higher in the presence of stearate with low (2.5mM) or high (20mM) concentrations of APAP. Levels of APAP-glucuronide were significantly enhanced by insulin. Hence, HepaRG cells can be used as a valuable model of NAFLD to unveil important metabolic and hormonal factors which can increase susceptibility to drug-induced hepatotoxicity. PMID:26739624

  4. A medaka model of cancer allowing direct observation of transplanted tumor cells in vivo at a cellular-level resolution.

    Science.gov (United States)

    Hasegawa, Sumitaka; Maruyama, Kouichi; Takenaka, Hikaru; Furukawa, Takako; Saga, Tsuneo

    2009-08-18

    The recent success with small fish as an animal model of cancer with the aid of fluorescence technique has attracted cancer modelers' attention because it would be possible to directly visualize tumor cells in vivo in real time. Here, we report a medaka model capable of allowing the observation of various cell behaviors of transplanted tumor cells, such as cell proliferation and metastasis, which were visualized easily in vivo. We established medaka melanoma (MM) cells stably expressing GFP and transplanted them into nonirradiated and irradiated medaka. The tumor cells were grown at the injection sites in medaka, and the spatiotemporal changes were visualized under a fluorescence stereoscopic microscope at a cellular-level resolution, and even at a single-cell level. Tumor dormancy and metastasis were also observed. Interestingly, in irradiated medaka, accelerated tumor growth and metastasis of the transplanted tumor cells were directly visualized. Our medaka model provides an opportunity to visualize in vivo tumor cells "as seen in a culture dish" and would be useful for in vivo tumor cell biology. PMID:19666513

  5. Using a Cellular Automata-Markov Model to Reconstruct Spatial Land-Use Patterns in Zhenlai County, Northeast China

    Directory of Open Access Journals (Sweden)

    Yuanyuan Yang

    2015-05-01

    Full Text Available Decadal to centennial land use and land cover change has been consistently singled out as a key element and an important driver of global environmental change, playing an essential role in balancing energy use. Understanding long-term human-environment interactions requires historical reconstruction of past land use and land cover changes. Most of the existing historical reconstructions have insufficient spatial and thematic detail and do not consider various land change types. In this context, this paper explored the possibility of using a cellular automata-Markov model in 90 m × 90 m spatial resolution to reconstruct historical land use in the 1930s in Zhenlai County, China. Then the three-map comparison methodology was employed to assess the predictive accuracy of the transition modeling. The model could produce backward projections by analyzing land use changes in recent decades, assuming that the present land use pattern is dynamically dependent on the historical one. The reconstruction results indicated that in the 1930s most of the study area was occupied by grasslands, followed by wetlands and arable land, while other land categories occupied relatively small areas. Analysis of the three-map comparison illustrated that the major differences among the three maps have less to do with the simulation model and more to do with the inconsistencies among the land categories during the study period. Different information provided by topographic maps and remote sensing images must be recognized.

  6. An improved Cellular Automata model to simulate the behavior of high density crowd and validation by experimental data

    Science.gov (United States)

    Feliciani, Claudio; Nishinari, Katsuhiro

    2016-06-01

    In this article we present an improved version of the Cellular Automata floor field model making use of a sub-mesh system to increase the maximum density allowed during simulation and reproduce phenomena observed in dense crowds. In order to calibrate the model's parameters and to validate it we used data obtained from an empirical observation of bidirectional pedestrian flow. A good agreement was found between numerical simulation and experimental data and, in particular, the double outflow peak observed during the formation of deadlocks could be reproduced in numerical simulations, thus allowing the analysis of deadlock formation and dissolution. Finally, we used the developed high density model to compute the flow-ratio dependent fundamental diagram of bidirectional flow, demonstrating the instability of balanced flow and predicting the bidirectional flow behavior at very high densities. The model we presented here can be used to prevent dense crowd accidents in the future and to investigate the dynamics of the accidents which already occurred in the past. Additionally, fields such as granular and active matter physics may benefit from the developed framework to study different collective phenomena.

  7. 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)

  8. Dynamical studies of model membrane and cellular response to nanosecond, high-intensity pulsed electric fields

    Science.gov (United States)

    Hu, Qin

    The dynamics of electroporation of biological cells subjected to nanosecond, high intensity pulses are studied based on a coupled scheme involving the current continuity and Smoluchowski equations. The improved pore formation energy model includes a dependence on pore population and density. It also allows for variable surface tension and incorporates the effects of finite conductivity on the electrostatic correction term, which was not considered by the simple energy models in the literature. It is shown that E(r) becomes self-adjusting with variations in its magnitude and profile. The whole scheme is self-consistent and dynamic. An electromechanical analysis based on thin-shell theory is presented to analyze cell shape changes in response to external electric fields. The calculations demonstrate that at large fields, the spherical cell geometry can be modified, and even ellipsoidal forms may not be appropriate to account for the resulting shape. It is shown that, in keeping with reports in the literature, the final shape depends on membrane thickness. This has direct implications for tissues in which significant molecular restructuring can occur. This study is also focused on obtaining qualitative predictions of pulse width dependence to apoptotic cell irreversibility that has been observed experimentally. The analysis couples a distributed electrical model for current flow with the Smoluchowski equation to provide self-consistent, time-dependent transmembrane voltages. The model captures the essence of the experimentally observed pulse-width dependence, and provides a possible physical picture that depends only on the electrical trigger. Different cell responses of normal and malignant (Farage) tonsillar B-cell are also compared and discussed. It is shown that subjecting a cell to an ultrashort, high-intensity electric pulse is the optimum way for reversible intracellular manipulation. Finally, a simple but physical atomistic model is presented for molecular

  9. Efficient Uplink Modeling for Dynamic System-Level Simulations of Cellular and Mobile Networks

    Directory of Open Access Journals (Sweden)

    Lobinger Andreas

    2010-01-01

    Full Text Available A novel theoretical framework for uplink simulations is proposed. It allows investigations which have to cover a very long (real- time and which at the same time require a certain level of accuracy in terms of radio resource management, quality of service, and mobility. This is of particular importance for simulations of self-organizing networks. For this purpose, conventional system level simulators are not suitable due to slow simulation speeds far beyond real-time. Simpler, snapshot-based tools are lacking the aforementioned accuracy. The runtime improvements are achieved by deriving abstract theoretical models for the MAC layer behavior. The focus in this work is long term evolution, and the most important uplink effects such as fluctuating interference, power control, power limitation, adaptive transmission bandwidth, and control channel limitations are considered. Limitations of the abstract models will be discussed as well. Exemplary results are given at the end to demonstrate the capability of the derived framework.

  10. A permeation-diffusion-reaction model of gas transport in cellular tissue of plant materials

    OpenAIRE

    Ho, Quang Tri; Verlinden, Bert; Verboven, Pieter; Vandewalle, Stefan; Nicolai, Bart

    2006-01-01

    Gas transport in fruit tissue is governed by both diffusion and permeation. The latter phenomenon is caused by overall pressure gradients which may develop due to the large difference in O-2 and CO2 diffusivity during controlled atmosphere storage of the fruit. A measurement set-up for tissue permeation based on unsteady-state gas exchange was developed. The gas permeability of pear tissue was determined based on an analytical gas transport model. The overall gas transport in pear tissue samp...

  11. Computational Model of Cellular Metabolic Dynamics in Skeletal Muscle Fibers during Moderate Intensity Exercise

    OpenAIRE

    Li, Yanjun; Lai, Nicola; Kirwan, John P; Saidel, Gerald M.

    2012-01-01

    Human skeletal muscles have different fiber types with distinct metabolic functions and physiological properties. The quantitative metabolic responses of muscle fibers to exercise provide essential information for understanding and modifying the regulatory mechanisms of skeletal muscle. Since in vivo data from skeletal muscle during exercise is limited, a computational, physiologically based model has been developed to quantify the dynamic metabolic responses of many key chemical species. Thi...

  12. Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running

    OpenAIRE

    Mondry Adrian; Rajagopal Gunaretnam; Sun Yan; Zhu Hao; Dhar Pawan

    2004-01-01

    Abstract Background Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. Methods We have developed a method to ...

  13. Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis

    OpenAIRE

    Praet, Jelle; Guglielmetti, Caroline; Berneman, Zwi; Van der Linden, Annemie; Ponsaerts, Peter

    2014-01-01

    Abstract: The cuprizone mouse model allows the investigation of the complex molecular mechanisms behind nonautoimmune-mediated demyelination and spontaneous remyelination. While it is generally accepted that oligodendrocytes are specifically vulnerable to cuprizone intoxication due to their high metabolic demands, a comprehensive overview of the etiology of cuprizone-induced pathology is still missing to date. In this review we extensively describe the physico-chemical mode of action of cupri...

  14. Effect of Driver Scope Awareness in the Lane Changing Maneuvers Using Cellular Automaton Model

    OpenAIRE

    Kohei Arai; Steven Ray Sentinuwo

    2013-01-01

    This paper investigated the effect of drivers’ visibility and their perception (e.g., to estimate the speed and arrival time of another vehicle) on the lane changing maneuver. The term of scope awareness was used to describe the visibility required by the driver to make a perception about road condition and the speed of vehicle that exist in that road. A computer simulation model was conducted to show this driver awareness behavior. This studying attempt to precisely catching the lane changin...

  15. Detection and Projection of Forest Changes by Using the Markov Chain Model and Cellular Automata

    OpenAIRE

    Griselda Vázquez-Quintero; Raúl Solís-Moreno; Marín Pompa-García; Federico Villarreal-Guerrero; Carmelo Pinedo-Alvarez; Alfredo Pinedo-Alvarez

    2016-01-01

    The spatio-temporal analysis of land use changes could provide basic information for managing the protection, conservation and production of forestlands, which promotes a sustainable resource use of temperate ecosystems. In this study we modeled and analyzed the spatial and temporal dynamics of land use of a temperate forests in the region of Pueblo Nuevo, Durango, Mexico. Data from the Landsat images Multispectral Scanner (MSS) 1973, Thematic Mapper (TM) 1990, and Operational Land Imager (OL...

  16. Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: synthesis, crystallography, modeling, kinetic and cellular based studies

    OpenAIRE

    Šilhár, Peter; Silvaggi, Nicholas R; Pellett, Sabine; Čapková, Kateřina; Johnson, Eric A.; Allen, Karen N.; Janda, Kim D.

    2012-01-01

    Botulinum neurotoxins (BoNTs) are the most lethal biotoxins known to mankind and are responsible for the neuroparalytic disease botulism. Current treatments for botulinum poisoning are all protein based and thus have a limited window of treatment opportunity. Inhibition of the BoNT light chain protease (LC) has emerged as a therapeutic strategy for the treatment of botulism as it may provide an effective post exposure remedy. Using a combination of crystallographic and modeling studies a seri...

  17. Olfactory Stem Cells, a New Cellular Model for Studying Molecular Mechanisms Underlying Familial Dysautonomia

    OpenAIRE

    Nathalie Boone; Béatrice Loriod; Aurélie Bergon; Oualid Sbai; Christine Formisano-Tréziny; Jean Gabert; Michel Khrestchatisky; Catherine Nguyen; François Féron; Axelrod, Felicia B.; El Chérif Ibrahim

    2010-01-01

    BACKGROUND: Familial dysautonomia (FD) is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and mod...

  18. A Simple Model of Protein Domain Swapping in Crowded Cellular Environments.

    Science.gov (United States)

    Woodard, Jaie C; Dunatunga, Sachith; Shakhnovich, Eugene I

    2016-06-01

    Domain swapping in proteins is an important mechanism of functional and structural innovation. However, despite its ubiquity and importance, the physical mechanisms that lead to domain swapping are poorly understood. Here, we present a simple two-dimensional coarse-grained model of protein domain swapping in the cytoplasm. In our model, two-domain proteins partially unfold and diffuse in continuous space. Monte Carlo multiprotein simulations of the model reveal that domain swapping occurs at intermediate temperatures, whereas folded dimers and folded monomers prevail at low temperatures, and partially unfolded monomers predominate at high temperatures. We use a simplified amino acid alphabet consisting of four residue types, and find that the oligomeric state at a given temperature depends on the sequence of the protein. We also show that hinge strain between domains can promote domain swapping, consistent with experimental observations for real proteins. Domain swapping depends nonmonotonically on the protein concentration, with domain-swapped dimers occurring at intermediate concentrations and nonspecific interactions between partially unfolded proteins occurring at high concentrations. For folded proteins, we recover the result obtained in three-dimensional lattice simulations, i.e., that functional dimerization is most prevalent at intermediate temperatures and nonspecific interactions increase at low temperatures. PMID:27276255

  19. A computational framework for 3D mechanical modeling of plant morphogenesis with cellular resolution.

    Directory of Open Access Journals (Sweden)

    Frédéric Boudon

    2015-01-01

    Full Text Available The link between genetic regulation and the definition of form and size during morphogenesis remains largely an open question in both plant and animal biology. This is partially due to the complexity of the process, involving extensive molecular networks, multiple feedbacks between different scales of organization and physical forces operating at multiple levels. Here we present a conceptual and modeling framework aimed at generating an integrated understanding of morphogenesis in plants. This framework is based on the biophysical properties of plant cells, which are under high internal turgor pressure, and are prevented from bursting because of the presence of a rigid cell wall. To control cell growth, the underlying molecular networks must interfere locally with the elastic and/or plastic extensibility of this cell wall. We present a model in the form of a three dimensional (3D virtual tissue, where growth depends on the local modulation of wall mechanical properties and turgor pressure. The model shows how forces generated by turgor-pressure can act both cell autonomously and non-cell autonomously to drive growth in different directions. We use simulations to explore lateral organ formation at the shoot apical meristem. Although different scenarios lead to similar shape changes, they are not equivalent and lead to different, testable predictions regarding the mechanical and geometrical properties of the growing lateral organs. Using flower development as an example, we further show how a limited number of gene activities can explain the complex shape changes that accompany organ outgrowth.

  20. Validity of the Cauchy-Born rule applied to discrete cellular-scale models of biological tissues

    KAUST Repository

    Davit, Y.

    2013-04-30

    The development of new models of biological tissues that consider cells in a discrete manner is becoming increasingly popular as an alternative to continuum methods based on partial differential equations, although formal relationships between the discrete and continuum frameworks remain to be established. For crystal mechanics, the discrete-to-continuum bridge is often made by assuming that local atom displacements can be mapped homogeneously from the mesoscale deformation gradient, an assumption known as the Cauchy-Born rule (CBR). Although the CBR does not hold exactly for noncrystalline materials, it may still be used as a first-order approximation for analytic calculations of effective stresses or strain energies. In this work, our goal is to investigate numerically the applicability of the CBR to two-dimensional cellular-scale models by assessing the mechanical behavior of model biological tissues, including crystalline (honeycomb) and noncrystalline reference states. The numerical procedure involves applying an affine deformation to the boundary cells and computing the quasistatic position of internal cells. The position of internal cells is then compared with the prediction of the CBR and an average deviation is calculated in the strain domain. For center-based cell models, we show that the CBR holds exactly when the deformation gradient is relatively small and the reference stress-free configuration is defined by a honeycomb lattice. We show further that the CBR may be used approximately when the reference state is perturbed from the honeycomb configuration. By contrast, for vertex-based cell models, a similar analysis reveals that the CBR does not provide a good representation of the tissue mechanics, even when the reference configuration is defined by a honeycomb lattice. The paper concludes with a discussion of the implications of these results for concurrent discrete and continuous modeling, adaptation of atom-to-continuum techniques to biological

  1. Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model.

    Directory of Open Access Journals (Sweden)

    Zi-Huan Yang

    Full Text Available BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat colonic crypts, mucosal addition of naringenin (100 microM elicited a concentration-dependent and sustained increase in the short-circuit current (I(SC, which could be inhibited in Cl- free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid, but not by DIDS (4, 4'- diisothiocyanatostilbene-2, 2'-disulfonic acid. Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N-(Cis-2-phenyl-cyclopentyl azacyclotridecan-2-imine-hydrochloride pretreatment reduced the naringenin-induced I(SC. In addition, significant inhibition of the naringenin-induced I(SC by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked whole cell current which exhibited a linear I-V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation.

  2. Properties of a Finite Stochastic Cellular Automaton Toy Model of Earthquakes

    Directory of Open Access Journals (Sweden)

    Białecki Mariusz

    2015-08-01

    Full Text Available Finite version of Random Domino Automaton - a recently proposed toy model of earthquakes - is investigated in detail. Respective set of equations describing stationary state of the FRDA is derived and compared with infinite case. It is shown that for a system of large size, these equations are coincident with RDA equations. We demonstrate a non-existence of exact equations for size N ≥ 5 and propose appropriate approximations, the quality of which is studied in examples obtained within the framework of Markov chains.

  3. Automatic TCAD model calibration for multi-cellular Trench-IGBTs

    Science.gov (United States)

    Maresca, Luca; Breglio, Giovanni; Irace, Andrea

    2014-01-01

    TCAD simulators are a consolidate tool in the field of the semiconductor research because of their predictive capability. However, an accurate calibration of the models is needed in order to get quantitative accurate results. In this work a calibration procedure of the TCAD elementary cell, specific for Trench IGBT with a blocking voltage of 600 V, is presented. It is based on the error minimization between the experimental and the simulated terminal curves of the device at two temperatures. The procedure is applied to a PT-IGBT and a good predictive capability is showed in the simulation of both the short-circuit and turn-off tests.

  4. New roles of glycosaminoglycans in α-synuclein aggregation in a cellular model of Parkinson disease.

    Directory of Open Access Journals (Sweden)

    Sonia Lehri-Boufala

    Full Text Available The causes of Parkinson disease (PD remain mysterious, although some evidence supports mitochondrial dysfunctions and α-synuclein accumulation in Lewy bodies as major events. The abnormal accumulation of α-synuclein has been associated with a deficiency in the ubiquitin-proteasome system and the autophagy-lysosomal pathway. Cathepsin D (cathD, the major lysosomal protease responsible of α-synuclein degradation was described to be up-regulated in PD model. As glycosaminoglycans (GAGs regulate cathD activity, and have been recently suggested to participate in PD physiopathology, we investigated their role in α-synuclein accumulation by their intracellular regulation of cathD activity. In a classical neuroblastoma cell model of PD induced by MPP+, the genetic expression of GAGs-biosynthetic enzymes was modified, leading to an increase of GAGs amounts whereas intracellular level of α-synuclein increased. The absence of sulfated GAGs increased intracellular cathD activity and limited α-synuclein accumulation. GAGs effects on cathD further suggested that specific sequences or sulfation patterns could be responsible for this regulation. The present study identifies, for the first time, GAGs as new regulators of the lysosome degradation pathway, regulating cathD activity and affecting two main biological processes, α-synuclein aggregation and apoptosis. Finally, this opens new insights into intracellular GAGs functions and new fields of investigation for glycobiological approaches in PD and neurobiology.

  5. Examining the impact of multi-layer graphene using cellular and amphibian models

    Science.gov (United States)

    Muzi, Laura; Mouchet, Florence; Cadarsi, Stéphanie; Janowska, Izabela; Russier, Julie; Ménard-Moyon, Cécilia; Risuleo, Gianfranco; Soula, Brigitte; Galibert, Anne-Marie; Flahaut, Emmanuel; Pinelli, Eric; Gauthier, Laury; Bianco, Alberto

    2016-06-01

    In the last few years, graphene has been defined as the revolutionary material showing an incredible expansion in industrial applications. Different graphene forms have been applied in several contexts, spreading from energy technologies and electronics to food and agriculture technologies. Graphene showed promises also in the biomedical field. Hopeful results have been already obtained in diagnostic, drug delivery, tissue regeneration and photothermal cancer ablation. In view of the enormous development of graphene-based technologies, a careful assessment of its impact on health and environment is demanded. It is evident how investigating the graphene toxicity is of fundamental importance in the context of medical purposes. On the other hand, the nanomaterial present in the environment, likely to be generated all along the industrial life-cycle, may have harmful effects on living organisms. In the present work, an important contribution on the impact of multi-layer graphene (MLG) on health and environment is given by using a multifaceted approach. For the first purpose, the effect of the material on two mammalian cell models was assessed. Key cytotoxicity parameters were considered such as cell viability and inflammatory response induction. This was combined with an evaluation of MLG toxicity towards Xenopus laevis, used as both in vivo and environmental model organism.

  6. Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer's disease.

    Science.gov (United States)

    Hagl, Stephanie; Grewal, Rekha; Ciobanu, Ion; Helal, Amr; Khayyal, Mohamed T; Muller, Walter E; Eckert, Gunter P

    2015-01-01

    Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD. PMID:25125472

  7. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Ying, Bo; Campbell, Robert B., E-mail: robert.campbell@mcphs.edu

    2014-04-04

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  8. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    International Nuclear Information System (INIS)

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  9. A three-dimensional frontal cellular automaton model for simulation of microstructure evolution—initial microstructure module

    International Nuclear Information System (INIS)

    This paper presents a three-dimensional frontal cellular automaton (FCA)-based model for modelling of microstructure evolution during technological processes. It is a hierarchical system. The first level is the FCAs, the second level contains modules of microstructural phenomena and the third level is presented by the models of technological processes. The module of the initial microstructure (IM) is one of the components of the second level. The IM allows one to obtain a digital material representation of given parameters, which can be used by other modules for further simulation. The parameters that must be assured by the IM module are the following: shape of the grains and distributions of the grain size, crystallographic orientation and boundary disorientation angles. To obtain the required parameters, the FCAs are first used as a tool for the creation of the basic microstructure characterized by the shape of the grains. The grain size distribution is obtained by the method, which changes nucleation and grain growth conditions. After the creation of the microstructure, crystallographic parameters are established. Distribution of the crystallographic orientation and boundary disorientation angles can be obtained independently or as associated parameters. Some examples of microstructures obtained by the IM module are presented in this paper. (paper)

  10. Local Cellular Immune Responses and Pathogenesis of Buruli Ulcer Lesions in the Experimental Mycobacterium Ulcerans Pig Infection Model

    Science.gov (United States)

    Bolz, Miriam; Ruggli, Nicolas; Borel, Nicole; Pluschke, Gerd; Ruf, Marie-Thérèse

    2016-01-01

    Background Buruli ulcer is a neglected tropical disease of the skin that is caused by infection with Mycobacterium ulcerans. We recently established an experimental pig (Sus scrofa) infection model for Buruli ulcer to investigate host-pathogen interactions, the efficacy of candidate vaccines and of new treatment options. Methodology/Principal Findings Here we have used the model to study pathogenesis and early host-pathogen interactions in the affected porcine skin upon infection with mycolactone-producing and non-producing M. ulcerans strains. Histopathological analyses of nodular lesions in the porcine skin revealed that six weeks after infection with wild-type M. ulcerans bacteria extracellular acid fast bacilli were surrounded by distinct layers of neutrophils, macrophages and lymphocytes. Upon ulceration, the necrotic tissue containing the major bacterial burden was sloughing off, leading to the loss of most of the mycobacteria. Compared to wild-type M. ulcerans bacteria, toxin-deficient mutants caused an increased granulomatous cellular infiltration without massive tissue necrosis, and only smaller clusters of acid fast bacilli. Conclusions/Significance In summary, the present study shows that the pathogenesis and early immune response to M. ulcerans infection in the pig is very well reflecting BU disease in humans, making the pig infection model an excellent tool for the profiling of new therapeutic and prophylactic interventions. PMID:27128097

  11. Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models

    International Nuclear Information System (INIS)

    Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression. The activity and mechanism of action of the dual CDC7/CDK9 inhibitor PHA-767491 was assessed in a panel of multiple myeloma cell lines, in primary samples from patients, in the presence of stromal cells and in combination with drugs used in current chemotherapeutic regimens. We report that in all conditions myeloma cells undergo cell death upon PHA-767491 treatment and we report an overall additive effect with melphalan, bortezomib and doxorubicin, thus supporting further assessment of targeting CDC7 and CDK9 in multiple myeloma

  12. Model-based traction force microscopy reveals differential tension in cellular actin bundles.

    Science.gov (United States)

    Soiné, Jérôme R D; Brand, Christoph A; Stricker, Jonathan; Oakes, Patrick W; Gardel, Margaret L; Schwarz, Ulrich S

    2015-03-01

    Adherent cells use forces at the cell-substrate interface to sense and respond to the physical properties of their environment. These cell forces can be measured with traction force microscopy which inverts the equations of elasticity theory to calculate them from the deformations of soft polymer substrates. We introduce a new type of traction force microscopy that in contrast to traditional methods uses additional image data for cytoskeleton and adhesion structures and a biophysical model to improve the robustness of the inverse procedure and abolishes the need for regularization. We use this method to demonstrate that ventral stress fibers of U2OS-cells are typically under higher mechanical tension than dorsal stress fibers or transverse arcs. PMID:25748431

  13. Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models

    Energy Technology Data Exchange (ETDEWEB)

    Natoni, Alessandro [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland); Coyne, Mark R. E. [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland); Department of Medicine, National University of Ireland Galway, Galway (Ireland); Department of Haematology, Galway University Hospital, Galway (Ireland); Jacobsen, Alan; Rainey, Michael D.; O’Brien, Gemma; Healy, Sandra [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland); Montagnoli, Alessia; Moll, Jürgen [Nerviano Medical Sciences S.r.l., Via Pasteur 10, Nerviano 20014 (Italy); O’Dwyer, Michael, E-mail: michael.odwyer@nuigalway.ie [Department of Medicine, National University of Ireland Galway, Galway (Ireland); Department of Haematology, Galway University Hospital, Galway (Ireland); Santocanale, Corrado, E-mail: michael.odwyer@nuigalway.ie [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland)

    2013-07-24

    Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression. The activity and mechanism of action of the dual CDC7/CDK9 inhibitor PHA-767491 was assessed in a panel of multiple myeloma cell lines, in primary samples from patients, in the presence of stromal cells and in combination with drugs used in current chemotherapeutic regimens. We report that in all conditions myeloma cells undergo cell death upon PHA-767491 treatment and we report an overall additive effect with melphalan, bortezomib and doxorubicin, thus supporting further assessment of targeting CDC7 and CDK9 in multiple myeloma.

  14. The biophysical model for accuracy of cellular sensing spatial gradients of multiple chemoattractants

    International Nuclear Information System (INIS)

    Spatial gradients of surrounding chemoattractants are the key factors in determining the directionality of eukaryotic cell movement. Thus, it is important for cells to accurately measure the spatial gradients of surrounding chemoattractants. Here, we study the precision of sensing the spatial gradients of multiple chemoattractants using cooperative receptor clusters. Cooperative receptors on cells are modeled as an Ising chain of Monod–Wyman–Changeux clusters subject to multiple chemical-gradient fields to study the physical limits of multiple chemoattractants spatial gradients sensing. We found that eukaryotic cells cannot sense each chemoattractant gradient individually. Instead, cells can only sense a weighted sum of surrounding chemical gradients. Moreover, the precision of sensing one chemical gradient is signicantly affected by coexisting chemoattractant concentrations. These findings can provide a further insight into the role of chemoattractants in immune response and help develop novel treatments for inflammatory diseases. (paper)

  15. Establishment of a cellular model to study TrkC-dependent neuritogenesis.

    Science.gov (United States)

    Krawczyk, Pawel; Twarog, Ewa; Kurowska, Ewa; Klopotowska, Dagmara; Matuszyk, Janusz

    2015-03-01

    The rat PC12 cell line has become a widely used research tool for many aspects of neurobiology. Nerve growth factor (NGF)-responsive PC12 cells were engineered to drive expression of doxycycline (Dox)-induced gene of interest in the Tet-On expression system that resulted in obtaining PC12-Tet-On cells. TrkA and TrkC are neurotrophin receptors derived from the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases. TrkA receptor binds and is activated mainly by NGF, while TrkC receptor binds and is activated by neurotrophin 3 (NT3). The purpose of this research was to design and describe PC12-based neuronal cell model to study TrkC-triggered versus TrkA-triggered neurite outgrowth. The second-generation tetracycline-responsive promoter (P tight) was used in order to provide low basal expression in the absence of Dox and high-level Dox-induced expression of TrkC. The main advantage of presented model system is dependence of TrkC level on Dox concentration. It also allows to compare activation of intracellular signaling proteins and neurite outgrowth following activation of TrkA and TrkC receptors by NGF and NT3, respectively, in the context of the same quality and quantity of intracellular adaptor proteins, Ras proteins, protein kinases and phosphatases, and phospholipase Cγ1, as a difference in the activation of intracellular signaling network by these two distinct although related receptor tyrosine kinases is expected. The results of our studies suggest that despite slightly weaker activation of ERK1/2 mitogen-activated protein kinases, NT3-triggered TrkC seems to provide apparently stronger than NGF-triggered TrkA signal for neurite elongation in differentiating PC12 cells. PMID:25398493

  16. Influence of multidrug resistance on 18F-FCH cellular uptake in a glioblastoma model

    International Nuclear Information System (INIS)

    Multidrug resistance, aggressiveness and accelerated choline metabolism are hallmarks of malignancy and have motivated the development of new PET tracers like 18F-FCH, an analogue of choline. Our aim was to study the relationship of multidrug resistance of cultured glioma cell lines and 18F-FCH tracer uptake. We used an in vitro multidrug-resistant (MDR) glioma model composed of sensitive parental U87MG and derived resistant cells U87MG-CIS and U87MG-DOX. Aggressiveness, choline metabolism and transport were studied, particularly the expression of choline kinase (CK) and high-affinity choline transporter (CHT1). FCH transport studies were assessed in our glioblastoma model. As expected, the resistant cell lines express P-glycoprotein (Pgp), multidrug resistance-associated protein isoform 1 (MRP1) and elevated glutathione (GSH) content and are also more mobile and more invasive than the sensitive U87MG cells. Our results show an overexpression of CK and CHT1 in the resistant cell lines compared to the sensitive cell lines. We found an increased uptake of FCH (in % of uptake per 200,000 cells) in the resistant cells compared to the sensitive ones (U87MG: 0.89±0.14; U87MG-CIS: 1.27±0.18; U87MG-DOX: 1.33±0.13) in line with accelerated choline metabolism and aggressive phenotype. FCH uptake is not influenced by the two ATP-dependant efflux pumps: Pgp and MRP1. FCH would be an interesting probe for glioma imaging which would not be effluxed from the resistant cells by the classic MDR ABC transporters. Our results clearly show that FCH uptake reflects accelerated choline metabolism and is related to tumour aggressiveness and drug resistance. (orig.)

  17. Influence of multidrug resistance on {sup 18}F-FCH cellular uptake in a glioblastoma model

    Energy Technology Data Exchange (ETDEWEB)

    Vanpouille, Claire; Jeune, Nathalie le; Clotagatide, Anthony; Dubois, Francis [Universite de Lyon, Universite Jean Monnet-Cancer Research Group IFRESIS 143, Saint-Etienne (France); Kryza, David; Janier, Marc [Hospice Civils de Lyon, Quai Des Celestins, CREATIS, UMR CNRS, Lyon (France); Perek, Nathalie [Universite de Lyon, Universite Jean Monnet-Cancer Research Group IFRESIS 143, Saint-Etienne (France); Laboratoire de Biophysique, Faculte de Medecine, Saint-Etienne (France)

    2009-08-15

    Multidrug resistance, aggressiveness and accelerated choline metabolism are hallmarks of malignancy and have motivated the development of new PET tracers like {sup 18}F-FCH, an analogue of choline. Our aim was to study the relationship of multidrug resistance of cultured glioma cell lines and {sup 18}F-FCH tracer uptake. We used an in vitro multidrug-resistant (MDR) glioma model composed of sensitive parental U87MG and derived resistant cells U87MG-CIS and U87MG-DOX. Aggressiveness, choline metabolism and transport were studied, particularly the expression of choline kinase (CK) and high-affinity choline transporter (CHT1). FCH transport studies were assessed in our glioblastoma model. As expected, the resistant cell lines express P-glycoprotein (Pgp), multidrug resistance-associated protein isoform 1 (MRP1) and elevated glutathione (GSH) content and are also more mobile and more invasive than the sensitive U87MG cells. Our results show an overexpression of CK and CHT1 in the resistant cell lines compared to the sensitive cell lines. We found an increased uptake of FCH (in % of uptake per 200,000 cells) in the resistant cells compared to the sensitive ones (U87MG: 0.89{+-}0.14; U87MG-CIS: 1.27{+-}0.18; U87MG-DOX: 1.33{+-}0.13) in line with accelerated choline metabolism and aggressive phenotype. FCH uptake is not influenced by the two ATP-dependant efflux pumps: Pgp and MRP1. FCH would be an interesting probe for glioma imaging which would not be effluxed from the resistant cells by the classic MDR ABC transporters. Our results clearly show that FCH uptake reflects accelerated choline metabolism and is related to tumour aggressiveness and drug resistance. (orig.)

  18. Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Yazhou Li

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1, facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4 is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex-4 may provide neuroprotective activity in ALS, and hence characterized Ex-4 actions in both cell culture (NSC-19 neuroblastoma cells and in vivo (SOD1 G93A mutant mice models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant SOD1 (G37R stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice. Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons. Together, our results suggest that GLP-1 receptor agonists warrant further evaluation to assess whether their neuroprotective potential is of therapeutic relevance in ALS.

  19. A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder

    Directory of Open Access Journals (Sweden)

    Keller Benjamin J

    2010-11-01

    Full Text Available Abstract Background Lithium is an effective treatment for Bipolar Disorder (BD and significantly reduces suicide risk, though the molecular basis of lithium's effectiveness is not well understood. We seek to improve our understanding of this effectiveness by posing hypotheses based on new experimental data as well as published data, testing these hypotheses in silico, and posing new hypotheses for validation in future studies. We initially hypothesized a gene-by-environment interaction where lithium, acting as an environmental influence, impacts signal transduction pathways leading to differential expression of genes important in the etiology of BD mania. Results Using microarray and rt-QPCR assays, we identified candidate genes that are differentially expressed with lithium treatment. We used a systems biology approach to identify interactions among these candidate genes and develop a network of genes that interact with the differentially expressed candidates. Notably, we also identified cocaine as having a potential influence on the network, consistent with the observed high rate of comorbidity for BD and cocaine abuse. The resulting network represents a novel hypothesis on how multiple genetic influences on bipolar disorder are impacted by both lithium treatment and cocaine use. Testing this network for association with BD and related phenotypes, we find that it is significantly over-represented for genes that participate in signal transduction, consistent with our hypothesized-gene-by environment interaction. In addition, it models related pharmacogenomic, psychiatric, and chemical dependence phenotypes. Conclusions We offer a network model of gene-by-environment interaction associated with lithium's effectiveness in treating BD mania, as well as the observed high rate of comorbidity of BD and cocaine abuse. We identified drug targets within this network that represent immediate candidates for therapeutic drug testing. Posing novel

  20. Cellular characterization of ultrasound-stimulated microbubble radiation enhancement in a prostate cancer xenograft model

    Directory of Open Access Journals (Sweden)

    Azza A. Al-Mahrouki

    2014-03-01

    Full Text Available Tumor radiation resistance poses a major obstacle in achieving an optimal outcome in radiation therapy. In the current study, we characterize a novel therapeutic approach that combines ultrasound-driven microbubbles with radiation to increase treatment responses in a prostate cancer xenograft model in mice. Tumor response to ultrasound-driven microbubbles and radiation was assessed 24 hours after treatment, which consisted of radiation treatments alone (2 Gy or 8 Gy or ultrasound-stimulated microbubbles only, or a combination of radiation and ultrasound-stimulated microbubbles. Immunohistochemical analysis using in situ end labeling (ISEL and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL revealed increased cell death within tumors exposed to combined treatments compared with untreated tumors or tumors exposed to radiation alone. Several biomarkers were investigated to evaluate cell proliferation (Ki67, blood leakage (factor VIII, angiogenesis (cluster of differentiation molecule CD31, ceramide-formation, angiogenesis signaling [vascular endothelial growth factor (VEGF], oxygen limitation (prolyl hydroxylase PHD2 and DNA damage/repair (γH2AX. Results demonstrated reduced vascularity due to vascular disruption by ultrasound-stimulated microbubbles, increased ceramide production and increased DNA damage of tumor cells, despite decreased tumor oxygenation with significantly less proliferating cells in the combined treatments. This combined approach could be a feasible option as a novel enhancing approach in radiation therapy.

  1. A cellular model reflecting the phenotypic heterogeneity of mutant HRAS driven squamous cell carcinoma.

    Science.gov (United States)

    Cantariño, Neus; Fernández-Figueras, M Teresa; Valero, Vanesa; Musulén, Eva; Malinverni, Roberto; Granada, Isabel; Goldie, Stephen J; Martín-Caballero, Juan; Douet, Julien; Forcales, Sonia-Vanina; Buschbeck, Marcus

    2016-09-01

    Squamous cell carcinomas have a range of histopathological manifestations. The parameters that determine this clinically observed heterogeneity are not fully understood. Here, we report the generation of a cell culture model that reflects part of this heterogeneity. We have used the catalytic subunit of human telomerase hTERT and large T to immortalize primary UV-unexposed keratinocytes. Then, mutant HRAS G12V has been introduced to transform these immortal keratinocytes. When injected into immunosuppressed mice, transformed cells grew as xenografts with distinct histopathological characteristics. We observed three major tissue architectures: solid, sarcomatoid and cystic growth types, which were primarily composed of pleomorphic and basaloid cells but in some cases displayed focal apocrine differentiation. We demonstrate that the cells generated represent different stages of skin cancerogenesis and as such can be used to identify novel tumor-promoting alterations such as the overexpression of the PADI2 oncogene in solid-type SCC. Importantly, the cultured cells maintain the characteristics from the xenograft they were derived from while being amenable to manipulation and analysis. The availability of cell lines representing different clinical manifestations opens a new tool to study the stochastic and deterministic factors that cause case-to-case heterogeneity despite departing from the same set of oncogenes and the same genetic background. PMID:27074337

  2. Amido analogs of mitoxantrone: physico-chemical properties, molecular modeling, cellular effects and antineoplastic potential.

    Science.gov (United States)

    Zagotto, G; Moro, S; Uriarte, E; Ferrazzi, E; Palù, G; Palumbo, M

    1997-03-01

    To assess the effects of amido substitution in the side-chains of the anticancer drug mitoxantrone (MX) two analogs were synthesized, having hydroxyethylaminoacetyl- and hydroxyethylaminopropionyl- substituents at the nitrogens located at positions 1, 4 of the anthracenedione ring system. The novel derivatives exhibit DNA-affinity and redox properties similar to the parent drug. However, unlike MX, they are not able to stimulate DNA cleavage, as shown by alkaline elution experiments. Molecular modeling studies using ab initio quantum mechanical methods show that, while the stereochemistry of the drug molecule is not appreciably affected when an amide group replaces the aromatic amino function, the reverse is true for the electrostatic properties. Indeed, overlapping of electron density of MX with its analogs is very poor. Moreover, a reversal in the direction of MX dipole moment occurs in the amido congeners. This may explain the lack of recognition of the cleavable topoisomerase II-DNA complex and loss of cleavage stimulation. However, the new derivatives exhibit pharmacological activity comparable to that found for MX, as they are remarkably cytotoxic and are active in vivo against P388 murine leukemia. Hence, amido substitution may lead to a different mechanism of cytotoxicity, not related to classical protein or free radical-mediated DNA damage, which points to a novel type of antineoplastic pharmacophore. PMID:9113065

  3. Ionization States, Cellular Toxicity and Molecular Modeling Studies of Midazolam Complexed with Trimethyl-β-Cyclodextrin

    Directory of Open Access Journals (Sweden)

    Sergey Shityakov

    2014-10-01

    Full Text Available We investigated the ionization profiles for open-ring (OR and closed-ring (CR forms of midazolam and drug-binding modes with heptakis-(2,3,6-tri-O-methyl-β-cyclodextrin (trimethyl-β-cyclodextrin; TRIMEB using molecular modeling techniques and quantum mechanics methods. The results indicated that the total net charges for different molecular forms of midazolam tend to be cationic for OR and neutral for CR at physiological pH levels. The thermodynamic calculations demonstrated that CR is less water-soluble than OR, mainly due to the maximal solvation energy (\\(\\Delta G_{solv}^{CR}\\ = −9.98 kcal·mol\\(^{−1}\\, which has a minimal \\(\\Delta G_{solv}^{OR}\\ of −67.01 kcal·mol\\(^{−1}\\. A cell viability assay did not detect any signs of TRIMEB and OR/CR-TRIMEB complex toxicity on the cEND cells after 24 h of incubation in either Dulbecco's Modified Eagles Medium or in heat-inactivated human serum. The molecular docking studies identified the more flexible OR form of midazolam as being a better binder to TRIMEB with the fluorophenyl ring introduced inside the amphiphilic cavity of the host molecule. The OR binding affinity was confirmed by a minimal Gibbs free energy of binding (\\(\\Delta G_{bind}\\ value of −5.57 ± 0.02 kcal·mol\\(^{−1}\\, an equilibrium binding constant (\\(K_{b}\\ of 79.89 ± 2.706 μM, and a ligand efficiency index (\\(LE_{lig}\\ of −0.21 ± 0.001. Our current data suggest that in order to improve the clinical applications of midazolam via its complexation with trimethyl-β-cyclodextrin to increase drug's overall aqueous solubility, it is important to concern the different forms and ionization states of this anesthetic. All mean values are indicated with their standard deviations.

  4. Ionization states, cellular toxicity and molecular modeling studies of midazolam complexed with trimethyl-β-cyclodextrin.

    Science.gov (United States)

    Shityakov, Sergey; Sohajda, Tamás; Puskás, István; Roewer, Norbert; Förster, Carola; Broscheit, Jens-Albert

    2014-01-01

    We investigated the ionization profiles for open-ring (OR) and closed-ring (CR) forms of midazolam and drug-binding modes with heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (trimethyl-β-cyclodextrin; TRIMEB) using molecular modeling techniques and quantum mechanics methods. The results indicated that the total net charges for different molecular forms of midazolam tend to be cationic for OR and neutral for CR at physiological pH levels. The thermodynamic calculations demonstrated that CR is less water-soluble than OR, mainly due to the maximal solvation energy (ΔG(CR)(solv = -9.98 kcal·mol ⁻¹), which has a minimal ΔG(OR)(solv) of -67.01 kcal·mol⁻¹. A cell viability assay did not detect any signs of TRIMEB and OR/CR-TRIMEB complex toxicity on the cEND cells after 24 h of incubation in either Dulbecco's Modified Eagles Medium or in heat-inactivated human serum. The molecular docking studies identified the more flexible OR form of midazolam as being a better binder to TRIMEB with the fluorophenyl ring introduced inside the amphiphilic cavity of the host molecule. The OR binding affinity was confirmed by a minimal Gibbs free energy of binding (ΔG(bind)) value of -5.57 ± 0.02 kcal·mol⁻¹, an equilibrium binding constant (K(b)) of 79.89 ± 2.706 μM, and a ligand efficiency index (LE(lig)) of -0.21 ± 0.001. Our current data suggest that in order to improve the clinical applications of midazolam via its complexation with trimethyl-β-cyclodextrin to increase drug's overall aqueous solubility, it is important to concern the different forms and ionization states of this anesthetic. All mean values are indicated with their standard deviations. PMID:25338177

  5. Cellular resilience.

    Science.gov (United States)

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

  6. Investigation of cellular and protein interactions with model self-assembled monolayer surfaces

    Science.gov (United States)

    Tegoulia, Vassiliki Apostolou

    Self-assembled monolayers (SAMs) of alkanethiolates on gold have been used to investigate the effect of substrate surface properties on bacterial and blood cell adhesion in the presence and absence of blood proteins. Protein adsorption and binding strength on SAMs as well as complement activation by these model surfaces were also studied. It is hoped that information gained, regarding factors that influence biological processes, will lead to strategies for designing materials and surfaces that specifically inhibit cell adhesion and protein adsorption. Single component SAMs of the general formula HS(CH2) 10X, where X = CH3, CH2OH. COOH and CH2(OCH 2CH2)3OH, and two component mixed SAMs created from binary solutions of HS(CH2), OCH3 and HS(CH 2)10CH2OH, were used. Adhesion was investigated under well-defined flow conditions. Adhesion was found to be higher for the hydrophobic methyl and minimal for the tri(ethyleneoxide) terminated SAM. Preincubation of the SAMs with fibrinogen led to an increase in cell adhesion for bacteria and a decrease for leukocyte adhesion. The effect of surface chemistry on protein adsorption was studied for three blood proteins, fibrinogen, fibronectin and albumin. Adsorption was found to be higher on the hydrophobic CH3 surface and lower but comparable for the other surfaces while proteins adsorbed strongly on all surfaces. SAMs were also used to evaluate complement activation by foreign surfaces. The hydroxyl rich SAMs were found to activate complement more significantly than the anionic carboxyl and the hydrophobic methyl terminated SAMs. A surface modification was introduced to incorporate a zwitterionic phosphorylcholine (PC) group on a hydroxyl monolayer in an effort to create a biomimetic surface that could minimize cell adhesion and protein adsorption. The good antifouling properties of the phosphorylcholine modified surface led to the synthesis of a novel phosphorylcholine functionalized thiol. Single component and two component

  7. Evidence for Bicarbonate Secretion by Ameloblasts in a Novel Cellular Model.

    Science.gov (United States)

    Bori, E; Guo, J; Rácz, R; Burghardt, B; Földes, A; Kerémi, B; Harada, H; Steward, M C; Den Besten, P; Bronckers, A L J J; Varga, G

    2016-05-01

    evidence for a regulated, vectorial, basolateral-to-apical bicarbonate transport in polarized HAT-7 cells. We therefore propose that the HAT-7 cell line is a useful functional model for studying electrolyte transport by ameloblasts. PMID:26792171

  8. Self-organized criticality in a two-dimensional cellular automaton model of a magnetic flux tube with background flow

    Science.gov (United States)

    Dănilă, B.; Harko, T.; Mocanu, G.

    2015-11-01

    We investigate the transition to self-organized criticality in a two-dimensional model of a flux tube with a background flow. The magnetic induction equation, represented by a partial differential equation with a stochastic source term, is discretized and implemented on a two-dimensional cellular automaton. The energy released by the automaton during one relaxation event is the magnetic energy. As a result of the simulations, we obtain the time evolution of the energy release, of the system control parameter, of the event lifetime distribution and of the event size distribution, respectively, and we establish that a self-organized critical state is indeed reached by the system. Moreover, energetic initial impulses in the magnetohydrodynamic flow can lead to one-dimensional signatures in the magnetic two-dimensional system, once the self-organized critical regime is established. The applications of the model for the study of gamma-ray bursts (GRBs) is briefly considered, and it is shown that some astrophysical parameters of the bursts, like the light curves, the maximum released energy and the number of peaks in the light curve can be reproduced and explained, at least on a qualitative level, by working in a framework in which the systems settles in a self-organized critical state via magnetic reconnection processes in the magnetized GRB fireball.

  9. A Babcock-Leighton solar dynamo model with multi-cellular meridional circulation in advection- and diffusion-dominated regimes

    CERN Document Server

    Belucz, Bernadett; Forgacs-Dajka, Emese

    2015-01-01

    Babcock-Leighton type solar dynamo models with single-celled meridional circulation are successful in reproducing many solar cycle features. Recent observations and theoretical models of meridional circulation do not indicate a single-celled flow pattern. We examine the role of complex multi-cellular circulation patterns in a Babcock-Leighton solar dynamo in advection- and diffusion-dominated regimes. We show from simulations that presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of butterfly wing to an anti-solar type. A butterfly diagram constructed from middle of convection zone yields a solar-like pattern, but this may be difficult to realize in the Sun because of magnetic buoyancy effects. Each of the above cases behaves similarly in higher and lower magnetic diffusivity regimes. However, our dynamo with a meridional circulation containing four cells in...

  10. A two-lane cellular automaton traffic flow model with the influence of driver, vehicle and road

    Science.gov (United States)

    Zhao, Han-Tao; Nie, Cen; Li, Jing-Ru; Wei, Yu-Ao

    2016-07-01

    On the basis of one-lane comfortable driving model, this paper established a two-lane traffic cellular automata model, which improves the slow randomization effected by brake light. Considering the driver psychological characteristics and mixed traffic, we studied the lateral influence between vehicles on adjacent lanes. Through computer simulation, the space-time diagram and the fundamental figure under different conditions are obtained. The study found that aggressive driver makes a slight congestion in low-density traffic and improves the capacity of high-density traffic, when the density exceeds 20pcu/km the more aggressive drivers the greater the flow, when the density below 40pcu/km driver character makes an effect, the more cautious driver, the lower the flow. The ratio of big cars has the same effect as the ratio of aggressive drivers. Brake lights have the greatest impact on traffic flow and when the density exceeds 10pcu/km the traffic flow fluctuates. Under periodic boundary conditions, the disturbance of road length on traffic is minimal. The lateral influence only play a limited role in the medium-density conditions, and only affect the average speed of traffic at low density.

  11. Spatiotemporal Simulation of Tourist Town Growth Based on the Cellular Automata Model: The Case of Sanpo Town in Hebei Province

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2013-01-01

    Full Text Available Spatiotemporal simulation of tourist town growth is important for research on land use/cover change under the influence of urbanization. Many scholars have shown great interest in the unique pattern of driving urban development with tourism development. Based on the cellular automata (CA model, we simulated and predicted the spatiotemporal growth of Sanpo town in Hebei Province, using the tourism urbanization growth model. Results showed that (1 average annual growth rate of the entire region was 1.5 Ha2 per year from 2005 to 2010, 4 Ha2 per year from 2010 to 2015, and 2.5 Ha2 per year from 2015 to 2020; (2 urban growth rate increased yearly, with regional differences, and had a high degree of correlation with the Euclidean distance of town center, traffic route, attractions, and other factors; (3 Gougezhuang, an important village center in the west of the town, demonstrated traffic advantages and increased growth rate since 2010; (4 Magezhuang village has the largest population in the region, so economic advantages have driven the development of rural urbanization. It showed that CA had high reliability in simulating the spatiotemporal evolution of tourist town, which assists the study of spatiotemporal growth under urbanization and rational protection of tourism resources.

  12. Suppression of cellular immunity by head and neck irradiation. Precipitating factors and reparative mechanisms in an experimental model

    International Nuclear Information System (INIS)

    A model was developed in C3H mice to investigate the immunosuppressive effects of head and neck irradiation and to explore mechanisms for repair of the defects. Mice receiving 1200 rad (12 Gy) of head and neck irradiation showed significant depression of delayed-type hypersensitivity, peripheral blood lymphocyte counts, spleen cell counts, and spleen cell production of interleukin-2. Treatment with optimal dosages of thymosin alpha 1 (T alpha-1) produced significant increases in all of these values, in some instances to levels higher than in the nonirradiated controls. In identical experiments with mice irradiated to a portal limited to the pelvic region, T alpha-1 induced only partial remission of the abnormalities. The dose response of T alpha-1 with head and neck irradiation showed a relatively limited dose range for immune restoration, a finding that warrants similar determinations in clinical trials with immunomodulating agents. The results suggest a potential clinical usefulness of T alpha-1 and also interleukin-2 in restoring cellular immunity after irradiation for head and neck cancers. The model appears to be useful for investigating immunomodulating agents before they are clinically evaluated as adjuvants with head and neck irradiation regimens

  13. Analytical modeling of mode selection and power control for underlay D2D communication in cellular networks

    KAUST Repository

    Elsawy, Hesham

    2014-11-01

    Device-to-device (D2D) communication enables the user equipments (UEs) located in close proximity to bypass the cellular base stations (BSs) and directly connect to each other, and thereby, offload traffic from the cellular infrastructure. D2D communication can improve spatial frequency reuse and energy efficiency in cellular networks. This paper presents a comprehensive and tractable analytical framework for D2D-enabled uplink cellular networks with a flexible mode selection scheme along with truncated channel inversion power control. The developed framework is used to analyze and understand how the underlaying D2D communication affects the cellular network performance. Through comprehensive numerical analysis, we investigate the expected performance gains and provide guidelines for selecting the network parameters.

  14. Changes in mangrove species assemblages and future prediction of the Bangladesh Sundarbans using Markov chain model and cellular automata.

    Science.gov (United States)

    Mukhopadhyay, Anirban; Mondal, Parimal; Barik, Jyotiskona; Chowdhury, S M; Ghosh, Tuhin; Hazra, Sugata

    2015-06-01

    The composition and assemblage of mangroves in the Bangladesh Sundarbans are changing systematically in response to several environmental factors. In order to understand the impact of the changing environmental conditions on the mangrove forest, species composition maps for the years 1985, 1995 and 2005 were studied. In the present study, 1985 and 1995 species zonation maps were considered as base data and the cellular automata-Markov chain model was run to predict the species zonation for the year 2005. The model output was validated against the actual dataset for 2005 and calibrated. Finally, using the model, mangrove species zonation maps for the years 2025, 2055 and 2105 have been prepared. The model was run with the assumption that the continuation of the current tempo and mode of drivers of environmental factors (temperature, rainfall, salinity change) of the last two decades will remain the same in the next few decades. Present findings show that the area distribution of the following species assemblages like Goran (Ceriops), Sundari (Heritiera), Passur (Xylocarpus), and Baen (Avicennia) would decrease in the descending order, whereas the area distribution of Gewa (Excoecaria), Keora (Sonneratia) and Kankra (Bruguiera) dominated assemblages would increase. The spatial distribution of projected mangrove species assemblages shows that more salt tolerant species will dominate in the future; which may be used as a proxy to predict the increase of salinity and its spatial variation in Sundarbans. Considering the present rate of loss of forest land, 17% of the total mangrove cover is predicted to be lost by the year 2105 with a significant loss of fresh water loving mangroves and related ecosystem services. This paper describes a unique approach to assess future changes in species composition and future forest zonation in mangroves under the 'business as usual' scenario of climate change. PMID:25719448

  15. Irregular Cellular Learning Automata.

    Science.gov (United States)

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

    Cellular learning automaton (CLA) is a recently introduced model that combines cellular automaton (CA) and learning automaton (LA). The basic idea of CLA is to use LA to adjust the state transition probability of stochastic CA. This model has been used to solve problems in areas such as channel assignment in cellular networks, call admission control, image processing, and very large scale integration placement. In this paper, an extension of CLA called irregular CLA (ICLA) is introduced. This extension is obtained by removing the structure regularity assumption in CLA. Irregularity in the structure of ICLA is needed in some applications, such as computer networks, web mining, and grid computing. The concept of expediency has been introduced for ICLA and then, conditions under which an ICLA becomes expedient are analytically found. PMID:25291810

  16. Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Wen Jen, E-mail: wjlin@ntu.edu.tw; Chien, Wei Hsuan [National Taiwan University, School of Pharmacy, Graduate Institute of Pharmaceutical Sciences (China)

    2015-09-15

    The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

  17. Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

    International Nuclear Information System (INIS)

    The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells

  18. Interlinked nonlinear subnetworks underlie the formation of robust cellular patterns in Arabidopsis epidermis: a dynamic spatial model

    Directory of Open Access Journals (Sweden)

    Padilla-Longoria Pablo

    2008-11-01

    Full Text Available Abstract Background Dynamical models are instrumental for exploring the way information required to generate robust developmental patterns arises from complex interactions among genetic and non-genetic factors. We address this fundamental issue of developmental biology studying the leaf and root epidermis of Arabidopsis. We propose an experimentally-grounded model of gene regulatory networks (GRNs that are coupled by protein diffusion and comprise a meta-GRN implemented on cellularised domains. Results Steady states of the meta-GRN model correspond to gene expression profiles typical of hair and non-hair epidermal cells. The simulations also render spatial patterns that match the cellular arrangements observed in root and leaf epidermis. As in actual plants, such patterns are robust in the face of diverse perturbations. We validated the model by checking that it also reproduced the patterns of reported mutants. The meta-GRN model shows that interlinked sub-networks contribute redundantly to the formation of robust hair patterns and permits to advance novel and testable predictions regarding the effect of cell shape, signalling pathways and additional gene interactions affecting spatial cell-patterning. Conclusion The spatial meta-GRN model integrates available experimental data and contributes to further understanding of the Arabidopsis epidermal system. It also provides a systems biology framework to explore the interplay among sub-networks of a GRN, cell-to-cell communication, cell shape and domain traits, which could help understanding of general aspects of patterning processes. For instance, our model suggests that the information needed for cell fate determination emerges from dynamic processes that depend upon molecular components inside and outside differentiating cells, suggesting that the classical distinction of lineage versus positional cell differentiation may be instrumental but rather artificial. It also suggests that interlinkage

  19. Mechanisms of shrub encroachment into Northern Chihuahuan Desert grasslands and impacts of climate change investigated using a cellular automata model

    Science.gov (United States)

    Caracciolo, Domenico; Istanbulluoglu, Erkan; Noto, Leonardo Valerio; Collins, Scott L.

    2016-05-01

    Arid and semiarid grasslands of southwestern North America have changed dramatically over the last 150 years as a result of woody plant encroachment. Overgrazing, reduced fire frequency, and climate change are known drivers of woody plant encroachment into grasslands. In this study, relatively simple algorithms for encroachment factors (i.e., grazing, grassland fires, and seed dispersal by grazers) are proposed and implemented in the ecohydrological Cellular-Automata Tree Grass Shrub Simulator (CATGraSS). CATGraSS is used in a 7.3 km2 rectangular domain located in central New Mexico along a zone of grassland to shrubland transition, where shrub encroachment is currently active. CATGraSS is calibrated and used to investigate the relative contributions of grazing, fire frequency, seed dispersal by herbivores and climate change on shrub abundance over a 150-year period of historical shrub encroachment. The impact of future climate change is examined using a model output that realistically represents current vegetation cover as initial condition, in a series of stochastic CATGraSS future climate simulations. Model simulations are found to be highly sensitive to the initial distribution of shrub cover. Encroachment factors more actively lead to shrub propagation within the domain when the model starts with randomly distributed individual shrubs. However, when shrubs are naturally evolved into clusters, the model response to encroachment factors is muted unless the effect of seed dispersal by herbivores is amplified. The relative contribution of different drivers on modeled shrub encroachment varied based on the initial shrub cover condition used in the model. When historical weather data is used, CATGraSS predicted loss of shrub and grass cover during the 1950 s drought. While future climate change is found to amplify shrub encroachment (∼13% more shrub cover by 2100), grazing remains the dominant factor promoting shrub encroachment. When we modeled future climate

  20. Methane excess production in oxygen-rich polar water and a model of cellular conditions for this paradox

    Science.gov (United States)

    Damm, E.; Thoms, S.; Beszczynska-Möller, A.; Nöthig, E. M.; Kattner, G.

    2015-09-01

    Summer sea ice cover in the Arctic Ocean has undergone a reduction in the last decade exposing the sea surface to unforeseen environmental changes. Melting sea ice increases water stratification and induces nutrient limitation, which is also known to play a crucial role in methane formation in oxygenated surface water. We report on an excess of methane in the marginal ice zone in the western Fram Strait. Our study is based on measurements of oxygen, methane, DMSP, nitrate and phosphate concentrations as well as on phytoplankton composition and light transmission, conducted along the 79°N oceanographic transect, in the western part of the Fram Strait and in Northeast Water Polynya region off Greenland. Between the eastern Fram Strait, where Atlantic water enters from the south and the western Fram Strait, where Polar water enters from the north, different nutrient limitations occurred and consequently different bloom conditions were established. Ongoing sea ice melting enhances the environmental differences between both water masses and initiates regenerated production in the western Fram Strait. We show that in this region methane is in situ produced while DMSP (dimethylsulfoniopropionate) released from sea ice may serve as a precursor for the methane formation. The methane production occured despite high oxygen concentrations in this water masses. As the metabolic activity (respiration) of unicellular organisms explains the presence of anaerobic conditions in the cellular environment we present a theoretical model which explains the maintenance of anaerobic conditions for methane formation inside bacterial cells, despite enhanced oxygen concentrations in the environment.

  1. Fate of PLA and PCL-Based Polymeric Nanocarriers in Cellular and Animal Models of Triple-Negative Breast Cancer.

    Science.gov (United States)

    Sitia, Leopoldo; Ferrari, Raffaele; Violatto, Martina B; Talamini, Laura; Dragoni, Luca; Colombo, Claudio; Colombo, Laura; Lupi, Monica; Ubezio, Paolo; D'Incalci, Maurizio; Morbidelli, Massimo; Salmona, Mario; Moscatelli, Davide; Bigini, Paolo

    2016-03-14

    An integrated platform to assess the interaction between nanocarriers and biological matrices has been developed by our group using poly methyl-methacrylate nanoparticles. In this study, we exploited this platform to evaluate the behavior of two biodegradable formulations, poly-ε-caprolactone (PCL3) and poly lactic-acid (PLA8), respectively, in cellular and animal models of triple-negative breast cancer (TNBC). Both NPs shared the main physicochemical parameters (size, shape, ζ-potential) and exclusively differentiated on the material on which they are composed. Our results showed that (1) PLA8 NPs, systemically injected in mice, underwent rapid degradation without penetration into tumors; (2) PLA8 NPs were not internalized in the human TNBC cell line (MDA-MB-231); (3) PCL3 NPs had a longer bioavailability, reached the tumor parenchyma, and efficiently penetrated in MDA-MB-231 cells. Our data highlight the relevance of the material selection to both improve bioavailability and target tropism, and make PCL3 NPs an interesting tool for the development of nanodrugs against TNBC. PMID:26791775

  2. Simulation of Regionally Ecological Land Based on a Cellular Automation Model: A Case Study of Beijing, China

    Directory of Open Access Journals (Sweden)

    Xiubin Li

    2012-08-01

    Full Text Available Ecological land is like the “liver” of a city and is very useful to public health. Ecological land change is a spatially dynamic non-linear process under the interaction between natural and anthropogenic factors at different scales. In this study, by setting up natural development scenario, object orientation scenario and ecosystem priority scenario, a Cellular Automation (CA model has been established to simulate the evolution pattern of ecological land in Beijing in the year 2020. Under the natural development scenario, most of ecological land will be replaced by construction land and crop land. But under the scenarios of object orientation and ecosystem priority, the ecological land area will increase, especially under the scenario of ecosystem priority. When considering the factors such as total area of ecological land, loss of key ecological land and spatial patterns of land use, the scenarios from priority to inferiority are ecosystem priority, object orientation and natural development, so future land management policies in Beijing should be focused on conversion of cropland to forest, wetland protection and prohibition of exploitation of natural protection zones, water source areas and forest parks to maintain the safety of the regional ecosystem.

  3. Exact modeling of finite temperature and quantum delocalization effects on reliability of quantum-dot cellular automata

    International Nuclear Information System (INIS)

    A thorough simulation study is carried out on thermal and quantum delocalization effects on the feasibility of a quantum-dot cellular automata (QCA) cell. The occupation correlation of two electrons is modeled with a simple four-site array of harmonic quantum dots (QD). QD sizes range from 20 nm to 40 nm with site separations from 20 nm to 100 nm, relevant for state-of-the-art GaAs/InAs semiconductor technology. The choice of parameters introduces QD overlap, which is only simulated properly with exact treatment of strong Coulombic correlation and thermal equilibrium quantum statistics. These are taken into account with path integral Monte Carlo approach. Thus, we demonstrate novel joint effects of quantum delocalization and decoherence in QCA, but also highly sophisticated quantitative evidence supporting the traditional relations in pragmatic QCA design. Moreover, we show the effects of dimensionality and spin state, and point out the parameter space conditions, where the ‘classical’ treatment becomes invalid. (paper)

  4. AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study

    Directory of Open Access Journals (Sweden)

    Knight Robert A

    2009-03-01

    Full Text Available Abstract Background Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI. In this study, we used superparamagentic iron oxide (SPIO-labeled APCs to carry the human sodium iodide symporter (hNIS gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m scan. Results Three million human breast cancer (MDA-MB-231 cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor was significantly different between animals that received non-transduced and transduced cells (P Conclusion This study indicates that genetically transformed

  5. Modeling and boundary force control of microcantilevers utilized in atomic force microscopy for cellular imaging and characterization

    Science.gov (United States)

    Eslami, Sohrab

    This dissertation undertakes the theoretical and experimental developments microcantilevers utilized in Atomic Force Microscopy (AFM) with applications to cellular imaging and characterization. The capability of revealing the inhomogeneties or interior of ultra-small materials has been of most interest to many researchers. However, the fundamental concept of signal and image formation remains unexplored and not fully understood. For his, a semi-empirical nonlinear force model is proposed to show that virtual frequency generation, regarded as the simplest synthesized subsurface probe, occurs optimally when the force is tuned to the van der Waals form. This is the first-time observation of a novel theoretical dynamic multi-frequency force microscopy that has not been already reported. Owing to the broad applications of microcantilevers in the nanoscale imaging and microscopic techniques, there is an essential feeling to study and propose a comprehensive model of such systems. Therefore, in the theoretical part of this dissertation, a distributed-parameters representation modeling of the microcantilever along with a general interaction force comprising of two attractive and repulsive components with general amplitude and power terms is studied. This model is investigated in a general 2D Cartesian coordinate to consider the motions of the probe with a tip mass. There is an excitation at the microcantilever's base such that the end of the beam is subject to the proposed general force. These forces are very sensitive to the amplitude and power terms of these parts; on the other hand, atomic intermolecular force is a function of the distance such that this distance itself is also a function of the interaction force that will result in a nonlinear implicit equation. From a parametric study in the probe-sample excitation, it is shown that the predicted behavior of the generated difference-frequency oscillation amplitude agrees well with experimental measurements. Following

  6. Cellular Homeostasis and Aging.

    Science.gov (United States)

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  7. Expression of matrix metalloproteinases (MMPs in primary human breast cancer and breast cancer cell lines: New findings and review of the literature

    Directory of Open Access Journals (Sweden)

    Dietl Johannes

    2009-06-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are a family of structural and functional related endopeptidases. They play a crucial role in tumor invasion and building of metastatic formations because of their ability to degrade extracellular matrix proteins. Under physiological conditions their activity is precisely regulated in order to prevent tissue disruption. This physiological balance seems to be disrupted in cancer making tumor cells capable of invading the tissue. In breast cancer different expression levels of several MMPs have been found. Methods To fill the gap in our knowledge about MMP expression in breast cancer, we analyzed the expression of all known human MMPs in a panel of twenty-five tissue samples (five normal breast tissues, ten grade 2 (G2 and ten grade 3 (G3 breast cancer tissues. As we found different expression levels for several MMPs in normal breast and breast cancer tissue as well as depending on tumor grade, we additionally analyzed the expression of MMPs in four breast cancer cell lines (MCF-7, MDA-MB-468, BT 20, ZR 75/1 commonly used in research. The results could thus be used as model for further studies on human breast cancer. Expression analysis was performed on mRNA and protein level using semiquantitative RT-PCR, Western blot, immunohistochemistry and immunocytochemistry. Results In summary, we identified several MMPs (MMP-1, -2, -8, -9, -10, -11, -12, -13, -15, -19, -23, -24, -27 and -28 with a stronger expression in breast cancer tissue compared to normal breast tissue. Of those, expression of MMP-8, -10, -12 and -27 is related to tumor grade since it is higher in analyzed G3 compared to G2 tissue samples. In contrast, MMP-7 and MMP-27 mRNA showed a weaker expression in tumor samples compared to healthy tissue. In addition, we demonstrated that the four breast cancer cell lines examined, are constitutively expressing a wide variety of MMPs. Of those, MDA-MB-468 showed the strongest mRNA and protein

  8. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature

    International Nuclear Information System (INIS)

    Matrix metalloproteinases (MMPs) are a family of structural and functional related endopeptidases. They play a crucial role in tumor invasion and building of metastatic formations because of their ability to degrade extracellular matrix proteins. Under physiological conditions their activity is precisely regulated in order to prevent tissue disruption. This physiological balance seems to be disrupted in cancer making tumor cells capable of invading the tissue. In breast cancer different expression levels of several MMPs have been found. To fill the gap in our knowledge about MMP expression in breast cancer, we analyzed the expression of all known human MMPs in a panel of twenty-five tissue samples (five normal breast tissues, ten grade 2 (G2) and ten grade 3 (G3) breast cancer tissues). As we found different expression levels for several MMPs in normal breast and breast cancer tissue as well as depending on tumor grade, we additionally analyzed the expression of MMPs in four breast cancer cell lines (MCF-7, MDA-MB-468, BT 20, ZR 75/1) commonly used in research. The results could thus be used as model for further studies on human breast cancer. Expression analysis was performed on mRNA and protein level using semiquantitative RT-PCR, Western blot, immunohistochemistry and immunocytochemistry. In summary, we identified several MMPs (MMP-1, -2, -8, -9, -10, -11, -12, -13, -15, -19, -23, -24, -27 and -28) with a stronger expression in breast cancer tissue compared to normal breast tissue. Of those, expression of MMP-8, -10, -12 and -27 is related to tumor grade since it is higher in analyzed G3 compared to G2 tissue samples. In contrast, MMP-7 and MMP-27 mRNA showed a weaker expression in tumor samples compared to healthy tissue. In addition, we demonstrated that the four breast cancer cell lines examined, are constitutively expressing a wide variety of MMPs. Of those, MDA-MB-468 showed the strongest mRNA and protein expression for most of the MMPs analyzed. MMP-1, -2

  9. Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells.

    Science.gov (United States)

    Coombs, Melanie R Power; Harrison, Megan E; Hoskin, David W

    2016-10-01

    Programmed death ligand 1 (PD-L1) is expressed by many cancer cell types, as well as by activated T cells and antigen-presenting cells. Constitutive and inducible PD-L1 expression contributes to immune evasion by breast cancer (BC) cells. We show here that the dietary phytochemical apigenin inhibited interferon (IFN)-γ-induced PD-L1 upregulation by triple-negative MDA-MB-468 BC cells, HER2(+) SK-BR-3 BC cells, and 4T1 mouse mammary carcinoma cells, as well as human mammary epithelial cells, but did not affect constitutive PD-L1 expression by triple-negative MDA-MB-231 BC cells. IFN-β-induced expression of PD-L1 by MDA-MB-468 cells was also inhibited by apigenin. In addition, luteolin, the major metabolite of apigenin, inhibited IFN-γ-induced PD-L1 expression by MDA-MB-468 cells. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 and 4T1 cells was associated with reduced phosphorylation of STAT1, which was early and transient at Tyr701 and sustained at Ser727. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 cells also increased proliferation and interleukin-2 synthesis by PD-1-expressing Jurkat T cells that were co-cultured with MDA-MB-468 cells. Apigenin therefore has the potential to increase the vulnerability of BC cells to T cell-mediated anti-tumor immune responses. PMID:27378243

  10. Modeling mechanical restriction differences between car and heavy truck in two-lane cellular automata traffic flow model

    Science.gov (United States)

    Li, Xin; Li, Xingang; Xiao, Yao; Jia, Bin

    2016-06-01

    Real traffic is heterogeneous with car and truck. Due to mechanical restrictions, the car and the truck have different limited deceleration capabilities, which are important factors in safety driving. This paper extends the single lane safety driving (SD) model with limited deceleration capability to two-lane SD model, in which car-truck heterogeneous traffic is considered. A car has a larger limited deceleration capability while a heavy truck has a smaller limited deceleration capability as a result of loaded goods. Then the safety driving conditions are different as the types of the following and the leading vehicles vary. In order to eliminate the well-known plug in heterogeneous two-lane traffic, it is assumed that heavy truck has active deceleration behavior when the heavy truck perceives the forming plug. The lane-changing decisions are also determined by the safety driving conditions. The fundamental diagram, spatiotemporal diagram, and lane-changing frequency were investigated to show the effect of mechanical restriction on heterogeneous traffic flow. It was shown that there would be still three traffic phases in heterogeneous traffic condition; the active deceleration of the heavy truck could well eliminate the plug; the lane-changing frequency was low in synchronized flow; the flow and velocity would decrease as the proportion of heavy truck grows or the limited deceleration capability of heavy truck drops; and the flow could be improved with lane control measures.

  11. An Option Pricing Model Based on Cellular Automaton%基于元胞自动机的期权定价模型

    Institute of Scientific and Technical Information of China (English)

    李捷

    2011-01-01

    Option pricing is one of the most difficult problems in financial research. The key to the problem is how to simulate the randomness of the underlying asset price. This paper designs and implements an option pricing model based on the cellular automaton, which treats market participants as the cells in the cellular automaton. The model uses cellular automaton rules to simulate the interactions between traders and the changes of underlying asset prices. The paper compares the output data of the model with the calculation results of the Black-Scholes model, tests the normality of the model's output data, and finds that the option pricing model based on the cellular automaton is not only feasible, but also more effective than the Black-Scholes model.%针对期权定价难于模拟基础资产价格波动随机性的问题,设计了基于元胞自动机的期权定价模型.该模型将市场参与者看作一个个的元胞,使用元胞规则来模拟金融市场中交易者之间的交互行为。从而在总体上模拟出基础资产价格的变化.比较了模型产出的数据和Black-Scholes模型的计算结果,检验了模型产出数据的正态性,发现基于元胞自动机的期权定价模型不仅具有可行性,而且比Black-Scholes模型更有效.

  12. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    NARCIS (Netherlands)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; Rye, Inga H; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-

  13. Employing z-scan method in lateral diffusion measurements by means of fluorescence correlation spectroscopy: Model systems versus cellular applications

    Czech Academy of Sciences Publication Activity Database

    Humpolíčková, Jana; Fagulová, Veronika; Gielen, E.; Benda, Aleš; Vercammen, J.; Engelborghs, Y.; Ameloot, M.; van de Ven, M.; Hof, Martin

    Berlin : Max Delbrück Center for Molecular Medicine, 2006 - (Cardoso, M.). s. 65 [International Symposium Optical Analysis of Biomolecular Machines. 13.07.2006-16.07.2006, Berlin] Institutional research plan: CEZ:AV0Z40400503 Keywords : fluorescence-correlation spectroscopy * cellular application * physical chemistry Subject RIV: CF - Physical ; Theoretical Chemistry

  14. Use of Magnetic Folate-Dextran-Retinoic Acid Micelles for Dual Targeting of Doxorubicin in Breast Cancer

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2013-01-01

    Full Text Available Amphiphilic copolymer of folate-conjugated dextran/retinoic acid (FA/DEX-RA was self-assembled into micelles by direct dissolution method. Magnetic iron oxide nanoparticles (MNPs coated with oleic acid (OA were prepared by hydrothermal method and encapsulated within the micelles. Doxorubicin HCl was loaded in the magnetic micelles. The characteristics of the magnetic micelles were determined by Fourier transform infrared (FT-IR spectroscopy, thermogravimetric analysis (TGA, transmission electron microscopy (TEM, and vibrating sample magnetometer (VSM. The crystalline state of OA-coated MNPs and their heat capacity were analyzed by X-ray diffraction (XRD and differential scanning calorimetry (DSC methods, respectively. The iron content of magnetic micelles was determined using inductively coupled plasma optical emission spectrometry (ICP-OES. Bovine serum albumin (BSA was used to test the protein binding of magnetic micelles. The cytotoxicity of doxorubicin loaded magnetic micelles was studied on MCF-7 and MDA-MB-468 cells using MTT assay and their quantitative cellular uptake by fluorimetry method. TEM results showed the MNPs in the hydrophobic core of the micelles. TGA results confirmed the presence of OA and FA/DEX-RA copolymer on the surface of MNPs and micelles, respectively. The magnetic micelles showed no significant protein bonding and reduced the IC50 of the drug to about 10 times lower than the free drug.

  15. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood–brain barrier permeability and cellular damage in the rat photothrombosis model

    Science.gov (United States)

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-01-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood–brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672

  16. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model.

    Science.gov (United States)

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-11-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672

  17. Autophagic flux inhibition and lysosomogenesis ensuing cellular capture and retention of the cationic drug quinacrine in murine models.

    Science.gov (United States)

    Parks, Alexandre; Charest-Morin, Xavier; Boivin-Welch, Michael; Bouthillier, Johanne; Marceau, Francois

    2015-01-01

    The proton pump vacuolar (V)-ATPase is the driving force that mediates the concentration of cationic drugs (weak bases) in the late endosome-lysosome continuum; secondary cell reactions include the protracted transformation of enlarged vacuoles into autophagosomes. We used the inherently fluorescent tertiary amine quinacrine in murine models to further assess the accumulation and signaling associated with cation trapping. Primary fibroblasts concentrate quinacrine ∼5,000-fold from their culture medium (KM 9.8 µM; transport studies). The drug is present in perinuclear granules that are mostly positive for Rab7 and LAMP1 (microscopy). Both drug uptake and retention are extensively inhibited by treatments with the V-ATPase inhibitor bafilomycin A1. The H(+) ionophore monensin also prevented quinacrine concentration by fibroblasts. However, inhibition of plasma membrane transporters or of the autophagic process with spautin-1 did not alter quinacrine transport parameters. Ancillary experiments did not support that low micromolar concentrations of quinacrine are substrates for organic cation transporters-1 to -3 or P-glycoprotein. The secondary autophagy induced by quinacrine in cells may derive from the accumulation of incompetent autophagolysosomes, as judged from the accumulation of p62/SQSTM1 and LC3 II (immunoblots). Accordingly, protracted lysosomogenesis is evidenced by increased expression of LAMP1 and LAMP2 in quinacrine-treated fibroblasts (48 h, immunoblots), a response that follows the nuclear translocation of the lysosomal genesis transcription factor TFEB and upregulation of LAMP1 and -2 mRNAs (24 h). Quinacrine administration to live mice evidenced variable distribution to various organs and heterogeneous accumulation within the lung (stereo-microscopy, extraction). Dose-dependent in vivo autophagic and lysosomal accumulation was observed in the lung (immunoblots). No evidence has been found for transport or extrusion mechanisms modulating the cellular

  18. Ethanol regulation of adenosine receptor-stimulated cAMP levels in a clonal neural cell line: an in vitro model of cellular tolerance to ethanol.

    OpenAIRE

    Gordon, A S; Collier, K; Diamond, I.

    1986-01-01

    The acute and chronic neurologic effects of ethanol appear to be due to its interaction with neural cell membranes. Chronic exposure to ethanol induces changes in the membrane that lead to tolerance to the effects of ethanol. However, the actual membrane changes that account for tolerance to ethanol are not understood. We have developed a model cell culture system, using NG108-15 neuroblastoma-glioma hybrid cells, to study cellular tolerance to ethanol. We have found that adenosine receptor-s...

  19. Cellular automaton for chimera states

    OpenAIRE

    García-Morales, Vladimir

    2016-01-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the...

  20. Cellular automata modelling of the cementation process of the Turin (Italy) subsoil conglomerate (``ceppo''),based on a three-dimensional geological model of the city subsoil.

    Science.gov (United States)

    Bello, S.; de Rienzo, F.; Nardi, G.

    2003-04-01

    The Turin (Italy) subsoil is mainly made up by alluvial gravels and sands (Pleistocene), characterised by high cementation degree variability, covered by a thin thickness of loess. These alluvial sediments, of about 40 m deep, overlay lacustrine clays (Villafranchiano), locally heteropic with marine sandstones (Pliocene). The reconstruction of the areal distribution of cementation phenomena of the Turin urban subsoil is of fundamental importance within the context of planning and carrying out works in the city subsoil, as well as for preliminary evaluating the stability of such underground works. Moreover, analyses of spatial distribution of soil cementation could be usefully applied for estimating the propagation of waste-polluted fluids, and for reducing either the natural or human-induced risk, related to the overworking of urban area subsoils. The development of mathematical models commonly needs to deal with several interacting physical and chemical phenomena. A deterministic Cellular Automata (CA) model for the evaluation of cementation processes in the conglomerates of the Turin urban subsoil has recently been developed, by using a three-dimensional geological model of the city subsoil based on boreholes data. The model is able to simulate the spatial distribution of the cementation process in the studied area: it has been derived from two pre-existing CA models, i.e. SCAVATU and CABOTO. Geological, mineralogical-petrographic and sedimentological studies of the soil cementation, and a chemical-physical study of the carbonatic equilibria, have first been carried out. These studies pointed out the presence of meniscus cements (which suggest a meteoric diagenesis) and gave fundamental cues for the development of base hypothesis on the genesis of cementation in the considered area. A macroscopic Cellular Automata model has accordingly been developed, in order to simulate the principal phenomena which take place during the cementation process. The model has a

  1. Integration of diffusion weighted MRI data and a simple mathematical model to predict breast tumor cellularity during neoadjuvant chemotherapy

    OpenAIRE

    Atuegwu, Nkiruka C.; Arlinghaus, Lori R.; Li, Xia; BrianWelch, E.; Chakravarthy, Bapsi A.; John C Gore; Yankeelov, Thomas E.

    2011-01-01

    Diffusion-weighted magnetic resonance imaging (DW-MRI) data obtained early in the course of therapy can be used to estimate tumor proliferation rates, and the estimated rates can be used to predict tumor cellularity at the conclusion of therapy. Six patients underwent DW-MRI immediately before, after one cycle, and after all cycles of neoadjuvant chemotherapy. Apparent diffusion coefficient (ADC) values were calculated for each voxel and for a whole tumor region of interest (ROI). Proliferati...

  2. Use of an in vitro muscle model to investigate cellular and molecular aspects of exercise physiology: Answering the key questions

    OpenAIRE

    Player, D. J.; Martin, N. R. W.; Davies, P; Sculthorpe, N.; Castle, P. C.; Passey, S.; Mudera, V.; Ferguson, R.; Lewis, M. P.

    2011-01-01

    Research within exercise physiology has traditionally focused upon measurements of gross physiological function of skeletal muscle. However, in order to develop a greater understanding of the exact mechanisms that contribute to skeletal muscle in response to exercise, the cellular and molecular determinants need to be investigated. There is a growing body of in vivo research utilising methods of molecular biology, which has led to the establishment of proposed genes and proteins involved in t...

  3. Modeling Urban Expansion in Bangkok Metropolitan Region Using Demographic–Economic Data through Cellular Automata-Markov Chain and Multi-Layer Perceptron-Markov Chain Models

    Directory of Open Access Journals (Sweden)

    Chudech Losiri

    2016-07-01

    Full Text Available Urban expansion is considered as one of the most important problems in several developing countries. Bangkok Metropolitan Region (BMR is the urbanized and agglomerated area of Bangkok Metropolis (BM and its vicinity, which confronts the expansion problem from the center of the city. Landsat images of 1988, 1993, 1998, 2003, 2008, and 2011 were used to detect the land use and land cover (LULC changes. The demographic and economic data together with corresponding maps were used to determine the driving factors for land conversions. This study applied Cellular Automata-Markov Chain (CA-MC and Multi-Layer Perceptron-Markov Chain (MLP-MC to model LULC and urban expansions. The performance of the CA-MC and MLP-MC yielded more than 90% overall accuracy to predict the LULC, especially the MLP-MC method. Further, the annual population and economic growth rates were considered to produce the land demand for the LULC in 2014 and 2035 using the statistical extrapolation and system dynamics (SD. It was evident that the simulated map in 2014 resulting from the SD yielded the highest accuracy. Therefore, this study applied the SD method to generate the land demand for simulating LULC in 2035. The outcome showed that urban occupied the land around a half of the BMR.

  4. Novel 3-Amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine Derivatives with Anticancer Activity: Synthesis and QSAR Study.

    Science.gov (United States)

    Pogorzelska, Aneta; Sławiński, Jarosław; Brożewicz, Kamil; Ulenberg, Szymon; Bączek, Tomasz

    2015-01-01

    A series of new 3-amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine derivatives 5a-j have been synthesized and evaluated in vitro for their antiproliferative activity at the U.S. National Cancer Institute. The most active compound 5h showed significant cytotoxic effects against ovarian (OVCAR-3) and breast (MDA-MB-468) cancer (10% and 47% cancer cell death, respectively) as well as a good selectivity toward prostate (DU-145), colon (SW-620) and renal (TK-10) cancer cell lines. To obtain a deeper insight into the structure-activity relationships of the new compounds 5a-j QSAR studies have been applied. Theoretical calculations allowed the identification of molecular descriptors belonging to the RDF (RDF055p and RDF145m in the MOLT-4 and UO-31 QSAR models, respectively) and 3D-MorSE (Mor32m and Mor16e for MOLT-4 and UO-31 QSAR models) descriptor classes. Based on these data, QSAR models with good robustness and predictive ability have been obtained. PMID:26690109

  5. Novel 3-Amino-6-chloro-7-(azol-2 or 5-yl-1,1-dioxo-1,4,2-benzodithiazine Derivatives with Anticancer Activity: Synthesis and QSAR Study

    Directory of Open Access Journals (Sweden)

    Aneta Pogorzelska

    2015-12-01

    Full Text Available A series of new 3-amino-6-chloro-7-(azol-2 or 5-yl-1,1-dioxo-1,4,2-benzodithiazine derivatives 5a–j have been synthesized and evaluated in vitro for their antiproliferative activity at the U.S. National Cancer Institute. The most active compound 5h showed significant cytotoxic effects against ovarian (OVCAR-3 and breast (MDA-MB-468 cancer (10% and 47% cancer cell death, respectively as well as a good selectivity toward prostate (DU-145, colon (SW-620 and renal (TK-10 cancer cell lines. To obtain a deeper insight into the structure-activity relationships of the new compounds 5a–j QSAR studies have been applied. Theoretical calculations allowed the identification of molecular descriptors belonging to the RDF (RDF055p and RDF145m in the MOLT-4 and UO-31 QSAR models, respectively and 3D-MorSE (Mor32m and Mor16e for MOLT-4 and UO-31 QSAR models descriptor classes. Based on these data, QSAR models with good robustness and predictive ability have been obtained.

  6. Quantum cellular automata

    Science.gov (United States)

    Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

    1994-06-01

    The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

  7. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain.

    Science.gov (United States)

    Kanojia, Deepak; Morshed, Ramin A; Zhang, Lingjiao; Miska, Jason M; Qiao, Jian; Kim, Julius W; Pytel, Peter; Balyasnikova, Irina V; Lesniak, Maciej S; Ahmed, Atique U

    2015-05-01

    Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells. PMID:25724666

  8. Anti-CEA monoclonal antibody: technetium-99m labeling and the validation process of a scintigraphic animal model with a non-cellular antigenic implant.

    Science.gov (United States)

    Sapienza, Marcelo Tatit; Marques, Fabio Luiz Navarro; Okamoto, Miriam Roseli Yoshie; Hironaka, Fausto Haruki; Buchpiguel, Carlos Alberto

    2002-07-01

    Animal models are currently used to verify the biodistribution of different radiopharmaceuticals before its clinical application in Nuclear Medicine; however, there may be some limitations. The utilization of labelled anti-tumor monoclonal antibodies (MoAb) in experimental models often requires implant of human antigens (usually a cellular implant), which cannot be achieved in immunocompetent animals. Our purpose was to label an anti-CEA MoAb with technetium-99m (99Tc) and to validate a simplified animal model using a noncellular antigenic implant. MoAb was directly labelled with 99mTc, after reduction with 2-mercaptoethanol. Labeling efficiency was checked by ascending chromatography and immunoreactive fraction was measured in plastic wells sensitized with the antigen. Radiopharmaceutical biodistribution was evaluated by dissection and scintigraphy in 5 mice groups; following the subcutaneous administration of Al(OH)3, CEA adsorbed Al(OH)2 and a control group evaluation. Labeling efficiency was 94+/-3%, which showed to be stable for 24 hr, with immunoreactive fraction above 50%. Invasive biodistribution evaluation showed prolonged blood retention, hepatic and renal uptake. A significant increase in uptake was observed in scintigraphic studies of animals with CEA-adsorbed Al(OH)3 implants compared with the other groups (p<0.05). The non-cellular antigenic implant model simplifies the pre-clinical evaluation of labelled MoAb. PMID:12146705

  9. Cellular neural network to the spherical harmonics approximation of neutron transport equation in x-y geometry. Part I: Modeling and verification for time-independent solution

    International Nuclear Information System (INIS)

    Highlights: → This paper describes the solution of time-independent neutron transport equation. → Using a novel method based on cellular neural networks (CNNs) coupled with PN method. → Utilize the CNN model to simulate spatial scalar flux distribution in steady state. → The accuracy, stability, and capabilities of CNN model are examined in x-y geometry. - Abstract: This paper describes a novel method based on using cellular neural networks (CNN) coupled with spherical harmonics method (PN) to solve the time-independent neutron transport equation in x-y geometry. To achieve this, an equivalent electrical circuit based on second-order form of neutron transport equation and relevant boundary conditions is obtained using CNN method. We use the CNN model to simulate spatial response of scalar flux distribution in the steady state condition for different order of spherical harmonics approximations. The accuracy, stability, and capabilities of CNN model are examined in 2D Cartesian geometry for fixed source and criticality problems.

  10. 考虑驾驶愤怒的元胞自动机交通流模型%Cellular Automaton Model for Urban Traffic Flow Considering Driving Anger

    Institute of Scientific and Technical Information of China (English)

    郑华荣; 吴超仲; 马晓凤

    2013-01-01

    Driving behaviors of the angry drivers are quite different from those of the normal drivers.Because of these behavioral differences,driving speed,driving track etc.can be influenced,resulting in a different state of the road traffic flow.This paper re-defined the typical cellular automaton updating rules in mainly three aspects,i.e.,speed,lane change conditions as well as the safe distance and established the periodic boundary two-lane cellular automata traffic flow model considering the characteristics of angry driving behaviors based on NaSch cellular automaton traffic flow model.Both the model constructed and the classical NaSch traffic flow model were simulated in MATLAB and the comparison show that the variance in speed caused by driving anger had the most significant impact on traffic flow.The research can provide as the guidance on establishing models for cellular automaton traffic flow with consideration of driving anger and studying the influence of it to the urban traffic flow; the influence on traffic flow of other driver concerned factors,e.g.,driving fatigue,driving distraction need further research following this method.%驾驶员在愤怒时的驾驶行为表现与正常驾驶时存在较大的差异,这些行为差异会影响车辆的运行速度、运行轨迹等,进而对道路交通流产生影响.文中在NaSch元胞自动机交通流模型的基础上,考虑愤怒驾驶行为的特点,从运行速度、换道条件和安全距离3个方面重新确定元胞更新规则,构建考虑驾驶愤怒情绪的周期边界条件下双车道元胞自动机交通流模型.在MATLAB环境下,对所建模型与普通NaSch交通流模型进行对比仿真分析.结果表明,驾驶愤怒所引起的行驶速度变化对交通流影响明显.

  11. LETTER TO THE EDITOR: Transfer-matrix density-matrix renormalization group for stochastic models: the Domany-Kinzel cellular automaton

    Science.gov (United States)

    Kemper, A.; Schadschneider, A.; Zittartz, J.

    2001-05-01

    We apply the transfer-matrix density-matrix renormalization group (TMRG) to a stochastic model, the Domany-Kinzel cellular automaton, which exhibits a non-equilibrium phase transition in the directed percolation universality class. Estimates for the stochastic time evolution, phase boundaries and critical exponents can be obtained with high precision. This is possible using only modest numerical effort since the thermodynamic limit can be taken analytically in our approach. We also point out further advantages of the TMRG over other numerical approaches, such as classical DMRG or Monte Carlo simulations.

  12. Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast

    Directory of Open Access Journals (Sweden)

    Lanthaler Karin

    2011-10-01

    Full Text Available Abstract Background The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. Results To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. Conclusions As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.

  13. Cellular and molecular biomarkers indicate precocious in vitro senescence in fibroblasts from SAMP6 mice. Evidence supporting a murine model of premature senescence and osteopenia.

    Science.gov (United States)

    Lecka-Czernik, B; Moerman, E J; Shmookler Reis, R J; Lipschitz, D A

    1997-11-01

    A variety of short-lived mouse strains (SAMP strains) and control strains of less abbreviated life span (SAMR strains) have been proposed as murine models of accelerated senescence. Each SAMP strain, in addition to displaying "progeroid" traits of accelerated aging, exhibits a singular age-related pathology. The application of this animal model to the study of normal aging processes has been and remains controversial. Therefore, we have undertaken a study of dermal fibroblasts derived from the short-lived SAMP6 strain, which shows early-onset and progressive osteopenia. We have investigated cellular and molecular characteristics that are associated with in vitro aging of normal human fibroblasts, and which are exacerbated in fibroblasts from patients with Werner syndrome, a human model of premature senescence. We found that SAMP6 dermal fibroblasts, relative to SAMR1 and C57BL/6 controls, exhibit characteristics of premature or accelerated cellular senescence with regard to in vitro life span, initial growth rate, and patterns of gene expression. PMID:9402934

  14. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

  15. Cellular Scanning Strategy for Selective Laser Melting: Capturing Thermal Trends with a Low-Fidelity, Pseudo-Analytical Model

    Directory of Open Access Journals (Sweden)

    Sankhya Mohanty

    2014-01-01

    Full Text Available Simulations of additive manufacturing processes are known to be computationally expensive. The resulting large runtimes prohibit their application in secondary analysis requiring several complete simulations such as optimization studies, and sensitivity analysis. In this paper, a low-fidelity pseudo-analytical model has been introduced to enable such secondary analysis. The model has been able to mimic a finite element model and was able to capture the thermal trends associated with the process. The model has been validated and subsequently applied in a small optimization case study. The pseudo-analytical modelling technique is established as a fast tool for primary modelling investigations.

  16. The protozoan, Paramecium primaurelia, as a non-sentient model to test laser light irradiation: The effects of an 808nm infrared laser diode on cellular respiration.

    Science.gov (United States)

    Amaroli, Andrea; Ravera, Silvia; Parker, Steven; Panfoli, Isabella; Benedicenti, Alberico; Benedicenti, Stefano

    2015-07-01

    Photobiomodulation (PBM) has been used in clinical practice for more than 40 years. Unfortunately, conflicting literature has led to the labelling of PBM as a complementary or alternative medicine approach. However, past and ongoing clinical and research studies by reputable investigators have re-established the merits of PBM as a genuine medical therapy, and the technique has, in the last decade, seen an exponential increase in the numbers of clinical instruments available, and their applications. This resurgence has led to a clear need for appropriate experimental models to test the burgeoning laser technology being developed for medical applications. In this context, an ethical model that employs the protozoan, Paramecium primaurelia, is proposed. We studied the possibility of using the measure of oxygen consumption to test PBM by irradiation with an infrared or near-infrared laser. The results show that an 808nm infrared laser diode (1W; 64J/cm²) affects cellular respiration in P. primaurelia, inducing, in the irradiated cells, a significantly (p testing. This test represents a fast, inexpensive and straightforward assay, which offers an alternative to both traditional in vivo testing and more expensive mammalian cellular cultures. PMID:26256394

  17. Xtoys cellular automata on xwindows

    CERN Document Server

    Creutz, M

    1995-01-01

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  18. Sevoflurane-Sulfobutylether-β-Cyclodextrin Complex: Preparation, Characterization, Cellular Toxicity, Molecular Modeling and Blood-Brain Barrier Transport Studies

    Directory of Open Access Journals (Sweden)

    Sergey Shityakov

    2015-06-01

    Full Text Available The objective of the present investigation was to study the ability of sulfobutylether-β-cyclodextrin (SBEβCD to form an inclusion complex with sevoflurane (SEV, a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBEβCD complex was nontoxic to the primary brain microvascular endothelial (pEND cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol concerning calculated apparent permeability values (Papp. In addition, SEV binding affinity to SBEβCD was confirmed by a minimal Gibbs free energy of binding (ΔGbind value of −1.727 ± 0.042 kcal·mol−1 and an average binding constant (Kb of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity.

  19. Sevoflurane-Sulfobutylether-β-Cyclodextrin Complex: Preparation, Characterization, Cellular Toxicity, Molecular Modeling and Blood-Brain Barrier Transport Studies.

    Science.gov (United States)

    Shityakov, Sergey; Puskás, István; Pápai, Katalin; Salvador, Ellaine; Roewer, Norbert; Förster, Carola; Broscheit, Jens-Albert

    2015-01-01

    The objective of the present investigation was to study the ability of sulfobutylether-β-cyclodextrin (SBEβCD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB) permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBEβCD complex was nontoxic to the primary brain microvascular endothelial (pEND) cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol) concerning calculated apparent permeability values (Papp). In addition, SEV binding affinity to SBEβCD was confirmed by a minimal Gibbs free energy of binding (ΔGbind) value of -1.727 ± 0.042 kcal·mol-1 and an average binding constant (Kb) of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity. PMID:26046323

  20. Optimizing cell seeding and retention in a three-dimensional bioengineered cardiac ventricle: The two-stage cellularization model.

    Science.gov (United States)

    Patel, Nikita M; Yazdi, Iman K; Tasciotti, Ennio; Birla, Ravi K

    2016-10-01

    Current cell seeding techniques focus on passively directing cells to a scaffold surface with the addition of dynamic culture to encourage cell permeation. In 3D tissue engineered constructs, cell retention efficiency is dependent on the cell delivery method, and biomaterial properties. Passive cell delivery relies on cell migration to the scaffold surface; biomaterial surface properties and porosity determine cell infiltration capacity. As a result, cell retention efficiencies remain low. The development of an effective two-stage cell seeding technique, coupled with perfusion culture, provides the potential to improve cellularization efficiency, and retention. This study, uses a chitosan bioengineered open ventricle (BEOV) scaffold to produce a two-stage perfusion cultured ventricle (TPCV). TPCV were fabricated by direct injection of 10 million primary rat neonatal cardiac cells, followed by wrapping of the outer scaffold surface with a 3D fibrin gel artificial heart muscle patch; TPCV were perfusion cultured for 3 days. The average biopotential output was 1.731 mV. TPCV cell retention following culture was approximately 5%. Cardiac cells were deposited on the scaffold surface and formed intercellular connections. Histological assessment displayed localized cell clusters, with some dissemination, and validated the observed presence of intercellular and gap-junction interactions. The study demonstrates initial effectiveness of our two-stage cell delivery concept, based on function and biological metrics. Biotechnol. Bioeng. 2016;113: 2275-2285. © 2016 Wiley Periodicals, Inc. PMID:27071026