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Sample records for cellular model mda-mb-468

  1. Selective regain of egfr gene copies in CD44+/CD24-/low breast cancer cellular model MDA-MB-468

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    Andreas Antje

    2010-03-01

    Full Text Available Abstract Background Increased transcription of oncogenes like the epidermal growth factor receptor (EGFR is frequently caused by amplification of the whole gene or at least of regulatory sequences. Aim of this study was to pinpoint mechanistic parameters occurring during egfr copy number gains leading to a stable EGFR overexpression and high sensitivity to extracellular signalling. A deeper understanding of those marker events might improve early diagnosis of cancer in suspect lesions, early detection of cancer progression and the prediction of egfr targeted therapies. Methods The basal-like/stemness type breast cancer cell line subpopulation MDA-MB-468 CD44high/CD24-/low, carrying high egfr amplifications, was chosen as a model system in this study. Subclones of the heterogeneous cell line expressing low and high EGF receptor densities were isolated by cell sorting. Genomic profiling was carried out for these by means of SNP array profiling, qPCR and FISH. Cell cycle analysis was performed using the BrdU quenching technique. Results Low and high EGFR expressing MDA-MB-468 CD44+/CD24-/low subpopulations separated by cell sorting showed intermediate and high copy numbers of egfr, respectively. However, during cell culture an increase solely for egfr gene copy numbers in the intermediate subpopulation occurred. This shift was based on the formation of new cells which regained egfr gene copies. By two parametric cell cycle analysis clonal effects mediated through growth advantage of cells bearing higher egfr gene copy numbers could most likely be excluded for being the driving force. Subsequently, the detection of a fragile site distal to the egfr gene, sustaining uncapped telomere-less chromosomal ends, the ladder-like structure of the intrachromosomal egfr amplification and a broader range of egfr copy numbers support the assumption that dynamic chromosomal rearrangements, like breakage-fusion-bridge-cycles other than proliferation drive the gain

  2. The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells.

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    Chen, Kai-Yun; Huang, Li-Ming; Kung, Hsing-Jien; Ann, David K; Shih, Hsiu-Ming

    2004-03-11

    Etk/Bmx, a member of the Tec family of tyrosine kinases, mediates various signaling pathways and confers several cellular functions. In the present study, we have explored the functional role of Etk in mediating EGF-induced apoptosis, using MDA-MB-468 cell line as a model. We first demonstrated that EGF treatment induces Etk tyrosine phosphorylation in both HeLa and MDA-MB-468 cells. Overexpression of Etk by recombinant adenovirus in MDA-MB-468 cells potentiates the extent of EGF-induced cell apoptosis. The observed Etk-enhanced MDA-MB-468 cell apoptosis is associated with the Stat1 activation, as demonstrated by electrophoresis mobility shift assays and reporter gene assays. By contrast, a kinase domain deletion mutant EtkDeltaK, functioning as a dominant-negative mutant, ameliorates EGF-induced Stat1 activation and apoptosis in MDA-MB-468 cells. To explore whether the activated Etk alone is sufficient for inducing apoptosis, a conditionally activated Etk (DeltaEtk-ER), a chimeric fusion protein of PH domain-truncated Etk and ligand-binding domain of estrogen receptor, was introduced into MDA-MB-468 cells. Upon beta-estradiol ligand activation, the DeltaEtk-ER could stimulate Stat1 activity and confer cell apoptosis independent of EGF treatment. Taken together, our findings indicate that Etk is a downstream signaling molecule of EGF receptor and suggest that Etk activation is essential for transducing the EGF-induced apoptotic signaling.

  3. N-acetylcysteine prevents cadmium-induced apoptosis in human breast cancer MDA-MB468 cell line.

    Science.gov (United States)

    Panjehpour, M; Alaie, S H

    2014-05-11

    Cadmium is a heavy metal posing severe risks and destructive effects on human health. Although cadmium was classified as a human carcinogen, it has been also shown to be a cytotoxic agent that induces cell death either by necrosis or apoptosis. In this study, we investigated the protective role of N-acetylcysteine, a free radical scavenger, on cadmium induced apoptosis in MDA-MB468 cells. The breast cancer cells were exposed to increasing concentrations of CdCl2 in the presence and absence of NAC and the cell viability was assessed using MTT assay. The microscopic studies of apoptosis were carried out with fluorescent staining. To investigate the induction of apoptosis, cellular DNA was isolated using DNA kit extraction and analyzed electrophoretically. The results showed significant decrease in cellular viability upon 48 hours exposure to CdCl2 in a dose-dependent manner (p cadmium cytotoxicity effects and protected cells from apoptotic death. DNA Hoechst staining showed the apoptotic bodies. The electrophoresis of extracted DNA identified a fragmentation pattern consistent with apoptosis mechanism. The results suggest that cytotoxic effects and induction of apoptosis caused by CdCl2 are mediated, by oxidative stress.

  4. Biological functions of the nude mice subcutaneous tumor established by MDA-MB-468 and SK-BR-3 breast cancer cells%MDA-MB-468和SK-BR-3乳腺癌细胞建立裸鼠皮下种植瘤的生物学功能

    Institute of Scientific and Technical Information of China (English)

    赵期康; 吴颖; 莫雪丽; 熊兵红

    2015-01-01

    目的 建立SK-BR-3和MDA-MB-468裸鼠皮下种植瘤模型,观察两种乳腺癌细胞株在建立裸鼠皮下移植瘤中的成瘤性和生物学与形态学特征.探讨阿霉素缓释剂对两种乳腺癌细胞裸鼠皮下种植瘤的生物学功能的影响.方法 将80只裸小鼠随机分为MDA-MB-468组和SK-BR-3组,MDA-MB-468组小鼠皮下注射乳腺癌MDA-MB-468细胞株,SK-BR-3组小鼠皮下注射乳腺癌SK-BR-3细胞株,每组40只.选取一半数量的小鼠,采用皮下注射法将细胞种植在裸鼠右侧腹股沟区,每天注射1次,连续注射4周后处死裸鼠,剥离瘤体,计算两组裸鼠皮下肿瘤的体积抑瘤率,取出两组小鼠模型中另一半小鼠,将阿霉素缓制剂注入两组小鼠模型皮下肿瘤旁,4周后处死两组小鼠,剥离瘤体,测量肿瘤大小.采用原位缺口末端标记法(TUNEL)法检测两组小鼠瘤体组织中肿瘤细胞的凋亡指数,观察阿霉素对两组乳腺癌细胞周期和凋亡的影响.结果 (1)肿瘤生长:至第8周时,两组小鼠肿瘤的体积分别为(3.212±0.151)和(2.924 ±0.316) cm3,两组间差异有统计学意义(t=2.758,P<0.05).(2)注射阿霉素后肿瘤体积抑制率结果:两组乳腺癌小鼠模型注射阿霉素缓释剂后,皮下瘤体停止生长并逐渐缩小,两组肿瘤体积差异有统计学意义(x2=2.53,P<0.05).(3)阿霉素对两组细胞周期和凋亡的影响:阿霉素使两组细胞生长阻滞在G0/G1期.阿霉素可显著引起MDA-MB-468细胞凋亡,最大凋亡率达62.5%.阿霉素处理SK-BR-3细胞后,亦可引起较明显的细胞凋亡,最大凋亡率可达53.8%.结论 成功制备两种乳腺癌转移瘤小鼠模型,同时制备阿霉素缓释剂,证实了其在乳腺癌转移瘤小鼠模型中抑制肿瘤生长的良好疗效.%Objective To establish the tumor models of SK-BR-3 and MDA-MB-468 in subcutaneous xenograft,observe the two breast cancer cell lines in the establishment of tumor and the biological and morphological

  5. The growth inhibitory effects of cadmium and copper on the MDA-MB468 human breast cancer cells

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    Mojtaba Panjehpour

    2010-01-01

    Full Text Available Background: Cadmium chloride is an important occupational and environmental pollutant. However, it can also be anti-carcinogenic under certain conditions. Copper, an essential trace element, has the ability to generate reactive oxygen species and induce cell apoptosis. This study was aimed to determine the growth inhibitory effects of cadmium and copper on the MDA-MB468 human breast cancer cells. Methods: By using MTT cell viability test, treatment of monolayer cell cultures with different metal concentrations (1-1000 μM showed a significant dose dependent decrease (p < 0.05 of viable cells in different times. Results: A considerable cytotoxicity was observed for CdCl2 at 200 μM and 1 μM after 48 and 72 hours incubations, respectively. The highest concentration of CuCl2 (1000 μM had little cytotoxic effects after 48 hours incubation period, but 1 μM of CuCl2 revealed a considerable cytotoxicity after 72 hours. The maximum synergic cytotoxic effect was observed at 0.5 μM of both metals. Conclusions: The results of the present study indicate that cytotoxic effect of CuCl2 is somehow lesser than that of CdCl2. This may be due to vital role of copper which is not known for cadmium so far.

  6. Extracts from Vatica diospyroides type SS fruit show low dose activity against MDA-MB-468 breast cancer cell-line via apoptotic action.

    Science.gov (United States)

    Srisawat, Theera; Sukpondma, Yaowapa; Chimplee, Siriphon; Kanokwiroon, Kanyanatt; Tedasen, Aman; Graidist, Potchanapond

    2014-01-01

    Very strong antiproliferative action of V. diospyroides type SS fruit extracts (IC50 range of 1.60-17.45 µg/mL) in MDA-MB-468 cell-line was observed in an MTT assay. After dosing of an extract concentration at half IC50 to cell line for 24 to 72 hours, treated cells were subjected to Annexin V-FITC/PI binding assay, followed by FACS and western blot analyses. Significant apoptotic death was observed with all extract treatments and both exposure times. Dosing with acetone extract of pericarp and cotyledon induced the highest apoptotic populations (33 and 32%, resp.), with the lowest populations of viable cells (65 and 67%, resp.). During 24 to 72 hours of dosing with methanolic extract of pericarp, the populations of viable and early apoptotic cells decreased significantly from 72.40 to 71.32% and from 12.00 to 6.36%, respectively, while the late apoptotic and nonviable cell populations continuously increased from 15.30 to 19.18% and from 0.30 to 3.14%, respectively. The expression of Bax increased within 12-48 hours of dosing, confirming apoptosis induced by time-dependent responses. The mutant p53 of MDA-MB-468 cells was expressed. Our results indicate that apoptosis and time-dependent therapeutic actions contribute to the cytotoxic effects of V. diospyroides type SS fruit on MDA-MB-468 cell.

  7. Silencing of High Mobility Group Isoform I-C (HMGI-C) Enhances Paclitaxel Chemosensitivity in Breast Adenocarcinoma Cells (MDA-MB-468)

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    Mansoori, Behzad; Mohammadi, Ali; Goldar, Samira; shanehbandi, Dariush; Mohammadnejad, Leila; Baghbani, Elham; Kazemi, Tohid; Kachalaki, Saeed; Baradaran, Behzad

    2016-01-01

    Purpose: HMGI-C (High Mobility Group protein Isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal protein that can modulate transcription of an ample number of genes. Genome-wide studies revealed up regulation of the HMGI-C gene in many human cancers. We suggested that HMGI-C might play a critical role in the progression and migration of various tumors. However, the exact role of HMGI-C in breast adenocarcinoma has not been cleared. Methods: The cells were transfected with siRNAs using transfection reagent. Relative HMGI-C mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. The cytotoxic effects of HMGI-C siRNA, Paclitaxel alone and combination on breast adenocarcinoma cells were determined using MTT assay. The migration after treatment by HMGI-C siRNA, Paclitaxel alone and combination were detected by wound-healing respectively. Results: HMGI-C siRNA significantly reduced both mRNA and protein expression levels in a 48 hours after transfection and dose dependent manner. We observed that the knockdown of HMGI-C led to the significant reduced cell viability and inhibited cells migration in MDA-MB-468 cells in vitro. Conclusion: These results propose that HMGI-C silencing and Paclitaxel treatment alone can inhibit the proliferation and migration significantly, furthermore, synergic effect of HMGI-C siRNA and Paclitaxel showed higher inhibition compared to mono treatment. Taken together, HMGI-C could be used as a promising therapeutic agent in the treatment of human breast adenocarcinoma. Therefore HMGI-C siRNA may be an effective adjuvant in human breast adenocarcinoma. PMID:27478778

  8. Evaluation of cytotoxic effects of several novel tetralin derivatives against Hela, MDA-MB-468, and MCF-7 cancer cells

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    Fateme Shafiee

    2012-01-01

    Conclusion: With the exception of compound 2, other tested compounds have potential for further cytotoxicity evaluation. Synthesizing other tetralin derivatives similar to compound 4 and studying their structure-activity relationships (SARs would be encouraged.

  9. Cellular models for Parkinson's disease.

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    Falkenburger, Björn H; Saridaki, Theodora; Dinter, Elisabeth

    2016-10-01

    Developing new therapeutic strategies for Parkinson's disease requires cellular models. Current models reproduce the two most salient changes found in the brains of patients with Parkinson's disease: The degeneration of dopaminergic neurons and the existence of protein aggregates consisting mainly of α-synuclein. Cultured cells offer many advantages over studying Parkinson's disease directly in patients or in animal models. At the same time, the choice of a specific cellular model entails the requirement to focus on one aspect of the disease while ignoring others. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types the aspects of Parkinson's disease they model along with technical advantages and disadvantages. It might also be helpful for researchers from other fields consulting literature on cellular models of Parkinson's disease. Important models for the study of dopaminergic neuron degeneration include Lund human mesencephalic cells and primary neurons, and a case is made for the use of non-dopaminergic cells to model pathogenesis of non-motor symptoms of Parkinson's disease. With regard to α-synuclein aggregates, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α-synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. This article is part of a special issue on Parkinson disease.

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

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    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.

  11. AlgiMatrix™-Based 3D Cell Culture System as an In Vitro Tumor Model: An Important Tool in Cancer Research.

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    Godugu, Chandraiah; Singh, Mandip

    2016-01-01

    Routinely used two-dimensional cell culture-based models often fail while translating the observations into in vivo models. This setback is more common in cancer research, due to several reasons. The extracellular matrix and cell-to-cell interactions are not present in two-dimensional (2D) cell culture models. Diffusion of drug molecules into cancer cells is hindered by barriers of extracellular components in in vivo conditions, these barriers are absent in 2D cell culture models. To better mimic or simulate the in vivo conditions present in tumors, the current study used the alginate based three-dimensional cell culture (AlgiMatrix™) model, which resembles close to the in vivo tumor models. The current study explains the detailed protocols involved in AlgiMatrix™ based in vitro non-small-cell lung cancer (NSCLC) models. The suitability of this model was studied by evaluating, cytotoxicity, apoptosis, and penetration of nanoparticles into the in vitro tumor spheroids. This study also demonstrated the effect of EphA2 receptor targeted docetaxel-loaded nanoparticles on MDA-MB-468 TNBC cell lines. The methods section is subdivided into three subsections such as (1) preparation of AlgiMatrix™-based 3D in vitro tumor models and cytotoxicity assays, (2) free drug and nanoparticle uptake into spheroid studies, and (3) western blot, IHC, and RT-PCR studies.

  12. Mathematical Modeling of Cellular Metabolism.

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    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

  13. EGFR tyrosine kinase targeted compounds: in vitro antitumor activity and molecular modeling studies of new benzothiazole and pyrimido[2,1-b]benzothiazole derivatives.

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    Gabr, Moustafa T; El-Gohary, Nadia S; El-Bendary, Eman R; El-Kerdawy, Mohamed M

    2014-01-01

    In this study, we illustrate computer aided drug design of new benzothiazole and pyrimido[2,1-b]benzothiazole derivatives as epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors. Compounds 1-5 were screened at NCI, USA, for antitumor activity against non-small cell lung cancer (NCI-H522), colon cancer (HCT-116, HCT-15 and HT29) and breast cancer (MDA-MB-468 and MDA-MB-231/ATCC) cell lines in which EGFR is overexpressed in varying levels. Results indicated that these compounds are more potent antitumor agents compared to erlotinib against HT29 and MDA-MB-231/ATCC cell lines. Compound 3 showed GI50 value of 22.3 nM against NCI-H522 cell line, while erlotinib exhibited GI50 value of 1 µM against the same cell line. In addition, these compounds were studied for their EGFR tyrosine kinase inhibitory activity. Virtual screening utilizing molecular modeling and QSAR techniques enabled the understanding of the pharmacophoric requirements for antitumor activity. Docking the designed compounds into the ATP binding site of EGFR-TK domain was done to predict the analogous binding mode of these compounds to the EGFR-TK inhibitors.

  14. 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.

  15. Cellular automata modelling of SEIRS

    Institute of Scientific and Technical Information of China (English)

    Liu Quan-Xing; Jin Zhen

    2005-01-01

    In this paper the SEIRS epidemic spread is analysed, and a two-dimensional probability cellular automata model for SEIRS is presented. Each cellular automation cell represents a part of the population that may be found in one of five states of individuals: susceptible, exposed (or latency), infected, immunized (or recovered) and death. Here studied are the effects of two cases on the epidemic spread. i.e. the effects of non-segregation and segregation on the latency and the infected of population. The conclusion is reached that the epidemic will persist in the case of non-segregation but it will decrease in the case of segregation. The proposed model can serve as a basis for the development of algorithms to simulate real epidemics based on real data. Last we find the density series of the exposed and the infected will fluctuate near a positive equilibrium point, when the constant for the immunized is less than its corresponding constant τ0. Our theoretical results are verified by numerical simulations.

  16. Cellular systems biology profiling applied to cellular models of disease.

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    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

  17. Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression.

    Science.gov (United States)

    Dai, Yumin; Hogan, Shelly; Schmelz, Eva M; Ju, Young H; Canning, Corene; Zhou, Kequan

    2011-01-01

    The epidermal growth factor receptor (EGFR) is an oncogene frequently overexpressed in breast cancer (BC), and its overexpression has been associated with poor prognosis and drug resistance. EGFR is therefore a rational target for BC therapy development. This study demonstrated that a graviola fruit extract (GFE) significantly downregulated EGFR gene expression and inhibited the growth of BC cells and xenografts. GFE selectively inhibited the growth of EGFR-overexpressing human BC (MDA-MB-468) cells (IC(50) = 4.8 μg/ml) but had no effect on nontumorigenic human breast epithelial cells (MCF-10A). GFE significantly downregulated EGFR mRNA expression, arrested cell cycle in the G0/G1 phase, and induced apoptosis in MDA-MB-468 cells. In the mouse xenograft model, a 5-wk dietary treatment of GFE (200 mg/kg diet) significantly reduced the protein expression of EGFR, p-EGFR, and p-ERK in MDA-MB-468 tumors by 56%, 54%, and 32.5%, respectively. Overall, dietary GFE inhibited tumor growth, as measured by wet weight, by 32% (P < 0.01). These data showed that dietary GFE induced significant growth inhibition of MDA-MB-468 cells in vitro and in vivo through a mechanism involving the EGFR/ERK signaling pathway, suggesting that GFE may have a protective effect for women against EGFR-overexpressing BC.

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

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    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. Cellular Automaton Modeling of Pattern Formation

    NARCIS (Netherlands)

    Boerlijst, M.C.

    2006-01-01

    Book review Andreas Deutsch and Sabine Dormann, Cellular Automaton Modeling of Biological Pattern Formation, Characterization, Applications, and Analysis, Birkhäuser (2005) ISBN 0-8176-4281-1 331pp..

  20. 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.

  1. 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.

  2. Flavopiridol Synergizes with Sorafenib to Induce Cytotoxicity and Potentiate Antitumorigenic Activity in EGFR/HER-2 and Mutant RAS/RAF Breast Cancer Model Systems

    Directory of Open Access Journals (Sweden)

    Teddy S Nagaria

    2013-08-01

    Full Text Available Oncogenic receptor tyrosine kinase (RTK signaling through the Ras-Raf-Mek-Erk (Ras-MAPK pathway is implicated in a wide array of carcinomas, including those of the breast. The cyclin-dependent kinases (CDKs are implicated in regulating proliferative and survival signaling downstream of this pathway. Here, we show that CDK inhibitors exhibit an order of magnitude greater cytotoxic potency than a suite of inhibitors targeting RTK and Ras-MAPK signaling in cell lines representative of clinically recognized breast cancer (BC subtypes. Drug combination studies show that the pan-CDK inhibitor, flavopiridol (FPD, synergistically potentiated cytotoxicity induced by the Raf inhibitor, sorafenib (SFN. This synergy was most pronounced at sub-EC50 SFN concentrations in MDA-MB-231 (KRAS-G13D and BRAF-G464V mutations, MDA-MB-468 [epidermal growth factor receptor (EGFR overexpression], and SKBR3 [ErbB2/EGFR2 (HER-2 overexpression] cells but not in hormone-dependent MCF-7 and T47D cells. Potentiation of SFN cytotoxicity by FPD correlated with enhanced apoptosis, suppression of retinoblastoma (Rb signaling, and reduced Mcl-1 expression. SFN and FPD were also tested in an MDA-MB-231 mammary fat pad engraftment model of tumorigenesis. Mice treated with both drugs exhibited reduced primary tumor growth rates and metastatic tumor load in the lungs compared to treatment with either drug alone, and this correlated with greater reductions in Rb signaling and Mcl-1 expression in resected tumors. These findings support the development of CDK and Raf co-targeting strategies in EGFR/HER-2-overexpressing or RAS/RAF mutant BCs.

  3. 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.

  4. Cellular automata modeling of pedestrian's crossing dynamics

    Institute of Scientific and Technical Information of China (English)

    张晋; 王慧; 李平

    2004-01-01

    Cellular automata modeling techniques and the characteristics of mixed traffic flow were used to derive the 2-dimensional model presented here for simulation of pedestrian's crossing dynamics.A conception of "stop point" is introduced to deal with traffic obstacles and resolve conflicts among pedestrians or between pedestrians and the other vehicles on the crosswalk.The model can be easily extended,is very efficient for simulation of pedestrian's crossing dynamics,can be integrated into traffic simulation software,and has been proved feasible by simulation experiments.

  5. Cellular automata models for synchronized traffic flow

    CERN Document Server

    Jiang Rui

    2003-01-01

    This paper presents a new cellular automata model for describing synchronized traffic flow. The fundamental diagrams, the spacetime plots and the 1 min average data have been analysed in detail. It is shown that the model can describe the outflow from the jams, the light synchronized flow as well as heavy synchronized flow with average speed greater than approximately 24 km h sup - sup 1. As for the synchronized flow with speed lower than 24 km h sup - sup 1 , it is unstable and will evolve into the coexistence of jams, free flow and light synchronized flow. This is consistent with the empirical findings (Kerner B S 1998 Phys. Rev. Lett. 81 3797).

  6. 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.

  7. Cellular Automata Model for Elastic Solid Material

    Institute of Scientific and Technical Information of China (English)

    DONG Yin-Feng; ZHANG Guang-Cai; XU Ai-Guo; GAN Yan-Biao

    2013-01-01

    The Cellular Automaton (CA) modeling and simulation of solid dynamics is a long-standing difficult problem.In this paper we present a new two-dimensional CA model for solid dynamics.In this model the solid body is represented by a set of white and black particles alternatively positioned in the x-and y-directions.The force acting on each particle is represented by the linear summation of relative displacements of the nearest-neighboring particles.The key technique in this new model is the construction of eight coefficient matrices.Theoretical and numerical analyses show that the present model can be mathematically described by a conservative system.So,it works for elastic material.In the continuum limit the CA model recovers the well-known Navier equation.The coefficient matrices are related to the shear module and Poisson ratio of the material body.Compared with previous CA model for solid body,this model realizes the natural coupling of deformations in the x-and y-directions.Consequently,the wave phenomena related to the Poisson ratio effects are successfully recovered.This work advances significantly the CA modeling and simulation in the field of computational solid dynamics.

  8. Statistical physical models of cellular motility

    Science.gov (United States)

    Banigan, Edward J.

    Cellular motility is required for a wide range of biological behaviors and functions, and the topic poses a number of interesting physical questions. In this work, we construct and analyze models of various aspects of cellular motility using tools and ideas from statistical physics. We begin with a Brownian dynamics model for actin-polymerization-driven motility, which is responsible for cell crawling and "rocketing" motility of pathogens. Within this model, we explore the robustness of self-diffusiophoresis, which is a general mechanism of motility. Using this mechanism, an object such as a cell catalyzes a reaction that generates a steady-state concentration gradient that propels the object in a particular direction. We then apply these ideas to a model for depolymerization-driven motility during bacterial chromosome segregation. We find that depolymerization and protein-protein binding interactions alone are sufficient to robustly pull a chromosome, even against large loads. Next, we investigate how forces and kinetics interact during eukaryotic mitosis with a many-microtubule model. Microtubules exert forces on chromosomes, but since individual microtubules grow and shrink in a force-dependent way, these forces lead to bistable collective microtubule dynamics, which provides a mechanism for chromosome oscillations and microtubule-based tension sensing. Finally, we explore kinematic aspects of cell motility in the context of the immune system. We develop quantitative methods for analyzing cell migration statistics collected during imaging experiments. We find that during chronic infection in the brain, T cells run and pause stochastically, following the statistics of a generalized Levy walk. These statistics may contribute to immune function by mimicking an evolutionarily conserved efficient search strategy. Additionally, we find that naive T cells migrating in lymph nodes also obey non-Gaussian statistics. Altogether, our work demonstrates how physical

  9. Exactly solvable cellular automaton traffic jam model.

    Science.gov (United States)

    Kearney, Michael J

    2006-12-01

    A detailed study is undertaken of the v{max}=1 limit of the cellular automaton traffic model proposed by Nagel and Paczuski [Phys. Rev. E 51, 2909 (1995)]. The model allows one to analyze the behavior of a traffic jam initiated in an otherwise freely flowing stream of traffic. By mapping onto a discrete-time queueing system, itself related to various problems encountered in lattice combinatorics, exact results are presented in relation to the jam lifetime, the maximum jam length, and the jam mass (the space-time cluster size or integrated vehicle waiting time), both in terms of the critical and the off-critical behavior. This sets existing scaling results in their natural context and also provides several other interesting results in addition.

  10. 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.

  11. Cellular Automata Models for Diffusion of Innovations

    CERN Document Server

    Fuks, H; Fuks, Henryk; Boccara, Nino

    1997-01-01

    We propose a probabilistic cellular automata model for the spread of innovations, rumors, news, etc. in a social system. The local rule used in the model is outertotalistic, and the range of interaction can vary. When the range R of the rule increases, the takeover time for innovation increases and converges toward its mean-field value, which is almost inversely proportional to R when R is large. Exact solutions for R=1 and $R=\\infty$ (mean-field) are presented, as well as simulation results for other values of R. The average local density is found to converge to a certain stationary value, which allows us to obtain a semi-phenomenological solution valid in the vicinity of the fixed point n=1 (for large t).

  12. Molecular Mechanism of BCAR3-p130Cas in Breast Cancer

    Science.gov (United States)

    2013-05-01

    et al. PEA-15 inhibits tumorigenesis in an MDA-MB-468 triple -negative breast cancer xenograft model through increased cytoplasmic localization of...was not included in the model . The C-terminal domain of p130Cas is defined by electron density from residues 739–872 and adopts the four- helix ...crystallization (months 3-6). 1c. Diffraction data collection and structure determination (months 6-12). 1d. Model building and analysis (months 6-12

  13. Development and characterization of 5-FU bearing ferritin appended solid lipid nanoparticles for tumour targeting.

    Science.gov (United States)

    Jain, Sanjay K; Chaurasiya, Akash; Gupta, Yashwant; Jain, Anekant; Dagur, Pradeep; Joshi, Beenu; Katoch, Vishwa M

    2008-08-01

    Ferritin coupled solid lipid nanoparticles were investigated for tumour targeting. Solid lipid nanoparticles were prepared using HSPC, cholesterol, DSPE and triolien. The SLNs without ferritin which has similar lipid composition were used for comparison. SLNs preparations were characterized for shape, size and percentage entrapment. The average size of SLNs was found to be in the range 110-152 nm and maximum drug entrapment was found to be 34.6-39.1%. In vitro drug release from the formulations is obeying fickian release kinetics. Cellular uptake and IC50 values of the formulation were determined in vitro in MDA-MB-468 breast cancer cells. In vitro cell binding of Fr-SLN exhibits 7.7-folds higher binding to MDA-MB-468 breast cancer cells in comparison to plain SLNs. Ex-vivo cytotoxicity assay on targeted nanoparticles gave IC50 of 1.28 microM and non-targeted nanoparticles gave IC50 of 3.56 microM. In therapeutic experiments, 5-FU, SLNs and Fr-SLNs were administered at the dose of 10 mg 5-FU/kg body weight to MDA-MB-468 tumour bearing Balb/c mice. Administration of Fr-SLNs formulation results in effective reduction in tumour growth as compared with free 5-FU and plain SLNs. The result demonstrates that this delivery system possessed an enhanced anti-tumour activity. The results warrant further evaluation of this delivery system.

  14. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines.

    Science.gov (United States)

    Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Shuji

    2014-03-01

    Although lycopene, a major carotenoid component of tomatoes, has been suggested to attenuate the risk of breast cancer, the underlying preventive mechanism remains to be determined. Moreover, it is not known whether there are any differences in lycopene activity among different subtypes of human breast cancer cells. Using ER/PR positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines, we investigated the cellular and molecular mechanism of the anticancer activity of lycopene. Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0 /G1 phase at physiologically achievable concentrations found in human plasma. The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0 /G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP. Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines. In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL. Taken together, these data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells suggests a potential role of lycopene for the prevention of triple negative breast cancer.

  15. 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...

  16. Infinite Time Cellular Automata: A Real Computation Model

    CERN Document Server

    Givors, Fabien; Ollinger, Nicolas

    2010-01-01

    We define a new transfinite time model of computation, infinite time cellular automata. The model is shown to be as powerful than infinite time Turing machines, both on finite and infinite inputs; thus inheriting many of its properties. We then show how to simulate the canonical real computation model, BSS machines, with infinite time cellular automata in exactly \\omega steps.

  17. SEM++: A particle model of cellular growth, signaling and migration

    Science.gov (United States)

    Milde, Florian; Tauriello, Gerardo; Haberkern, Hannah; Koumoutsakos, Petros

    2014-06-01

    We present a discrete particle method to model biological processes from the sub-cellular to the inter-cellular level. Particles interact through a parametrized force field to model cell mechanical properties, cytoskeleton remodeling, growth and proliferation as well as signaling between cells. We discuss the guiding design principles for the selection of the force field and the validation of the particle model using experimental data. The proposed method is integrated into a multiscale particle framework for the simulation of biological systems.

  18. Cellular modelling using P systems and process algebra

    Institute of Scientific and Technical Information of China (English)

    Francisco J.Romero-Campero; Marian Gheorghe; Gabriel Ciobanu; John M. Auld; Mario J. Pérez-Jiménez

    2007-01-01

    In this paper various molecular chemical interactions are modelled under different computational paradigms. P systems and π-calculus are used to describe intra-cellular reactions like protein-protein interactions and gene regulation control.

  19. 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.

  20. Cell tracing dyes significantly change single cell mechanics.

    Science.gov (United States)

    Lulevich, Valentin; Shih, Yi-Ping; Lo, Su Hao; Liu, Gang-Yu

    2009-05-07

    Cell tracing dyes are very frequently utilized in cellular biology research because they provide highly sensitive fluorescent tags that do not compromise cellular functions such as growth and proliferation. In many investigations concerning cellular adhesion and mechanics, fluorescent dyes have been employed with the assumption of little impact on the results. Using the single cell compression technique developed by our team, the single cell mechanics of MDA-MB-468 and MLC-SV40 cells were investigated as a function of dye uptake. Cell tracing dyes increase living cell stiffness 3-6 times and cell-to-probe adhesion up to 7 times. These results suggest a more significant effect than toxins, such as thrombin. A simple analytical model was derived to enable the extraction of the Young's moduli of the cell membrane and cytoskeleton from the force-deformation profiles measured for individual cells. The increase in Young's modulus of the membrane is 3-7 times, which is more significant than that of the cytoskeleton (1.1-3.4 times). We propose that changes in cell mechanics upon the addition of fluorescent tracing dye are primarily due to the incorporation of amphiphilic dye molecules into the cellular plasma membrane, which increases the lateral interaction among phospholipid chains and thus enhances their rigidity and adhesion.

  1. 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.

  2. Cellular automaton for realistic modelling of landslides

    CERN Document Server

    Segrè, E; Enrico Segre; Chiara Deangeli

    1994-01-01

    We develop a numerical model for the simulation of debris flow in landslides over a complex three dimensional topography. The model is based on a lattice, in which debris can be transferred among nearest neighbours according to established empirical relationships for granular flows. The model is validated comparing its results 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, showing that the model has an intermittent behaviour.

  3. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity

    Science.gov (United States)

    Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

    2017-01-01

    Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

  4. Minimal model for complex dynamics in cellular processes.

    Science.gov (United States)

    Suguna, C; Chowdhury, K K; Sinha, S

    1999-11-01

    Cellular functions are controlled and coordinated by the complex circuitry of biochemical pathways regulated by genetic and metabolic feedback processes. This paper aims to show, with the help of a minimal model of a regulated biochemical pathway, that the common nonlinearities and control structures present in biomolecular interactions are capable of eliciting a variety of functional dynamics, such as homeostasis, periodic, complex, and chaotic oscillations, including transients, that are observed in various cellular processes.

  5. Simulation of primary static recrystallization with cellular operator model

    OpenAIRE

    Mukhopadhyay, Prantik

    2005-01-01

    1. Based on the modified cellular automata approach of Reher [60] a cellular operator model has been developed that is capable of accounting for spatial and temporal inhomogeneity on a finer scale. For this a scalable subgrid automaton is introduced that allows for a high spatial resolution on demand and still high computational efficiency. The scalable subgrid permits to track the minute changes of growth front during recrystallization owing to local variations of boundary mobility and net d...

  6. 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.

  7. A cellular automaton evacuation model based on mobile robot's behaviors

    Institute of Scientific and Technical Information of China (English)

    WENG WenGuo; YUAN HongYong; FAN WeiCheng

    2007-01-01

    The research of evacuation in some emergencies, e.g. fire, is of great benefit to reducing the injuries of persons. In this paper, a cellular automaton evacuation model based on mobile robot's behaviors is presented. Each person is treated as an intelligent mobile robot, and motor schemas, including move-to-goal, avoid-obstacle, swirl-obstacle and nervous-motion, drive persons to interact with their environment. The motor schemas are combined with cellular automaton theory, and an evacuation model is built. Evacuation simulation of persons with different move velocities shows that the presented model can predict accurately the evacuation phenomena in some emergencies.

  8. 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

  9. Modeling diffusion of innovations with probabilistic cellular automata

    CERN Document Server

    Boccara, N; 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.

  10. Modeling Integrated Cellular Machinery Using Hybrid Petri-Boolean Networks

    Science.gov (United States)

    Berestovsky, Natalie; Zhou, Wanding; Nagrath, Deepak; Nakhleh, Luay

    2013-01-01

    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 using such more

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Empirical study on entropy models of cellular manufacturing systems

    Institute of Scientific and Technical Information of China (English)

    Zhifeng Zhang; Renbin Xiao

    2009-01-01

    From the theoretical point of view,the states of manufacturing resources can be monitored and assessed through the amount of information needed to describe their technological structure and operational state.The amount of information needed to describe cellular manufacturing systems is investigated by two measures:the structural entropy and the operational entropy.Based on the Shannon entropy,the models of the structural entropy and the operational entropy of cellular manufacturing systems are developed,and the cognizance of the states of manufacturing resources is also illustrated.Scheduling is introduced to measure the entropy models of cellular manufacturing systems,and the feasible concepts of maximum schedule horizon and schedule adherence are advanced to quantitatively evaluate the effectiveness of schedules.Finally,an example is used to demonstrate the validity of the proposed methodology.

  16. 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.

  17. 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.

  18. A simplified cellular automation model for city traffic

    Energy Technology Data Exchange (ETDEWEB)

    Simon, P.M.; Nagel, K. [Los Alamos National Lab., NM (United States)]|[Santa Fe Inst., NM (United States)

    1997-12-31

    The authors systematically investigate the effect of blockage sites in a cellular automata model for traffic flow. Different scheduling schemes for the blockage sites are considered. None of them returns a linear relationship between the fraction of green time and the throughput. The authors use this information for a fast implementation of traffic in Dallas.

  19. Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.

    Science.gov (United States)

    Yadav, Babasaheb; Taurin, Sebastien; Rosengren, Rhonda J; Schumacher, Marc; Diederich, Marc; Somers-Edgar, Tiffany J; Larsen, Lesley

    2010-09-15

    A series of 18 heterocyclic cyclohexanone analogues of curcumin have been synthesised and screened for their activity in both adherent and non-adherent cancer cell models. Cytotoxicity towards MBA-MB-231 breast cancer cells, as well as ability to inhibit NF-kappaB transactivation in non-adherent K562 leukemia cells were investigated. Three of these analogues 3,5-bis(pyridine-4-yl)-1-methylpiperidin-4-one B1, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one B10, and 8-methyl-2,4-bis((pyridine-4-yl)methylene)-8-aza-bicyclo[3.2.1]octan-3-one C1 showed potent cytotoxicity towards MBA-MB-231, MDA-MB-468, and SkBr3 cell lines with EC50 values below 1 microM and inhibition of NF-kappaB activation below 7.5 microM. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18 h. This level of activity warrants further investigation for the treatment of ER-negative breast cancer and/or chronic myelogenous leukemia as prototypical cellular models for solid and liquid tumors.

  20. Analytical modeling of bargaining solutions for multicast cellular services

    Directory of Open Access Journals (Sweden)

    Giuseppe Araniti

    2013-07-01

    Full Text Available Nowadays, the growing demand for group-oriented services over mobile devices has lead to the definition of new communication standards and multimedia applications in cellular systems. In this article we study the use of game theoretic solutions for these services to model and perform a trade-off analysis between fairness and efficiency in the resources allocation. More precisely, we model bargaining solutions for the multicast data services provisioning and introduce the analytical resolution for the proposed solutions.

  1. Fiber-bundle microendoscopy with sub-diffuse reflectance spectroscopy and intensity mapping for multimodal optical biopsy of stratified epithelium.

    Science.gov (United States)

    Greening, Gage J; James, Haley M; Powless, Amy J; Hutcheson, Joshua A; Dierks, Mary K; Rajaram, Narasimhan; Muldoon, Timothy J

    2015-12-01

    Early detection of structural or functional changes in dysplastic epithelia may be crucial for improving long-term patient care. Recent work has explored myriad non-invasive or minimally invasive "optical biopsy" techniques for diagnosing early dysplasia, such as high-resolution microendoscopy, a method to resolve sub-cellular features of apical epithelia, as well as broadband sub-diffuse reflectance spectroscopy, a method that evaluates bulk health of a small volume of tissue. We present a multimodal fiber-based microendoscopy technique that combines high-resolution microendoscopy, broadband (450-750 nm) sub-diffuse reflectance spectroscopy (sDRS) at two discrete source-detector separations (374 and 730 μm), and sub-diffuse reflectance intensity mapping (sDRIM) using a 635 nm laser. Spatial resolution, magnification, field-of-view, and sampling frequency were determined. Additionally, the ability of the sDRS modality to extract optical properties over a range of depths is reported. Following this, proof-of-concept experiments were performed on tissue-simulating phantoms made with poly(dimethysiloxane) as a substrate material with cultured MDA-MB-468 cells. Then, all modalities were demonstrated on a human melanocytic nevus from a healthy volunteer and on resected colonic tissue from a murine model. Qualitative in vivo image data is correlated with reduced scattering and absorption coefficients.

  2. An efficient Cellular Potts Model algorithm that forbids cell fragmentation

    Science.gov (United States)

    Durand, Marc; Guesnet, Etienne

    2016-11-01

    The Cellular Potts Model (CPM) is a lattice based modeling technique which is widely used for simulating cellular patterns such as foams or biological tissues. Despite its realism and generality, the standard Monte Carlo algorithm used in the scientific literature to evolve this model preserves connectivity of cells on a limited range of simulation temperature only. We present a new algorithm in which cell fragmentation is forbidden for all simulation temperatures. This allows to significantly enhance realism of the simulated patterns. It also increases the computational efficiency compared with the standard CPM algorithm even at same simulation temperature, thanks to the time spared in not doing unrealistic moves. Moreover, our algorithm restores the detailed balance equation, ensuring that the long-term stage is independent of the chosen acceptance rate and chosen path in the temperature space.

  3. Modeling cellular networks in fading environments with dominant specular components

    KAUST Repository

    AlAmmouri, Ahmad

    2016-07-26

    Stochastic geometry (SG) has been widely accepted as a fundamental tool for modeling and analyzing cellular networks. However, the fading models used with SG analysis are mainly confined to the simplistic Rayleigh fading, which is extended to the Nakagami-m fading in some special cases. However, neither the Rayleigh nor the Nakagami-m accounts for dominant specular components (DSCs) which may appear in realistic fading channels. In this paper, we present a tractable model for cellular networks with generalized two-ray (GTR) fading channel. The GTR fading explicitly accounts for two DSCs in addition to the diffuse components and offers high flexibility to capture diverse fading channels that appear in realistic outdoor/indoor wireless communication scenarios. It also encompasses the famous Rayleigh and Rician fading as special cases. To this end, the prominent effect of DSCs is highlighted in terms of average spectral efficiency. © 2016 IEEE.

  4. Modelling Nonlinear Sequence Generators in terms of Linear Cellular Automata

    CERN Document Server

    Fúster-Sabater, Amparo; 10.1016/j.apm.2005.08.013

    2010-01-01

    In this work, a wide family of LFSR-based sequence generators, the so-called Clock-Controlled Shrinking Generators (CCSGs), has been analyzed and identified with a subset of linear Cellular Automata (CA). In fact, a pair of linear models describing the behavior of the CCSGs can be derived. The algorithm that converts a given CCSG into a CA-based linear model is very simple and can be applied to CCSGs in a range of practical interest. The linearity of these cellular models can be advantageously used in two different ways: (a) for the analysis and/or cryptanalysis of the CCSGs and (b) for the reconstruction of the output sequence obtained from this kind of generators.

  5. 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.

  6. Multiscale mathematical modeling and simulation of cellular dynamical process.

    Science.gov (United States)

    Nakaoka, Shinji

    2014-01-01

    Epidermal homeostasis is maintained by dynamic interactions among molecules and cells at different spatiotemporal scales. Mathematical modeling and simulation is expected to provide clear understanding and precise description of multiscaleness in tissue homeostasis under systems perspective. We introduce a stochastic process-based description of multiscale dynamics. Agent-based modeling as a framework of multiscale modeling to achieve consistent integration of definitive subsystems is proposed. A newly developed algorithm that particularly aims to perform stochastic simulations of cellular dynamical process is introduced. Finally we review applications of multiscale modeling and quantitative study to important aspects of epidermal and epithelial homeostasis.

  7. 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.

  8. Public Evacuation Process Modeling and Simulatiaon Based on Cellular Automata

    Directory of Open Access Journals (Sweden)

    Zhikun Wang

    2013-11-01

    Full Text Available Considering attraction of the nearest exit, repulsive force of the fire, barrier and its display style, effect of fire exit location on escape time in fire hazard, a mathematical model of evacuation process model was build based on cellular automatic theory. The program was developed by JavaScript. The influencing factors of evacuation were obtained through the simulation model by inputting crew size, creating initial positions of crew and fire seat stochastically. The experimental results show that the evacuation simulation model with authenticity and validity, which has guiding significance for people evacuation and public escape system design.  

  9. Parallelizing the Cellular Potts Model on graphics processing units

    Science.gov (United States)

    Tapia, José Juan; D'Souza, Roshan M.

    2011-04-01

    The Cellular Potts Model (CPM) is a lattice based modeling technique used for simulating cellular structures in computational biology. The computational complexity of the model means that current serial implementations restrict the size of simulation to a level well below biological relevance. Parallelization on computing clusters enables scaling the size of the simulation but marginally addresses computational speed due to the limited memory bandwidth between nodes. In this paper we present new data-parallel algorithms and data structures for simulating the Cellular Potts Model on graphics processing units. Our implementations handle most terms in the Hamiltonian, including cell-cell adhesion constraint, cell volume constraint, cell surface area constraint, and cell haptotaxis. We use fine level checkerboards with lock mechanisms using atomic operations to enable consistent updates while maintaining a high level of parallelism. A new data-parallel memory allocation algorithm has been developed to handle cell division. Tests show that our implementation enables simulations of >10 cells with lattice sizes of up to 256 3 on a single graphics card. Benchmarks show that our implementation runs ˜80× faster than serial implementations, and ˜5× faster than previous parallel implementations on computing clusters consisting of 25 nodes. The wide availability and economy of graphics cards mean that our techniques will enable simulation of realistically sized models at a fraction of the time and cost of previous implementations and are expected to greatly broaden the scope of CPM applications.

  10. 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...

  11. A cellular automata model with probability infection and spatial dispersion

    Institute of Scientific and Technical Information of China (English)

    Jin Zhen; Liu Quan-Xing; Mainul Haque

    2007-01-01

    In this article, we have proposed an epidemic model based on the probability cellular automata theory. The essential mathematical features are analysed with the help of stability theory. We have given an alternative modelling approach for the spatiotemporal system which is more realistic from the practical point of view. A discrete and spatiotemporal approach is shown by using cellular automata theory. It is interesting to note that both the size of the endemic equilibrium and the density of the individuals increase with the increase of the neighbourhood size and infection rate, but the infections decrease with the increase of the recovery rate. The stability of the system around the positive interior equilibrium has been shown by using a suitable Lyapunov function. Finally, experimental data simulation for SARS disease in China in 2003 and a brief discussion are given.

  12. A COLLABORATIVE LOCATION MODEL FOR CELLULAR MOBILE POSITION LOCATION

    Institute of Scientific and Technical Information of China (English)

    Deng Ping; Liu Lin; Fan Pingzhi

    2004-01-01

    In cellular network, several Time Difference Of Arrival (TDOA) location algorithms can be applied to mobile position estimation. However, each algorithm has its own limitations and none of them is proved to be the most reliable one in different channel environments. In this paper Kleine-Ostmann's data fusion model is modified and a collaborative location model which incorporates position estimate of two TDOA location algorithms is proposed.Analysis and simulation show that more reliable and accurate mobile position estimation can be achieved based on this model.

  13. Microbial Growth Modeling and Simulation Based on Cellular Automata

    Directory of Open Access Journals (Sweden)

    Hong Men

    2013-07-01

    Full Text Available In order to simulate the micro-evolutionary process of the microbial growth, [Methods] in this study, we adopt two-dimensional cellular automata as its growth space. Based on evolutionary mechanism of microbial and cell-cell interactions, we adopt Moore neighborhood and make the transition rules. Finally, we construct the microbial growth model. [Results] It can describe the relationships among the cell growth, division and death. And also can effectively reflect spatial inhibition effect and substrate limitation effect. [Conclusions] The simulation results show that CA model is not only consistent with the classic microbial kinetic model, but also be able to simulate the microbial growth and evolution.

  14. Unified Stochastic Geometry Model for MIMO Cellular Networks with Retransmissions

    KAUST Repository

    Afify, Laila H.

    2016-10-11

    This paper presents a unified mathematical paradigm, based on stochastic geometry, for downlink cellular networks with multiple-input-multiple-output (MIMO) base stations (BSs). The developed paradigm accounts for signal retransmission upon decoding errors, in which the temporal correlation among the signal-to-interference-plus-noise-ratio (SINR) of the original and retransmitted signals is captured. In addition to modeling the effect of retransmission on the network performance, the developed mathematical model presents twofold analysis unification for MIMO cellular networks literature. First, it integrates the tangible decoding error probability and the abstracted (i.e., modulation scheme and receiver type agnostic) outage probability analysis, which are largely disjoint in the literature. Second, it unifies the analysis for different MIMO configurations. The unified MIMO analysis is achieved by abstracting unnecessary information conveyed within the interfering signals by Gaussian signaling approximation along with an equivalent SISO representation for the per-data stream SINR in MIMO cellular networks. We show that the proposed unification simplifies the analysis without sacrificing the model accuracy. To this end, we discuss the diversity-multiplexing tradeoff imposed by different MIMO schemes and shed light on the diversity loss due to the temporal correlation among the SINRs of the original and retransmitted signals. Finally, several design insights are highlighted.

  15. Occupant evacuation model based on cellular automata in fire

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    By applying the rules set in traffic flow and pedestrian flow models, a basic cellular automata model is presented to simulate occupant evacuation in fire. Some extended models are introduced to study the special phenomena of evacuation from the fire room. The key of the models is the introduction of the danger grade which makes the route choice convenient and reasonable. Fire not only influences the emotional and behavioral characteristics of an individual but also affects his physical constitution, which reduces his maximal possible velocity. The models consider these influence factors by applying a set of simple but effective rules. It is needed to emphasize that all rules are established according to the essential phenomenon in fire evacuation, that is, all the occupants would try to move to the safest place as fast as possible. Some simulation examples are also presented to validate the applicability of the models.

  16. Infinity computations in cellular automaton forest-fire model

    Science.gov (United States)

    Iudin, D. I.; Sergeyev, Ya. D.; Hayakawa, M.

    2015-03-01

    Recently a number of traditional models related to the percolation theory has been considered by means of a new computational methodology that does not use Cantor's ideas and describes infinite and infinitesimal numbers in accordance with the principle 'The whole is greater than the part' (Euclid's Common Notion 5). Here we apply the new arithmetic to a cellular automaton forest-fire model which is connected with the percolation methodology and in some sense combines the dynamic and the static percolation problems and under certain conditions exhibits critical fluctuations. It is well known that there exist two versions of the model: real forest-fire model where fire catches adjacent trees in the forest in the step by step manner and simplified version with instantaneous combustion. Using new approach we observe that in both situations we deal with the same model but with different time resolution. We show that depending on the "microscope" we use the same cellular automaton forest-fire model reveals either instantaneous forest combustion or step by step firing. By means of the new approach it was also observed that as far as we choose an infinitesimal tree growing rate and infinitesimal ratio between the ignition probability and the growth probability we determine the measure or extent of the system size infinity that provides the criticality of the system dynamics. Correspondent inequalities for grosspowers are derived.

  17. 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.

  18. Modeling cellular lysis in skeletal muscle due to electric shock.

    Science.gov (United States)

    Cela, Carlos J; Lee, Raphael C; Lazzi, Gianluca

    2011-05-01

    High-voltage electrical trauma frequently results in injury patterns that cannot be completely attributed to Joule heating. An electrical-injury model describing cellular lysis damage caused by supraphysiological electric fields is introduced, and used to evaluate the effects of high-voltage electric shock on the skeletal muscle of a human upper limb in a configuration that simulates hand-to-hand contact. A novel multiresolution admittance method, capable of efficiently handling large computational models while maintaining excellent accuracy, was used to perform the numerical computations. Values for the computed current through the arm and the upper limb impedance are reported.

  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. A cellular automaton model for a bridge traffic bottleneck

    Institute of Scientific and Technical Information of China (English)

    Shifa Xiao; Lingjiang Kong; Muren Liu

    2005-01-01

    A cellular automaton (CA) model is proposed in this paper to analyze a bridge traffic bottleneck. The simulation results with this model show that there are several phase transitions in the traffic average density, velocity and flow for each lane under a periodic boundary condition. An unstable phase in the traffic average density and velocity for the upstream and downstream lanes of the bridge is shown in a range of initial traffic densities. The critical points of the phase transitions and the phenomenon of the unstable phase found in the simulation are also explained with the mean-field theory.

  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. Cancer models, genomic instability and somatic cellular Darwinian evolution

    Directory of Open Access Journals (Sweden)

    Little Mark P

    2010-04-01

    Full Text Available Abstract The biology of cancer is critically reviewed and evidence adduced that its development can be modelled as a somatic cellular Darwinian evolutionary process. The evidence for involvement of genomic instability (GI is also reviewed. A variety of quasi-mechanistic models of carcinogenesis are reviewed, all based on this somatic Darwinian evolutionary hypothesis; in particular, the multi-stage model of Armitage and Doll (Br. J. Cancer 1954:8;1-12, the two-mutation model of Moolgavkar, Venzon, and Knudson (MVK (Math. Biosci. 1979:47;55-77, the generalized MVK model of Little (Biometrics 1995:51;1278-1291 and various generalizations of these incorporating effects of GI (Little and Wright Math. Biosci. 2003:183;111-134; Little et al. J. Theoret. Biol. 2008:254;229-238. Reviewers This article was reviewed by RA Gatenby and M Kimmel.

  3. Cellular automaton model considering headway-distance effect

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    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-tostart 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 velocitydependent 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.

  4. 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.

  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. 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.

  7. Structural modeling of sandwich structures with lightweight cellular cores

    Science.gov (United States)

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

    2007-10-01

    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 can give 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.

  8. 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...

  9. A modified weighted probabilistic cellular automaton traffic flow model

    Institute of Scientific and Technical Information of China (English)

    Zhuang Qian; Jia Bin; Li Xin-Gang

    2009-01-01

    This paper modifies the weighted probabilistic cellular automaton model (Li X L,Kuang H,Song T,et al 2008Chin.Phys.B 17 2366) which considered a diversity of traffic behaviors under real traffic situations induced by various driving characters and habits.In the new model,the effects of the velocity at the last time step and drivers' desire for acceleration are taken into account.The fundamental diagram,spatial-temporal diagram,and the time series of one-minute data axe analyzed.The results show that this model reproduces synchronized flow.Finally,it simulates the on-ramp system with the proposed model.Some characteristics including the phase diagram are studied.

  10. Study of contact angle hysteresis using the Cellular Potts Model.

    Science.gov (United States)

    Mortazavi, Vahid; D'Souza, Roshan M; Nosonovsky, Michael

    2013-02-28

    We use the Cellular Potts Model (CPM) to study the contact angle (CA) hysteresis in multiphase (solid-liquid-vapour) systems. We simulate a droplet over the tilted patterned surface, and a bubble placed under the surface immersed in liquid. The difference between bubbles and droplets was discussed through their CA hysteresis. Dependency of CA hysteresis on the surface structure and other parameters was also investigated. This analysis allows decoupling of the 1D (pinning of the triple line) and 2D (adhesion hysteresis in the contact area) effects and provides new insight into the nature of CA hysteresis.

  11. Network modeling of membrane-based artificial cellular systems

    Science.gov (United States)

    Freeman, Eric C.; Philen, Michael K.; Leo, Donald J.

    2013-04-01

    Computational models are derived for predicting the behavior of artificial cellular networks for engineering applications. The systems simulated involve the use of a biomolecular unit cell, a multiphase material that incorporates a lipid bilayer between two hydrophilic compartments. These unit cells may be considered building blocks that enable the fabrication of complex electrochemical networks. These networks can incorporate a variety of stimuli-responsive biomolecules to enable a diverse range of multifunctional behavior. Through the collective properties of these biomolecules, the system demonstrates abilities that recreate natural cellular phenomena such as mechanotransduction, optoelectronic response, and response to chemical gradients. A crucial step to increase the utility of these biomolecular networks is to develop mathematical models of their stimuli-responsive behavior. While models have been constructed deriving from the classical Hodgkin-Huxley model focusing on describing the system as a combination of traditional electrical components (capacitors and resistors), these electrical elements do not sufficiently describe the phenomena seen in experiment as they are not linked to the molecular scale processes. From this realization an advanced model is proposed that links the traditional unit cell parameters such as conductance and capacitance to the molecular structure of the system. Rather than approaching the membrane as an isolated parallel plate capacitor, the model seeks to link the electrical properties to the underlying chemical characteristics. This model is then applied towards experimental cases in order that a more complete picture of the underlying phenomena responsible for the desired sensing mechanisms may be constructed. In this way the stimuli-responsive characteristics may be understood and optimized.

  12. 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.

  13. 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}).

  14. A cellular automaton model for ship traffic flow in waterways

    Science.gov (United States)

    Qi, Le; Zheng, Zhongyi; Gang, Longhui

    2017-04-01

    With the development of marine traffic, waterways become congested and more complicated traffic phenomena in ship traffic flow are observed. It is important and necessary to build a ship traffic flow model based on cellular automata (CAs) to study the phenomena and improve marine transportation efficiency and safety. Spatial discretization rules for waterways and update rules for ship movement are two important issues that are very different from vehicle traffic. To solve these issues, a CA model for ship traffic flow, called a spatial-logical mapping (SLM) model, is presented. In this model, the spatial discretization rules are improved by adding a mapping rule. And the dynamic ship domain model is considered in the update rules to describe ships' interaction more exactly. Take the ship traffic flow in the Singapore Strait for example, some simulations were carried out and compared. The simulations show that the SLM model could avoid ship pseudo lane-change efficiently, which is caused by traditional spatial discretization rules. The ship velocity change in the SLM model is consistent with the measured data. At finally, from the fundamental diagram, the relationship between traffic ability and the lengths of ships is explored. The number of ships in the waterway declines when the proportion of large ships increases.

  15. Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives

    Institute of Scientific and Technical Information of China (English)

    Hai-hong LI; Jian DING; Hua-liang JIANG; Xiu-hua ZHANG; Jin-zhi TAN; Li-li CHEN; Hong LIU; Xiao-min LUO; Xu SHEN; Li-ping LIN; Kai-xian CHEN

    2007-01-01

    Aim: To design and synthesize a novel class of antitumor agents, featuring the 3,5-substituted indolin-2-one framework. Methods: Based on enzyme binding fea-tures of (Z)-SU5402, introducing a β-pyrrole group at the 3-position of the indolin-2-one core, a series of novel 3,5-substituted indolin-2-ones were designed and synthesized. Four human Carcinoma cell lines of A-431, A-549, MDA-MB-468,and Autosomal Dominant Polycystic Kidney disease were chosen for the cell proliferation assay. Results: Twenty new compounds (la-t) with E configuration have been designed, synthesized and bioassayed. Their structural features were determined by nuclear magnetic resonance (NMR) spectra, low- and high-resolu-tion mass spectra, and confirmed by X-ray crystallography. Although the enzyme assay showed a weak inhibition effect against the epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor tyrosine kinases, the cell-based antitumor activity was promising. Compounds 1g and 1h showed higher inhibitory activity toward the A-549 and MDA-MB-468 cell lines with IC50 of 0.065-9.4 μmol/L. Conclusion: This study provides a new template for further development of potent antitumor drugs.

  16. 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.

  17. 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...

  18. A dynamic cellular vertex model of growing epithelial tissues

    Science.gov (United States)

    Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

    2017-03-01

    Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

  19. 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...

  20. A cellular automaton model for evacuation flow using game theory

    Science.gov (United States)

    Guan, Junbiao; Wang, Kaihua; Chen, Fangyue

    2016-11-01

    Game theory serves as a good tool to explore crowd dynamic conflicts during evacuation processes. The purpose of this study is to simulate the complicated interaction behavior among the conflicting pedestrians in an evacuation flow. Two types of pedestrians, namely, defectors and cooperators, are considered, and two important factors including fear index and cost coefficient are taken into account. By combining the snowdrift game theory with a cellular automaton (CA) model, it is shown that the increase of fear index and cost coefficient will lengthen the evacuation time, which is more apparent for large values of cost coefficient. Meanwhile, it is found that the defectors to cooperators ratio could always tend to consistent states despite different values of parameters, largely owing to self-organization effects.

  1. 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.

  2. Two dimensional cellular automaton for evacuation modeling: hybrid shuffle update

    CERN Document Server

    Arita, Chikashi; Appert-Rolland, Cécile

    2015-01-01

    We consider a cellular automaton model with a static floor field for pedestrians evacuating a room. After identifying some properties of real pedestrian flows, we discuss various update schemes, and we introduce a new one, the hybrid shuffle update. The properties specific to pedestrians are incorporated in variables associated to particles called phases, that represent their step cycles. The dynamics of the phases gives naturally raise to some friction, and allows to reproduce several features observed in experiments. We study in particular the crossover between a low- and a high-density regime that occurs when the density of pedestrian increases, the dependency of the outflow in the strength of the floor field, and the shape of the queue in front of the exit.

  3. The importance of volume exclusion in modelling cellular migration.

    Science.gov (United States)

    Dyson, Louise; Baker, Ruth E

    2015-09-01

    The modelling of collective migration has traditionally been undertaken in a continuous framework, with little reference to the individual-level mechanisms that give rise to such a concerted movement. One factor whose importance is now coming to light is that the individuals themselves occupy space in the domain, thus obstructing others from moving past them (volume exclusion). In this work, we systematically derive continuous descriptions of cellular migration with volume exclusion for a wide range of individual-based mechanisms and in one, two and three dimensions. We also consider subpopulations of migrating individuals, which may have different characteristics, such as differing sizes and speeds of migration. We demonstrate that volume exclusion is of particular importance when biased movement is included, and thus conclude that volume exclusion may have its greatest effect when considering directed migratory mechanisms such as chemotaxis.

  4. Predictability of the large relaxations in a cellular automaton model

    Energy Technology Data Exchange (ETDEWEB)

    Tejedor, Alejandro; Ambroj, Samuel; Gomez, Javier B; Pacheco, Amalio F [Faculty of Sciences, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain)

    2008-09-19

    A simple one-dimensional cellular automaton model with threshold dynamics is introduced. It is loaded at a uniform rate and unloaded by abrupt relaxations. The cumulative distribution of the size of the relaxations is analytically computed and behaves as a power law with an exponent equal to -1. This coincides with the phenomenological Gutenberg-Richter behavior observed in seismology for the cumulative statistics of earthquakes at the regional or global scale. The key point of the model is the zero-load state of the system after the occurrence of any relaxation, no matter what its size. This leads to an equipartition of probability between all possible load configurations in the system during the successive loading cycles. Each cycle ends with the occurrence of the greatest-or characteristic-relaxation in the system. The duration of the cycles in the model is statistically distributed with a coefficient of variation ranging from 0.5 to 1. The predictability of the characteristic relaxations is evaluated by means of error diagrams. This model illustrates the value taking into account the refractory periods to obtain a considerable gain in the quality of the predictions.

  5. Modeling dynamics of HIV infected cells using stochastic cellular automaton

    Science.gov (United States)

    Precharattana, Monamorn; Triampo, Wannapong

    2014-08-01

    Ever since HIV was first diagnosed in human, a great number of scientific works have been undertaken to explore the biological mechanisms involved in the infection and progression of the disease. Several cellular automata (CA) models have been introduced to gain insights into the dynamics of the disease progression but none of them has taken into account effects of certain immune cells such as the dendritic cells (DCs) and the CD8+ T lymphocytes (CD8+ T cells). In this work, we present a CA model, which incorporates effects of the HIV specific immune response focusing on the cell-mediated immunities, and investigate the interaction between the host immune response and the HIV infected cells in the lymph nodes. The aim of our work is to propose a model more realistic than the one in Precharattana et al. (2010) [10], by incorporating roles of the DCs, the CD4+ T cells, and the CD8+ T cells into the model so that it would reproduce the HIV infection dynamics during the primary phase of HIV infection.

  6. 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

  7. A cellular automata model of epidemics of a heterogeneous susceptibility

    Institute of Scientific and Technical Information of China (English)

    Jin Zhen; Liu Quan-Xing

    2006-01-01

    In this paper we present a model with spatial heterogeneity based on cellular automata (CA). In the model we consider the relevant heterogeneity of host (susceptible) mixing and the natural birth rate. We divide the susceptible population into three groups according to the immunity of each individual based on the classical susceptible-infectedremoved (SIR) epidemic models, and consider the spread of an infectious disease transmitted by direct contact among humans and vectors that have not an incubation period to become infectious. We test the local stability and instability of the disease-free equilibrium by the spectrum radii of Jacobian. The simulation shows that the structure of the nearest neighbour size of the cell (or the degree of the scale-free networks) plays a very important role in the spread properties of infectious disease. The positive equilibrium of the infections versus the neighbour size follows the third power law if an endemic equilibrium point exists. Finally, we analyse the feature of the infection waves for the homogeneity and heterogeneous cases respectively.

  8. Modeling psychiatric disorders: from genomic findings to cellular phenotypes

    Science.gov (United States)

    Falk, A; Heine, V M; Harwood, A J; Sullivan, P F; Peitz, M; Brüstle, O; Shen, S; Sun, Y-M; Glover, J C; Posthuma, D; Djurovic, S

    2016-01-01

    Major programs in psychiatric genetics have identified >150 risk loci for psychiatric disorders. These loci converge on a small number of functional pathways, which span conventional diagnostic criteria, suggesting a partly common biology underlying schizophrenia, autism and other psychiatric disorders. Nevertheless, the cellular phenotypes that capture the fundamental features of psychiatric disorders have not yet been determined. Recent advances in genetics and stem cell biology offer new prospects for cell-based modeling of psychiatric disorders. The advent of cell reprogramming and induced pluripotent stem cells (iPSC) provides an opportunity to translate genetic findings into patient-specific in vitro models. iPSC technology is less than a decade old but holds great promise for bridging the gaps between patients, genetics and biology. Despite many obvious advantages, iPSC studies still present multiple challenges. In this expert review, we critically review the challenges for modeling of psychiatric disorders, potential solutions and how iPSC technology can be used to develop an analytical framework for the evaluation and therapeutic manipulation of fundamental disease processes. PMID:27240529

  9. A Computational model for compressed sensing RNAi cellular screening

    Science.gov (United States)

    2012-01-01

    Background RNA interference (RNAi) becomes an increasingly important and effective genetic tool to study the function of target genes by suppressing specific genes of interest. This system approach helps identify signaling pathways and cellular phase types by tracking intensity and/or morphological changes of cells. The traditional RNAi screening scheme, in which one siRNA is designed to knockdown one specific mRNA target, needs a large library of siRNAs and turns out to be time-consuming and expensive. Results In this paper, we propose a conceptual model, called compressed sensing RNAi (csRNAi), which employs a unique combination of group of small interfering RNAs (siRNAs) to knockdown a much larger size of genes. This strategy is based on the fact that one gene can be partially bound with several small interfering RNAs (siRNAs) and conversely, one siRNA can bind to a few genes with distinct binding affinity. This model constructs a multi-to-multi correspondence between siRNAs and their targets, with siRNAs much fewer than mRNA targets, compared with the conventional scheme. Mathematically this problem involves an underdetermined system of equations (linear or nonlinear), which is ill-posed in general. However, the recently developed compressed sensing (CS) theory can solve this problem. We present a mathematical model to describe the csRNAi system based on both CS theory and biological concerns. To build this model, we first search nucleotide motifs in a target gene set. Then we propose a machine learning based method to find the effective siRNAs with novel features, such as image features and speech features to describe an siRNA sequence. Numerical simulations show that we can reduce the siRNA library to one third of that in the conventional scheme. In addition, the features to describe siRNAs outperform the existing ones substantially. Conclusions This csRNAi system is very promising in saving both time and cost for large-scale RNAi screening experiments which

  10. Stochastic cellular automata model for stock market dynamics

    Science.gov (United States)

    Bartolozzi, M.; Thomas, A. W.

    2004-04-01

    In the present work we introduce a stochastic cellular automata model in order to simulate the dynamics of the stock market. A direct percolation method is used to create a hierarchy of clusters of active traders on a two-dimensional grid. Active traders are characterized by the decision to buy, σi (t)=+1 , or sell, σi (t)=-1 , a stock at a certain discrete time step. The remaining cells are inactive, σi (t)=0 . The trading dynamics is then determined by the stochastic interaction between traders belonging to the same cluster. Extreme, intermittent events, such as crashes or bubbles, are triggered by a phase transition in the state of the bigger clusters present on the grid, where almost all the active traders come to share the same spin orientation. Most of the stylized aspects of the financial market time series, including multifractal proprieties, are reproduced by the model. A direct comparison is made with the daily closures of the S&P500 index.

  11. A Computational Model of Cellular Engraftment on Lung Scaffolds

    Directory of Open Access Journals (Sweden)

    Joshua J. Pothen

    2016-10-01

    Full Text Available The possibility that stem cells might be used to regenerate tissue is now being investigated for a variety of organs, but these investigations are still essentially exploratory and have few predictive tools available to guide experimentation. We propose, in this study, that the field of lung tissue regeneration might be better served by predictive tools that treat stem cells as agents that obey certain rules of behavior governed by both their phenotype and their environment. Sufficient knowledge of these rules of behavior would then, in principle, allow lung tissue development to be simulated computationally. Toward this end, we developed a simple agent-based computational model to simulate geographic patterns of cells seeded onto a lung scaffold. Comparison of the simulated patterns to those observed experimentally supports the hypothesis that mesenchymal stem cells proliferate preferentially toward the scaffold boundary, whereas alveolar epithelial cells do not. This demonstrates that a computational model of this type has the potential to assist in the discovery of rules of cellular behavior

  12. Cortical factor feedback model for cellular locomotion and cytofission.

    Directory of Open Access Journals (Sweden)

    Shin I Nishimura

    2009-03-01

    Full Text Available Eukaryotic cells can move spontaneously without being guided by external cues. For such spontaneous movements, a variety of different modes have been observed, including the amoeboid-like locomotion with protrusion of multiple pseudopods, the keratocyte-like locomotion with a widely spread lamellipodium, cell division with two daughter cells crawling in opposite directions, and fragmentations of a cell to multiple pieces. Mutagenesis studies have revealed that cells exhibit these modes depending on which genes are deficient, suggesting that seemingly different modes are the manifestation of a common mechanism to regulate cell motion. In this paper, we propose a hypothesis that the positive feedback mechanism working through the inhomogeneous distribution of regulatory proteins underlies this variety of cell locomotion and cytofission. In this hypothesis, a set of regulatory proteins, which we call cortical factors, suppress actin polymerization. These suppressing factors are diluted at the extending front and accumulated at the retracting rear of cell, which establishes a cellular polarity and enhances the cell motility, leading to the further accumulation of cortical factors at the rear. Stochastic simulation of cell movement shows that the positive feedback mechanism of cortical factors stabilizes or destabilizes modes of movement and determines the cell migration pattern. The model predicts that the pattern is selected by changing the rate of formation of the actin-filament network or the threshold to initiate the network formation.

  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 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

  15. Modeling of coupled differential equations for cellular chemical signaling pathways: Implications for assay protocols utilized in cellular engineering.

    Science.gov (United States)

    O'Clock, George D

    2016-08-01

    Cellular engineering involves modification and control of cell properties, and requires an understanding of fundamentals and mechanisms of action for cellular derived product development. One of the keys to success in cellular engineering involves the quality and validity of results obtained from cell chemical signaling pathway assays. The accuracy of the assay data cannot be verified or assured if the effect of positive feedback, nonlinearities, and interrelationships between cell chemical signaling pathway elements are not understood, modeled, and simulated. Nonlinearities and positive feedback in the cell chemical signaling pathway can produce significant aberrations in assay data collection. Simulating the pathway can reveal potential instability problems that will affect assay results. A simulation, using an electrical analog for the coupled differential equations representing each segment of the pathway, provides an excellent tool for assay validation purposes. With this approach, voltages represent pathway enzyme concentrations and operational amplifier feedback resistance and input resistance values determine pathway gain and rate constants. The understanding provided by pathway modeling and simulation is strategically important in order to establish experimental controls for assay protocol structure, time frames specified between assays, and assay concentration variation limits; to ensure accuracy and reproducibility of results.

  16. 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.

  17. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    Science.gov (United States)

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

  18. Computational energetic model of morphogenesis based on multi-agent Cellular Potts Model.

    Science.gov (United States)

    Tripodi, Sébastien; Ballet, Pascal; Rodin, Vincent

    2010-01-01

    The Cellular Potts Model (CPM) is a cellular automaton (CA), developed by Glazier and Graner in 1992, to model the morphogenesis. In this model, the entities are the cells. It has already been improved in many ways; however, a key point in biological systems, not defined in CPM, is energetic exchange between entities. We integrate this energetic concept inside the CPM. We simulate a cell differentiation inside a growing cell tissue. The results are the emergence of dynamic patterns coming from the consumption and production of energy. A model described by CA is less scalable than one described by a multi-agent system (MAS). We have developed a MAS based on the CPM, where a cell agent is implemented from the cell of CPM together with several behaviours, in particular the consumption and production of energy from the consumption of molecules.

  19. Simple Cellular Automata-Based Linear Models for the Shrinking Generator

    CERN Document Server

    Fúster-Sabater, Amparo

    2010-01-01

    Structural properties of two well-known families of keystream generators, Shrinking Generators and Cellular Automata, have been analyzed. Emphasis is on the equivalence of the binary sequences obtained from both kinds of generators. In fact, Shrinking Generators (SG) can be identified with a subset of linear Cellular Automata (mainly rule 90, rule 150 or a hybrid combination of both rules). The linearity of these cellular models can be advantageously used in the cryptanalysis of those keystream generators.

  20. 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...

  1. 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.

  2. Development of three-dimensional collagen scaffolds with controlled architecture for cell migration studies using breast cancer cell lines.

    Science.gov (United States)

    Campbell, Jonathan J; Husmann, Anke; Hume, Robert D; Watson, Christine J; Cameron, Ruth E

    2017-01-01

    Cancer is characterized by cell heterogeneity and the development of 3D in vitro assays that can distinguish more invasive or migratory phenotypes could enhance diagnosis or drug discovery. 3D collagen scaffolds have been used to develop analogues of complex tissues in vitro and are suited to routine biochemical and immunological assays. We sought to increase 3D model tractability and modulate the migration rate of seeded cells using an ice-templating technique to create either directional/anisotropic or non-directional/isotropic porous architectures within cross-linked collagen scaffolds. Anisotropic scaffolds supported the enhanced migration of an invasive breast cancer cell line MDA-MB-231 with an altered spatial distribution of proliferative cells in contrast to invasive MDA-MB-468 and non-invasive MCF-7 cells lines. In addition, MDA-MB-468 showed increased migration upon epithelial-to-mesenchymal transition (EMT) in anisotropic scaffolds. The provision of controlled architecture in this system may act both to increase assay robustness and as a tuneable parameter to capture detection of a migrated population within a set time, with consequences for primary tumour migration analysis. The separation of invasive clones from a cancer biomass with in vitro platforms could enhance drug development and diagnosis testing by contributing assay metrics including migration rate, as well as modelling cell-cell and cell-matrix interaction in a system compatible with routine histopathological testing.

  3. 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.

  4. Sorafenib analogue SC-60 induces apoptosis through the SHP-1/STAT3 pathway and enhances docetaxel cytotoxicity in triple-negative breast cancer cells.

    Science.gov (United States)

    Liu, Chun-Yu; Su, Jung-Chen; Huang, Tzu-Ting; Chu, Pei-Yi; Huang, Chun-Teng; Wang, Wan-Lun; Lee, Chia-Han; Lau, Ka-Yi; Tsai, Wen-Chun; Yang, Hsiu-Ping; Shiau, Chung-Wai; Tseng, Ling-Ming; Chen, Kuen-Feng

    2017-03-01

    Recurrent triple-negative breast cancer (TNBC) needs new therapeutic targets. Src homology region 2 domain-containing phosphatase-1 (SHP-1) can act as a tumor suppressor by dephosphorylating oncogenic kinases. One major target of SHP-1 is STAT3, which is highly activated in TNBC. In this study, we tested a sorafenib analogue SC-60, which lacks angiokinase inhibition activity, but acts as a SHP-1 agonist, in TNBC cells. SC-60 inhibited proliferation and induced apoptosis by dephosphorylating STAT3 in both a dose- and time-dependent manner in TNBC cells (MDA-MB-231, MDA-MB-468, and HCC1937). By contrast, ectopic expression of STAT3 rescued the anticancer effect induced by SC-60. SC-60 also increased the SHP-1 activity, but this effect was inhibited when the N-SH2 domain (DN1) was deleted or with SHP-1 point mutation (D61A), implying that SHP-1 is the major target of SC-60 in TNBC. The use of SC-60 in combination with docetaxel synergized the anticancer effect induced by SC-60 through the SHP-1/STAT3 pathway in TNBC cells. Importantly, SC-60 also displayed a significant antitumor effect in an MDA-MB-468 xenograft model by modulating the SHP-1/STAT3 axis, indicating the anticancer potential of SC-60 in TNBC treatment. Targeting SHP-1/p-STAT3 and the potential combination of SHP-1 agonist with chemotherapeutic docetaxel is a feasible therapeutic strategy for TNBC.

  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. 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

  7. 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...

  8. 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.

  9. Modeling collective & intelligent decision making of multi-cellular populations.

    Science.gov (United States)

    Shin, Yong-Jun; Mahrou, Bahareh

    2014-01-01

    In the presence of unpredictable disturbances and uncertainties, cells intelligently achieve their goals by sharing information via cell-cell communication and making collective decisions, which are more reliable compared to individual decisions. Inspired by adaptive sensor network algorithms studied in communication engineering, we propose that a multi-cellular adaptive network can convert unreliable decisions by individual cells into a more reliable cell-population decision. It is demonstrated using the effector T helper (a type of immune cell) population, which plays a critical role in initiating immune reactions in response to invading foreign agents (e.g., viruses, bacteria, etc.). While each individual cell follows a simple adaptation rule, it is the combined coordination among multiple cells that leads to the manifestation of "self-organizing" decision making via cell-cell communication.

  10. A cellular automata traffic flow modeling of desired speed variability

    Institute of Scientific and Technical Information of China (English)

    K.Bentaleb; K.Jetto; H.Ez-Zahraouy; A.Benyoussef

    2013-01-01

    The satisfaction rate of desired velocity in the case of a mixture of fast and slow vehicles is studied by using a cellular automaton method.It is found that at low density the satisfaction rate depends on the maximal velocity.However,the behavior of the satisfaction rate as a function of the coefficient of variance is independent of the maximal velocity.This is in good agreement with empirical results obtained by Lipshtat [Phys.Rev.E 79 066110 (2009)].Furthermore,our numerical result demonstrates that at low density the satisfaction rate takes higher values,whereas the coefficient of variance is close to zero.The coefficient of variance increases with increasing density,while the satisfaction rate decreases to zero.Moreover,we have also shown that,at low density the coefficient variance depends strongly on the probability of overtaking.

  11. 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.

  12. A multiscale theoretical model for diffusive mass transfer in cellular biological media.

    Science.gov (United States)

    Kapellos, George E; Alexiou, Terpsichori S; Payatakes, Alkiviades C

    2007-11-01

    An integrated methodology is developed for the theoretical analysis of solute transport and reaction in cellular biological media, such as tissues, microbial flocs, and biofilms. First, the method of local spatial averaging with a weight function is used to establish the equation which describes solute conservation at the cellular biological medium scale, starting with a continuum-based formulation of solute transport at finer spatial scales. Second, an effective-medium model is developed for the self-consistent calculation of the local diffusion coefficient in the cellular biological medium, including the effects of the structural heterogeneity of the extra-cellular space and the reversible adsorption to extra-cellular polymers. The final expression for the local effective diffusion coefficient is: D(Abeta)=lambda(beta)D(Aupsilon), where D(Aupsilon) is the diffusion coefficient in water, and lambda(beta) is a function of the composition and fundamental geometric and physicochemical system properties, including the size of solute molecules, the size of extra-cellular polymer fibers, and the mass permeability of the cell membrane. Furthermore, the analysis sheds some light on the function of the extra-cellular hydrogel as a diffusive barrier to solute molecules approaching the cell membrane, and its implications on the transport of chemotherapeutic agents within a cellular biological medium. Finally, the model predicts the qualitative trend as well as the quantitative variability of a large number of published experimental data on the diffusion coefficient of oxygen in cell-entrapping gels, microbial flocs, biofilms, and mammalian tissues.

  13. 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.

  14. 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.

  15. Establishment of a novel cellular model for myxofibrosarcoma heterogeneity

    Science.gov (United States)

    Lohberger, Birgit; Stuendl, Nicole; Leithner, Andreas; Rinner, Beate; Sauer, Stefan; Kashofer, Karl; Liegl-Atzwanger, Bernadette

    2017-01-01

    Human cancers frequently display substantial intra-tumoural heterogeneity in virtually all distinguishable phenotypic features, such as cellular morphology, gene expression, and metastatic potential. In order to investigate tumour heterogeneity in myxofibrosarcoma, we established a novel myxofibrosarcoma cell line with two well defined sub-clones named MUG-Myx2a and MUG-Myx2b. The parental tumour tissue and both MUG-Myx2 cell lines showed the same STR profile. The fact that MUG-Myx2a showed higher proliferation activity, faster migration and enhanced tumourigenicity was of particular interest. NGS mutation analysis revealed corresponding mutations in the FGFR3, KIT, KDR and TP53 genes. In contrast, the MUG-Myx2a cell lines showed an additional PTEN mutation. Analysis of CNV uncovered a highly aberrant karyotype with frequent losses and gains in the tumour sample. The two MUG-Myx2 cell lines share several CNV features of the tumour tissue, while some CNVs are present only in the two cell lines. Furthermore, certain CNV gains and losses that are exclusive to either MUG-Myx2a or MUG-Myx2b, distinguish the two cell lines. As it is currently not possible to purchase two different sarcoma cell lines derived from the same patient, the novel myxofibrosarcoma cell lines MUG-Myx2a and MUG-Myx2b will be useful tools to study pathogenesis, tumour heterogeneity and treatment options. PMID:28304377

  16. Logical Modeling and Dynamical Analysis of Cellular Networks.

    Science.gov (United States)

    Abou-Jaoudé, Wassim; Traynard, Pauline; Monteiro, Pedro T; Saez-Rodriguez, Julio; Helikar, Tomáš; Thieffry, Denis; Chaouiya, Claudine

    2016-01-01

    The logical (or logic) formalism is increasingly used to model regulatory and signaling networks. Complementing these applications, several groups contributed various methods and tools to support the definition and analysis of logical models. After an introduction to the logical modeling framework and to several of its variants, we review here a number of recent methodological advances to ease the analysis of large and intricate networks. In particular, we survey approaches to determine model attractors and their reachability properties, to assess the dynamical impact of variations of external signals, and to consistently reduce large models. To illustrate these developments, we further consider several published logical models for two important biological processes, namely the differentiation of T helper cells and the control of mammalian cell cycle.

  17. 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.

  18. Boolean network models of cellular regulation: prospects and limitations.

    Science.gov (United States)

    Bornholdt, Stefan

    2008-08-06

    Computer models are valuable tools towards an understanding of the cell's biochemical regulatory machinery. Possible levels of description of such models range from modelling the underlying biochemical details to top-down approaches, using tools from the theory of complex networks. The latter, coarse-grained approach is taken where regulatory circuits are classified in graph-theoretical terms, with the elements of the regulatory networks being reduced to simply nodes and links, in order to obtain architectural information about the network. Further, considering dynamics on networks at such an abstract level seems rather unlikely to match dynamical regulatory activity of biological cells. Therefore, it came as a surprise when recently examples of discrete dynamical network models based on very simplistic dynamical elements emerged which in fact do match sequences of regulatory patterns of their biological counterparts. Here I will review such discrete dynamical network models, or Boolean networks, of biological regulatory networks. Further, we will take a look at such models extended with stochastic noise, which allow studying the role of network topology in providing robustness against noise. In the end, we will discuss the interesting question of why at all such simple models can describe aspects of biology despite their simplicity. Finally, prospects of Boolean models in exploratory dynamical models for biological circuits and their mutants will be discussed.

  19. 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.

  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. 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.

  2. Individual Subjective Initiative Merge Model Based on Cellular Automaton

    Directory of Open Access Journals (Sweden)

    Yin-Jie Xu

    2013-01-01

    Full Text Available The merge control models proposed for work zones are classified into two types (Hard Control Merge (HCM model and Soft Control Merge (SCM model according to their own control intensity and are compared with a new model, called Individual Subjective Initiative Merge (ISIM model, which is based on the linear lane-changing probability strategy in the merging area. The attention of this paper is paid to the positive impact of the individual subjective initiative for the whole traffic system. Three models (ISIM, HCM, and SCM are established and compared with each other by two order parameters, that is, system output and average vehicle travel time. Finally, numerical results show that both ISIM and SCM perform better than HCM. Compared with SCM, the output of ISIM is 20 vehicles per hour higher under the symmetric input condition and is more stable under the asymmetric input condition. Meanwhile, the average travel time of ISIM is 2000 time steps less under the oversaturated input condition.

  3. Macromolecular Chain at a Cellular Surface: a Computer Simulation Model

    Science.gov (United States)

    Xie, Jun; Pandey, Ras

    2001-06-01

    Computer simulations are performed to study conformation and dynamics of relatively large chain macromolecule at the surface of a model cell membrane - a preliminary attempt to ultimately realistic model for protein on a cell membrane. We use a discrete lattice of size Lx × L × L. The chain molecule of length Lc is modelled by consecutive nodes connected by bonds on the trail of a random walk with appropriate constraints such as excluded volume, energy dependent configurational bias, etc. Monte Carlo method is used to move chains via segmental dynamics, i.e., end-move, kink-jump, crank-shaft, reptation, etc. Membrane substrate is designed by an ensemble of short chains on a flat surface. Large chain molecule is then driven toward the membrane by a field. We plan to examine the dynamics of chain macromolecule, spread of its density, and its conformation.

  4. Dynamical modeling and analysis of large cellular regulatory networks

    Science.gov (United States)

    Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.

    2013-06-01

    The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

  5. Mechanism involved in the UCB neurotoxicity on cellular models

    OpenAIRE

    Giraudi, Pablo Jose'

    2009-01-01

    Summary This doctoral thesis covers three years period (2006-2008) during which I have investigated the bilirubin neurotoxicity in the neuroblastoma SH-SY5Y cell line, a neuronal cell model widely used in the study of the pathogenesis and in the development of new therapeutic compounds for neurodegenerative diseases. In the first chapter is summarized the current knowledge about bilirubin chemistry and metabolism including disorders of bilirubin metabolism and the neuronal disturbanc...

  6. Generic framework for mining cellular automata models on protein-folding simulations.

    Science.gov (United States)

    Diaz, N; Tischer, I

    2016-05-13

    Cellular automata model identification is an important way of building simplified simulation models. In this study, we describe a generic architectural framework to ease the development process of new metaheuristic-based algorithms for cellular automata model identification in protein-folding trajectories. Our framework was developed by a methodology based on design patterns that allow an improved experience for new algorithms development. The usefulness of the proposed framework is demonstrated by the implementation of four algorithms, able to obtain extremely precise cellular automata models of the protein-folding process with a protein contact map representation. Dynamic rules obtained by the proposed approach are discussed, and future use for the new tool is outlined.

  7. 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.

  8. 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.

  9. A cellular automata intraurban model with prices and income-differentiated actors

    NARCIS (Netherlands)

    Furtado, B.A.; Ettema, D.F.; Ruiz, R.M.; Hurkens, J.; Delden, H. van

    2012-01-01

    This paper presents an intraurban cellular automata model that is an extension to White and Engelen’s pioneering model. The paper’s main contribution is to distinguish between agglomerative eff ects, determined by the attraction of the neighbourhood, and disagglomerative eff ects, driven by land pri

  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. Quantitative model of cell cycle arrest and cellular senescence in primary human fibroblasts.

    Directory of Open Access Journals (Sweden)

    Sascha Schäuble

    Full Text Available Primary human fibroblasts in tissue culture undergo a limited number of cell divisions before entering a non-replicative "senescent" state. At early population doublings (PD, fibroblasts are proliferation-competent displaying exponential growth. During further cell passaging, an increasing number of cells become cell cycle arrested and finally senescent. This transition from proliferating to senescent cells is driven by a number of endogenous and exogenous stress factors. Here, we have developed a new quantitative model for the stepwise transition from proliferating human fibroblasts (P via reversibly cell cycle arrested (C to irreversibly arrested senescent cells (S. In this model, the transition from P to C and to S is driven by a stress function γ and a cellular stress response function F which describes the time-delayed cellular response to experimentally induced irradiation stress. The application of this model based on senescence marker quantification at the single-cell level allowed to discriminate between the cellular states P, C, and S and delivers the transition rates between the P, C and S states for different human fibroblast cell types. Model-derived quantification unexpectedly revealed significant differences in the stress response of different fibroblast cell lines. Evaluating marker specificity, we found that SA-β-Gal is a good quantitative marker for cellular senescence in WI-38 and BJ cells, however much less so in MRC-5 cells. Furthermore we found that WI-38 cells are more sensitive to stress than BJ and MRC-5 cells. Thus, the explicit separation of stress induction from the cellular stress response, and the differentiation between three cellular states P, C and S allows for the first time to quantitatively assess the response of primary human fibroblasts towards endogenous and exogenous stress during cellular ageing.

  12. Interaction of tea tree oil with model and cellular membranes.

    Science.gov (United States)

    Giordani, Cristiano; Molinari, Agnese; Toccacieli, Laura; Calcabrini, Annarica; Stringaro, Annarita; Chistolini, Pietro; Arancia, Giuseppe; Diociaiuti, Marco

    2006-07-27

    Tea tree oil (TTO) is the essential oil steam-distilled from Melaleuca alternifolia, a species of northern New South Wales, Australia. It exhibits a broad-spectrum antimicrobial activity and an antifungal activity. Only recently has TTO been shown to inhibit the in vitro growth of multidrug resistant (MDR) human melanoma cells. It has been suggested that the effect of TTO on tumor cells could be mediated by its interaction with the plasma membrane, most likely by inducing a reorganization of lipid architecture. In this paper we report biophysical and structural results obtained using simplified planar model membranes (Langmuir films) mimicking lipid "rafts". We also used flow cytometry analysis (FCA) and freeze-fracturing transmission electron microscopy to investigate the effects of TTO on actual MDR melanoma cell membranes. Thermodynamic (compression isotherms and adsorption kinetics) and structural (Brewster angle microscopy) investigation of the lipid monolayers clearly indicates that TTO interacts preferentially with the less ordered DPPC "sea" and that it does not alter the more ordered lipid "rafts". Structural observations, performed by freeze fracturing, confirm that TTO interacts with the MDR melanoma cell plasma membrane. Moreover, experiments performed by FCA demonstrate that TTO does not interfere with the function of the MDR drug transporter P-gp. We therefore propose that the effect exerted on MDR melanoma cells is mediated by the interaction with the fluid DPPC phase, rather than with the more organized "rafts" and that this interaction preferentially influences the ATP-independent antiapoptotic activity of P-gp likely localized outside "rafts".

  13. Reverse engineering cellular decisions for hybrid reconfigurable network modeling

    Science.gov (United States)

    Blair, Howard A.; Saranak, Jureepan; Foster, Kenneth W.

    2011-06-01

    Cells as microorganisms and within multicellular organisms make robust decisions. Knowing how these complex cells make decisions is essential to explain, predict or mimic their behavior. The discovery of multi-layer multiple feedback loops in the signaling pathways of these modular hybrid systems suggests their decision making is sophisticated. Hybrid systems coordinate and integrate signals of various kinds: discrete on/off signals, continuous sensory signals, and stochastic and continuous fluctuations to regulate chemical concentrations. Such signaling networks can form reconfigurable networks of attractors and repellors giving them an extra level of organization that has resilient decision making built in. Work on generic attractor and repellor networks and on the already identified feedback networks and dynamic reconfigurable regulatory topologies in biological cells suggests that biological systems probably exploit such dynamic capabilities. We present a simple behavior of the swimming unicellular alga Chlamydomonas that involves interdependent discrete and continuous signals in feedback loops. We show how to rigorously verify a hybrid dynamical model of a biological system with respect to a declarative description of a cell's behavior. The hybrid dynamical systems we use are based on a unification of discrete structures and continuous topologies developed in prior work on convergence spaces. They involve variables of discrete and continuous types, in the sense of type theory in mathematical logic. A unification such as afforded by convergence spaces is necessary if one wants to take account of the affect of the structural relationships within each type on the dynamics of the system.

  14. The natural alternative: protozoa as cellular models for Legionella infection.

    Science.gov (United States)

    Hoffmann, Christine; Harrison, Christopher F; Hilbi, Hubert

    2014-01-01

    The severe pneumonia known as Legionnaires' disease occurs following infection by the Gram-negative bacterium Legionella pneumophila. Normally resident in fresh-water sources, Legionella are subject to predation by eukaryotic phagocytes such as amoeba and ciliates. To counter this, L. pneumophila has evolved a complex system of effector proteins which allow the bacteria to hijack the phagocytic vacuole, hiding and replicating within their erstwhile killers. These same mechanisms allow L. pneumophila to hijack another phagocyte, lung-based macrophages, which thus avoids a vital part of the immune system and leads to infection. The course of infection can be divided into five main categories: pathogen uptake, formation of the replication-permissive vacuole, intracellular replication, host cell response, and bacterial exit. L. pneumophila effector proteins target every stage of this process, interacting with secretory, endosomal, lysosomal, retrograde and autophagy pathways, as well as with mitochondria. Each of these steps can be studied in protozoa or mammalian cells, and the knowledge gained can be readily applied to human pathogenicity. Here we describe the manner whereby L. pneumophila infects host protozoa, the various techniques which are available to analyse these processes and the implications of this model for Legionella virulence and the pathogenesis of Legionnaires' disease.

  15. Evaluation of BACE1 Silencing in Cellular Models

    Directory of Open Access Journals (Sweden)

    Malgorzata Sierant

    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.

  16. 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].

  17. Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

    Directory of Open Access Journals (Sweden)

    Jinpeng Qi

    Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

  18. Use of hybrid discrete cellular models for identification of macroscopic nutrient loss in reaction-diffusion models of tissues.

    Science.gov (United States)

    Aristotelous, Andreas C; Haider, Mansoor A

    2014-08-01

    Macroscopic models accounting for cellular effects in natural or engineered tissues may involve unknown constitutive terms that are highly dependent on interactions at the scale of individual cells. Hybrid discrete models, which represent cells individually, were used to develop and apply techniques for modeling diffusive nutrient transport and cellular uptake to identify a nonlinear nutrient loss term in a macroscopic reaction-diffusion model of the system. Flexible and robust numerical methods were used, based on discontinuous Galerkin finite elements in space and a Crank-Nicolson temporal discretization. Scales were bridged via averaging operations over a complete set of subdomains yielding data for identification of a macroscopic nutrient loss term that was accurately captured via a fifth-order polynomial. Accuracy of the identified macroscopic model was demonstrated by direct, quantitative comparisons of the tissue and cellular scale models in terms of three error norms computed on a mesoscale mesh.

  19. Solving the Advection-Diffusion Equations in Biological Contexts using the Cellular Potts Model

    CERN Document Server

    Dan, D; Chen, K; Glazier, J A; Dan, Debasis; Mueller, Chris; Chen, Kun; Glazier, James A.

    2005-01-01

    The Cellular Potts Model (CPM) is a robust, cell-level methodology for simulation of biological tissues and morphogenesis. Both tissue physiology and morphogenesis depend on diffusion of chemical morphogens in the extra-cellular fluid or matrix (ECM). Standard diffusion solvers applied to the cellular potts model use finite difference methods on the underlying CPM lattice. However, these methods produce a diffusing field tied to the underlying lattice, which is inaccurate in many biological situations in which cell or ECM movement causes advection rapid compared to diffusion. Finite difference schemes suffer numerical instabilities solving the resulting advection-diffusion equations. To circumvent these problems we simulate advection-diffusion within the framework of the CPM using off-lattice finite-difference methods. We define a set of generalized fluid particles which detach advection and diffusion from the lattice. Diffusion occurs between neighboring fluid particles by local averaging rules which approxi...

  20. 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.

  1. Calibrating floor field cellular automaton models for pedestrian dynamics by using likelihood function optimization

    Science.gov (United States)

    Lovreglio, Ruggiero; Ronchi, Enrico; Nilsson, Daniel

    2015-11-01

    The formulation of pedestrian floor field cellular automaton models is generally based on hypothetical assumptions to represent reality. This paper proposes a novel methodology to calibrate these models using experimental trajectories. The methodology is based on likelihood function optimization and allows verifying whether the parameters defining a model statistically affect pedestrian navigation. Moreover, it allows comparing different model specifications or the parameters of the same model estimated using different data collection techniques, e.g. virtual reality experiment, real data, etc. The methodology is here implemented using navigation data collected in a Virtual Reality tunnel evacuation experiment including 96 participants. A trajectory dataset in the proximity of an emergency exit is used to test and compare different metrics, i.e. Euclidean and modified Euclidean distance, for the static floor field. In the present case study, modified Euclidean metrics provide better fitting with the data. A new formulation using random parameters for pedestrian cellular automaton models is also defined and tested.

  2. 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

  3. A coarse-grained model for the simulations of biomolecular interactions in cellular environments

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Zhong-Ru; Chen, Jiawen; Wu, Yinghao, E-mail: yinghao.wu@einstein.yu.edu [Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461 (United States)

    2014-02-07

    The interactions of bio-molecules constitute the key steps of cellular functions. However, in vivo binding properties differ significantly from their in vitro measurements due to the heterogeneity of cellular environments. Here we introduce a coarse-grained model based on rigid-body representation to study how factors such as cellular crowding and membrane confinement affect molecular binding. The macroscopic parameters such as the equilibrium constant and the kinetic rate constant are calibrated by adjusting the microscopic coefficients used in the numerical simulations. By changing these model parameters that are experimentally approachable, we are able to study the kinetic and thermodynamic properties of molecular binding, as well as the effects caused by specific cellular environments. We investigate the volumetric effects of crowded intracellular space on bio-molecular diffusion and diffusion-limited reactions. Furthermore, the binding constants of membrane proteins are currently difficult to measure. We provide quantitative estimations about how the binding of membrane proteins deviates from soluble proteins under different degrees of membrane confinements. The simulation results provide biological insights to the functions of membrane receptors on cell surfaces. Overall, our studies establish a connection between the details of molecular interactions and the heterogeneity of cellular environments.

  4. Modeling the shrub encroachment in the Northern Chihuahuan desert Grasslands using a Cellular Automata model

    Science.gov (United States)

    Caracciolo, Domenico; Istanbulluoglu, Erkan; Noto, Leonardo V.

    2014-05-01

    Arid grasslands of southwestern North America have changed dramatically over the last 150 years as a result of the shrub encroachment, i.e. the increase in density and biomass of indigenous shrubby plants in grasslands. Numerous studies have documented the expansion of shrublands in the southwestern America Grasslands; in particular the encroachment of shrubs in american deserts has strongly occurred in the Chihuahuan deserts from 1860. The Sevilleta National Wildlife Refuge (SNWR), located in the northern Chihuahuan desert shows a dramatic encroachment front of creosote bush (i.e., shrub) into native desert grassland. This encroachment has been here simulated using an Ecohydrological Cellular Automata Model, CATGraSS. CATGraSS is a spatially distributed model driven by spatially explicit irradiance and runs on a fine-resolution gridded domain. In the model, each cell can hold a single plant type or can represent bare soil. Plant competition is modeled by keeping track of mortality and establishment of plants, both calculated probabilistically based on soil moisture stress. For this study, the model is improved with a stochastic fire and a grazing function, and its plant establishment algorithm is modified. CATGraSS is implemented in a small area (7.3 km2) in SNWR, characterized by two vegetation types: grass savanna and creosote bush. The causes that have been considered for the encroachment in this case study are: the fire return period increase, the grazing increase, the seed dispersal caused by animals, the role of wind direction and the shrub-grass inhibition effect. The model is able to reproduce the encroachment occurred in the SNWR basin, simulating an increasing of the shrub from 2% in 1860 to 42% (i.e., current shrub percentage) in 2010 highlighting as more influent factors the reduced fire frequency and the increased grazing intensity. For the future management and encroachment control, the reduction of the fire return period and the grazing removal

  5. 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.

  6. Two-dimensional cellular automaton model of traffic flow with open boundaries

    CERN Document Server

    Tadaki, S I

    1996-01-01

    A two-dimensional cellular automaton model of traffic flow with open boundaries are investigated by computer simulations. The outflow of cars from the system and the average velocity are investigated. The time sequences of the outflow and average velocity have flicker noises in a jamming phase. The low density behavior are discussed with simple jam-free approximation.

  7. A mathematical model representing cellular immune development and response to Salmonella of chicken intestinal tissue

    NARCIS (Netherlands)

    Schokker, D.; Bannink, A.; Smits, M.A.; Rebel, J.M.J.

    2013-01-01

    The aim of this study was to create a dynamic mathematical model of the development of the cellular branch of the intestinal immune system of poultry during the first 42 days of life and of its response towards an oral infection with Salmonella enterica serovar Enteritidis. The system elements were

  8. 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

  9. Performance Evaluation of Road Traffic Control Using a Fuzzy Cellular Model

    CERN Document Server

    Płaczek, Bartłomiej

    2011-01-01

    In this paper a method is proposed for performance evaluation of road traffic control systems. The method is designed to be implemented in an on-line simulation environment, which enables optimisation of adaptive traffic control strategies. Performance measures are computed using a fuzzy cellular traffic model, formulated as a hybrid system combining cellular automata and fuzzy calculus. Experimental results show that the introduced method allows the performance to be evaluated using imprecise traffic measurements. Moreover, the fuzzy definitions of performance measures are convenient for uncertainty determination in traffic control decisions.

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

    KAUST Repository

    Elsawy, Hesham

    2016-11-03

    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 baseline single-tier downlink cellular network with single antenna base stations and universal frequency reuse. Then, it characterizes signal-to-interference-plus-noise-ratio (SINR) and its related performance metrics. In particular, a unified approach to conduct error probability, outage probability, and transmission 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 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. To this end, the paper highlights the state-of-the- art research and points out future research directions.

  11. Antitumor effects of naturally occurring cardiac glycosides convallatoxin and peruvoside on human ER+ and triple-negative breast cancers

    Science.gov (United States)

    Kaushik, Vivek; Azad, Neelam; Yakisich, Juan Sebastian; Iyer, Anand Krishnan V

    2017-01-01

    Breast cancer is second most prevalent cancer in women, and the second only to lung cancer in cancer-related deaths. It is a heterogeneous disease and has several subtypes based on the presence or absence of hormone receptors and/or human epidermal growth factor receptor 2 (HER2). Hormone receptor-positive and HER2-enriched cancers can be targeted using hormone and HER2-targeting therapies such as trastuzumab or lapatinib. However, triple-negative breast cancers (TNBCs) do not express any of the receptors and therefore are resistant to most targeted therapies, and cytotoxic chemotherapies are the only viable option available for the treatment of TNBCs. Recently, cardiac glycosides (CGs) have emerged as potential anticancer agents that impart their antiproliferative effect by targeting multiple pathways. In this study our aim was to evaluate anticancer effects of two naturally occurring CGs, Convallatoxin (CT) and Peruvoside (PS), on ER+ and TNBCs cells. CT and PS demonstrated dose- and time-dependent cytotoxic effect on MCF-7 cells, which was further supported by loss of colony formation on drug treatment. CT and PS arrested MCF-7 cells in the G0/G1 phase and reduced the viability of MCF-7-derived mammospheres (MMs). Interestingly, while CT and PS imparted cell death in TNBCs cells from both Caucasians (MDA-MB-231 cells) and African Americans (MDA-MB-468 cells) in a dose- and time-dependent manner, the drugs were much more potent in MDA-MB-468 as compared with TNBC MDA-MB-231 cells. Both drugs significantly inhibited migration and invasion of both MCF-7 and MDA-MB-468 cells. An assessment of intracellular pathways indicated that both drugs were able to modulate several key cellular pathways such as EMT, cell cycle, proliferation and cell death in both cell types. Our data suggest a promising role for CGs in breast cancer treatment specifically in targeting TNBCs derived from African Americans, and provides impetus for further investigation of the anticancer

  12. 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.

  13. Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

    Science.gov (United States)

    Johnson, Lee James

    2001-08-01

    The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is

  14. Protective Role of Endogenous Gangliosides for Lysosomal Pathology in a Cellular Model of Synucleinopathies

    OpenAIRE

    Wei, Jianshe; Fujita, Masayo; Nakai, Masaaki; Waragai, Masaaki; Sekigawa, Akio; Sugama, Shuei; Takenouchi, Takato; Masliah, Eliezer; Hashimoto,Makoto

    2009-01-01

    Gangliosides may be involved in the pathogenesis of Parkinson’s disease and related disorders, although the precise mechanisms governing this involvement remain unknown. In this study, we determined whether changes in endogenous ganglioside levels affect lysosomal pathology in a cellular model of synucleinopathy. For this purpose, dementia with Lewy body-linked P123H β-synuclein (β-syn) neuroblastoma cells transfected with α-synuclein were used as a model system because these cells were chara...

  15. Modeling Recrystallization of Austenite for C-Mn Steels during Hot Deformation by Cellular Automaton

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    By using a cellular automaton method, microstructure evolution of recrystallization in austenite during hot deformation was simulated for C-Mn steels. A model takes into account the influence of deformation temperature, strain, and strain rate on the dynamic recrystallization fraction, and the effect of the keeping time on the static recrystallization fraction based on a hot deformation test on a Gleeble-1500 simulator. In addition, the size changing of γ grains during continuous hot deformation was simulated by applying the model.

  16. Cellular Automaton Rule 184++C A Simple Model for the Complex Dynamics of Various Particles Flow

    CERN Document Server

    Awazu, A

    1999-01-01

    A cellular automaton named Rule 184++C is proposed as a meta-model to investigate the flow of various complex particles. In this model, unlike the granular pipe flow and the traffic flow, not only the free-jam phase transition but also the free-intermediate, the intermediate-jam, and the dilute-dense phase transitions appear. Moreover, the freezing phenomena appear if the system contains two types of different particles.

  17. A nonstandard finite difference scheme for a basic model of cellular immune response to viral infection

    Science.gov (United States)

    Korpusik, Adam

    2017-02-01

    We present a nonstandard finite difference scheme for a basic model of cellular immune response to viral infection. The main advantage of this approach is that it preserves the essential qualitative features of the original continuous model (non-negativity and boundedness of the solution, equilibria and their stability conditions), while being easy to implement. All of the qualitative features are preserved independently of the chosen step-size. Numerical simulations of our approach and comparison with other conventional simulation methods are presented.

  18. Dunes morphologies and superimposed bedforms in a cellular automaton dune model

    Science.gov (United States)

    Zhang, D.; Narteau, C.; Rozier, O.; Claudin, P.

    2009-04-01

    We use a new 3D cellular automaton model for bedform dynamics in which individual physical processes such as erosion, deposition and transport are implemented by nearest neighbor interactions and a time-dependent stochastic process. Simultaneously, a lattice gas cellular automaton model is used to compute the flow and quantify the bed shear stress on the topography. Local erosion rates are taken proportional to the shear stress in such a way that there is a complete feedback mechanism between flow and bedform dynamics. In the numerical simulations of dune fields, we observe the formation and the evolution of barchan, transverse, longitudinal and star dunes. For all these types of dunes, we observe the emergence of superimposed bedforms when dunes are large enough. Then, we use the same model under different initial conditions, and we perform the linear stability analysis of a flat sand bed disturbed by a small sinusoidal perturbation. Comparing the most unstable wavelength in the model with the characteristic size of secondary bedforms in nature, we determine the length and time scales of our cellular automaton model. Thus, we establish a link between discrete and continuous approaches and open new perspectives for modeling and quantification of complex patterns in dune fields.

  19. 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/

  20. 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

  1. Theoretical model for cellular shapes driven by protrusive and adhesive forces.

    Directory of Open Access Journals (Sweden)

    Doron Kabaso

    2011-05-01

    Full Text Available The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix.

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. A mathematical model to study the dynamics of epithelial cellular networks.

    Science.gov (United States)

    Abate, Alessandro; Vincent, Stéphane; Dobbe, Roel; Silletti, Alberto; Master, Neal; Axelrod, Jeffrey D; Tomlin, Claire J

    2012-01-01

    Epithelia are sheets of connected cells that are essential across the animal kingdom. Experimental observations suggest that the dynamical behavior of many single-layered epithelial tissues has strong analogies with that of specific mechanical systems, namely large networks consisting of point masses connected through spring-damper elements and undergoing the influence of active and dissipating forces. Based on this analogy, this work develops a modeling framework to enable the study of the mechanical properties and of the dynamic behavior of large epithelial cellular networks. The model is built first by creating a network topology that is extracted from the actual cellular geometry as obtained from experiments, then by associating a mechanical structure and dynamics to the network via spring-damper elements. This scalable approach enables running simulations of large network dynamics: the derived modeling framework in particular is predisposed to be tailored to study general dynamics (for example, morphogenesis) of various classes of single-layered epithelial cellular networks. In this contribution, we test the model on a case study of the dorsal epithelium of the Drosophila melanogaster embryo during early dorsal closure (and, less conspicuously, germband retraction).

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Baltzis KonstantinosB

    2008-01-01

    Full Text Available Abstract 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.

  9. Realistic multi-cellular dosimetry for 177Lu-labelled antibodies: model and application

    Science.gov (United States)

    Marcatili, S.; Pichard, A.; Courteau, A.; Ladjohounlou, R.; Navarro-Teulon, I.; Repetto-Llamazares, A.; Heyerdahl, H.; Dahle, J.; Pouget, J. P.; Bardiès, M.

    2016-10-01

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin®, a novel 177Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of 177Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  10. From Cells to Islands: An unified Model of Cellular Parallel Genetic Algorithms

    CERN Document Server

    Simoncini, David; Verel, Sébastien; Clergue, Manuel

    2008-01-01

    This paper presents the Anisotropic selection scheme for cellular Genetic Algorithms (cGA). This new scheme allows to enhance diversity and to control the selective pressure which are two important issues in Genetic Algorithms, especially when trying to solve difficult optimization problems. Varying the anisotropic degree of selection allows swapping from a cellular to an island model of parallel genetic algorithm. Measures of performances and diversity have been performed on one well-known problem: the Quadratic Assignment Problem which is known to be difficult to optimize. Experiences show that, tuning the anisotropic degree, we can find the accurate trade-off between cGA and island models to optimize performances of parallel evolutionary algorithms. This trade-off can be interpreted as the suitable degree of migration among subpopulations in a parallel Genetic Algorithm.

  11. Modeling virtualized downlink cellular networks with ultra-dense small cells

    KAUST Repository

    Ibrahim, Hazem

    2015-09-11

    The unrelenting increase in the mobile users\\' populations and traffic demand drive cellular network operators to densify their infrastructure. Network densification increases the spatial frequency reuse efficiency while maintaining the signal-to-interference-plus-noise-ratio (SINR) performance, hence, increases the spatial spectral efficiency and improves the overall network performance. However, control signaling in such dense networks consumes considerable bandwidth and limits the densification gain. Radio access network (RAN) virtualization via control plane (C-plane) and user plane (U-plane) splitting has been recently proposed to lighten the control signaling burden and improve the network throughput. In this paper, we present a tractable analytical model for virtualized downlink cellular networks, using tools from stochastic geometry. We then apply the developed modeling framework to obtain design insights for virtualized RANs and quantify associated performance improvement. © 2015 IEEE.

  12. Hyperspectral fluorescence imaging for cellular iron mapping in the in vitro model of Parkinson's disease

    Science.gov (United States)

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

    2014-05-01

    Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss in the substantia nigra (SN) and elevated iron levels demonstrated by autopsy. 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 exposed to iron with ferric ammonium citrate (FAC, 100 μM). The hyperspectral fluorescence signal of iron was examined using a high-resolution dark-field optical microscope system with signal absorption for the visible/near infrared spectral range. The 6-h group showed heavy cellular iron deposition compared with the 1-h group. The cellular iron was dispersed in a small particulate form, whereas the extracellular iron was aggregated. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The iron accumulation readily occurred in MPP+-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN. This direct iron imaging could be applied to analyze the physiological role of iron, and its application might be expanded to various neurological disorders involving metals, such as copper, manganese, or zinc.

  13. 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.

  14. Synthesis of biocompatible multicolor luminescent carbon dots for bioimaging applications

    Directory of Open Access Journals (Sweden)

    Nagaprasad Puvvada, B N Prashanth Kumar, Suraj Konar, Himani Kalita, Mahitosh Mandal and Amita Pathak

    2012-01-01

    Full Text Available Water-soluble carbon dots (C-dots were prepared through microwave-assisted pyrolysis of an aqueous solution of dextrin in the presence of sulfuric acid. The C-dots produced showed multicolor luminescence in the entire visible range, without adding any surface-passivating agent. X-ray diffraction and Fourier transform infrared spectroscopy studies revealed the graphitic nature of the carbon and the presence of hydrophilic groups on the surface, respectively. The formation of uniformly distributed C-dots and their luminescent properties were, respectively, revealed from transmission electron microscopy and confocal laser scanning microscopy. The biocompatible nature of C-dots was confirmed by a cytotoxicity assay on MDA-MB-468 cells and their cellular uptake was assessed through a localization study.

  15. Constitutively activated ERK sensitizes cancer cells to doxorubicin: Involvement of p53-EGFR-ERK pathway

    Indian Academy of Sciences (India)

    RATNA KUMARI; SURBHI CHOUHAN; SNAHLATA SINGH; RISHI RAJ CHHIPA; AMRENDRA KUMAR AJAY; MANOJ KUMAR BHAT

    2017-03-01

    The tumour suppressor gene p53 is mutated in approximately 50% of the human cancers. p53 is involved in genotoxicstress-induced cellular responses. The role of EGFR and ERK in DNA-damage-induced apoptosis is well known. Weinvestigated the involvement of activation of ERK signalling as a consequence of non-functional p53, in sensitivity ofcells to doxorubicin. We performed cell survival assays in cancer cell lines with varying p53 status: MCF-7 (wild-typep53, WTp53), MDA MB-468 (mutant p53, MUTp53), H1299 (absence of p53, NULLp53) and an isogenic cell lineMCF-7As (WTp53 abrogated). Our results indicate that enhanced chemosensitivity of cells lacking wild-type p53function is because of elevated levels of EGFR which activates ERK. Additionally, we noted that independent of p53status, pERK contributes to doxorubicin-induced cell death.

  16. Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer.

    Science.gov (United States)

    Zhu, Qihua; Wang, Xueyan; Hu, Yan; He, Xiaorong; Gong, Guoqing; Xu, Yungen

    2015-10-15

    A series of imidazo[4,5-c]pyridine-7-carboxamide derivatives as poly(ADP-ribose) polymerase (PARP) inhibitors have been developed. All target compounds were evaluated for their PARP-1 inhibitory activity and some were further assessed for cellular potency. These efforts led to identification of a novel PARP-1 inhibitor 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide 11a (XZ-120312). 11a displayed strong inhibition against the PARP-1 enzyme with an IC50 of 8.6±0.6 nM and excellent potentiation of temozolomide cytotoxicity in cancer cell lines SW-620, MDA-MB-468 and A549 by 4.0, 3.0 and 7.7 times, respectively.

  17. Modeling and Experimental Study of Soft Error Propagation Based on Cellular Automaton

    OpenAIRE

    2016-01-01

    Aiming to estimate SEE soft error performance of complex electronic systems, a soft error propagation model based on cellular automaton is proposed and an estimation methodology based on circuit partitioning and error propagation is presented. Simulations indicate that different fault grade jamming and different coupling factors between cells are the main parameters influencing the vulnerability of the system. Accelerated radiation experiments have been developed to determine the main paramet...

  18. A Real-Space Cellular Automaton Laboratory for the modeling of complex dunefields

    Science.gov (United States)

    Rozier, Olivier; Narteau, Clement

    2013-04-01

    Using applications in the physics of sand dunes, we explore the capabilities of a Real Space Cellular Automaton Laboratory (ReSCAL), a generator of 3D stochastic cellular automaton stochastic cellular automaton models with continuous time. The objective of this software is to develop interdisciplinary research collaboration to investigate the dynamics of complex systems. In the vast majority of numerical models, any point in space is entirely characterized by a local set of physical variables (e. g. temperature, pressure, velocity) that are recalculated over time according to some predetermined set of fundamental laws. However, there is not always a satisfactory theoretical framework from which we can try to quantify the overall dynamics of the system. For this reason, we prefer concentrate on features of organization and ReSCAL is entirely constructed from a finite number of discrete states that represent the different phases of matter involved in the system under consideration. Then, an elementary cell is a real-space representation of the physical environment. Pairs of nearest neighbor cells are called doublets and each individual physical process is associated with a set of doublet transitions and a characteristic transition rate. Using a modular approach, we show how it is possible to model and combine a wide range of physical, chemical and/or anthropological processes. As an example, we discuss different dune morphologies with respect to rotating wind conditions.

  19. 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.

  20. 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.

  1. Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-09-01

    Full Text Available Silver nanoparticles (AgNPs have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with

  2. Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

    Science.gov (United States)

    Zhang, Xi-Feng; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

    Silver nanoparticles (AgNPs) have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with future perspectives

  3. Chronobiology at the cellular and molecular levels: models and mechanisms for circadian timekeeping.

    Science.gov (United States)

    Edmunds, L N

    1983-12-01

    This review considers cellular chronobiology and examines, at least in a superficial way, several classes of models and mechanisms that have been proposed for circadian rhythmicity and some of the experimental approaches that have appeared to be most productive. After a brief discussion of temporal organization and the metabolic, epigenetic, and circadian time domains, the general properties of circadian rhythms are enumerated. A survey of independent oscillations in isolated organs, tissues, and cells is followed by a review of selected circadian rhythms in eukaryotic microorganisms, with particular emphasis placed on the rhythm of cell division in the algal flagellate Euglena as a model system illustrating temporal differentiation. In the ensuing section, experimental approaches to circadian clock mechanisms are considered. The dissection of the clock by the use of chemical inhibitors is illustrated for the rhythm of bioluminescence in the marine dinoflagellate Gonyaulax and for the rhythm of photosynthetic capacity in the unicellular green alga Acetabularia. Alternatively, genetic analysis of circadian oscillators is considered in the green alga Chlamydomonas and in the bread mold Neurospora, both of which have yielded clock mutants and mutants having biochemical lesions that exhibit altered clock properties. On the basis of the evidence generated by these experimental approaches, several classes of biochemical and molecular models for circadian clocks have been proposed. These include strictly molecular models, feedback loop (network) models, transcriptional (tape-reading) models, and membrane models; some of their key elements and predictions are discussed. Finally, a number of general unsolved problems at the cellular level are briefly mentioned: cell cycle interfaces, the evolution of circadian rhythmicity, the possibility of multiple cellular oscillators, chronopharmacology and chronotherapy, and cell-cycle clocks in development and aging.

  4. Unified tractable model for downlink MIMO cellular networks using stochastic geometry

    KAUST Repository

    Afify, Laila H.

    2016-07-26

    Several research efforts are invested to develop stochastic geometry models for cellular networks with multiple antenna transmission and reception (MIMO). On one hand, there are models that target abstract outage probability and ergodic rate for simplicity. On the other hand, there are models that sacrifice simplicity to target more tangible performance metrics such as the error probability. Both types of models are completely disjoint in terms of the analytic steps to obtain the performance measures, which makes it challenging to conduct studies that account for different performance metrics. This paper unifies both techniques and proposes a unified stochastic-geometry based mathematical paradigm to account for error probability, outage probability, and ergodic rates in MIMO cellular networks. The proposed model is also unified in terms of the antenna configurations and leads to simpler error probability analysis compared to existing state-of-the-art models. The core part of the analysis is based on abstracting unnecessary information conveyed within the interfering signals by assuming Gaussian signaling. To this end, the accuracy of the proposed framework is verified against state-of-the-art models as well as system level simulations. We provide via this unified study insights on network design by reflecting system parameters effect on different performance metrics. © 2016 IEEE.

  5. 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.

  6. A model of how different biology experts explain molecular and cellular mechanisms.

    Science.gov (United States)

    Trujillo, Caleb M; Anderson, Trevor R; Pelaez, Nancy J

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations.

  7. 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.

  8. Drosophila as a genetic and cellular model for studies on axonal growth

    Directory of Open Access Journals (Sweden)

    Whitington Paul

    2007-05-01

    Full Text Available Abstract One of the most fascinating processes during nervous system development is the establishment of stereotypic neuronal networks. An essential step in this process is the outgrowth and precise navigation (pathfinding of axons and dendrites towards their synaptic partner cells. This phenomenon was first described more than a century ago and, over the past decades, increasing insights have been gained into the cellular and molecular mechanisms regulating neuronal growth and navigation. Progress in this area has been greatly assisted by the use of simple and genetically tractable invertebrate model systems, such as the fruit fly Drosophila melanogaster. This review is dedicated to Drosophila as a genetic and cellular model to study axonal growth and demonstrates how it can and has been used for this research. We describe the various cellular systems of Drosophila used for such studies, insights into axonal growth cones and their cytoskeletal dynamics, and summarise identified molecular signalling pathways required for growth cone navigation, with particular focus on pathfinding decisions in the ventral nerve cord of Drosophila embryos. These Drosophila-specific aspects are viewed in the general context of our current knowledge about neuronal growth.

  9. Mechanistic Modelling of DNA Repair and Cellular Survival Following Radiation-Induced DNA Damage

    Science.gov (United States)

    McMahon, Stephen J.; Schuemann, Jan; Paganetti, Harald; Prise, Kevin M.

    2016-09-01

    Characterising and predicting the effects of ionising radiation on cells remains challenging, with the lack of robust models of the underlying mechanism of radiation responses providing a significant limitation to the development of personalised radiotherapy. In this paper we present a mechanistic model of cellular response to radiation that incorporates the kinetics of different DNA repair processes, the spatial distribution of double strand breaks and the resulting probability and severity of misrepair. This model enables predictions to be made of a range of key biological endpoints (DNA repair kinetics, chromosome aberration and mutation formation, survival) across a range of cell types based on a set of 11 mechanistic fitting parameters that are common across all cells. Applying this model to cellular survival showed its capacity to stratify the radiosensitivity of cells based on aspects of their phenotype and experimental conditions such as cell cycle phase and plating delay (correlation between modelled and observed Mean Inactivation Doses R2 > 0.9). By explicitly incorporating underlying mechanistic factors, this model can integrate knowledge from a wide range of biological studies to provide robust predictions and may act as a foundation for future calculations of individualised radiosensitivity.

  10. Reprint of Infinity computations in cellular automaton forest-fire model

    Science.gov (United States)

    Iudin, D. I.; Sergeyev, Ya. D.; Hayakawa, M.

    2015-04-01

    Recently a number of traditional models related to the percolation theory has been considered by means of a new computational methodology that does not use Cantor's ideas and describes infinite and infinitesimal numbers in accordance with the principle 'The whole is greater than the part' (Euclid's Common Notion 5). Here we apply the new arithmetic to a cellular automaton forest-fire model which is connected with the percolation methodology and in some sense combines the dynamic and the static percolation problems and under certain conditions exhibits critical fluctuations. It is well known that there exist two versions of the model: real forest-fire model where fire catches adjacent trees in the forest in the step by step manner and simplified version with instantaneous combustion. Using new approach we observe that in both situations we deal with the same model but with different time resolution. We show that depending on the "microscope" we use the same cellular automaton forest-fire model reveals either instantaneous forest combustion or step by step firing. By means of the new approach it was also observed that as far as we choose an infinitesimal tree growing rate and infinitesimal ratio between the ignition probability and the growth probability we determine the measure or extent of the system size infinity that provides the criticality of the system dynamics. Correspondent inequalities for grosspowers are derived.

  11. 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.

  12. Modeling the dendritic evolution and micro-segregation of cast alloy with cellular automaton

    Institute of Scientific and Technical Information of China (English)

    Qiang Li; Dianzhong Li; Bainian Qian

    2004-01-01

    In order to precisely describe the dendritic morphology and micro-segregation during solidification process, a novel continuous model concerning the different physical properties in the solid phase, liquid phase and interface is developed. Coupling the heat and solute diffusion with the transition rules, the dendrite evolution is simulated by cellular automaton method. Then, the solidification microstructure evolution of a small ingot is simulated by using this method. The simulated results indicate that this model can simulate the dendrite growth, show the second dendrite arm and tertiary dendrite arm, and reveal the micro-segregation in the inter-dendritic zones. Furthermore, the columnar-to-equiaxed transition (CET) is predicted.

  13. 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.

  14. On a cellular automaton with time delay for modelling cancer tumors

    Energy Technology Data Exchange (ETDEWEB)

    Iarosz, K C; Martins, C C; Batista, A M [Departamento de Matematica e EstatIstica, Universidade Estadual de Ponta Grossa, 84030-900, Ponta Grossa, PR (Brazil); Viana, R L; Lopes, S R [Departamento de Fisica, Universidade Federal do Parana, 81531-990, Curitiba, PR (Brazil); Caldas, I L [Instituto de Fisica, Universidade de Sao Paulo, Caixa Postal 66316, 05315-970, Sao Paulo, SP (Brazil); Penna, T J P, E-mail: antoniomarcosbatista@gmail.com [Instituto de Fisica, Universidade Federal Fluminense, 24210-340, Niteroi, RJ (Brazil)

    2011-03-01

    In this work we considered cellular automaton model with time delay. Time delay included in this model reflects the delay between the time in which the site is affected and the time in which its variable is updated. We analyzed the effect of the rules on the dynamics through the cluster counting. According to this cluster counting, the dynamics behavior is investigated. We verified periodic oscillations same as delay differential equation. We also studied the relation between the time delay in the cell cycle and the time to start the metastasis, using suitable numerical diagnostics.

  15. 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.

  16. 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...

  17. 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.

  18. Multiscale systems analysis of root growth and development: modeling beyond the network and cellular scales.

    Science.gov (United States)

    Band, Leah R; Fozard, John A; Godin, Christophe; Jensen, Oliver E; Pridmore, Tony; Bennett, Malcolm J; King, John R

    2012-10-01

    Over recent decades, we have gained detailed knowledge of many processes involved in root growth and development. However, with this knowledge come increasing complexity and an increasing need for mechanistic modeling to understand how those individual processes interact. One major challenge is in relating genotypes to phenotypes, requiring us to move beyond the network and cellular scales, to use multiscale modeling to predict emergent dynamics at the tissue and organ levels. In this review, we highlight recent developments in multiscale modeling, illustrating how these are generating new mechanistic insights into the regulation of root growth and development. We consider how these models are motivating new biological data analysis and explore directions for future research. This modeling progress will be crucial as we move from a qualitative to an increasingly quantitative understanding of root biology, generating predictive tools that accelerate the development of improved crop varieties.

  19. Cellular Automata Modelling of Photo-Induced Oxidation Processes in Molecularly Doped Polymers

    Directory of Open Access Journals (Sweden)

    David M. Goldie

    2016-11-01

    Full Text Available The possibility of employing cellular automata (CA to model photo-induced oxidation processes in molecularly doped polymers is explored. It is demonstrated that the oxidation dynamics generated using CA models exhibit stretched-exponential behavior. This dynamical characteristic is in general agreement with an alternative analysis conducted using standard rate equations provided the molecular doping levels are sufficiently low to prohibit the presence of safe-sites which are impenetrable to dissolved oxygen. The CA models therefore offer the advantage of exploring the effect of dopant agglomeration which is difficult to assess from standard rate equation solutions. The influence of UV-induced bleaching or darkening upon the resulting oxidation dynamics may also be easily incorporated into the CA models and these optical effects are investigated for various photo-oxidation product scenarios. Output from the CA models is evaluated for experimental photo-oxidation data obtained from a series of hydrazone-doped polymers.

  20. Comparative Analysis of Empirical Path Loss Model for Cellular Transmission in Rivers State

    Directory of Open Access Journals (Sweden)

    B.O.H Akinwole, Biebuma J.J

    2013-08-01

    Full Text Available This paper presents a comparative analysis of three empirical path loss models with measured data for urban, suburban, and rural areas in Rivers State. The three models investigated were COST 231 Hata, SUI,ECC-33models. A downlink data was collected at operating frequency of 2100MHz using drive test procedure consisting of test mobile phones to determine the received signal power (RSCP at specified receiver distanceson a Globacom Node Bs located in some locations in the State. This test was carried out for investigating the effectiveness of the commonly used existing models for Cellular transmission. The results analysed were based on Mean Square Error (MSE and Standard Deviation (SD and were simulated on MATLAB (7.5.0. The results show that COST 231 Hata model gives better predictions and therefore recommended for path loss predictions in River State.

  1. 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.

  2. 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.

  3. A new cellular automata model of traffic flow with negative exponential weighted look-ahead potential

    Science.gov (United States)

    Ma, Xiao; Zheng, Wei-Fan; Jiang, Bao-Shan; Zhang, Ji-Ye

    2016-10-01

    With the development of traffic systems, some issues such as traffic jams become more and more serious. Efficient traffic flow theory is needed to guide the overall controlling, organizing and management of traffic systems. On the basis of the cellular automata model and the traffic flow model with look-ahead potential, a new cellular automata traffic flow model with negative exponential weighted look-ahead potential is presented in this paper. By introducing the negative exponential weighting coefficient into the look-ahead potential and endowing the potential of vehicles closer to the driver with a greater coefficient, the modeling process is more suitable for the driver’s random decision-making process which is based on the traffic environment that the driver is facing. The fundamental diagrams for different weighting parameters are obtained by using numerical simulations which show that the negative exponential weighting coefficient has an obvious effect on high density traffic flux. The complex high density non-linear traffic behavior is also reproduced by numerical simulations. Project supported by the National Natural Science Foundation of China (Grant Nos. 11572264, 11172247, 11402214, and 61373009).

  4. 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.

  5. Synchronized Flow in a Cellular Automaton Model with Time Headway Dependent Randomization

    Institute of Scientific and Technical Information of China (English)

    CHEN Tao; JIA Bin; LI Xin-Gang; JIANG Rui; GAO Zi-You

    2008-01-01

    @@ We propose another possible mechanism of synchronized flow, I.e. That a time headway dependent randomization can exhibit synchronized flow. Based on this assumption, we present a new cellular automaton (CA) model for traffic flow, in which randomization effect is enhanced with the decrease of time headway. We study fundamental diagram and spatial-temporal diagrams of the model and perform microscopic analysis of time series data, which shows the model could reproduce synchronized flow as expected. It is also shown that a spontaneous transition from synchronized flow to jam could be observed by incorporating slow-to-start effect into the model. We expect that our work could contribute to the understanding of the real origin of synchronized flow.

  6. 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.

  7. Cellular automaton modeling of ductile iron microstructure in the thin wall

    Directory of Open Access Journals (Sweden)

    A.A. Burbelko

    2011-10-01

    Full Text Available The mathematical model of the globular eutectic solidification in 2D was designed. Proposed model is based on the Cellular Automaton Finite Differences (CA-FD calculation method. Model has been used for studies of the primary austenite and of globular eutectic grains growth during the solidification of the ductile iron with different carbon equivalent in the thin wall casting. Model takes into account, among other things, non-uniform temperature distribution in the casting wall cross-section, kinetics of the austenite and graphite grains nucleation, and non-equilibrium nature of the interphase boundary migration. Solidification of the DI with different carbon equivalents was analyzed. Obtained results were compared with the solidification path calculated by CALPHAD method.

  8. A self-modifying cellular automaton model of historical urbanization in the San Francisco Bay area

    Science.gov (United States)

    Clarke, K.C.; Hoppen, S.; Gaydos, L.

    1997-01-01

    In this paper we describe a cellular automaton (CA) simulation model developed to predict urban growth as part of a project for estimating the regional and broader impact of urbanization on the San Francisco Bay area's climate. The rules of the model are more complex than those of a typical CA and involve the use of multiple data sources, including topography, road networks, and existing settlement distributions, and their modification over time. In addition, the control parameters of the model are allowed to self-modify: that is, the CA adapts itself to the circumstances it generates, in particular, during periods of rapid growth or stagnation. In addition, the model was written to allow the accumulation of probabilistic estimates based on Monte Carlo methods. Calibration of the model has been accomplished by the use of historical maps to compare model predictions of urbanization, based solely upon the distribution in year 1900, with observed data for years 1940, 1954, 1962, 1974, and 1990. The complexity of this model has made calibration a particularly demanding step. Lessons learned about the methods, measures, and strategies developed to calibrate the model may be of use in other environmental modeling contexts. With the calibration complete, the model is being used to generate a set of future scenarios for the San Francisco Bay area along with their probabilities based on the Monte Carlo version of the model. Animated dynamic mapping of the simulations will be used to allow visualization of the impact of future urban growth.

  9. 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

  10. 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.

  11. Modeling Mixed Traffic Flow at Crosswalks in Micro-Simulations Using Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    DUAN Houli; ZHANG Yi

    2007-01-01

    The cellular automata (CA) micro-simulation model was used to describe the behavior of the mixed traffic flows at crosswalks where the pedestrians compete with the vehicles to cross the roadway. The focus of this paper is the behavior of pedestrians and the influence of pedestrians' behavior on the vehicle flow, pedestrian flows, and the vehicle waiting time. The proportion of pedestrians who do not obey traffic laws, the group effect, and expected waiting time of pedestrians, regarded as the most important pedestrian characteristics, are taken into consideration in the analysis. Simulation results show the ability of the microsimulation to capture the most important features of mixed traffic flow.

  12. Computational models of atrial cellular electrophysiology and calcium handling, and their role in atrial fibrillation.

    Science.gov (United States)

    Heijman, Jordi; Erfanian Abdoust, Pegah; Voigt, Niels; Nattel, Stanley; Dobrev, Dobromir

    2016-02-01

    The complexity of the heart makes an intuitive understanding of the relative contribution of ion channels, transporters and signalling pathways to cardiac electrophysiology challenging. Computational modelling of cardiac cellular electrophysiology has proven useful to integrate experimental findings, extrapolate results obtained in expression systems or animal models to other systems, test quantitatively ideas based on experimental data and provide novel hypotheses that are experimentally testable. While the bulk of computational modelling has traditionally been directed towards ventricular bioelectricity, increasing recognition of the clinical importance of atrial arrhythmias, particularly atrial fibrillation, has led to widespread efforts to apply computational approaches to understanding atrial electrical function. The increasing availability of detailed, atrial-specific experimental data has stimulated the development of novel computational models of atrial-cellular electrophysiology and Ca(2+) handling. To date, more than 300 studies have employed mathematical simulations to enhance our understanding of atrial electrophysiology, arrhythmogenesis and therapeutic responses. Future modelling studies are likely to move beyond current whole-cell models by incorporating new data on subcellular architecture, macromolecular protein complexes, and localized ion-channel regulation by signalling pathways. At the same time, more integrative multicellular models that take into account regional electrophysiological and Ca(2+) handling properties, mechano-electrical feedback and/or autonomic regulation will be needed to investigate the mechanisms governing atrial arrhythmias. A combined experimental and computational approach is expected to provide the more comprehensive understanding of atrial arrhythmogenesis that is required to develop improved diagnostic and therapeutic options. Here, we review this rapidly expanding area, with a particular focus on Ca(2+) handling, and

  13. Transfer matrix modeling and experimental validation of cellular porous material with resonant inclusions.

    Science.gov (United States)

    Doutres, Olivier; Atalla, Noureddine; Osman, Haisam

    2015-06-01

    Porous materials are widely used for improving sound absorption and sound transmission loss of vibrating structures. However, their efficiency is limited to medium and high frequencies of sound. A solution for improving their low frequency behavior while keeping an acceptable thickness is to embed resonant structures such as Helmholtz resonators (HRs). This work investigates the absorption and transmission acoustic performances of a cellular porous material with a two-dimensional periodic arrangement of HR inclusions. A low frequency model of a resonant periodic unit cell based on the parallel transfer matrix method is presented. The model is validated by comparison with impedance tube measurements and simulations based on both the finite element method and a homogenization based model. At the HR resonance frequency (i) the transmission loss is greatly improved and (ii) the sound absorption of the foam can be either decreased or improved depending on the HR tuning frequency and on the thickness and properties of the host foam. Finally, the diffuse field sound absorption and diffuse field sound transmission loss performance of a 2.6 m(2) resonant cellular material are measured. It is shown that the improvements observed at the Helmholtz resonant frequency on a single cell are confirmed at a larger scale.

  14. 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.

  15. 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...

  16. Comparison of Cellular Automaton and Phase Field Models to Simulate Dendrite Growth in Hexagonal Crystals

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    A cellular automaton (CA)-finite element (FE) model and a phase field (PF)-FE model were used to simulate equiaxed dendritic growth during the solidification of hexagonal metals. In the CA-FE model, the conservation equations of mass and energy were solved in order to calculate the temperature field, solute concentration, and the dendritic growth morphology. CA-FE simulation results showed reasonable agreement with the previously reported experimental data on secondary dendrite arm spacing (SDAS) vs cooling rate. In the PF model, a PF variable was used to distinguish solid and liquid phases similar to the conventional PF models for solidification of pure materials. Another PF variable was considered to determine the evolution of solute concentration. Validation of both models was performed by comparing the simulation results with the analytical model developed by Lipton-Glicksman-Kurz (LGK), showing quantitatively good agreement in the tip growth velocity at a given melt undercooling. Application to magnesium alloy AZ91 (approximated with the binary Mg-8.9 wt% AI) illustrates the difficulty of modeling dendrite growth in hexagonal systems using CA-FE regarding mesh-induced anisotropy and a better performance of PF-FE in modeling multiple arbitrarily-oriented dendrites growth.

  17. 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.

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    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.

  19. A three-dimensional cellular automaton model for simulation of dendritic growth of magnesium alloy

    Institute of Scientific and Technical Information of China (English)

    Mengwu WU; Shoumei XIONG

    2012-01-01

    A numerical model based on the cellular automaton method for the three-dimensional simulation of dendritic growth of magnesium alloy was developed.The growth kinetics was calculated from the complete solution of the transport equations.By constructing a three-dimensional anisotropy model with the cubic CA cells,simulation of dendritic growth of magnesium alloy with six-fold symmetry in the basal plane was achieved.The model was applied to simulate the equiaxed dendritic growth and columnar dendritic growth under directional solidification,and its capability was addressed by comparing the simulated results to experimental results and those in the previously published works.Meanwhile,the three-dimensional simulated results were also compared with that of in two dimensions,offering a deep insight into the microstructure formation of magnesium alloy during solidification.

  20. 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.

  1. An Integrated Framework to Model Cellular Phenotype as a Component of Biochemical Networks

    Directory of Open Access Journals (Sweden)

    Michael Gormley

    2011-01-01

    Full Text Available Identification of regulatory molecules in signaling pathways is critical for understanding cellular behavior. Given the complexity of the transcriptional gene network, the relationship between molecular expression and phenotype is difficult to determine using reductionist experimental methods. Computational models provide the means to characterize regulatory mechanisms and predict phenotype in the context of gene networks. Integrating gene expression data with phenotypic data in transcriptional network models enables systematic identification of critical molecules in a biological network. We developed an approach based on fuzzy logic to model cell budding in Saccharomyces cerevisiae using time series expression microarray data of the cell cycle. Cell budding is a phenotype of viable cells undergoing division. Predicted interactions between gene expression and phenotype reflected known biological relationships. Dynamic simulation analysis reproduced the behavior of the yeast cell cycle and accurately identified genes and interactions which are essential for cell viability.

  2. 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.

  3. Dynamical critical behavior in a cellular model of superconducting vortex avalanches

    Science.gov (United States)

    Vadakkan, Tegy John

    Bak, Tang, and Wiesenfeld showed that certain driven dissipative systems with many degrees of freedom organize into a critical state characterized by avalanche dynamics and power law distribution of avalanche sizes and durations. They called this phenomenon self-organized criticality and sandpile became the prototype of such dynamical systems. Universality in these systems is not yet well established. Forty years ago, de Gennes noted that the Bean state in a type-II superconductor is similar to a sandpile. Motivated by strong experimental evidences, Bassler and Paczuski (BP) proposed a 2D sandpile model to study self-organization in the dynamics of vortices in superconductors. In this dissertation, the effect of anisotropy in the vortex-vortex interaction, stochasticity in the vortex toppling rule, and the configuration of the pinning centers on the scaling properties of the avalanches in the BP model is studied. Also, universality in the cellular model of vortex dynamics is investigated.

  4. Partitioning, diffusion, and ligand binding of raft lipid analogs in model and cellular plasma membranes.

    Science.gov (United States)

    Sezgin, Erdinc; Levental, Ilya; Grzybek, Michal; Schwarzmann, Günter; Mueller, Veronika; Honigmann, Alf; Belov, Vladimir N; Eggeling, Christian; Coskun, Unal; Simons, Kai; Schwille, Petra

    2012-07-01

    Several simplified membrane models featuring coexisting liquid disordered (Ld) and ordered (Lo) lipid phases have been developed to mimic the heterogeneous organization of cellular membranes, and thus, aid our understanding of the nature and functional role of ordered lipid-protein nanodomains, termed "rafts". In spite of their greatly reduced complexity, quantitative characterization of local lipid environments using model membranes is not trivial, and the parallels that can be drawn to cellular membranes are not always evident. Similarly, various fluorescently labeled lipid analogs have been used to study membrane organization and function in vitro, although the biological activity of these probes in relation to their native counterparts often remains uncharacterized. This is particularly true for raft-preferring lipids ("raft lipids", e.g. sphingolipids and sterols), whose domain preference is a strict function of their molecular architecture, and is thus susceptible to disruption by fluorescence labeling. Here, we analyze the phase partitioning of a multitude of fluorescent raft lipid analogs in synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). We observe complex partitioning behavior dependent on label size, polarity, charge and position, lipid headgroup, and membrane composition. Several of the raft lipid analogs partitioned into the ordered phase in GPMVs, in contrast to fully synthetic GUVs, in which most raft lipid analogs mis-partitioned to the disordered phase. This behavior correlates with the greatly enhanced order difference between coexisting phases in the synthetic system. In addition, not only partitioning, but also ligand binding of the lipids is perturbed upon labeling: while cholera toxin B binds unlabeled GM1 in the Lo phase, it binds fluorescently labeled GMI exclusively in the Ld phase. Fluorescence correlation spectroscopy (FCS) by stimulated emission depletion (STED) nanoscopy on intact

  5. Mathematical modeling of ultrasound in tissue engineering: From bioreactors to the cellular scale

    Science.gov (United States)

    Louw, Tobias M.

    Tissue engineering seeks to provide a means to treat injuries that are beyond the body's natural ability to repair without the issues associated with allografts. Autologous cells are cultured in a bioreactor which controls the cellular environment (including mechanical stimulation) for optimal tissue growth. We investigate ultrasound as an effective means of mechanical stimulation by predicting the ultrasonic field in a bioreactor, as well as ultrasonic bioeffects at the cellular level. The Transfer Matrix Angular Spectrum Approach was found to be the most accurate and computationally efficient bioreactor model. Three critical factors influence experimental results: (1) the diameter of the tissue engineering scaffold greatly affects the ultrasonic field; (2) the position of the ultrasonic transducer and liquid level in the tissue culture well determines the maximum pressure amplitude in the bioreactor, but the pressure can be controlled by measuring the transducer input electrical impedance and manipulating the applied voltage; and (3) the position of pressure nodes are influenced by ultrasonic frequency and liquid level; this will affect the response of cells to applied ultrasound. On the cellular level, it was shown that chondrocytes respond to ultrasound with frequency dependence. A predicted resonance frequency near 5MHz matched experimental results showing maximum expression of load inducible genes at 5MHz. Mechanical stresses are concentrated near the nucleus at resonance, alluding to the possibility that the nucleus may directly sense ultrasonic stimulation. We postulate that ultrasound influences the transport of p-ERK to the nucleus or causes minor chromatin reorganization, leading to the observed frequency dependent gene expression. We linked in vitro ultrasonic stimulation to in vivo mechanical stimulation generated by natural movement. The chondrocyte's response to impact is under-damped, and the cell oscillates with a frequency close to the model

  6. A hybrid cellular automaton model of solid tumor growth and bioreductive drug transport.

    Science.gov (United States)

    Kazmi, Nabila; Hossain, M A; Phillips, Roger M

    2012-01-01

    Bioreductive drugs are a class of hypoxia selective drugs that are designed to eradicate the hypoxic fraction of solid tumors. Their activity depends upon a number of biological and pharmacological factors and we used a mathematical modeling approach to explore the dynamics of tumor growth, infusion, and penetration of the bioreductive drug Tirapazamine (TPZ). An in-silico model is implemented to calculate the tumor mass considering oxygen and glucose as key microenvironmental parameters. The next stage of the model integrated extra cellular matrix (ECM), cell-cell adhesion, and cell movement parameters as growth constraints. The tumor microenvironments strongly influenced tumor morphology and growth rates. Once the growth model was established, a hybrid model was developed to study drug dynamics inside the hypoxic regions of tumors. The model used 10, 50 and 100 \\mu {\\rm M} as TPZ initial concentrations and determined TPZ pharmacokinetic (PK) (transport) and pharmacodynamics (cytotoxicity) properties inside hypoxic regions of solid tumor. The model results showed that diminished drug transport is a reason for TPZ failure and recommend the optimization of the drug transport properties in the emerging TPZ generations. The modeling approach used in this study is novel and can be a step to explore the behavioral dynamics of TPZ.

  7. A cellular automaton model for microstructural simulation of friction stir welded AZ91 magnesium alloy

    Science.gov (United States)

    Akbari, Mostafa; Asadi, Parviz; Besharati Givi, MohammadKazem; Zolghadr, Parisa

    2016-03-01

    To predict the grain size and microstructure evolution during friction stir welding (FSW) of AZ91 magnesium alloy, a finite element model (FEM) is developed based on the combination of a cellular automaton model and the Kocks  -  Mecking and Laasraoui-Jonas models. First, according to the flow stress curves and using the Kocks  -  Mecking model, the hardening and recovery parameters and the strain rate sensitivity were calculated. Next, an FEM model was established in Deform-3D software to simulate the FSW of AZ91 magnesium alloy. The results of the FEM model are used in microstructure evolution models to predict the grain size and microstructure of the weld zone. There is a good agreement between the simulated and experimental microstructures, and the proposed model can simulate the dynamic recrystallization (DRX) process during FSW of AZ91 alloy. Moreover, microstructural properties of different points in the SZ as well as the effect of the w/v parameter on the grain size and microstructure are considered.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Cellular automaton model in the fundamental diagram approach reproducing the synchronized outflow of wide moving jams

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Jun-fang, E-mail: tianhustbjtu@hotmail.com [MOE Key Laboratory for Urban Transportation Complex Systems Theory and Technology, Beijing Jiaotong University, Beijing 100044 (China); Yuan, Zhen-zhou; Jia, Bin; Fan, Hong-qiang; Wang, Tao [MOE Key Laboratory for Urban Transportation Complex Systems Theory and Technology, Beijing Jiaotong University, Beijing 100044 (China)

    2012-09-10

    Velocity effect and critical velocity are incorporated into the average space gap cellular automaton model [J.F. Tian, et al., Phys. A 391 (2012) 3129], which was able to reproduce many spatiotemporal dynamics reported by the three-phase theory except the synchronized outflow of wide moving jams. The physics of traffic breakdown has been explained. Various congested patterns induced by the on-ramp are reproduced. It is shown that the occurrence of synchronized outflow, free outflow of wide moving jams is closely related with drivers time delay in acceleration at the downstream jam front and the critical velocity, respectively. -- Highlights: ► Velocity effect is added into average space gap cellular automaton model. ► The physics of traffic breakdown has been explained. ► The probabilistic nature of traffic breakdown is simulated. ► Various congested patterns induced by the on-ramp are reproduced. ► The occurrence of synchronized outflow of jams depends on drivers time delay.

  13. Cellular model studies of brain-mediated phototherapy on Alzheimer's disease

    Science.gov (United States)

    Zhu, Ling; Liu, Timon Cheng-Yi; Hu, Bina; Li, Xiao-Yun; Wang, Yong-Qing

    2008-12-01

    Alzheimer's disease (AD) is now the most common neurodegenerative disease. Despite approval of several drugs for AD, the disease continues to rob millions of their memories and their lives. We have studied the cellular models of brain-mediated phototherapy on AD, and the studies will be reviewed in this paper. Genetic studies have shown that dysfunction of amyloid β-protein (Aβ) or tau is sufficient to cause AD. Aβ or Aβ induced redox stress induced neuron apoptosis might be as a cellular model of AD. We found red light at 640+/-15 nm from light emitting diode array (RLED640) might inhibit Aβ 25-35 induced PC12 cell apoptosis, which is mediated by cyclic adenosine monophosphate, and it might inhibit hydrogen peroxide (H2O2) induced differentiated PC12 cell (dPC12) apoptosis, which is mediated by tyrosine hydroxylase. There is rhythm dysfunction in AD. We found low intensity 810 nm laser irradiation might rehabilitate TNF-alpha induced inhibition of clock gen expression of NIH 3T3 fibroblasts. Our studies provide a foundation for photobiomodulation on brain to rehabilitate AD.

  14. Computation of steady-state probability distributions in stochastic models of cellular networks.

    Directory of Open Access Journals (Sweden)

    Mark Hallen

    2011-10-01

    Full Text Available Cellular processes are "noisy". In each cell, concentrations of molecules are subject to random fluctuations due to the small numbers of these molecules and to environmental perturbations. While noise varies with time, it is often measured at steady state, for example by flow cytometry. When interrogating aspects of a cellular network by such steady-state measurements of network components, a key need is to develop efficient methods to simulate and compute these distributions. We describe innovations in stochastic modeling coupled with approaches to this computational challenge: first, an approach to modeling intrinsic noise via solution of the chemical master equation, and second, a convolution technique to account for contributions of extrinsic noise. We show how these techniques can be combined in a streamlined procedure for evaluation of different sources of variability in a biochemical network. Evaluation and illustrations are given in analysis of two well-characterized synthetic gene circuits, as well as a signaling network underlying the mammalian cell cycle entry.

  15. A cellular automaton model adapted to sandboxes to simulate the transport of solutes

    Science.gov (United States)

    Lora, Boris; Donado, Leonardo; Castro, Eduardo; Bayuelo, Alfredo

    2016-04-01

    The increasingly use of groundwater sources for human consumption and the growth of the levels of these hydric sources contamination make imperative to reach a deeper understanding how the contaminants are transported by the water, in particular through a heterogeneous porous medium. Accordingly, the present research aims to design a model, which simulates the transport of solutes through a heterogeneous porous medium, using cellular automata. Cellular automata (CA) are a class of spatially (pixels) and temporally discrete mathematical systems characterized by local interaction (neighborhoods). The pixel size and the CA neighborhood were determined in order to reproduce accurately the solute behavior (Ilachinski, 2001). For the design and corresponding validation of the CA model were developed different conservative tracer tests using a sandbox packed heterogeneously with a coarse sand (size # 20 grain diameter 0,85 to 0,6 mm) and clay. We use Uranine and a saline solution with NaCl as a tracer which were measured taking snapshots each 20 seconds. A calibration curve (pixel intensity Vs Concentration) was used to obtain concentration maps. The sandbox was constructed of acrylic (caliber 0,8 cms) with 70 x 45 x 4 cms of dimensions. The "sandbox" had a grid of 35 transversal holes with a diameter of 4 mm each and an uniform separation from one to another of 10 cms. To validate the CA-model it was used a metric consisting in rating the number of correctly predicted pixels over the total per image throughout the entire test run. The CA-model shows that calibrations of pixels and neighborhoods allow reaching results over the 60 % of correctly predictions usually. This makes possible to think that the application of the CA- model could be useful in further researches regarding the transport of contaminants in hydrogeology.

  16. 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.

  17. Modeling rice metabolism: from elucidating environmental effects on cellular phenotype to guiding crop improvement

    Directory of Open Access Journals (Sweden)

    Meiyappan Lakshmanan

    2016-11-01

    Full Text Available Crop productivity is severely limited by various biotic and abiotic stresses. Thus, it is highly needed to understand the underlying mechanisms of environmental stress response and tolerance in plants, which could be addressed by systems biology approach. To this end, high-throughput omics profiling and in silico modeling can be considered to explore the environmental effects on phenotypic states and metabolic behaviors of rice crops at the systems level. Especially, the advent of constraint-based metabolic reconstruction and analysis paves a way to characterize the plant cellular physiology under various stresses by combining the mathematical network models with multi-omics data. Rice metabolic networks have been reconstructed since 2013 and currently 6 such networks are available, where 5 are at genome-scale. Since their publication, these models have been utilized to systematically elucidate the rice abiotic stress responses and identify agronomic traits for crop improvement. In this review, we summarize the current status of the existing rice metabolic networks and models with their applications. Furthermore, we also highlight future directions of rice modeling studies, particularly stressing how these models can be used to contextualize the affluent multi-omics data that are readily available in the public domain. Overall, we envisage a number of studies in the future, exploiting the available metabolic models to enhance the yield and quality of rice and other food crops.

  18. Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data

    Science.gov (United States)

    Liu, Hui; Zhang, Fan; Mishra, Shital Kumar; Zhou, Shuigeng; Zheng, Jie

    2016-10-01

    Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data. In particular, the dynamic time warping algorithm is employed to measure the goodness of fit between experimental and predicted data, so that our method can model temporally-ordered experimental observations. We evaluated the proposed method on a synthetic dataset and two real phosphoproteomic datasets. The experimental results demonstrate that our model can uncover drug-induced alterations in signaling pathways in cancer cells. Compared with existing hybrid models, our method can model feedback loops so that the dynamical mechanisms of signaling networks can be uncovered from time-series data. By calibrating generic models of signaling pathways against real data, our method supports precise predictions of context-specific anticancer drug effects, which is an important step towards precision medicine.

  19. Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data

    Science.gov (United States)

    Liu, Hui; Zhang, Fan; Mishra, Shital Kumar; Zhou, Shuigeng; Zheng, Jie

    2016-01-01

    Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data. In particular, the dynamic time warping algorithm is employed to measure the goodness of fit between experimental and predicted data, so that our method can model temporally-ordered experimental observations. We evaluated the proposed method on a synthetic dataset and two real phosphoproteomic datasets. The experimental results demonstrate that our model can uncover drug-induced alterations in signaling pathways in cancer cells. Compared with existing hybrid models, our method can model feedback loops so that the dynamical mechanisms of signaling networks can be uncovered from time-series data. By calibrating generic models of signaling pathways against real data, our method supports precise predictions of context-specific anticancer drug effects, which is an important step towards precision medicine. PMID:27774993

  20. Mechanisms of stochastic onset and termination of atrial fibrillation studied with a cellular automaton model

    Science.gov (United States)

    2017-01-01

    Mathematical models of cardiac electrical excitation are increasingly complex, with multiscale models seeking to represent and bridge physiological behaviours across temporal and spatial scales. The increasing complexity of these models makes it computationally expensive to both evaluate long term (more than 60 s) behaviour and determine sensitivity of model outputs to inputs. This is particularly relevant in models of atrial fibrillation (AF), where individual episodes last from seconds to days, and interepisode waiting times can be minutes to months. Potential mechanisms of transition between sinus rhythm and AF have been identified but are not well understood, and it is difficult to simulate AF for long periods of time using state-of-the-art models. In this study, we implemented a Moe-type cellular automaton on a novel, topologically equivalent surface geometry of the left atrium. We used the model to simulate stochastic initiation and spontaneous termination of AF, arising from bursts of spontaneous activation near pulmonary veins. The simplified representation of atrial electrical activity reduced computational cost, and so permitted us to investigate AF mechanisms in a probabilistic setting. We computed large numbers (approx. 105) of sample paths of the model, to infer stochastic initiation and termination rates of AF episodes using different model parameters. By generating statistical distributions of model outputs, we demonstrated how to propagate uncertainties of inputs within our microscopic level model up to a macroscopic level. Lastly, we investigated spontaneous termination in the model and found a complex dependence on its past AF trajectory, the mechanism of which merits future investigation. PMID:28356539

  1. Micro-macroscopic coupling in the cellular automaton model of solidification

    Directory of Open Access Journals (Sweden)

    Vinicius Bertolazzi Biscuola

    2010-12-01

    Full Text Available A cellular automaton (CA model to predict the formation of grain macrostructure during solidification has been implemented and the coupling between the microscopic and the macroscopic submodels has been investigated. The microscopic submodel simulates the nucleation and growth of grains, whereas the macroscopic solves the heat conduction equation. The directional solidification of an Al-7 wt. (% Si alloy was simulated, enabling the calculation of the temperature and solid fraction profiles. The calculated temperature was used to obtain the solid fraction profile by an application of Scheil equation. This solid fraction disagrees with that calculated in the micro-macro coupling of the model, although this coupling is completely based on Scheil equation. Careful examination of the discrepancies shows that it is a result of the undercoolings for nucleation and growth of grains and also of the interpolations of enthalpy change and temperature from the finite volume mesh to the CA cell mesh.

  2. Cellular automaton model of precipitation/dissolution coupled with solute transport

    CERN Document Server

    Karapiperis, T

    1995-01-01

    ABSTRACT Precipitation/dissolution reactions coupled with solute transport are modelled as a cellular automaton in which solute molecules perform a random walk on a regular lattice and react according to a local probabilistic rule. Stationary solid particles dissolve with a certain probability and, provided solid is already present or the solution is saturated, solute particles have a probability to precipitate. In our simulation of the dissolution of a solid block inside uniformly flowing water we obtain solid precipitation downstream from the original solid edge, in contrast to the standard reaction-transport equations. The observed effect is the result of fluctuations in solute density and diminishes when we average over a larger ensemble. The additional precipitation of solid is accompanied by a substantial reduction in the relatively small solute concentration. The model is appropriate for the study of the rôle of intrinsic fluctuations in the presence of reaction thresholds and can be employed to inves...

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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 singlelane 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.

  4. 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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

    Musunuru, Kiran

    2013-07-01

    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.

  8. Cellular Automaton Models of Highway Traffic Flow Considering Lane-Control and Speed-Control

    Institute of Scientific and Technical Information of China (English)

    钱勇生; 李文俊; 曾俊伟; 王敏; 杜加伟; 广晓平

    2011-01-01

    As two kinds of management modes of highway tramc control, lane-control, and speed-control produce different effect under different conditions. In this paper, traffic flow cellular automaton models for four-lane highway system with two opposing directions under the above two modes are established considering car and truck mixed running. Through computer numerical simulating, the fundamental diagrams with different parameters are obtained, and after the analysis of density-flux diagrams, the variation discipline of flux with traffic density under different control models is gained. The results indicate that, compared with lane-control, utilization ratio of road can be further improved with speed-control when the truck number increases. The research result is of great significance for reasonable providing theoretical guidance for highway traffic control.

  9. An Urban Cellular Automata Model for Simulating Dynamic States on a Local Scale

    Directory of Open Access Journals (Sweden)

    Jenni Partanen

    2016-12-01

    Full Text Available In complex systems, flexibility and adaptability to changes are crucial to the systems’ dynamic stability and evolution. Such resilience requires that the system is able to respond to disturbances by self-organizing, which implies a certain level of entropy within the system. Dynamic states (static, cyclical/periodic, complex, and chaotic reflect this generative capacity, and correlate with the level of entropy. For planning complex cities, we need to develop methods to guide such autonomous progress in an optimal manner. A classical apparatus, cellular automaton (CA, provides such a tool. Applications of CA help us to study temporal dynamics in self-organizing urban systems. By exploring the dynamic states of the model’s dynamics resulting from different border conditions it is possible to discover favorable set(s of rules conductive to the self-organizing dynamics and enable the system’s recovery at the time of crises. Level of entropy is a relevant measurement for evaluation of these dynamic states. The 2-D urban cellular automaton model studied here is based on the microeconomic principle that similar urban activities are attracted to each other, especially in certain self-organizing areas, and that the local dynamics of these enclaves affect the dynamics of the urban region by channeling flows of information, goods and people. The results of the modeling experiment indicate that the border conditions have a major impact on the model’s dynamics generating various dynamic states of the system. Most importantly, it seemed that the model could simulate a favorable, complex dynamic state with medium entropy level which may refer to the continuous self-organization of the system. The model provides a tool for exploring and understanding the effects of boundary conditions in the planning process as various scenarios are tested: resulting dynamics of the system can be explored with such “planning rules” prior to decisions, helping to

  10. A refined cellular automaton model to rectify impractical vehicular movement behavior

    Science.gov (United States)

    Lan, Lawrence W.; Chiou, Yu-Chiun; Lin, Zih-Shin; Hsu, Chih-Cheng

    2009-09-01

    When implementing cellular automata (CA) into a traffic simulation, one common defect yet to be rectified is the abrupt deceleration when vehicles encounter stationary obstacles or traffic jams. To be more in line with real world vehicular movement, this paper proposes a piecewise-linear movement to replace the conventional particle-hopping movement adopted in most previous CA models. Upon this adjustment and coupled with refined cell system, a new CA model is developed using the rationale of Forbes’ et al. car-following concept. The proposed CA model is validated on a two-lane freeway mainline context. It shows that this model can fix the unrealistic deceleration behaviors, and thus can reflect genuine driver behavior in the real world. The model is also capable of revealing Kerner’s three-phase traffic patterns and phase transitions among them. Furthermore, the proposed CA model is applied to simulate a highway work zone wherein traffic efficiency (maximum flow rates) and safety (speed deviations) impacted by various control schemes are tested.

  11. A Multitarget Land Use Change Simulation Model Based on Cellular Automata and Its Application

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2014-01-01

    Full Text Available Based on the analysis of the existing land use change simulation model, combined with macroland use change driving factors and microlocal land use competition, and through the application of Python language integrated technical approaches such as CA, GIS, AHP, and Markov, a multitarget land use change simulation model based on cellular automata(CA is established. This model was applied to conduct scenario simulation of land use/cover change of the Jinzhou New District, based on 1:10000 map scale land use, planning, topography, statistics, and other data collected in the year of 1988, 2003, and 2012. The simulation results indicate the following: (1 this model can simulate the mutual transformation of multiple land use types in a relatively satisfactory way; it takes land use system as a whole and simultaneously takes the land use demand in the macrolevel and the land use suitability in the local scale into account; and (2 the simulation accuracy of the model reaches 72%, presenting higher creditability. The model is capable of providing auxiliary decision-making support for coastal regions with the analysis of the land use change driving mechanism, prediction of land use change tendencies, and establishment of land resource sustainable utilization policies.

  12. 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.

  13. 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

  14. Modeling and Analysis of K-Tier Downlink Heterogeneous Cellular Networks

    CERN Document Server

    Dhillon, Harpreet S; Baccelli, Francois; Andrews, Jeffrey G

    2011-01-01

    Cellular networks are in a major transition from a carefully planned set of large tower-mounted base-stations (BSs) to an irregular deployment of heterogeneous infrastructure elements that often additionally includes micro, pico, and femtocells, as well as distributed antennas. In this paper, we develop a tractable, flexible, and accurate model for a downlink heterogeneous cellular network (HCN) consisting of K tiers of randomly located BSs, where each tier may differ in terms of average transmit power, supported data rate and BS density. Assuming a mobile user connects to the strongest candidate BS, the resulting Signal-to-Interference-plus-Noise-Ratio (SINR) is greater than 1 when in coverage, Rayleigh fading, we derive an expression for the probability of coverage (equivalently outage) over the entire network under both open and closed access, which assumes a strikingly simple closed-form in the high SINR regime and is accurate down to -4 dB even under weaker assumptions. For external validation, we compar...

  15. 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.

  16. Integrating the system dynamic and cellular automata models to predict land use and land cover change

    Science.gov (United States)

    Xu, Xiaoming; Du, Ziqiang; Zhang, Hong

    2016-10-01

    Land use and land cover change (LULCC) is a widely researched topic in related studies. A number of models have been established to simulate LULCC patterns. However, the integration of the system dynamic (SD) and the cellular automata (CA) model have been rarely employed in LULCC simulations, although it allows for combining the advantages of each approach and therefore improving the simulation accuracy. In this study, we integrated an SD model and a CA model to predict LULCC under three future development scenarios in Northern Shanxi province of China, a typical agro-pastoral transitional zone. The results indicated that our integrated approach represented the impacts of natural and socioeconomic factors on LULCC well, and could accurately simulate the magnitude and spatial pattern of LULCC. The modeling scenarios illustrated that different development pathways would lead to various LULCC patterns. This study demonstrated the advantages of the integration approach for simulating LULCC and suggests that LULCC is affected to a large degree by natural and socioeconomic factors.

  17. A cellular automata-based model of Earth's magnetosphere in relation with Dst index

    Science.gov (United States)

    Banerjee, Adrija; Bej, Amaresh; Chatterjee, T. N.

    2015-05-01

    The disturbance storm time (Dst) index, a measure of the strength of a geomagnetic storm, is difficult to predict by some conventional methods due to its abstract structural complexity and stochastic nature though a timely geomagnetic storm warning could save society from huge economic losses and hours of related hazards. Self-organized criticality and the concept of many-body interactive nonlinear system can be considered an explanation for the fundamental mechanism of the nonstationary geomagnetic disturbances controlled by the perturbed interplanetary conditions. The present paper approaches this natural phenomena by a sandpile-like cellular automata-based model of magnetosphere, taking the real-time solar wind and both the direction and magnitude of the BZ component of the real-time interplanetary magnetic field as the system-controlling input parameters. Moreover, three new parameters had been introduced in the model which modify the functional relationships between the variables and regulate the dynamical behavior of the model to closely approximate the actual geomagnetic fluctuations. The statistical similarities between the dynamics of the model and that of the actual Dst index series during the entire 22nd solar cycle signifies the acceptability of the model.

  18. A Modified Cellular Automaton Method for the Modeling of the Dendritic Morphology of Binary Alloys

    Institute of Scientific and Technical Information of China (English)

    LIU Ying; XU Qingyan; LIU Baicheng

    2006-01-01

    A cellular automaton (CA)-based model for the precise two-dimensional simulation of the dendritic morphology of cast aluminum alloys was developed. Compared with previous CA models, the new model considers the solidification process in more detail, solving the solute and heat conservation equations in the modeling domain, including calculation of the solid fraction, the tip velocity, and the solute diffusion process, all of which have significant influence on the dendrite evolution. The rotating grids technique was used in the simulation to avoid anisotropy introduced by the square grid. Dendritic grain profiles for different crystallographic orientations show the existence of a great number of regular and parallel secondary and tertiary arms. The simulation results for the secondary arm spacing and grain size were compared with experimental data and with results reported in the literature. A good agreement was found between the simulated results and the experimental data. It can be concluded that the model can be used to predict the dendritic microstructure of aluminum alloy in a quantitative manner.

  19. Simple cellular automaton model for traffic breakdown, highway capacity, and synchronized flow.

    Science.gov (United States)

    Kerner, Boris S; Klenov, Sergey L; Schreckenberg, Michael

    2011-10-01

    We present a simple cellular automaton (CA) model for two-lane roads explaining the physics of traffic breakdown, highway capacity, and synchronized flow. The model consists of the rules "acceleration," "deceleration," "randomization," and "motion" of the Nagel-Schreckenberg CA model as well as "overacceleration through lane changing to the faster lane," "comparison of vehicle gap with the synchronization gap," and "speed adaptation within the synchronization gap" of Kerner's three-phase traffic theory. We show that these few rules of the CA model can appropriately simulate fundamental empirical features of traffic breakdown and highway capacity found in traffic data measured over years in different countries, like characteristics of synchronized flow, the existence of the spontaneous and induced breakdowns at the same bottleneck, and associated probabilistic features of traffic breakdown and highway capacity. Single-vehicle data derived in model simulations show that synchronized flow first occurs and then self-maintains due to a spatiotemporal competition between speed adaptation to a slower speed of the preceding vehicle and passing of this slower vehicle. We find that the application of simple dependences of randomization probability and synchronization gap on driving situation allows us to explain the physics of moving synchronized flow patterns and the pinch effect in synchronized flow as observed in real traffic data.

  20. ONE-DIMENSIONAL CELLULAR AUTOMATON MODEL OF TRAFFIC FLOW BASED ON CAR-FOLLOWING IDEA

    Institute of Scientific and Technical Information of China (English)

    董力耘; 薛郁; 戴世强

    2002-01-01

    An improved one-dimensional CA (Cellular Automaton) traffic model was proposed to describe the highway traffic under the periodic boundary conditions. This model was based on the idea of the car-following model, which claims that the motion of a vehicle at one time step depends on both its headway and the synchronous motion of the front vehicle,thus including indirectly the influence of its sub-neighboring vehicle. In addition, the socalled safety distance was introduced to consider the deceleration behavior of vehicles and the stochastic factor was taken into account by introducing the deceleration probability.Meanwhile, the conditional deceleration in the model gives a better description of the phenomena observed on highways. It is found that there exists the metastability and hysteresis effect of traffic flow in the neighborhood of critical density under different initial conditions.Since this model gives a reasonable depiction of the motion of a single vehicle, it is easy to be extended to the case of traffic flow under the control of traffic lights in cities.

  1. S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation.

    Directory of Open Access Journals (Sweden)

    Vikram Paruchuri

    Full Text Available S100A7 is a small calcium binding protein, which has been shown to be differentially expressed in psoriatic skin lesions, as well as in squamous cell tumors of the skin, lung and breast. Although its expression has been correlated to HER+ high-grade tumors and to a high risk of progression, the molecular mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here, we showed for the first time that epidermal growth factor (EGF induces S100A7 expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines. Furthermore, our signaling studies revealed that EGF induced simultaneous EGF receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7-downregulated cell lines as compared to the vector-transfected controls. In addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine 542 was observed in these downregulated cell lines. Further studies revealed that S100A7-downregulated cells had reduced angiogenesis in vivo based on matrigel plug assays. Our results also showed decreased tumor-induced osteoclastic resorption in an intra-tibial bone injection model involving SCID mice. S100A7-downregulated cells had decreased osteoclast number and size as compared to the vector controls, and this decrease was associated with variations in IL-8 expression in in vitro cell cultures. This is a novel report on the role of S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast formation.

  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. 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...

  4. 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.

  5. Cellular uptake of antisense oligonucleotides after complexing or conjugation with cell-penetrating model peptides.

    Science.gov (United States)

    Oehlke, J; Birth, P; Klauschenz, E; Wiesner, B; Beyermann, M; Oksche, A; Bienert, M

    2002-08-01

    The uptake by mammalian cells of phosphorothioate oligonucleotides was compared with that of their respective complexes or conjugates with cationic, cell-penetrating model peptides of varying helix-forming propensity and amphipathicity. An HPLC-based protocol for the synthesis and purification of disulfide bridged conjugates in the 10-100 nmol range was developed. Confocal laser scanning microscopy (CLSM) in combination with gel-capillary electrophoresis and laser induced fluorescence detection (GCE-LIF) revealed cytoplasmic and nuclear accumulationin all cases. The uptake differences between naked oligonucleotides and their respective peptide complexes or conjugates were generally confined to one order of magnitude. No significant influence of the structural properties of the peptide components upon cellular uptake was found. Our results question the common belief that the increased biological activity of oligonucleotides after derivatization with membrane permeable peptides may be primarily due to improved membrane translocation.

  6. 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.

  7. 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...

  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. Biopolymer stochastic moments. I. Modeling human rhinovirus cellular recognition with protein surface electrostatic moments.

    Science.gov (United States)

    González-Díaz, Humberto; Uriarte, Eugenio

    2005-04-05

    Stochastic moments may be applied as molecular descriptors in quantitative structure-activity relationship (QSAR) studies for small molecules (H. González-Dìaz et al., Journal of Molecular Modeling, 2002, Vol. 8, pp. 237-245; 2003, Vol. 9, pp. 395-407). However, applications in the field of biopolymers are less known. Recently, the MARCH-INSIDE approach has been generalized to encode structural features of proteins and other biopolymers (H. González-Dáaz et al., Bioinformatics, 2003, Vol. 19, pp. 2079-2087; Bioorganic & Medicinal Chemistry Letters, 2004, Vol. 14, pp. 4691-4695; Polymers, 2004, Vol. 45, pp. 3845-3853; Bioorganic & Medicinal Chemistry, 2005, Vol. 13, pp. 323-331). The present article attempts to extend this research by introducing for the first time stochastic moments for a surface road map of viral proteins. These moments are afterward used to seek a model that predicts the cellular receptor for human rhinoviruses. The model correctly classified 100% of 10 viruses binding to low-density lipoprotein receptor (LDLR) and 88.9% of 9 viruses binding to the intracellular adhesion molecule (ICAM) receptors in training. The same results have been obtained in four cross-validation experiments using a resubstitution technique. The present model favorably compares, in terms of complexity, with other previously reported based on entropy considerations, and offers a quantitative basis for the visual rule previously reported by Vlasak et al.

  10. 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.

  11. Realistic numerical modelling of human head tissue exposure to electromagnetic waves from cellular phones

    Science.gov (United States)

    Scarella, Gilles; Clatz, Olivier; Lanteri, Stéphane; Beaume, Grégory; Oudot, Steve; Pons, Jean-Philippe; Piperno, Sergo; Joly, Patrick; Wiart, Joe

    2006-06-01

    The ever-rising diffusion of cellular phones has brought about an increased concern for the possible consequences of electromagnetic radiation on human health. Possible thermal effects have been investigated, via experimentation or simulation, by several research projects in the last decade. Concerning numerical modeling, the power absorption in a user's head is generally computed using discretized models built from clinical MRI data. The vast majority of such numerical studies have been conducted using Finite Differences Time Domain methods, although strong limitations of their accuracy are due to heterogeneity, poor definition of the detailed structures of head tissues (staircasing effects), etc. In order to propose numerical modeling using Finite Element or Discontinuous Galerkin Time Domain methods, reliable automated tools for the unstructured discretization of human heads are also needed. Results presented in this article aim at filling the gap between human head MRI images and the accurate numerical modeling of wave propagation in biological tissues and its thermal effects. To cite this article: G. Scarella et al., C. R. Physique 7 (2006).

  12. Development of in vitro models for cellular and molecular studies in toxicology and chemoprevention

    Energy Technology Data Exchange (ETDEWEB)

    Mace, K.; Offord, E.A.; Harris, C.C.; Pfeifer, A.M.A. [Nestle Research Center, Lausanne (Switzerland)

    1998-12-31

    Many natural dietary phytochemicals found compounds found in fruits, vegetables, spices and tea have been shown in recent years to be protective against cancer in various animal models. In the light of the potential impact of these compounds on human health it is important to elucidate the mechanisms involved. We therefore developed and characterized relevant in vitro models using immortalized human epithelial cell lines derived from target tissues in carcinogenesis, such as lung, liver and colon. Assays were established, allowing the evaluation of the cytotoxic and genotoxic effects of various procarcinogens, including nitrosamines, mycotoxins and heterocyclic amines on these metabolically-competent human epithelial cell lines. These cellular models appeared to be a useful tool to study the capacity of certain food components to block the initiation stage of carcinogenesis. The ability of carnosol and carnosic acid from rosemary as well as the synthetic dithiolethione, oltipraz, to block the formation of DNA adducts, and their effects on the expression of phase I and phase II enzymes was investigated. We have observed that both rosemary extracts and oltiprax inhibited benzo(a)pyrene- or aflatoxin B{sub 1}-induced DNA adduct formation by strongly inhibiting CYP{sub 450} activities and inducing the expression of glutathione S-transferase. These results in human cell models give some insight into the different mechanisms involved in the chemopreventive action of both natural and synthetic compounds in relation to phase I and phase II enzymes. (orig.)

  13. Evaluation of biological activities of highly diluted nucleotide sequences by using cellular models

    Directory of Open Access Journals (Sweden)

    Pierre Dorfman

    2012-09-01

    Full Text Available Background: highly diluted specific nucleic acids (SNA®, designed to modulate viral and cytokine genes expression, are currently used in Micro-Immunotherapy to treat viral infections and immune disorders. Although some preliminary studies have showed clinical benefit of these homeopathic preparations [1], no experimental data are available to explain their mechanism of action. Aims: to investigate the in vitro effect of two sets of highly diluted (HD SNA targeting i latent/lytic Epstein-Barr virus (SNA EBV and ii TNF-α and its receptor p55 involved in rheumatoid arthritis (SNA RA on cellular models. Methodology: serial homeopathic dilutions of SNA EBV and SNA RA (15cH-18cH were tested on a EBV-positive B-lymphoblastoid (B95-8 and on a LPS-stimulated macrophage (THP1 cell lines respectively, in comparison with agitated/diluted water and scramble DNA sequences prepared in the same conditions (negative controls. For B95-8 proliferative model, high mobility group box 1 protein (HMGB1 was used as reference. Analyzed biological parameters on B95-8 were i cell proliferation measured after 24 and 48h of incubation with HD SNA and ii expression of the EBV ZEBRA protein in response to TGF-β by Western-blotting (T+24h. For THP1 model, TNF-α synthesis and release were determined by RT-qPCR and ELISA (protein, after stimulation by LPS (1µg/ml and HD SNA co-administration. Results: we demonstrated that HD SNA RA significantly down-regulated TNF-α synthesis and release. This biological activity was showed to be specific (no effect of HD scramble SNA and related to the level of dilution (maximal effect with higher dilutions. Unexpectedly, a biological effect of agitated/diluted water was also detected in both cellular models. For B95-8 model, this effect resulted in a significant decrease of B95-8 proliferation (comparable to the HMGB1 reference and an inhibition of ZEBRA expression. Similarly, a reproducible

  14. 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.

  15. Cellular automaton modelling of lightning-induced and man made forest fires

    Science.gov (United States)

    Krenn, R.; Hergarten, S.

    2009-10-01

    The impact of forest fires on nature and civilisation is conflicting: on one hand, they play an irreplaceable role in the natural regeneration process, but on the other hand, they come within the major natural hazards in many regions. Their frequency-area distributions show power-law behaviour with scaling exponents α in a quite narrow range, relating wildfire research to the theoretical framework of self-organised criticality. Examples of self-organised critical behaviour can be found in computer simulations of simple cellular automaton models. The established self-organised critical Drossel-Schwabl forest fire model is one of the most widespread models in this context. Despite its qualitative agreement with event-size statistics from nature, its applicability is still questioned. Apart from general concerns that the Drossel-Schwabl model apparently oversimplifies the complex nature of forest dynamics, it significantly overestimates the frequency of large fires. We present a modification of the model rules that distinguishes between lightning-induced and man made forest fires and enables a systematic increase of the scaling exponent α by approximately 1/3. In addition, combined simulations using both the original and the modified model rules predict a dependence of the overall event-size distribution on the ratio of lightning induced and man made fires as well as a splitting of their partial distributions. Lightning is identified as the dominant mechanism in the regime of the largest fires. The results are confirmed by the analysis of the Canadian Large Fire Database and suggest that lightning-induced and man made forest fires cannot be treated separately in wildfire modelling, hazard assessment and forest management.

  16. How students learn to coordinate knowledge of physical and mathematical models in cellular physiology

    Science.gov (United States)

    Lira, Matthew

    This dissertation explores the Knowledge in Pieces (KiP) theory to account for how students learn to coordinate knowledge of mathematical and physical models in biology education. The KiP approach characterizes student knowledge as a fragmented collection of knowledge elements as opposed to stable and theory-like knowledge. This dissertation sought to use this theoretical lens to account for how students understand and learn with mathematical models and representations, such as equations. Cellular physiology provides a quantified discipline that leverages concepts from mathematics, physics, and chemistry to understand cellular functioning. Therefore, this discipline provides an exemplary context for assessing how biology students think and learn with mathematical models. In particular, the resting membrane potential provides an exemplary concept well defined by models of dynamic equilibrium borrowed from physics and chemistry. In brief, membrane potentials, or voltages, "rest" when the electrical and chemical driving forces for permeable ionic species are equal in magnitude but opposite in direction. To assess students' understandings of this concept, this dissertation employed three studies: the first study employed the cognitive clinical interview to assess student thinking in the absence and presence of equations. The second study employed an intervention to assess student learning and the affordances of an innovative assessment. The third student employed a human-computer-interaction paradigm to assess how students learn with a novel multi-representational technology. Study 1 revealed that students saw only one influence--the chemical gradient--and that students coordinated knowledge of only this gradient with the related equations. Study 2 revealed that students benefited from learning with the multi-representational technology and that the assessment detected performance gains across both calculation and explanation tasks. Last, Study 3 revealed how students

  17. A refined and dynamic cellular automaton model for pedestrian-vehicle mixed traffic flow

    Science.gov (United States)

    Liu, Mianfang; Xiong, Shengwu

    2016-12-01

    Mixed traffic flow sharing the “same lane” and having no discipline on road is a common phenomenon in the developing countries. For example, motorized vehicles (m-vehicles) and nonmotorized vehicles (nm-vehicles) may share the m-vehicle lane or nm-vehicle lane and pedestrians may share the nm-vehicle lane. Simulating pedestrian-vehicle mixed traffic flow consisting of three kinds of traffic objects: m-vehicles, nm-vehicles and pedestrians, can be a challenge because there are some erratic drivers or pedestrians who fail to follow the lane disciplines. In the paper, we investigate various moving and interactive behavior associated with mixed traffic flow, such as lateral drift including illegal lane-changing and transverse crossing different lanes, overtaking and forward movement, and propose some new moving and interactive rules for pedestrian-vehicle mixed traffic flow based on a refined and dynamic cellular automaton (CA) model. Simulation results indicate that the proposed model can be used to investigate the traffic flow characteristic in a mixed traffic flow system and corresponding complicated traffic problems, such as, the moving characteristics of different traffic objects, interaction phenomenon between different traffic objects, traffic jam, traffic conflict, etc., which are consistent with the actual mixed traffic system. Therefore, the proposed model provides a solid foundation for the management, planning and evacuation of the mixed traffic flow.

  18. Simulation of Evacuation Characteristics Using a 2-Dimensional Cellular Automata Model for Pedestrian Dynamics

    Directory of Open Access Journals (Sweden)

    Liqiang Ji

    2013-01-01

    Full Text Available In public places, the high pedestrian density is one of the direct causes leading to crowding and trample disaster, so it is very necessary to investigate the collective and evacuation characteristics for pedestrian movement. In the occupants’ evacuation process, the people-people interaction and the people-environment interaction are sufficiently considered in this paper, which have been divided into the exit attraction, the repulsion force between people, the friction between people, the repulsion force between human and barrier, and the attraction of surrounding people. Through analyzing the existing models, a new occupant evacuation cellular automata (CA model based on the social force model is presented, which overcomes the shortage of the high density crowd simulation and combines the advantages that CA has sample rules and faster calculating speed. The simulating result shows a great applicability for evacuation under the high density crowd condition, and the segregation phenomena have also been found in the bidirectional pedestrian flow. Besides these, setting isolated belt near the exit or entrance of underpass not only remarkably decreases the density and the risk of tramper disaster but also increases the evacuation efficiency, so it provides a new idea for infrastructure design about the exits and entrances.

  19. Application of GA in optimization of pore network models generated by multi-cellular growth algorithms

    Science.gov (United States)

    Jamshidi, Saeid; Boozarjomehry, Ramin Bozorgmehry; Pishvaie, Mahmoud Reza

    2009-10-01

    In pore network modeling, the void space of a rock sample is represented at the microscopic scale by a network of pores connected by throats. Construction of a reasonable representation of the geometry and topology of the pore space will lead to a reliable prediction of the properties of porous media. Recently, the theory of multi-cellular growth (or L-systems) has been used as a flexible tool for generation of pore network models which do not require any special information such as 2D SEM or 3D pore space images. In general, the networks generated by this method are irregular pore network models which are inherently closer to the complicated nature of the porous media rather than regular lattice networks. In this approach, the construction process is controlled only by the production rules that govern the development process of the network. In this study, genetic algorithm has been used to obtain the optimum values of the uncertain parameters of these production rules to build an appropriate irregular lattice network capable of the prediction of both static and hydraulic information of the target porous medium.

  20. Channel modeling for fifth generation cellular networks and wireless sensor networks

    Science.gov (United States)

    Torabi, Amir

    In view of exponential growth in data traffic demand, the wireless communications industry has aimed to increase the capacity of existing networks by 1000 times over the next 20 years. A combination of extreme cell densification, more bandwidth, and higher spectral efficiency is needed to support the data traffic requirements for fifth generation (5G) cellular communications. In this research, the potential improvements achieved by using three major 5G enabling technologies (i.e., small cells, millimeter-wave spectrum, and massive MIMO) in rural and urban environments are investigated. This work develops SPM and KA-based ray models to investigate the impact of geometrical parameters on terrain-based multiuser MIMO channel characteristic. Moreover, a new directional 3D channel model is developed for urban millimeter-wave (mmW) small cells. Path-loss, spatial correlation, coverage distance, and coherence length are studied in urban areas. Exploiting physical optics (PO) and geometric optics (GO) solutions, closed form expressions are derived for spatial correlation. Achievable spatial diversity is evaluated using horizontal and vertical linear arrays as well as planar 2D arrays. In another study, a versatile near-ground field prediction model is proposed to facilitate accurate wireless sensor network (WSN) simulations. Monte Carlo simulations are used to investigate the effects of antenna height, frequency of operation, polarization, and terrain dielectric and roughness properties on WSNs performance.

  1. A computational approach to modeling cellular-scale blood flow in complex geometry

    Science.gov (United States)

    Balogh, Peter; Bagchi, Prosenjit

    2017-04-01

    We present a computational methodology for modeling cellular-scale blood flow in arbitrary and highly complex geometry. Our approach is based on immersed-boundary methods, which allow modeling flows in arbitrary geometry while resolving the large deformation and dynamics of every blood cell with high fidelity. The present methodology seamlessly integrates different modeling components dealing with stationary rigid boundaries of complex shape, moving rigid bodies, and highly deformable interfaces governed by nonlinear elasticity. Thus it enables us to simulate 'whole' blood suspensions flowing through physiologically realistic microvascular networks that are characterized by multiple bifurcating and merging vessels, as well as geometrically complex lab-on-chip devices. The focus of the present work is on the development of a versatile numerical technique that is able to consider deformable cells and rigid bodies flowing in three-dimensional arbitrarily complex geometries over a diverse range of scenarios. After describing the methodology, a series of validation studies are presented against analytical theory, experimental data, and previous numerical results. Then, the capability of the methodology is demonstrated by simulating flows of deformable blood cells and heterogeneous cell suspensions in both physiologically realistic microvascular networks and geometrically intricate microfluidic devices. It is shown that the methodology can predict several complex microhemodynamic phenomena observed in vascular networks and microfluidic devices. The present methodology is robust and versatile, and has the potential to scale up to very large microvascular networks at organ levels.

  2. Quasi-classical modeling of molecular quantum-dot cellular automata multidriver gates

    Science.gov (United States)

    Rahimi, Ehsan; Nejad, Shahram Mohammad

    2012-05-01

    Molecular quantum-dot cellular automata (mQCA) has received considerable attention in nanoscience. Unlike the current-based molecular switches, where the digital data is represented by the on/off states of the switches, in mQCA devices, binary information is encoded in charge configuration within molecular redox centers. The mQCA paradigm allows high device density and ultra-low power consumption. Digital mQCA gates are the building blocks of circuits in this paradigm. Design and analysis of these gates require quantum chemical calculations, which are demanding in computer time and memory. Therefore, developing simple models to probe mQCA gates is of paramount importance. We derive a semi-classical model to study the steady-state output polarization of mQCA multidriver gates, directly from the two-state approximation in electron transfer theory. The accuracy and validity of this model are analyzed using full quantum chemistry calculations. A complete set of logic gates, including inverters and minority voters, are implemented to provide an appropriate test bench in the two-dot mQCA regime. We also briefly discuss how the QCADesigner tool could find its application in simulation of mQCA devices.

  3. 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.

  4. Understanding the cellular mode of action of vernakalant using a computational model: answers and new questions

    Directory of Open Access Journals (Sweden)

    Loewe Axel

    2015-09-01

    Full Text Available Vernakalant is a new antiarrhythmic agent for the treatment of atrial fibrillation. While it has proven to be effective in a large share of patients in clinical studies, its underlying mode of action is not fully understood. In this work, we aim to link experimental data from the subcellular, tissue, and system level using an in-silico approach. A Hill’s equation-based drug model was extended to cover the frequency dependence of sodium channel block. Two model variants were investigated: M1 based on subcellular data and M2 based on tissue level data. 6 action potential (AP markers were evaluated regarding their dose, frequency and substrate dependence. M1 comprising potassium, sodium, and calcium channel block reproduced the reported prolongation of the refractory period. M2 not including the effects on potassium channels reproduced reported AP morphology changes on the other hand. The experimentally observed increase of ERP accompanied by a shortening of APD90 was not reproduced. Thus, explanations for the drug-induced changes are provided while none of the models can explain the effects in their entirety. These results foster the understanding of vernakalant’s cellular mode of action and point out relevant gaps in our current knowledge to be addressed in future in-silico and experimental research on this aspiring antiarrhythmic agent.

  5. Expression of cellular components in granulomatous inflammatory response in Piaractus mesopotamicus model.

    Directory of Open Access Journals (Sweden)

    Wilson Gómez Manrique

    Full Text Available The present study aimed to describe and characterize the cellular components during the evolution of chronic granulomatous inflammation in the teleost fish pacus (P. mesopotamicus induced by Bacillus Calmette-Guerin (BCG, using S-100, iNOS and cytokeratin antibodies. 50 fish (120±5.0 g were anesthetized and 45 inoculated with 20 μL (40 mg/mL (2.0 x 10(6 CFU/mg and five inoculated with saline (0,65% into muscle tissue in the laterodorsal region. To evaluate the inflammatory process, nine fish inoculated with BCG and one control were sampled in five periods: 3rd, 7th, 14th, 21st and 33rd days post-inoculation (DPI. Immunohistochemical examination showed that the marking with anti-S-100 protein and anti-iNOS antibodies was weak, with a diffuse pattern, between the third and seventh DPI. From the 14th to the 33rd day, the marking became stronger and marked the cytoplasm of the macrophages. Positivity for cytokeratin was initially observed in the 14th DPI, and the stronger immunostaining in the 33rd day, period in which the epithelioid cells were more evident and the granuloma was fully formed. Also after the 14th day, a certain degree of cellular organization was observed, due to the arrangement of the macrophages around the inoculated material, with little evidence of edema. The arrangement of the macrophages around the inoculum, the fibroblasts, the lymphocytes and, in most cases, the presence of melanomacrophages formed the granuloma and kept the inoculum isolated in the 33rd DPI. The present study suggested that the granulomatous experimental model using teleost fish P. mesopotamicus presented a similar response to those observed in mammals, confirming its importance for studies of chronic inflammatory reaction.

  6. Extracts from two ubiquitous Mediterranean plants ameliorate cellular and animal models of neurodegenerative proteinopathies.

    Science.gov (United States)

    Briffa, Michelle; Ghio, Stephanie; Neuner, Johanna; Gauci, Alison J; Cacciottolo, Rebecca; Marchal, Christelle; Caruana, Mario; Cullin, Christophe; Vassallo, Neville; Cauchi, Ruben J

    2017-01-18

    A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities. In the present report, we investigated whether extracts derived from two ubiquitous Mediterranean plants namely, the prickly pear Opuntia ficus-indica (EOFI) and the brown alga Padina pavonica (EPP) alleviate neurodegenerative phenotypes in yeast (Saccharomyces cerevisiae) and fly (Drosophila melanogaster) models of AD and PD. Pre-treatment with EPP or EOFI in the culture medium significantly improved the viability of yeast expressing the Arctic Aβ42 (E22G) mutant. Supplementing food with EOFI or EPP dramatically ameliorated lifespan and behavioural signs of flies with brain-specific expression of wild-type Aβ42 (model of late-onset AD) or the Arctic Aβ42 variant (model of early-onset AD). Additionally, we show that either extract prolonged the survival of a PD fly model based on transgenic expression of the human α-syn A53T mutant. Taken together, our findings suggest that the plant-derived extracts interfere with shared mechanisms of neurodegeneration in AD and PD. This notion is strengthened by evidence demonstrating that EOFI and to a greater extent EPP, while strongly inhibiting the fibrillogenesis of both Aβ42 and α-syn, accumulate remodelled oligomeric aggregates that are less effective at disrupting lipid membrane integrity. Our work therefore opens new avenues for developing therapeutic applications of these natural plant extracts in the treatment of amyloidogenic

  7. 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.

  8. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Directory of Open Access Journals (Sweden)

    Ángel Monteagudo

    Full Text Available Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  9. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modeling.

    Science.gov (United States)

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2014-11-10

    Following partial hepatectomy, the liver initiates a regenerative program involving hepatocyte priming and replication driven by coordinated cytokine and growth factor actions. We investigated the mechanisms underlying Adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn-/- mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn-/- mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to IL-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. This article is protected by copyright. All rights reserved.

  10. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modelling.

    Science.gov (United States)

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2015-01-15

    Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn(-/-) mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn(-/-) mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver.

  11. 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.

  12. Cellular automata model for urban road traffic flow considering pedestrian crossing street

    Science.gov (United States)

    Zhao, Han-Tao; Yang, Shuo; Chen, Xiao-Xu

    2016-11-01

    In order to analyze the effect of pedestrians' crossing street on vehicle flows, we investigated traffic characteristics of vehicles and pedestrians. Based on that, rules of lane changing, acceleration, deceleration, randomization and update are modified. Then we established two urban two-lane cellular automata models of traffic flow, one of which is about sections with non-signalized crosswalk and the other is on uncontrolled sections with pedestrians crossing street at random. MATLAB is used for numerical simulation of the different traffic conditions; meanwhile space-time diagram and relational graphs of traffic flow parameters are generated and then comparatively analyzed. Simulation results indicate that when vehicle density is lower than around 25 vehs/(km lane), pedestrians have modest impact on traffic flow, whereas when vehicle density is higher than about 60 vehs/(km lane), traffic speed and volume will decrease significantly especially on sections with non-signal-controlled crosswalk. The results illustrate that the proposed models reconstruct the traffic flow's characteristic with the situation where there are pedestrians crossing and can provide some practical reference for urban traffic management.

  13. Computation of interface curvature in modelling of solidification by the method of cellular automaton

    Directory of Open Access Journals (Sweden)

    Burbelko A. A.

    2007-01-01

    Full Text Available Modelling of solidification process by the method of cellular automaton (CA requires determination of geometrical characteristics of the interface, i.e. of its direction and curvature. In previous studies the authors proposed a method to reduce the well-known effect of an artificial symmetry of the simulation results caused by the anisotropy of the CA computation grid (e.g. a preferred growth of the main dendrite arms along the grid lines or at an angle of 45° in the case of grids with square cells. The aim was achieved by application of the developed methods of computation of the transformation rate and front direction. In this study the authors examined the problem of an accuracy of the computations of an interface curvature. The obtained results show us that the error of the curvature computation introduced by some well-known methods exceeds by 100% a nominal value of this parameter. A method to estimate the accuracy of the applied solution has been proposed. Practical application of the proposed tests enables selection of a best solution, including the authors' own solutions, thus considerably improving an accuracy of the solidification modelling by the method of CA.

  14. Muscle memory and a new cellular model for muscle atrophy and hypertrophy.

    Science.gov (United States)

    Gundersen, Kristian

    2016-01-01

    Memory is a process in which information is encoded, stored, and retrieved. For vertebrates, the modern view has been that it occurs only in the brain. This review describes a cellular memory in skeletal muscle in which hypertrophy is 'remembered' such that a fibre that has previously been large, but subsequently lost its mass, can regain mass faster than naive fibres. A new cell biological model based on the literature, with the most reliable methods for identifying myonuclei, can explain this phenomenon. According to this model, previously untrained fibres recruit myonuclei from activated satellite cells before hypertrophic growth. Even if subsequently subjected to grave atrophy, the higher number of myonuclei is retained, and the myonuclei seem to be protected against the elevated apoptotic activity observed in atrophying muscle tissue. Fibres that have acquired a higher number of myonuclei grow faster when subjected to overload exercise, thus the nuclei represent a functionally important 'memory' of previous strength. This memory might be very long lasting in humans, as myonuclei are stable for at least 15 years and might even be permanent. However, myonuclei are harder to recruit in the elderly, and if the long-lasting muscle memory also exists in humans, one should consider early strength training as a public health advice. In addition, myonuclei are recruited during steroid use and encode a muscle memory, at least in rodents. Thus, extending the exclusion time for doping offenders should be considered.

  15. Cellular resolution models for even skipped regulation in the entire Drosophila embryo

    Science.gov (United States)

    Ilsley, Garth R; Fisher, Jasmin; Apweiler, Rolf; DePace, Angela H; Luscombe, Nicholas M

    2013-01-01

    Transcriptional control ensures genes are expressed in the right amounts at the correct times and locations. Understanding quantitatively how regulatory systems convert input signals to appropriate outputs remains a challenge. For the first time, we successfully model even skipped (eve) stripes 2 and 3+7 across the entire fly embryo at cellular resolution. A straightforward statistical relationship explains how transcription factor (TF) concentrations define eve’s complex spatial expression, without the need for pairwise interactions or cross-regulatory dynamics. Simulating thousands of TF combinations, we recover known regulators and suggest new candidates. Finally, we accurately predict the intricate effects of perturbations including TF mutations and misexpression. Our approach imposes minimal assumptions about regulatory function; instead we infer underlying mechanisms from models that best fit the data, like the lack of TF-specific thresholds and the positional value of homotypic interactions. Our study provides a general and quantitative method for elucidating the regulation of diverse biological systems. DOI: http://dx.doi.org/10.7554/eLife.00522.001 PMID:23930223

  16. Inferring cellular regulatory networks with Bayesian model averaging for linear regression (BMALR).

    Science.gov (United States)

    Huang, Xun; Zi, Zhike

    2014-08-01

    Bayesian network and linear regression methods have been widely applied to reconstruct cellular regulatory networks. In this work, we propose a Bayesian model averaging for linear regression (BMALR) method to infer molecular interactions in biological systems. This method uses a new closed form solution to compute the posterior probabilities of the edges from regulators to the target gene within a hybrid framework of Bayesian model averaging and linear regression methods. We have assessed the performance of BMALR by benchmarking on both in silico DREAM datasets and real experimental datasets. The results show that BMALR achieves both high prediction accuracy and high computational efficiency across different benchmarks. A pre-processing of the datasets with the log transformation can further improve the performance of BMALR, leading to a new top overall performance. In addition, BMALR can achieve robust high performance in community predictions when it is combined with other competing methods. The proposed method BMALR is competitive compared to the existing network inference methods. Therefore, BMALR will be useful to infer regulatory interactions in biological networks. A free open source software tool for the BMALR algorithm is available at https://sites.google.com/site/bmalr4netinfer/.

  17. Should big cities grow? Scenario-based cellular automata urban growth modeling and policy applications

    Directory of Open Access Journals (Sweden)

    ChengHe Guan

    2016-12-01

    Full Text Available The formation of ‘Urban Networks’ has become a wide-spread phenomenon around the world. In the study of metropolitan regions, there are competing or diverging views about management and control of environmental and land-use factors as well as about scales and arrangements of settlements. Especially in China, these matters alongside of regulatory aspects, infrastructure applications, and resource allocations, are important because of population concentrations and the overlapping of urban areas with other land resources. On the other hand, the increasing sophistication of models operating on iterative computational power and widely-available spatial information and analytical techniques make it possible to simulate and investigate the spatial distribution of urban territories at a regional scale. This research applies a scenario-based Cellular Automata model to a case study of the Changjiang Delta Region, which produces useful and predictive scenario-based projections within the region, using quantitative methods and baseline conditions that address issues of regional urban development. The contribution of the research includes the improvement of computer simulation of urban growth, the application of urban form and other indices to evaluate complex urban conditions, and a heightened understanding of the performance of an urban network in the Changjiang Delta Region composed of big, medium, and small-sized cities and towns.

  18. A biofidelic 3D culture model to study the development of brain cellular systems

    Science.gov (United States)

    Ren, M.; Du, C.; Herrero Acero, E.; Tang-Schomer, M. D.; Özkucur, N.

    2016-01-01

    Little is known about how cells assemble as systems during corticogenesis to generate collective functions. We built a neurobiology platform that consists of fetal rat cerebral cortical cells grown within 3D silk scaffolds (SF). Ivermectin (Ivm), a glycine receptor (GLR) agonist, was used to modulate cell resting membrane potential (Vmem) according to methods described in a previous work that implicated Ivm in the arrangement and connectivity of cortical cell assemblies. The cells developed into distinct populations of neuroglial stem/progenitor cells, mature neurons or epithelial-mesenchymal cells. Importantly, the synchronized electrical activity in the newly developed cortical assemblies could be recorded as local field potential (LFP) measurements. This study therefore describes the first example of the development of a biologically relevant cortical plate assembly outside of the body. This model provides i) a preclinical basis for engineering cerebral cortex tissue autografts and ii) a biofidelic 3D culture model for investigating biologically relevant processes during the functional development of cerebral cortical cellular systems. PMID:27112667

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

    KAUST Repository

    AlAmmouri, Ahmad

    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.

  20. 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

  1. A new in vitro model to study cellular responses after thermomechanical damage in monolayer cultures.

    Directory of Open Access Journals (Sweden)

    Alice Hettler

    Full Text Available Although electrosurgical instruments are widely used in surgery to cut tissue layers or to achieve hemostasis by coagulation (electrocautery, only little information is available concerning the inflammatory or immune response towards the debris generated. Given the elevated local temperatures required for successful electrocautery, the remaining debris is likely to contain a plethora of compounds entirely novel to the intracorporal setting. A very common in vitro method to study cell migration after mechanical damage is the scratch assay, however, there is no established model for thermomechanical damage to characterise cellular reactions. In this study, we established a new in vitro model to investigate exposure to high temperature in a carefully controlled cell culture system. Heatable thermostat-controlled aluminium stamps were developed to induce local damage in primary human umbilical vein endothelial cells (HUVEC. The thermomechanical damage invoked is reproducibly locally confined, therefore allowing studies, under the same experimental conditions, of cells affected to various degrees as well as of unaffected cells. We show that the unaffected cells surrounding the thermomechanical damage zone are able to migrate into the damaged area, resulting in a complete closure of the 'wound' within 48 h. Initial studies have shown that there are significant morphological and biological differences in endothelial cells after thermomechanical damage compared to the mechanical damage inflicted by using the unheated stamp as a control. Accordingly, after thermomechanical damage, cell death as well as cell protection programs were activated. Mononuclear cells adhered in the area adjacent to thermomechanical damage, but not to the zone of mechanical damage. Therefore, our model can help to understand the differences in wound healing during the early phase of regeneration after thermomechanical vs. mechanical damage. Furthermore, this model lends itself

  2. 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.

  3. 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

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

    Institute of Scientific and Technical Information of China (English)

    Rui Chen; Qing-yan Xu; Bai-cheng Liu

    2016-01-01

    Due to the extensive application of Al-Si aloys 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 celular 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 inlfuence of cooling rate and Sr modiifcation 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 wel as the anisotropic characteristic of eutectic Si growth. The capturing rule takes into account the effects of modiifcation on the silicon growth behaviors. The simulated results indicate that for unmodiifed aloy, the higher eutectic undercooling results in the higher eutectic growth velocity, and a more reifned eutectic microstructure as wel as narrower eutectic lamelar spacing. For modiifed aloy, the eutectic silicon tends to be obvious ifbrous morphology and the morphology of eutectic Si is determined by both chemical modiifer and cooling rate. The predicted microstructure of Al-7Si aloy under different solidiifcation conditions shows that this proposed model can successfuly reproduce both dendrite and eutectic microstructures.

  5. Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Sara Anjomani Virmouni

    Full Text Available Friedreich ataxia (FRDA is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats, YG8R (90 and 190 GAA repeats and YG22R (190 GAA repeats.We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R.Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.

  6. Phase transitions in cellular automata models of spatial susceptible-infected-resistant-susceptible epidemics

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhi-Zhen; Wang Ai-Ling

    2009-01-01

    Spatially explicit models have become widely used in today's mathematical ecology and epidemiology to study the persistence of populations. For simplicity, population dynamics is often analysed by using ordinary differential equations (ODEs) or partial differential equations (PDEs) in the one-dimensional (1D) space. An important question is to predict species extinction or persistence rate by mean of computer simulation based on the spatial model. Recently, it has been reported that stable turbulent and regular waves are persistent based on the spatial susceptible-infected-resistant-susceptible (SIRS) model by using the cellular automata (CA) method in the two-dimensional (2D) space [Proc. Natl. Acad. Sci. USA 101, 18246 (2004)]. In this paper, we address other important issues relevant to phase transitions of epidemic persistence. We are interested in assessing the significance of the risk of extinction in 1D space. Our results show that the 2D space can considerably increase the possibility of persistence of spread of epidemics when the degree distribution of the individuals is uniform, I.e. The pattern of 2D spatial persistence corresponding to extinction in a 1D system with the same parameters. The trade-offs of extinction and persistence between the infection period and infection rate are observed in the 1D case. Moreover, near the trade-off (phase transition) line, an independent estimation of the dynamic exponent can be performed, and it is in excellent agreement with the result obtained by using the conjectured relationship of directed percolation. We find that the introduction of a short-range diffusion and a long-range diffusion among the neighbourhoods can enhance the persistence and global disease spread in the space.

  7. Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.

    Science.gov (United States)

    Gérard, Claude; Goldbeter, Albert

    2012-05-01

    The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values.

  8. Toward a biaxial model of "bipolar" affective disorders: further exploration of genetic, molecular and cellular substrates.

    Science.gov (United States)

    Askland, Kathleen

    2006-08-01

    Current epidemiologic and genetic evidence strongly supports the heritability of bipolar disease. Inconsistencies across linkage and association analyses have been primarily interpreted as suggesting polygenic, nonMendelian and variably-penetrant inheritance (i.e., in terms of interacting disease models). An equally-likely explanation for this genetic complexity is that trait, locus and allelic heterogeneities (i.e., a heterogeneous disease model) are primarily responsible for observed variability at the population level. The two models of genetic complexity are not mutually-exclusive, and are in fact likely to co-exist both in trait determination and disease expression. However, the current model proposes that, while both types of complex genetics are likely central to observable affective trait spectra, inheritance patterns, gross phenotypic categories and treatment-responsiveness in affective disease (as well as the widespread inconsistencies across such studies) may be primarily explained in terms of a heterogeneous disease model. Gene-gene, gene-protein and protein-protein interactions, then, are most likely to serve as trait determinants and 'phenotypic modifiers' rather than as primary pathogenic determinants. Moreover, while locus heterogeneity indicates the presence of multiple susceptibility genes at the population level, it does not necessitate polygenic inheritance at the individual or pedigree level. Rather, it is compatible with the possibility of mono- or bigenic determination of disease susceptibility within individuals/pedigrees. More specifically, the biaxial model proposes that integration of specific findings from genetic linkage and association studies, ion channels research as well as pharmacologic mechanism, phenotypic specificity and effectiveness studies suggests that each gene of potential etiologic significance in primary affective illness might be categorized into one of two classes, according to their primary role in neuronal

  9. Directed Ligand Passage Over the Surface of Diffusion-Controlled Enzymes: A Cellular Automata Model

    CERN Document Server

    Ghaemi, M; Sarbolouki, M N; Ghaemi, Mehrdad; Rezaei-Ghaleh, Nasrollah; Sarbolouki, Mohammad-Nabi

    2004-01-01

    The rate-limiting step of some enzymatic reactions is a physical step, i.e. diffusion. The efficiency of such reactions can be improved through an increase in the arrival rate of the substrate molecules, e.g. by a directed passage of substrate (ligand) to active site after its random encounter with the enzyme surface. Herein, we introduce a cellular automata model simulating the ligand passage over the protein surface to its destined active site. The system is simulated using the lattice gas automata with probabilistic transition rules. Different distributions of amino acids over the protein surface are examined. For each distribution, the hydration pattern is achieved and the mean number of iteration steps needed for the ligand to arrive at the active site calculated. Comparison of results indicates that the rate at which ligand arrives at the active site is clearly affected by the distribution of amino acids outside the active side. Such a process can facilitate the ligand diffusion towards the active site ...

  10. Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality

    Directory of Open Access Journals (Sweden)

    M.A. Al-Griw

    2016-09-01

    Full Text Available Exposures to a wide variety of environmental substances are negatively associated with many biological cell systems both in humans and rodents. Trichloroethane (TCE, a ubiquitous environmental toxicant, is used in large quantities as a dissolvent, metal degreaser, chemical intermediate, and component of consumer products. This increases the likelihood of human exposure to these compounds through dermal, inhalation and oral routes. The present in vivo study was aimed to investigate the possible cellular and molecular etiology of liver abnormality induced by early exposure to TCE using a murine model. The results showed a significant increase in liver weight. Histopathological examination revealed a TCE-induced hepatotoxicity which appeared as heavily congested central vein and blood sinusoids as well as leukocytic infiltration. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates hepatocellular apoptosis was evident in the treated mice compared to control. TCE was also found to induce oxidative stress as indicated by an increase in the levels of lipid peroxidation, an oxidative stress marker. There was also a significant decrease in the DNA content of the hepatocytes of the treated groups compared to control. Agarose gel electrophoresis also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation in the liver cells, indicating oxidative stress as the cause of DNA damage. These results suggest the need for a complete risk assessment of any new chemical prior to its arrival into the consumer market.

  11. The Investigation of the Traffic Flow Behavior in Tollbooths Using Cellular Automaton Model

    Science.gov (United States)

    Jetto, K.; Ez-Zahraouy, H.; Benyoussef, A.

    Tollbooths are used to collect tolls and to control traffic flow. However, the presence of these tollbooths will slow down traffic, especially in heavily traveled roads. As a consequence, drivers and goods will spend more time and fuel waiting in a long queue. Unfortunately, there are a few papers in the literature, which have been addressed the effect of tollbooths on the traffic flow; whereas in this paper is, the properties of traffic flow inside the tollbooths are investigated. The proposed cellular automaton traffic model, with open boundaries, is based on some changing lane rules, which are inspired on the situations inside the toll plaza. The vehicles enter the plaza with an injecting rate α, and they leave with an extracting rate β, which is inversely proportional to the time service Tw. The simulation results show the existence of three phases in the phase diagram (α, β), namely: the low density phase, the congested phase, and the jamming phase. Furthermore, it is found that the vehicles does not spend the same time Tm in the plaza, even if they have the same time service. This analysis states clearly that the existence of the congested phase and the fluctuation Tm are due to the non-zero values of the probability P of changing the lane. Such phenomena disappear when P = 0, i.e., the drivers move without changing their lane. In other words, the human behavior (spontaneous changing lanes) is responsible for the congestion observed in the tollbooth.

  12. The Toxic Effects of Pathogenic Ataxin-3 Variants in a Yeast Cellular Model.

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    Marcella Bonanomi

    Full Text Available Ataxin-3 (AT3 is a deubiquitinating enzyme that triggers an inherited neurodegenerative disorder, spinocerebellar ataxia type 3, when its polyglutamine (polyQ stretch close to the C-terminus exceeds a critical length. AT3 variants carrying the expanded polyQ are prone to associate with each other into amyloid toxic aggregates, which are responsible for neuronal death with ensuing neurodegeneration. We employed Saccharomyces cerevisiae as a eukaryotic cellular model to better clarify the mechanism by which AT3 triggers the disease. We expressed three variants: one normal (Q26, one expanded (Q85 and one truncated for a region lying from the beginning of its polyQ stretch to the end of the protein (291Δ. We found that the expression of the expanded form caused reduction in viability, accumulation of reactive oxygen species, imbalance of the antioxidant defense system and loss in cell membrane integrity, leading to necrotic death. The truncated variant also exerted a qualitatively similar, albeit milder, effect on cell growth and cytotoxicity, which points to the involvement of also non-polyQ regions in cytotoxicity. Guanidine hydrochloride, a well-known inhibitor of the chaperone Hsp104, almost completely restored wild-type survival rate of both 291Δ- and Q85-expressing strains. This suggests that AT3 aggregation and toxicity is mediated by prion forms of yeast proteins, as this chaperone plays a key role in their propagation.

  13. The Toxic Effects of Pathogenic Ataxin-3 Variants in a Yeast Cellular Model

    Science.gov (United States)

    Bonanomi, Marcella; Visentin, Cristina; Invernizzi, Gaetano; Tortora, Paolo; Regonesi, Maria Elena

    2015-01-01

    Ataxin-3 (AT3) is a deubiquitinating enzyme that triggers an inherited neurodegenerative disorder, spinocerebellar ataxia type 3, when its polyglutamine (polyQ) stretch close to the C-terminus exceeds a critical length. AT3 variants carrying the expanded polyQ are prone to associate with each other into amyloid toxic aggregates, which are responsible for neuronal death with ensuing neurodegeneration. We employed Saccharomyces cerevisiae as a eukaryotic cellular model to better clarify the mechanism by which AT3 triggers the disease. We expressed three variants: one normal (Q26), one expanded (Q85) and one truncated for a region lying from the beginning of its polyQ stretch to the end of the protein (291Δ). We found that the expression of the expanded form caused reduction in viability, accumulation of reactive oxygen species, imbalance of the antioxidant defense system and loss in cell membrane integrity, leading to necrotic death. The truncated variant also exerted a qualitatively similar, albeit milder, effect on cell growth and cytotoxicity, which points to the involvement of also non-polyQ regions in cytotoxicity. Guanidine hydrochloride, a well-known inhibitor of the chaperone Hsp104, almost completely restored wild-type survival rate of both 291Δ- and Q85-expressing strains. This suggests that AT3 aggregation and toxicity is mediated by prion forms of yeast proteins, as this chaperone plays a key role in their propagation. PMID:26052945

  14. 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].

  15. 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.

  16. 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.

  17. 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 measure...

  18. Simulating Debris Flows Through A Hexagonal Cellular Automata Model: Sciddica (release S3a).

    Science.gov (United States)

    Iovine, G.; di Gregorio, S.; D'Ambrosio, D.; Lupiano, V.; Rongo, R.; Spataro, W.

    Cellular Automata (CA) are a powerful tool for modelling natural and artificial sys- tems that can be described in terms of local interactions among their constituent parts. Some types of landslides, such as debris flows, match well this requirement. The general frame and the latest, hexagonal release (S3a) of the deterministic, CA-based model SCIDDICA - specifically developed for simulating debris flows - are described. For simulation purposes, landslides can be viewed as a dynamical system, subdivided into elementary parts, whose state evolves exclusively as a consequence of local in- teractions within a spatial and temporal discretum. Space is the world of the CA, constituted by hexagonal cells. The attributes of each cell (namely "substates") de- scribe their average, physical characteristics. For computational reasons, the natural phenomenon to be simulated is "decomposed" into a number of elementary processes (local interactions), 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- S3a exhibited great flexibility in modelling debris flows. With respect to its previous releases, the mechanism of progressive erosion of the detrital cover has been added to the transition function. Considered substates are: altitude, landslide debris amount and energy, depth and type of detrital cover, water content of the debris, debris out- flows and inflows. Considered elementary processes are: outflows and inflows, energy variation, detrital cover mobilisation, water loss, debris solidification. Simulations of real debris flows, occurred in Campania (Southern Italy) on May 1998 (Sarno) and on December 1999 (San Martino V.C. and Cervinara), are presented. The validation of the model required the best assessment of values to be assigned to empirical param- eters. After that, the application of the

  19. 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

  20. 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 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.

  1. 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.

  2. N-acetyl-L-cysteine prevents stress-induced desmin aggregation in cellular models of desminopathy.

    Directory of Open Access Journals (Sweden)

    Bertrand-David Segard

    Full Text Available Mutations within the human desmin gene are responsible for a subcategory of myofibrillar myopathies called desminopathies. However, a single inherited mutation can produce different phenotypes within a family, suggesting that environmental factors influence disease states. Although several mouse models have been used to investigate organ-specific desminopathies, a more general mechanistic perspective is required to advance our knowledge toward patient treatment. To improve our understanding of disease pathology, we have developed cellular models to observe desmin behaviour in early stages of disease pathology, e.g., upon formation of cytoplasmic desmin aggregates, within an isogenic background. We cloned the wildtype and three mutant desmin cDNAs using a Tet-On Advanced® expression system in C2C12 cells. Mutations were selected based on positioning within desmin and capacity to form aggregates in transient experiments, as follows: DesS46Y (head domain; low aggregation, DesD399Y (central rod domain; high aggregation, and DesS460I (tail domain; moderate aggregation. Introduction of these proteins into a C2C12 background permitted us to compare between desmin variants as well as to determine the role of external stress on aggregation. Three different types of stress, likely encountered during muscle activity, were introduced to the cell models-thermal (heat shock, redox-associated (H2O2 and cadmium chloride, and mechanical (stretching stresses-after which aggregation was measured. Cells containing variant DesD399Y were more sensitive to stress, leading to marked cytoplasmic perinuclear aggregations. We then evaluated the capacity of biochemical compounds to prevent this aggregation, applying dexamethasone (an inducer of heat shock proteins, fisetin or N-acetyl-L-cysteine (antioxidants before stress induction. Interestingly, N-acetyl-L-cysteine pre-treatment prevented DesD399Y aggregation during most stress. N-acetyl-L-cysteine has recently been

  3. EXISTENCE AND ATTRACTIVITY OF k-ALMOST AUTOMORPHIC SEQUENCE SOLUTION OF A MODEL OF CELLULAR NEURAL NETWORKS WITH DELAY

    Institute of Scientific and Technical Information of China (English)

    Syed ABBAS; Yonghui XIA

    2013-01-01

    In this paper we discuss the existence and global attractivity of k-almost automorphic sequence solution of a model of cellular neural networks.We consider the corresponding difference equation analogue of the model system using suitable discretization method and obtain certain conditions for the existence of solution.Almost automorphic function is a good generalization of almost periodic function.This is the first paper considering such solutions of the neural networks.

  4. 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...... 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....

  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. A conceptual mathematical model of the dynamic self-organisation of distinct cellular organelles.

    Directory of Open Access Journals (Sweden)

    Bernd Binder

    Full Text Available Formation, degradation and renewal of cellular organelles is a dynamic process based on permanent budding, fusion and inter-organelle traffic of vesicles. These processes include many regulatory proteins such as SNAREs, Rabs and coats. Given this complex machinery, a controversially debated issue is the definition of a minimal set of generic mechanisms necessary to enable the self-organization of organelles differing in number, size and chemical composition. We present a conceptual mathematical model of dynamic organelle formation based on interacting vesicles which carry different types of fusogenic proteins (FP playing the role of characteristic marker proteins. Our simulations (ODEs show that a de novo formation of non-identical organelles, each accumulating a different type of FP, requires a certain degree of disproportionation of FPs during budding. More importantly however, the fusion kinetics must indispensably exhibit positive cooperativity among these FPs, particularly for the formation of larger organelles. We compared different types of cooperativity: sequential alignment of corresponding FPs on opposite vesicle/organelles during fusion and pre-formation of FP-aggregates (equivalent, e.g., to SNARE clusters prior to fusion described by Hill kinetics. This showed that the average organelle size in the system is much more sensitive to the disproportionation strength of FPs during budding if the vesicular transport system gets along with a fusion mechanism based on sequential alignments of FPs. Therefore, pre-formation of FP aggregates within the membranes prior to fusion introduce robustness with respect to organelle size. Our findings provide a plausible explanation for the evolution of a relatively large number of molecules to confer specificity on the fusion machinery compared to the relatively small number involved in the budding process. Moreover, we could speculate that a specific cooperativity which may be described by Hill

  7. Cellular mechanisms underlying spontaneous interictal spikes in an acute model of focal cortical epileptogenesis.

    Science.gov (United States)

    de Curtis, M; Radici, C; Forti, M

    1999-01-01

    The cellular mechanisms involved in the generation of spontaneous epileptiform potentials were investigated in the pirifom cortex of the in vitro isolated guinea-pig brain. A single, unilateral injection of bicuculline (150-200 nmol) in the anterior piriform cortex induced locally spontaneous interictal spikes that recurred with a period of 8.81+/-4.47 s and propagated caudally to the ipsi- and contralateral hemispheres. Simultaneous extra- and intracellular recordings from layer II and III principal cells showed that the spontaneous interictal spike correlates to a burst of action potentials followed by a large afterdepolarization. Intracellular application of the sodium conductance blocker, QX-314 (80 mM), abolished bursting activity and unmasked a high-threshold slow spike enhanced by the calcium chelator EGTA (50 mM). The slow spike was abolished by membrane hyperpolarization and by local perfusion with 2 mM cadmium. The depolarizing potential that followed the primary burst was reduced by arterial perfusion with the N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (100-200 microM). The non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM), completely and reversibly blocked the spontaneous spikes. The interictal spikes were terminated by a large afterpotential blocked either by intracellular QX-314 (80 mM) or by extracellular application of phaclofen and 2-hydroxysaclofen (10 and 4 mM, respectively). The present study demonstrates that, in an acute model of epileptogenesis, spontaneous interictal spikes are fostered by a primary burst of fast action potentials that ride on a regenerative high-threshold, possibly calcium-mediated spike, which activates a recurrent, glutamate-mediated potential responsible for the entrainment of adjacent and remote cortical regions. The bursting activity is controlled by a GABA(B) receptor-mediated inhibitory synaptic potential.

  8. 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.

  9. 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.

  10. 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.

  11. Cellular parameters for track structure modelling of radiation hazard in space

    Science.gov (United States)

    Hollmark, M.; Lind, B.; Gudowska, I.; Waligorski, M.

    Based on irradiation with 45 MeV/u N and B ions and with Co-60 gamma rays, track structure cellular parameters have been fitted for V 79-379A Chinese hamster lung fibroblasts and for human melanoma cells (AA wtp53). These sets of parameters will be used to develop a calculation of radiation hazard in deep space, based on the system for evaluating, summing and reporting occupational exposures proposed in 1967 by subcommittee of the NCRP, but never issued as an NCRP report. The key concepts of this system were: i) expression of the risk from all radiation exposures relative to that from a whole-body exposure to Co-60 radiation; ii) relating the risk from any exposure to that of the standard (Co-60) radiation through an "effectiveness factor" (ef), a product of sub-factors representing radiation quality, body region irradiated, and depth of penetration of radiation; the product of absorbed dose by ef being termed the "exposure record unit" (eru); iii) development of ef values and a cumulative eru record for external and internal emitters. Application of this concept should provide a better description of the Gy -equivalent presently in use by NASA for evaluating risk in deep space than the equivalent dose, following ICRP-60 recommendations. Dose and charged particle fluence levels encountered in space, particularly after Solar Particle Events, require that deterministic rather than stochastic effects be considered. Also, synergistic effects due to simultaneous multiple charged particle transfers, may have to be considered. Thus, models applicable in radiotherapy, where the Gy -equivalent is also applied, in conjunction with transport calculations performed using, e.g. the ADAM and EVA phantoms, along the concepts of the 1967 NCRP system, may be more appropriate for evaluating the radiation hazard from external fields with a large flux and a major high-LET component.

  12. 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...... cellular model. With the use of the developed hierarchical model, the influence of the microstructure, including microfibril angles (MFAs, which characterizes the orientation of the cellulose fibrils with respect to the cell axis), the thickness of the cell wall, the shape of the cell cross...

  13. Induced pluripotent stem cells as a cellular model for studying Down Syndrome

    Science.gov (United States)

    Brigida, Anna Lisa; Siniscalco, Dario

    2016-01-01

    Down Syndrome (DS), or Trisomy 21 Syndrome, is one of the most common genetic diseases. It is a chromosomal abnormality caused by a duplication of chromosome 21. DS patients show the presence of a third copy (or a partial third copy) of chromosome 21 (trisomy), as result of meiotic errors. These patients suffer of many health problems, such as intellectual disability, congenital heart disease, duodenal stenosis, Alzheimer’s disease, leukemia, immune system deficiencies, muscle hypotonia and motor disorders. About one in 1000 babies born each year are affected by DS. Alterations in the dosage of genes located on chromosome 21 (also called HSA21) are responsible for the DS phenotype. However, the molecular pathogenic mechanisms of DS triggering are still not understood; newest evidences suggest the involvement of epigenetic mechanisms. For obvious ethical reasons, studies performed on DS patients, as well as on human trisomic tissues are limited. Some authors have proposed mouse models of this syndrome. However, not all the features of the syndrome are represented. Stem cells are considered the future of molecular and regenerative medicine. Several types of stem cells could provide a valid approach to offer a potential treatment for some untreatable human diseases. Stem cells also represent a valid system to develop new cell-based drugs and/or a model to study molecular disease pathways. Among stem cell types, patient-derived induced pluripotent stem (iPS) cells offer some advantages for cell and tissue replacement, engineering and studying: self-renewal capacity, pluripotency and ease of accessibility to donor tissues. These cells can be reprogrammed into completely different cellular types. They are derived from adult somatic cells via reprogramming with ectopic expression of four transcription factors (Oct3/4, Sox2, c-Myc and Klf4; or, Oct3/4, Sox2, Nanog, and Lin28). By reprogramming cells from DS patients, it is possible to obtain new tissue with the same

  14. 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...

  15. Confocal microscopy-based three-dimensional cell-specific modeling for large deformation analyses in cellular mechanics.

    Science.gov (United States)

    Slomka, Noa; Gefen, Amit

    2010-06-18

    This study introduces a new confocal microscopy-based three-dimensional cell-specific finite element (FE) modeling methodology for simulating cellular mechanics experiments involving large cell deformations. Three-dimensional FE models of undifferentiated skeletal muscle cells were developed by scanning C2C12 myoblasts using a confocal microscope, and then building FE model geometries from the z-stack images. Strain magnitudes and distributions in two cells were studied when the cells were subjected to compression and stretching, which are used in pressure ulcer and deep tissue injury research to induce large cell deformations. Localized plasma membrane and nuclear surface area (NSA) stretches were observed for both the cell compression and stretching simulation configurations. It was found that in order to induce large tensile strains (>5%) in the plasma membrane and NSA, one needs to apply more than approximately 15% of global cell deformation in cell compression tests, or more than approximately 3% of tensile strains in the elastic plate substrate in cell stretching experiments. Utilization of our modeling can substantially enrich experimental cellular mechanics studies in classic cell loading designs that typically involve large cell deformations, such as static and cyclic stretching, cell compression, micropipette aspiration, shear flow and hydrostatic pressure, by providing magnitudes and distributions of the localized cellular strains specific to each setup and cell type, which could then be associated with the applied stimuli.

  16. 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.

  17. 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.

  18. Cell models lead to understanding of multi-cellular morphogenesis consisting of successive self-construction of cells.

    Science.gov (United States)

    Honda, Hisao; Nagai, Tatsuzo

    2015-03-01

    Morphogenesis of multi-cellular organisms occurs through cell behaviours within a cell aggregate. Cell behaviours have been described using cell models involving equations of motion for cells. Cells in cell models construct shapes of the cell aggregate by themselves. Here, a history of cell models, the cell centre model and the vertex cell model, which we have constructed, are described. Furthermore, the application of these cell models is explained in detail. These cell models have been applied to transformation of cell aggregates to become spherical, formation of mammalian blastocysts and cell intercalation in elongating tissues. These are all elemental processes of morphogenesis and take place in succession during the whole developmental process. A chain of successive elemental processes leads to morphogenesis. Finally, we highlight that cell models are indispensable to understand the process whereby genes direct biological shapes.

  19. Finite-size scaling relations for a four-dimensional Ising model on Creutz cellular automatons

    Science.gov (United States)

    Merdan, Z.; Güzelsoy, E.

    2011-06-01

    The four-dimensional Ising model is simulated on Creutz cellular automatons using finite lattices with linear dimensions 4 ≤ L ≤ 8. The temperature variations and finite-size scaling plots of the specific heat and the Binder parameter verify the theoretically predicted expression near the infinite lattice critical temperature for 7, 14, and 21 independent simulations. Approximate values for the critical temperature of the infinite lattice of Tc(∞) = 6.6965(35), 6.6961(30), 6.6960(12), 6.6800(3), 6.6801(2), 6.6802(1) and 6.6925(22) (without the logarithmic factor), 6.6921(22) (without the logarithmic factor), 6.6909(2) (without the logarithmic factor), 6.6822(13) (with the logarithmic factor), 6.6819(11) (with the logarithmic factor), and 6.6808(8) (with the logarithmic factor) are obtained from the intersection points of the specific heat curves, the Binder parameter curves, and straight line fits of specific heat maxima for 7, 14, and 21 independent simulations, respectively. As the number of independent simulations increases, the results, 6.6802(1) and 6.6808(8), are in very good agreement with the results of a series expansion of Tc(∞), 6.6817(15) and 6.6802(2), the dynamic Monte Carlo value Tc(∞) = 6.6803(1), the cluster Monte Carlo value Tc(∞) = 6.680(1), and the Monte Carlo value using the Metropolis-Wolff cluster algorithm Tc(∞) = 6.6802632 ± 5 . 10-5. The average values calculated for the critical exponent of the specific heat are α =- 0.0402(15), - 0.0393(12), - 0.0391(11) with 7, 14, and 21 independent simulations, respectively. As the number of independent simulations increases, the result, α =- 0.0391(11), agrees with the series expansions result, α =- 0.12 ± 0.03 and the Monte Carlo result using the Metropolis-Wolff cluster algorithm, α ≥ 0 ± 0.04. However, α =- 0.0391(11) is inconsistent with the renormalization group prediction of α = 0.

  20. A numerical modelling of non linear 2D-frictional multicontact problems: application to post-buckling in cellular media

    Science.gov (United States)

    Alart, P.; Barboteu, M.; Gril, J.

    2004-09-01

    In this paper a numerical modelling of non linear problems involving large deformations and frictional contact conditions is proposed. The motivation of this work comes from the study of the cellular materials (such as wood or foams) undergoing strong deformations. We restrict our study to a regular cellular network of hexagonal cells with thin walls. Strong loadings can generate at first buckling phenomena, then self-contact in the cell. Renouncing homogenization procedures, not always pertinent in this case, we have developed direct simulations. After giving the mechanical and mathematical formulations of the problem, we present two advanced numerical tools to solve large non linear frictional multicontact problems. This numerical modelling is based on an arc-length continuation method which permits to snap through singular points due to buckling phenomena and on an optimal domain decomposition method adapted to frictional contact problems. Finally, mechanical investigations of the contactless buckling and the post-buckling provide some pertinent parameters controlling the deformation process.

  1. Parameter estimation with a novel gradient-based optimization method for biological lattice-gas cellular automaton models.

    Science.gov (United States)

    Mente, Carsten; Prade, Ina; Brusch, Lutz; Breier, Georg; Deutsch, Andreas

    2011-07-01

    Lattice-gas cellular automata (LGCAs) can serve as stochastic mathematical models for collective behavior (e.g. pattern formation) emerging in populations of interacting cells. In this paper, a two-phase optimization algorithm for global parameter estimation in LGCA models is presented. In the first phase, local minima are identified through gradient-based optimization. Algorithmic differentiation is adopted to calculate the necessary gradient information. In the second phase, for global optimization of the parameter set, a multi-level single-linkage method is used. As an example, the parameter estimation algorithm is applied to a LGCA model for early in vitro angiogenic pattern formation.

  2. Application of Local Activity Theory of Cellular Neural Network with Two Ports to the Coupled Lorenz-Cell Model

    Institute of Scientific and Technical Information of China (English)

    MIN LeQuan; YU Na

    2002-01-01

    Some criteria for the local activity theory in two-port cellular neural network cells with three local state variables are applied to a coupled Lorenz-cell model. The numerical simulation exhibited that emergence may exist if the selected cell parameters are nearby or on the edge of chaos domain. The local activity theory has provided a new tool of studying the complexity of high dimensional coupled nonlinear physical systems.

  3. 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.

  4. 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.

  5. Final Report - Modeling the Physics of Damage Cluster Formation in a Cellular Environment Modeling the Physics of Damage Cluster Formation in a Cellular Environment

    Energy Technology Data Exchange (ETDEWEB)

    L.H. Toburen, Principal Investigator; J.L. Shinpaugh; M. Dingfelder; and G. Lapicki; Co-Investigators

    2007-01-07

    Modern tools of radiobiology are leading to many new discoveries regarding how cells and tissues respond to radiation exposure. We can now irradiate single cells and observe responses in adjacent cells. We can also measure clusters of radiation damage produced in DNA. Our primary objective has been to understand the underling physics associated with these new biological responses. The primary tools available to describe the initial spatial pattern of damage formed by the absorption of ionizing radiation are based on Monte Carlo simulation of the structure of charged particle tracks. Although many Monte Carlo codes exist and considerable progress is being made in the incorporation of detailed macromolecular target structures into these codes, much of the interaction physics is still based on gas phase measurements and/or untested theoretical calculations that focus on water as the transport medium. Our objectives were threefold, (1) to expand the applicability of Monte Carlo track structure simulation to tissue-like material beyond the current focus on water, (2) to incorporate the most recent experimental information on electron interactions in biologically relevant material, and (3) to compare recent measurements of electron emissions induced by charged particles in thin foils with Monte Carlo predictions. We addressed these research objectives in three ways. First we applied theoretical techniques, similar to those used to derive data for water, to obtain cross sections for other condensed phase materials. This served two purposes. One was to provide testability of the theoretical technique by comparison to existing experimental data for electron transport (similar data does not exist for water), and the other was to expand the target database for use in modeling tissue. Second, we carefully reviewed published data, and ongoing experiments, for electron interaction cross-sections in biologically relevant condensed phase material. Results for low-energy electron

  6. Activity-based Calculation Models for the Brazilian Air Force Cellular Unit of Intendancy

    Science.gov (United States)

    2013-03-01

    readiness (Operations “Aghata” and “Cruzex”), humanitarian missions (support to combat dengue in the city of Rio de Janeiro ; support of the military...disinfection, sanitary and barber shop; u) water supply ; v) water treatment; x) providing electrical power. 1.8 Organization This research will be...recreation, and water and electricity supply . 2.1.1 Cellular Unit of Intendancy. The CUI provides the Air Force with the necessary mobility to

  7. Expression kinetics of hepatic progenitor markers in cellular models of human liver development recapitulating hepatocyte and biliary cell fate commitment.

    Science.gov (United States)

    Chaudhari, Pooja; Tian, Lipeng; Deshmukh, Abhijeet; Jang, Yoon-Young

    2016-09-01

    Due to the limitations of research using human embryos and the lack of a biological model of human liver development, the roles of the various markers associated with liver stem or progenitor cell potential in humans are largely speculative, and based on studies utilizing animal models and certain patient tissues. Human pluripotent stem cell-based in vitro multistage hepatic differentiation systems may serve as good surrogate models for mimicking normal human liver development, pathogenesis and injury/regeneration studies. Here, we describe the implications of various liver stem or progenitor cell markers and their bipotency (i.e. hepatocytic- and biliary-epithelial cell differentiation), based on the pluripotent stem cell-derived model of human liver development. Future studies using the human cellular model(s) of liver and biliary development will provide more human relevant biological and/or pathological roles of distinct markers expressed in heterogeneous liver stem/progenitor cell populations.

  8. Simple Cellular Model of Long-Range Multiplicity and $p_t$ Correlations in High-Energy Nuclear Collisions

    CERN Document Server

    Vechernin, V V

    2003-01-01

    A simple cellular model for the description of the long-range multiplicity and $p_t$ correlations in high-energy nuclear collisions originating from the string fusion model is proposed. Three versions of the model: without fusion, with local and with global string fusion are formulated. A Gauss approximation which enables explicit analytical calculations of the correlation functions in some asymptotic cases in the framework of the model is developed. The assumptions of the model and the validity of a Gauss approximation are checked up in the simplest (no fusion) case when the explicit solution of the model can be found. The role of a size of cells is analysed. The modification of the results in the case of non-Poissonian distributions is also discussed.

  9. 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...

  10. The cellular immune response plays an important role in protecting against dengue virus in the mouse encephalitis model.

    Science.gov (United States)

    Gil, Lázaro; López, Carlos; Blanco, Aracelys; Lazo, Laura; Martín, Jorge; Valdés, Iris; Romero, Yaremis; Figueroa, Yassel; Guillén, Gerardo; Hermida, Lisset

    2009-02-01

    For several years, researchers have known that the generation of neutralizing antibodies is a prerequisite for attaining adequate protection against dengue virus. Nevertheless, the cellular immune response is the principal arm of the adaptive immune system against non-cytopathic viruses such as dengue, as once the virus enters into the cell it is necessary to destroy it to eliminate the virus. To define the role of the cellular immune response in the protection against dengue, we selected the mouse encephalitis model. Mice were immunized with a single dose of infective dengue 2 virus and different markers of both branches of the induced adaptive immunity were measured. Animals elicited a broad antibody response against the four dengue virus serotypes, but neutralizing activity was only detected against the homologous serotype. On the other hand, the splenocytes of the infected animals strongly proliferated after in vitro stimulation with the homologous virus, and specifically the CD8 T-cell subset was responsible for the secretion of the cytokine IFN-gamma. Finally, to define the role of T cells in in vivo protection, groups of animals were inoculated with the depleting monoclonal antibodies anti-CD4 or anti-CD8. Only depletion with anti-CD8 decreased to 50% the level of protection reached in the non-depleted mice. The present work constitutes the first report defining the role of the cellular immune response in protection against dengue virus in the mouse model.

  11. Mobility-Aware Modeling and Analysis of Dense Cellular Networks With $C$ -Plane/ $U$ -Plane Split Architecture

    KAUST Repository

    Ibrahim, Hazem

    2016-09-19

    The unrelenting increase in the population of mobile users and their traffic demands drive cellular network operators to densify their network infrastructure. Network densification shrinks the footprint of base stations (BSs) and reduces the number of users associated with each BS, leading to an improved spatial frequency reuse and spectral efficiency, and thus, higher network capacity. However, the densification gain comes at the expense of higher handover rates and network control overhead. Hence, user’s mobility can diminish or even nullifies the foreseen densification gain. In this context, splitting the control plane ( C -plane) and user plane ( U -plane) is proposed as a potential solution to harvest densification gain with reduced cost in terms of handover rate and network control overhead. In this paper, we use stochastic geometry to develop a tractable mobility-aware model for a two-tier downlink cellular network with ultra-dense small cells and C -plane/ U -plane split architecture. The developed model is then used to quantify the effect of mobility on the foreseen densification gain with and without C -plane/ U -plane split. To this end, we shed light on the handover problem in dense cellular environments, show scenarios where the network fails to support certain mobility profiles, and obtain network design insights.

  12. Mathematical modeling of sub-cellular asymmetry of fat-dachsous heterodimer for generation of planar cell polarity.

    Directory of Open Access Journals (Sweden)

    Mohit Kumar Jolly

    Full Text Available Planar Cell Polarity (PCP is an evolutionarily conserved characteristic of animal tissues marked by coordinated polarization of cells or structures in the plane of a tissue. In insect wing epithelium, for instance, PCP is characterized by en masse orientation of hairs orthogonal to its apical-basal axis and pointing along the proximal-distal axis of the organ. Directional cue for PCP has been proposed to be generated by complex sets of interactions amongst three proteins - Fat (Ft, Dachsous (Ds and Four-jointed (Fj. Ft and Ds are two atypical cadherins, which are phosphorylated by Fj, a Golgi kinase. Ft and Ds from adjacent cells bind heterophilically via their tandem cadherin repeats, and their binding affinities are regulated by Fj. Further, in the wing epithelium, sub-cellular levels of Ft-Ds heterodimers are seen to be elevated at the distal edges of individual cells, prefiguring their PCP. Mechanisms generating this sub-cellular asymmetry of Ft-Ds heterodimer in proximal and distal edges of cells, however, have not been resolved yet. Using a mathematical modeling approach, here we provide a framework for generation of this sub-cellular asymmetry of Ft-Ds heterodimer. First, we explain how the known interactions within Ft-Ds-Fj system translate into sub-cellular asymmetry of Ft-Ds heterodimer. Second, we show that this asymmetric localization of Ft-Ds heterodimer is lost when tissue-level gradient of Fj is flattened, or when phosphorylation of Ft by Fj is abolished, but not when tissue-level gradient of Ds is flattened or when phosphorylation of Ds is abrogated. Finally, we show that distal enrichment of Ds also amplifies Ft-Ds asymmetry. These observations reveal that gradient of Fj expression, phosphorylation of Ft by Fj and sub-cellular distal accumulation of Ds are three critical elements required for generating sub-cellular asymmetry of Ft-Ds heterodimer. Our model integrates the known experimental data and presents testable predictions

  13. 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

  14. Cellular Approach to Long-Range $p_t$ and Multiplicity Correlations in the String Fusion Model

    CERN Document Server

    Vechernin, V V

    2003-01-01

    The long-range $p_t$ and multiplicity($n$) correlations in high-energy nuclear collisions are studied in the framework of a simple cellular analog of the string fusion model. Two cases with local and global string fusion is considered. The $p_t$--$n$ and $n$--$n$ correlation functions and correlation coefficients are calculated analytically in some asymptotic cases using suggested Gauss approximation. It's shown that at large string density the $p_t$--$n$ and $n$--$n$ correlation coefficients are connected and the scaling takes place. The behavior of the correlations at small string density is also studied. The asymptotic results are compared with results of the numerical calculations in the framework of proposed cellular approach.

  15. 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

  16. The simulation and prediction of spatio-temporal urban growth trends using cellular automata models: A review

    Science.gov (United States)

    Aburas, Maher Milad; Ho, Yuek Ming; Ramli, Mohammad Firuz; Ash'aari, Zulfa Hanan

    2016-10-01

    In recent years, several types of simulation and prediction models have been used within a GIS environment to determine a realistic future for urban growth patterns. These models include quantitative and spatio-temporal techniques that are implemented to monitor urban growth. The results derived through these techniques are used to create future policies that take into account sustainable development and the demands of future generations. The aim of this paper is to provide a basis for a literature review of urban Cellular Automata (CA) models to find the most suitable approach for a realistic simulation of land use changes. The general characteristics of simulation models of urban growth and urban CA models are described, and the different techniques used in the design of these models are classified. The strengths and weaknesses of the various models are identified based on the analysis and discussion of the characteristics of these models. The results of the review confirm that the CA model is one of the strongest models for simulating urban growth patterns owing to its structure, simplicity, and possibility of evolution. Limitations of the CA model, namely weaknesses in the quantitative aspect, and the inability to include the driving forces of urban growth in the simulation process, may be minimized by integrating it with other quantitative models, such as via the Analytic Hierarchy Process (AHP), Markov Chain and frequency ratio models. Realistic simulation can be achieved when socioeconomic factors and spatial and temporal dimensions are integrated in the simulation process.

  17. Cellular resolution models for even skipped regulation in the entire Drosophila embryo

    OpenAIRE

    Ilsley, Garth R; Fisher, Jasmin; Apweiler, Rolf; Angela H. DePace; Nicholas M Luscombe

    2013-01-01

    eLife digest The transcription of genes into messenger RNA (mRNA) molecules is one of the most important processes in biology, but our present understanding of this process is largely qualitative. Molecules such as transcription factors and regions of DNA other than the region that codes for the mRNA are known to interact with each other to influence the onset of transcription, and also the rate at which it occurs. However, given the cellular concentrations of transcription factors in a devel...

  18. An analytical model for evaluating outage and handover probability of cellular wireless networks

    CERN Document Server

    Decreusefond, Laurent; Vu, Than-Tung

    2010-01-01

    We consider stochastic cellular networks where base stations locations form a homogenous Poisson point process and each mobile is attached to the base station that provides the best mean signal power. The mobile is in outage if the SINR falls below some threshold. The handover decision has to be made if the mobile is in outage for some time slots. The outage probability and the handover probability is evaluated in taking into account the effect of path loss, shadowing, Rayleigh fast fading, frequency factor reuse and conventional beamforming. The main assumption is that the Rayleigh fast fading changes each time slot while other network components remain static during the period of study.

  19. 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....

  20. Condition monitoring of 3G cellular networks through competitive neural models.

    Science.gov (United States)

    Barreto, Guilherme A; Mota, João C M; Souza, Luis G M; Frota, Rewbenio A; Aguayo, Leonardo

    2005-09-01

    We develop an unsupervised approach to condition monitoring of cellular networks using competitive neural algorithms. Training is carried out with state vectors representing the normal functioning of a simulated CDMA2000 network. Once training is completed, global and local normality profiles (NPs) are built from the distribution of quantization errors of the training state vectors and their components, respectively. The global NP is used to evaluate the overall condition of the cellular system. If abnormal behavior is detected, local NPs are used in a component-wise fashion to find abnormal state variables. Anomaly detection tests are performed via percentile-based confidence intervals computed over the global and local NPs. We compared the performance of four competitive algorithms [winner-take-all (WTA), frequency-sensitive competitive learning (FSCL), self-organizing map (SOM), and neural-gas algorithm (NGA)] and the results suggest that the joint use of global and local NPs is more efficient and more robust than current single-threshold methods.

  1. Modeling Cellular Networks with Full Duplex D2D Communication: A Stochastic Geometry Approach

    KAUST Repository

    Ali, Konpal S.

    2016-08-24

    Full-duplex (FD) communication is optimistically promoted to double the spectral efficiency if sufficient self-interference cancellation (SIC) is achieved. However, this is not true when deploying FD-communication in a large-scale setup due to the induced mutual interference. Therefore, a large-scale study is necessary to draw legitimate conclusions about gains associated with FD-communication. This paper studies the FD operation for underlay device-to-device (D2D) communication sharing the uplink resources in cellular networks. We propose a disjoint fine-tuned selection criterion for the D2D and FD modes of operation. Then, we develop a tractable analytical paradigm, based on stochastic geometry, to calculate the outage probability and rate for cellular and D2D users. The results reveal that even in the case of perfect SIC, due to the increased interference injected to the network by FD-D2D communication, having all proximity UEs transmit in FD-D2D is not beneficial for the network. However, if the system parameters are carefully tuned, non-trivial network spectral-efficiency gains (64% shown) can be harvested. We also investigate the effects of imperfect SIC and D2D-link distance distribution on the harvested FD gains.

  2. Multiplex profiling of cellular invasion in 3D cell culture models.

    Directory of Open Access Journals (Sweden)

    Gerald Burgstaller

    Full Text Available To-date, most invasion or migration assays use a modified Boyden chamber-like design to assess migration as single-cell or scratch assays on coated or uncoated planar plastic surfaces. Here, we describe a 96-well microplate-based, high-content, three-dimensional cell culture assay capable of assessing invasion dynamics and molecular signatures thereof. On applying our invasion assay, we were able to demonstrate significant effects on the invasion capacity of fibroblast cell lines, as well as primary lung fibroblasts. Administration of epidermal growth factor resulted in a substantial increase of cellular invasion, thus making this technique suitable for high-throughput pharmacological screening of novel compounds regulating invasive and migratory pathways of primary cells. Our assay also correlates cellular invasiveness to molecular events. Thus, we argue of having developed a powerful and versatile toolbox for an extensive profiling of invasive cells in a 96-well format. This will have a major impact on research in disease areas like fibrosis, metastatic cancers, or chronic inflammatory states.

  3. Modeling and Analysis of Hybrid Cellular/WLAN Systems with Integrated Service-Based Vertical Handoff Schemes

    Science.gov (United States)

    Xia, Weiwei; Shen, Lianfeng

    We propose two vertical handoff schemes for cellular network and wireless local area network (WLAN) integration: integrated service-based handoff (ISH) and integrated service-based handoff with queue capabilities (ISHQ). Compared with existing handoff schemes in integrated cellular/WLAN networks, the proposed schemes consider a more comprehensive set of system characteristics such as different features of voice and data services, dynamic information about the admitted calls, user mobility and vertical handoffs in two directions. The code division multiple access (CDMA) cellular network and IEEE 802.11e WLAN are taken into account in the proposed schemes. We model the integrated networks by using multi-dimensional Markov chains and the major performance measures are derived for voice and data services. The important system parameters such as thresholds to prioritize handoff voice calls and queue sizes are optimized. Numerical results demonstrate that the proposed ISHQ scheme can maximize the utilization of overall bandwidth resources with the best quality of service (QoS) provisioning for voice and data services.

  4. 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)

  5. Development of a model of sacrocaudal spinal cord injury in cloned Yucatan minipigs for cellular transplantation research.

    Science.gov (United States)

    Lim, Ji-Hey; Piedrahita, Jorge A; Jackson, Lauren; Ghashghaei, Troy; Olby, Natasha J

    2010-12-01

    Research into transplantation strategies to treat spinal cord injury (SCI) is frequently performed in rodents, but translation of results to clinical patients can be poor and a large mammalian model of severe SCI is needed. The pig has been considered an optimal model species in which to perform preclinical testing, and the Yucatan minipig can be cloned successfully utilizing somatic cell nuclear transfer (SCNT). However, induction of paralysis in pigs poses significant welfare and nursing challenges. The present study was conducted to determine whether Yucatan SCNT clones could be used to develop an SCI animal model for cellular transplantation research. First, we demonstrated that transection of the sacrocaudal spinal cord in Yucatan SCNT clones produces profound, quantifiable neurological deficits restricted to the tail. We then established that neurospheres could be isolated from brain tissue of green fluorescence protein (GFP) transfected SCNT clones. Finally, we confirmed survival of transplanted GFP-expressing neural stem cells in the SCI lesion and their differentiation into glial and neuronal lineages for up to 4 weeks without immunosuppression. We conclude that this model of sacrocaudal SCI in Yucatan SCNT clones represents a powerful research tool to investigate the effect of cellular transplantation on axonal regeneration and functional recovery.

  6. Modeling of Solidification Microstructures Based on Fully Coupling of Macro-transport Phenomena with Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper has attempted to simulate the microstructure formation based on fully coupling of temperature field, concentration field and velocity field with micro-kinetics. The authors presented a new way, wlich is the combination of FDM and cellular automata (CAFD) to visualize the microstructure formation of the thin complex superalloy turbine blades cast by the vacuum investment process. The distribution, orientation and mechanism of the heterogeneous nucleation, the growth kinetics of dendrites and the columnar to equiaxed transition (CET) are considered. Capitalizing on these simulating schemes, the comprehensive influence of key process variables on the scale and uniformity of grains has been investigated quantitatively. The simulated grain size and morphology agree well with the experimental results.

  7. 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.

  8. Instantaneous information propagation in free flow, synchronized flow, stop-and-go waves in a cellular automaton model

    Institute of Scientific and Technical Information of China (English)

    Jiang Rui; Jin Wen-Long; Wu Qing-Song

    2008-01-01

    Recently, a number of efforts are underway to investigate inter-vehicle communications (IVC). This paper studies the instantaneous information propagation behaviours based on IVC in three different traffic situations (free flow,synchronized flow and stop-and-go waves) in a cellular automaton model. It is shown that different behaviours appear in stop-and-go waves from those in free flow and synchronized flow. While the distribution of Multi-hop Communication Distance (MhCD) is either exponential or uniform in free flow and synchronized flow, the distribution of MhCD is either exponential or with a single peak in stop-and-go waves.

  9. Investigation of cellular and molecular responses to pulsed focused ultrasound in a mouse model.

    Directory of Open Access Journals (Sweden)

    Scott R Burks

    Full Text Available Continuous focused ultrasound (cFUS has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation. pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules. We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1α, IL-1β, TNFα, INFγ, MIP-1α, MCP-1, and GMCSF creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1α and cell adhesion molecules (e.g., ICAM-1 and VCAM-1 on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology.

  10. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients.

    Science.gov (United States)

    Lee, C; Longo, V D

    2011-07-28

    The dietary recommendation for cancer patients receiving chemotherapy, as described by the American Cancer Society, is to increase calorie and protein intake. Yet, in simple organisms, mice, and humans, fasting--no calorie intake--induces a wide range of changes associated with cellular protection, which would be difficult to achieve even with a cocktail of potent drugs. In mammals, the protective effect of fasting is mediated, in part, by an over 50% reduction in glucose and insulin-like growth factor 1 (IGF-I) levels. Because proto-oncogenes function as key negative regulators of the protective changes induced by fasting, cells expressing oncogenes, and therefore the great majority of cancer cells, should not respond to the protective signals generated by fasting, promoting the differential protection (differential stress resistance) of normal and cancer cells. Preliminary reports indicate that fasting for up to 5 days followed by a normal diet, may also protect patients against chemotherapy without causing chronic weight loss. By contrast, the long-term 20 to 40% restriction in calorie intake (dietary restriction, DR), whose effects on cancer progression have been studied extensively for decades, requires weeks-months to be effective, causes much more modest changes in glucose and/or IGF-I levels, and promotes chronic weight loss in both rodents and humans. In this study, we review the basic as well as clinical studies on fasting, cellular protection and chemotherapy resistance, and compare them to those on DR and cancer treatment. Although additional pre-clinical and clinical studies are necessary, fasting has the potential to be translated into effective clinical interventions for the protection of patients and the improvement of therapeutic index.

  11. 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.

  12. 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.

  13. DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for studying cellular response to acute ischemia and regeneration.

    Directory of Open Access Journals (Sweden)

    Sina Haas

    Full Text Available Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy.With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research.

  14. 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...

  15. Second-order phase transition in two-dimensional cellular automaton model of traffic flow containing road sections

    Science.gov (United States)

    Shi, Xiao-Qiu; Wu, Yi-Qi; Li, Hong; Zhong, Rui

    2007-11-01

    Two-dimensional cellular automaton model has been broadly researched for traffic flow, as it reveals the main characteristics of the traffic networks in cities. Based on the BML models, a first-order phase transition occurs between the low-density moving phase in which all cars move at maximal speed and the high-density jammed phase in which all cars are stopped. However, it is not a physical result of a realistic system. We propose a new traffic rule in a two-dimensional traffic flow model containing road sections, which reflects that a car cannot enter into a road crossing if the road section in front of the crossing is occupied by another car. The simulation results reveal a second-order phase transition that separates the free flow phase from the jammed phase. In this way the system will not be entirely jammed (“don’t block the box” as in New York City).

  16. Modeling of Cell/Dendrite Transition During Directional Solidification of Ti-AI Alloy Using Cellular Automaton Method

    Institute of Scientific and Technical Information of China (English)

    WANG Kuang-fei; LI Bang-sheng; MI Guo-fa; GUO Jing-jie; FU Heng-zhi

    2008-01-01

    Solute diffusion controlled solidification model was used to simulate the initial stage cellular to dendrite transition of Ti44AI alloys during directional solidification at different velocities. The simulation results show that during this process, a mixed structure composed of cells and dendrites was observed, where secondary dendrites are absent at facing surface with parallel closely spaced dendrites, which agrees with the previous experimental observa-tion. The dendrite spacings are larger than cellular spacings at a given rate, and the columnar grain spacing sharply increases to a maximum as solidification advance to coexistence zone. In addition, simulation also revealed that decreasing the numbers of the seed causes the trend of unstable dendrite transition to increase. Finally, the main influence factors affecting cell/dendrite transition were analyzed, which could be the change of growth rates resulting in slight fluctuations of liquid composition occurred at growth front. The simulation results are in reasonable agreement with the results of previous theoretical models and experimental observation at low cooling rates.

  17. 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.

  18. Modeling the effect of microscopic driving behaviors on Kerner's time-delayed traffic breakdown at traffic signal using cellular automata

    Science.gov (United States)

    Wang, Yang; Chen, Yan-Yan

    2016-12-01

    The signalized traffic is considerably complex due to the fact that various driving behaviors have emerged to respond to traffic signals. However, the existing cellular automaton models take the signal-vehicle interactions into account inadequately, resulting in a potential risk that vehicular traffic flow dynamics may not be completely explored. To remedy this defect, this paper proposes a more realistic cellular automaton model by incorporating a number of the driving behaviors typically observed when the vehicles are approaching a traffic light. In particular, the anticipatory behavior proposed in this paper is realized with a perception factor designed by considering the vehicle speed implicitly and the gap to its preceding vehicle explicitly. Numerical simulations have been performed based on a signal controlled road which is partitioned into three sections according to the different reactions of drivers. The effects of microscopic driving behaviors on Kerner's time-delayed traffic breakdown at signal (Kerner 2011, 2013) have been investigated with the assistance of spatiotemporal pattern and trajectory analysis. Furthermore, the contributions of the driving behaviors on the traffic breakdown have been statistically examined. Finally, with the activation of the anticipatory behavior, the influences of the other driving behaviors on the formation of platoon have been investigated in terms of the number of platoons, the averaged platoon size, and the averaged flow rate.

  19. An extended cost potential field cellular automata model considering behavior variation of pedestrian flow

    Science.gov (United States)

    Guo, Fang; Li, Xingli; Kuang, Hua; Bai, Yang; Zhou, Huaguo

    2016-11-01

    The original cost potential field cellular automata describing normal pedestrian evacuation is extended to study more general evacuation scenarios. Based on the cost potential field function, through considering the psychological characteristics of crowd under emergencies, the quantitative formula of behavior variation is introduced to reflect behavioral changes caused by psychology tension. The numerical simulations are performed to investigate the effects of the magnitude of behavior variation, the different pedestrian proportions with different behavior variation and other factors on the evacuation efficiency and process in a room. The spatiotemporal dynamic characteristic during the evacuation process is also discussed. The results show that compared with the normal evacuation, the behavior variation under an emergency does not necessarily lead to the decrease of the evacuation efficiency. At low density, the increase of the behavior variation can improve the evacuation efficiency, while at high density, the evacuation efficiency drops significantly with the increasing amplitude of the behavior variation. In addition, the larger proportion of pedestrian affected by the behavior variation will prolong the evacuation time.

  20. Investigating the Effects of Stress Interaction Using a Cellular-automaton Based Model in Fault Networks of Varying Complexity.

    Science.gov (United States)

    Hetherington, A. P.; Steacy, S.; McCloskey, J.

    2007-12-01

    Seismicity spatial and temporal patterns are strongly influenced by stress interaction between faults. However the effects of such interaction on earthquake statistics is not yet well understood. Computer models provide accurate, large and complete datasets to investigate this issue and also have the benefit of allowing direct comparison of seismicity behavior in time and space in networks, with and without fault interaction. We investigate the effect of such interaction on modeled real-world fault networks of varying complexity using a cellular-automata based model. Each 3-D fault within the fault network is modeled by a discrete cellular automaton. The cell size is 1 km square which allows for a minimum earthquake size of approximately Mw=4. The cell strength is distributed fractally across each fault and all cells are loaded by a remote tectonic stressing rate. When the stress on a cell exceeds its strength, the cell fails and stress is transferred to its nearest neighbors which may in turn cause them to break allowing the earthquake to grow. These stress transfer rules allow realistic stress concentrations to develop at the boundary of the rupture. If the extent of the rupture exceeds a user defined minimum length, and if interaction between faults is allowed, a boundary element method is used to calculate stress transfer to neighboring faults. Here we present results from four simulated fault networks based on active faults in the San Francisco Bay Area, California, the Northern Anatolian Fault, Turkey, Southern California, and the Marlborough Fault System, South Island, New Zealand. These are chosen for their varying level of fault complexity and we examine both interacting and non-interacting models in terms of their b-value and recurrence intervals for each region. Results will be compared and discussed.

  1. Maintaining accuracy of cellular Yule-Nielsen spectral Neugebauer models for different ink cartridges using principal component analysis.

    Science.gov (United States)

    Wang, Binyu; Xu, Haisong; Luo, M Ronnier; Guo, Jinyi

    2011-07-01

    The replacement of used-up ink cartridges is unavoidable, but it makes the existing characterization model far from accurate, while recharacterization is labor intensive. In this study, we propose a new correction method for cellular Yule-Nielsen spectral Neugebauer (CYNSN) models based on principal component analysis (PCA). First, a small set of correction samples are predicted, printed using new ink cartridges, and then measured. Second, the link between the predicted and measured reflectance weights, generated by PCA, is determined. The experimental results show that the proposed method provides a significant and robust improvement, since not only the color change between original and new inks but also the systemic error of CYNSN modelsis taken into account in the method.

  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 model for Intelligent Random Access Memory architecture (IRAM) cellular automata algorithms on the Associative String Processing machine (ASTRA)

    CERN Document Server

    Rohrbach, F; Vesztergombi, G

    1997-01-01

    In the near future, the computer performance will be completely determined by how long it takes to access memory. There are bottle-necks in memory latency and memory-to processor interface bandwidth. The IRAM initiative could be the answer by putting Processor-In-Memory (PIM). Starting from the massively parallel processing concept, one reached a similar conclusion. The MPPC (Massively Parallel Processing Collaboration) project and the 8K processor ASTRA machine (Associative String Test bench for Research \\& Applications) developed at CERN \\cite{kuala} can be regarded as a forerunner of the IRAM concept. The computing power of the ASTRA machine, regarded as an IRAM with 64 one-bit processors on a 64$\\times$64 bit-matrix memory chip machine, has been demonstrated by running statistical physics algorithms: one-dimensional stochastic cellular automata, as a simple model for dynamical phase transitions. As a relevant result for physics, the damage spreading of this model has been investigated.

  4. 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.

  5. 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

  6. Modeling water sorption dynamics of cellular solid food systems using free volume theory

    NARCIS (Netherlands)

    Meinders, M.B.J.; Vliet, van T.

    2009-01-01

    Water sorption and dynamical properties of bread crust were studied using gravimetric sorption experiments. Water uptake and loss were measured while relative humidity (RH) was step-wise in- or decreased. Experimental results were compared with Fickian diffusion models and empirical models like the

  7. 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...

  8. A cellular and molecular model of response kinetics and adaptation in primate cones and horizontal cells

    NARCIS (Netherlands)

    Hateren, Hans van

    2005-01-01

    A model for the sensitivity regulation in the primate outer retina is developed and validated using horizontal cell measurements from the literature. The main conclusion is that the phototransduction of the cones is the key factor regulating sensitivity. The model consists of a nonlinearity cascaded

  9. Optical imaging as a link between cellular neurophysiology and circuit modeling

    Directory of Open Access Journals (Sweden)

    Walther Akemann

    2009-07-01

    Full Text Available The relatively simple and highly modular circuitry of the cerebellum raised expectations decades ago that a realistic computational model of cerebellar circuit operations would be feasible, and prove insightful for unraveling cerebellar information processing. To this end, the biophysical properties of most cerebellar cell types and their synaptic connections have been well characterized and integrated into realistic single cell models. Furthermore, large scale models of cerebellar circuits that extrapolate from single cell properties to circuit dynamics have been constructed. While the development of single cell models have been constrained by microelectrode recordings, guidance and validation as these models are scaled up to study network interactions requires an experimental methodology capable of monitoring cerebellar dynamics at the population level. Here we review the potential of optical imaging techniques to serve this purpose.

  10. 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.

  11. 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.

  12. Different reactive oxygen species lead to distinct changes of cellular metal ions in the eukaryotic model organism Saccharomyces cerevisiae.

    Science.gov (United States)

    Wu, Ming J; O'Doherty, Patrick J; Murphy, Patricia A; Lyons, Victoria; Christophersen, Melinda; Rogers, Peter J; Bailey, Trevor D; Higgins, Vincent J

    2011-01-01

    Elemental uptake and export of the cell are tightly regulated thereby maintaining the ionomic homeostasis. This equilibrium can be disrupted upon exposure to exogenous reactive oxygen species (ROS), leading to reduction or elevation of the intracellular metal ions. In this study, the ionomic composition in the eukaryotic model organism Saccharomyces cerevisiae was profiled using the inductively-coupled plasma optical emission spectrometer (ICP-OES) following the treatment with individual ROS, including hydrogen peroxide, cumen hydroperoxide, linoleic acid hydroperoxide (LAH), the superoxide-generating agent menadione, the thiol-oxidising agent diamide [diazine-dicarboxylic acid-bis(dimethylamide)], dimedone and peroxynitrite. The findings demonstrated that different ROS resulted in distinct changes in cellular metal ions. Aluminium (Al(3+)) level rose up to 50-fold after the diamide treatment. Cellular potassium (K(+)) in LAH-treated cells was 26-fold less compared to the non-treated controls. The diamide-induced Al(3+) accumulation was further validated by the enhanced Al(3+) uptake along the time course and diamide doses. Pre-incubation of yeast with individual elements including iron, copper, manganese and magnesium failed to block diamide-induced Al(3+) uptake, suggesting Al(3+)-specific transporters could be involved in Al(3+) uptake. Furthermore, LAH-induced potassium depletion was validated by a rescue experiment in which addition of potassium increased yeast growth in LAH-containing media by 26% compared to LAH alone. Taken together, the data, for the first time, demonstrated the linkage between ionomic profiles and individual oxidative conditions.

  13. Phenylpyrazole insecticides induce cytotoxicity by altering mechanisms involved in cellular energy supply in the human epithelial cell model Caco-2.

    Science.gov (United States)

    Vidau, Cyril; Brunet, Jean-Luc; Badiou, Alexandra; Belzunces, Luc P

    2009-06-01

    Phenylpyrazoles are relatively new insecticides designed to manage problematic insect resistance and public health hazards encountered with older pesticide families. In vitro cytotoxicity induced by the phenylpyrazole insecticides, Ethiprol and Fipronil, and Fipronil metabolites, sulfone and sulfide, was studied in Caco-2 cells. This cellular model was chosen because it made possible to mimic the primary site of oral exposure to xenobiotics, the intestinal epithelium. Assessment of the barrier function of Caco-2 epithelium was assessed by TEER measurement and showed a major loss of barrier integrity after exposure to Fipronil and its metabolites, but not to Ethiprol. The disruption of the epithelial barrier was attributed to severe ATP depletion independent of cell viability, as revealed by LDH release. The origin of energetic metabolism failure was investigated and revealed a transient enhancement of tetrazolium salt reduction and an increase in lactate production by Caco-2 cells, suggesting an increase in glucose metabolism by pesticides. Cellular symptoms observed in these experiments lead us to hypothesize that phenylpyrazole insecticides interacted with mitochondria.

  14. Iron deposition is independent of cellular inflammation in a cerebral model of multiple sclerosis

    OpenAIRE

    Lee Phil; Choi In-Young; Wang Wen-Tung; Rohr Aaron M; Williams Rachel; Berman Nancy EJ; Lynch Sharon G; LeVine Steven M

    2011-01-01

    Abstract Background Perivenular inflammation is a common early pathological feature in multiple sclerosis (MS). A recent hypothesis stated that CNS inflammation is induced by perivenular iron deposits that occur in response to altered blood flow in MS subjects. In order to evaluate this hypothesis, an animal model was developed, called cerebral experimental autoimmune encephalomyelitis (cEAE), which presents with CNS perivascular iron deposits. This model was used to investigate the relations...

  15. A conceptual model for quantifying connectivity using graph theory and cellular (per-pixel) approach

    Science.gov (United States)

    Singh, Manudeo; Sinha, Rajiv; Tandon, Sampat K.

    2016-04-01

    The concept of connectivity is being increasingly used for understanding hydro-geomorphic processes at all spatio-temporal scales. Connectivity is defined as the potential for energy and material flux (water, sediments, nutrients, heat, etc.) to navigate within or between the landscape systems and has two components, structural connectivity and dynamic connectivity. Structural connectivity is defined by the spatially connected features (physical linkages) through which energy and materials flow. Dynamic connectivity is a process defined connectivity component. These two connectivity components also interact with each other by forming a feedback system. This study attempts to explore a method to quantify structural and dynamic connectivity. In fluvial transport systems, sediment and water can flow in either a diffused manner or in a channelized way. At all the scales, hydrological and sediment fluxes can be tracked using a cellular (per-pixel) approach and can be quantified using graphical approach. The material flux, slope and LULC (Land Use Land Cover) weightage factors of a pixel together determine if it will contribute towards connectivity of the landscape/system. In a graphical approach, all the contributing pixels will form a node at their centroid and this node will be connected to the next 'down-node' via a directed edge with 'least cost path'. The length of the edge will depend on the desired spatial scale and its path direction will depend on the traversed pixel's slope and the LULC (weightage) factors. The weightage factors will lie in-between 0 to 1. This value approaches 1 for the LULC factors which promote connectivity. For example, in terms of sediment connectivity, the weightage could be RUSLE (Revised Universal Soil Loss Equation) C-factors with bare unconsolidated surfaces having values close to 1. This method is best suited for areas with low slopes, where LULC can be a deciding as well as dominating factor. The degree of connectivity and its

  16. Simplification of the tug-of-war model for cellular transport in cells

    CERN Document Server

    Zhang, Yunxin

    2010-01-01

    The transport of organelles and vesicles in living cells can be well described by a kinetic tug-of-war model advanced by M\\"uller, Klumpp and Lipowsky. In which, the cargo is attached by two motor species, kinesin and dynein, and the direction of motion is determined by the number of motors which bind to the track. In recent work [Phys. Rev. E 79, 061918 (2009)], this model was studied by mean field theory, and it was found that, usually the tug-of-war model has one, two, or three distinct stable stationary points. However, the results there are mostly obtained by numerical calculations, since it is hard to do detailed theoretical studies to a two-dimensional nonlinear system. In this paper, we will carry out further detailed analysis about this model, and try to find more properties theoretically. Firstly, the tug-of-war model is simplified to a one-dimensional equation. Then we claim that the stationary points of the tug-of-war model correspond to the roots of the simplified equation, and the stable station...

  17. miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN

    Science.gov (United States)

    Fang, Hong; Xie, Jiping; Zhang, Min; Zhao, Ziwei; Wan, Yi; Yao, Yongqiang

    2017-01-01

    MicroRNAs (miRNAs) are small single-stranded RNAs that bind to the 3’UTR of the mRNAs of target genes. They can target multiple genes and regulate translation or degradation of the mRNA. miRNAs target genes in a tissue-specific manner, and the role of a particular miRNA varies according to tumor origin or even subtype within the same cancer. This study evaluated the effect of miR-21 expression in triple-negative breast cancer (TNBC) tissues and MDA-MB-468, a cell line derived from TNBC tissues. miR-21 was consistently upregulated in TNBC and MDA-MB-468 cells compared to normal tissues. Inhibition of miR-21 by miR-21 antisense oligonucleotides decreased the proliferation, viability, and invasiveness of MDA-MB-468 cells and enhanced apoptosis. Furthermore, we confirmed that PTEN was downregulated by miR-21 in MDA-MB-468 cells. The results indicated that PTEN may mediate the oncogenic properties of miR-21 in TNBC. In summary, miR-21 was upregulated in TNBC tissues and cells, and promoted the proliferation and invasion of MDA-MB-468 cells, but negatively regulated the expression of PTEN protein. Inhibition of miR-21 or overexpression of PTEN protein could be promising strategies for the treatment of patients with TNBC.

  18. 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...

  19. 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.

  20. PATHLOGIC-S: a scalable Boolean framework for modelling cellular signalling.

    Directory of Open Access Journals (Sweden)

    Liam G Fearnley

    Full Text Available Curated databases of signal transduction have grown to describe several thousand reactions, and efficient use of these data requires the development of modelling tools to elucidate and explore system properties. We present PATHLOGIC-S, a Boolean specification for a signalling model, with its associated GPL-licensed implementation using integer programming techniques. The PATHLOGIC-S specification has been designed to function on current desktop workstations, and is capable of providing analyses on some of the largest currently available datasets through use of Boolean modelling techniques to generate predictions of stable and semi-stable network states from data in community file formats. PATHLOGIC-S also addresses major problems associated with the presence and modelling of inhibition in Boolean systems, and reduces logical incoherence due to common inhibitory mechanisms in signalling systems. We apply this approach to signal transduction networks including Reactome and two pathways from the Panther Pathways database, and present the results of computations on each along with a discussion of execution time. A software implementation of the framework and model is freely available under a GPL license.

  1. Universality in the Self Organized Critical behavior of a cellular model of superconducting vortex dynamics

    Science.gov (United States)

    Sun, Yudong; Vadakkan, Tegy; Bassler, Kevin

    2007-03-01

    We study the universality and robustness of variants of the simple model of superconducting vortex dynamics first introduced by Bassler and Paczuski in Phys. Rev. Lett. 81, 3761 (1998). The model is a coarse-grained model that captures the essential features of the plastic vortex motion. It accounts for the repulsive interaction between vortices, the pining of vortices at quenched disordered locations in the material, and the over-damped dynamics of the vortices that leads to tearing of the flux line lattice. We report the results of extensive simulations of the critical ``Bean state" dynamics of the model. We find a phase diagram containing four distinct phases of dynamical behavior, including two phases with distinct Self Organized Critical (SOC) behavior. Exponents describing the avalanche scaling behavior in the two SOC phases are determined using finite-size scaling. The exponents are found to be robust within each phase and for different variants of the model. The difference of the scaling behavior in the two phases is also observed in the morphology of the avalanches.

  2. 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

    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...... case. By considering all sources of explicit diffusion in the model, the budgets were balanced. In comparison with previous work based on observational studies, the use of three-dimensional, gridded model data afforded the possibility of calculating all terms in the budgets, which showed...... that the 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...

  3. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  4. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

    Science.gov (United States)

    Anderson, Christopher S.; DeDiego, Marta L.; Topham, David J.; Thakar, Juilee

    2016-01-01

    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. PMID:26981147

  5. Feeding Behavior of Aplysia: A Model System for Comparing Cellular Mechanisms of Classical and Operant Conditioning

    Science.gov (United States)

    Baxter, Douglas A.; Byrne, John H.

    2006-01-01

    Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural…

  6. 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

  7. 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.

  8. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection.

    Science.gov (United States)

    Anderson, Christopher S; DeDiego, Marta L; Topham, David J; Thakar, Juilee

    2016-01-01

    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.

  9. Investigation of the Nonlinear Model of the Cellular Population System Development

    Directory of Open Access Journals (Sweden)

    M. S. Vinogradova

    2014-01-01

    Full Text Available An isolated population system is considered which consists of two types of human stem cells: normal cells and cells with chromosomal anomalies (abnormal. In the paper the nonlinear dynamic model which describes dynamics of cell populations developing in vitro is elaborated. The model allows to investigate the processes of the formation of the abnormal cells population from the abnormal cells population of normal cells as well as joint development of these populations. The model takes into account the limited resources.An important feature of the developed model is the use of biological characteristics of processes in the cell population system, such as the proportion of cells, divided over a specified time, the proportion of cells whish are not divided, and which are "lost" and which are passed in the population of abnormal cells from the normal population. This approach allows a more detailed analysis of the impact of various "primary" parameters on the evolution of the population system.Under cultivation of cell populations in vitro a struggle for resources primarily affects the processes of the cell reproduction. This is reflected in the existence of the dividing cells frequency dependence of the total population of normal and abnormal cells. For the account of such dependencies different non-linear functions are typically used. However, the use of such non-linear relationships leads to the difficulties in finding confidence intervals for the estimates of the model parameters at subsequent stages of research. At the same time, the problem of the system parameters estimating and finding of the corresponding confidence intervals for estimates can be solved easy in case when the nonlinear system is linear with respect to the unknown parameters. In the paper it is achieved due to the piecewise linear approximation of nonlinear dependencies.An important feature of the model is a different view of the right part of the differential equations system

  10. Evaluation of Spatiotemporal Dynamics of Simulated Land Use/Cover in China Using a Probabilistic Cellular Automata-Markov Model

    Institute of Scientific and Technical Information of China (English)

    CHEN Xu; YU Shi-Xiao; ZHANG Ya-Ping

    2013-01-01

    Using the fuzzy rule-based classification method,normalized difference vegetation index (NDVI) images acquired from 1982 to 1998 were classified into seventeen phases.Based on these classification images,a probabilistic cellular automata-Markov Chain model was developed and used to simulate a land cover scenario of China for the year 2014.Spatiotemporal dynamics of land use/cover in China from 1982 to 2014 were then analyzed and evaluated.The results showed that the change trends of land cover type from 1998 to 2014 would be contrary to those from 1982 to 1998.In particular,forestland and grassland areas decreased by 1.56% and 1.46%,respectively,from 1982 to 1998,and should increase by 1.5% and 2.3% from 1998 to 2014,respectively.

  11. 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

    2016-01-01

    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 (2.5 mM) or high (20 mM) 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

  12. 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.

  13. 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.

  14. A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability.

    Science.gov (United States)

    Barik, Debashis; Ball, David A; Peccoud, Jean; Tyson, John J

    2016-12-01

    The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs) and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization) of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of ~30 mutant yeast strains that have not yet been characterized experimentally.

  15. GLOMERULAR CAPILLARY GROWTH AND CELLULAR HYPERPLASIA IN A MODEL OF FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS

    Directory of Open Access Journals (Sweden)

    John F Bertram

    2011-05-01

    Full Text Available Focal and segmental glomerulosclerosis (FSGS is a chronic renal disorder characterized by segmental glomerular lesions and widespread podocyte foot process effacement. We have previously shown that glomerular enlargement (hypertrophy precedes the development of FSGS in an animal model not previously thought to involve glomerular hypertrophy. This hypertrophy involved growth of glomerular capillaries. The aim of the present study was to determine whether the capillary growth involved an increase in the number of capillaries per glomerulus, or lengthening of existing capillaries. In addition, we examined the contribution of glomerular cell hyperplasia to the hypertrophy. We found that glomerular capillary growth in this model appears to primarily involve lengthening of existing capillaries rather that sprouting of new capillaries, and that glomerular cell proliferation contributes to the glomerular hypertrophy.

  16. A Traffic Information Estimation Model Using Periodic Location Update Events from Cellular Network

    Science.gov (United States)

    Lin, Bon-Yeh; Chen, Chi-Hua; Lo, Chi-Chun

    In recent years considerable concerns have arisen over building Intelligent Transportation System (ITS) which focuses on efficiently managing the road network. One of the important purposes of ITS is to improve the usability of transportation resources so as extend the durability of vehicle, reduce the fuel consumption and transportation times. Before this goal can be achieved, it is vital to obtain correct and real-time traffic information, so that traffic information services can be provided in a timely and effective manner. Using Mobile Stations (MS) as probe to tracking the vehicle movement is a low cost and immediately solution to obtain the real-time traffic information. In this paper, we propose a model to analyze the relation between the amount of Periodic Location Update (PLU) events and traffic density. Finally, the numerical analysis shows that this model is feasible to estimate the traffic density.

  17. 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.

  18. GLOMERULAR CAPILLARY GROWTH AND CELLULAR HYPERPLASIA IN A MODEL OF FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS

    OpenAIRE

    John F Bertram; Cahill, Meroe M

    2011-01-01

    Focal and segmental glomerulosclerosis (FSGS) is a chronic renal disorder characterized by segmental glomerular lesions and widespread podocyte foot process effacement. We have previously shown that glomerular enlargement (hypertrophy) precedes the development of FSGS in an animal model not previously thought to involve glomerular hypertrophy. This hypertrophy involved growth of glomerular capillaries. The aim of the present study was to determine whether the capillary growth involved an incr...

  19. Multiscale modeling of bacterial colonies: how pili mediate the dynamics of single cells and cellular aggregates

    Science.gov (United States)

    Pönisch, Wolfram; Weber, Christoph A.; Juckeland, Guido; Biais, Nicolas; Zaburdaev, Vasily

    2017-01-01

    Neisseria gonorrhoeae is the causative agent of one of the most common sexually transmitted diseases, gonorrhea. Over the past two decades there has been an alarming increase of reported gonorrhea cases where the bacteria were resistant to the most commonly used antibiotics thus prompting for alternative antimicrobial treatment strategies. The crucial step in this and many other bacterial infections is the formation of microcolonies, agglomerates consisting of up to several thousands of cells. The attachment and motility of cells on solid substrates as well as the cell-cell interactions are primarily mediated by type IV pili, long polymeric filaments protruding from the surface of cells. While the crucial role of pili in the assembly of microcolonies has been well recognized, the exact mechanisms of how they govern the formation and dynamics of microcolonies are still poorly understood. Here, we present a computational model of individual cells with explicit pili dynamics, force generation and pili-pili interactions. We employ the model to study a wide range of biological processes, such as the motility of individual cells on a surface, the heterogeneous cell motility within the large cell aggregates, and the merging dynamics and the self-assembly of microcolonies. The results of numerical simulations highlight the central role of pili generated forces in the formation of bacterial colonies and are in agreement with the available experimental observations. The model can quantify the behavior of multicellular bacterial colonies on biologically relevant temporal and spatial scales and can be easily adjusted to include the geometry and pili characteristics of various bacterial species. Ultimately, the combination of the microbiological experimental approach with the in silico model of bacterial colonies might provide new qualitative and quantitative insights on the development of bacterial infections and thus pave the way to new antimicrobial treatments.

  20. A cellular automaton based model simulating HVAC fluid and heat transport in a building. Modeling approach and comparison with experimental results

    Energy Technology Data Exchange (ETDEWEB)

    Saiz, A. [Department of Applied Mathematics, Polytechnic University of Valencia, ETSGE School, Camino de Vera s/n, 46022 Valencia (Spain); Urchueguia, J.F. [Department of Applied Physics, Polytechnic University of Valencia, ETSII School, Camino de Vera s/n, 46022 Valencia (Spain); Martos, J. [Superior Technical School of Engineering, Department of Electronic Engineering, University of Valencia, Vicente Andres Estelles s/n, Burjassot 46100, Valencia (Spain)

    2010-09-15

    A discrete model characterizing heat and fluid flow in connection with thermal fluxes in a building is described and tested against experiment in this contribution. The model, based on a cellular automaton approach, relies on a set of a few quite simple rules and parameters in order to simulate the dynamic evolution of temperatures and energy flows in any water or brine based thermal energy distribution network in a building or system. Using an easy-to-record input, such as the instantaneous electrical power demand of the heating or cooling system, our model predicts time varying temperatures in characteristic spots and the related enthalpy flows whose simulation usually requires heavy computational tools and detailed knowledge of the network elements. As a particular example, we have applied our model to simulate an existing fan coil based hydronic heating system driven by a geothermal heat pump. When compared to the experimental temperature and thermal energy records, the outcome of the model coincides. (author)

  1. 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

  2. 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.

  3. 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.

  4. Literature mining supports a next-generation modeling approach to predict cellular byproduct secretion

    DEFF Research Database (Denmark)

    King, Zachary A.; O'Brien, Edward J.; Feist, Adam M.;

    2017-01-01

    The metabolic byproducts secreted by growing cells can be easily measured and provide a window into the state of a cell; they have been essential to the development of microbiology, cancer biology, and biotechnology. Progress in computational modeling of cells has made it possible to predict...... metabolic byproduct secretion with bottom-up reconstructions of metabolic networks. However, owing to a lack of data, it has not been possible to validate these predictions across a wide range of strains and conditions. Through literature mining, we were able to generate a database of Escherichia coli...

  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. New Roles of Glycosaminoglycans in α-Synuclein Aggregation in a Cellular Model of Parkinson Disease

    Science.gov (United States)

    Lehri-Boufala, Sonia; Ouidja, Mohand-Ouidir; Barbier-Chassefière, Véronique; Hénault, Emilie; Raisman-Vozari, Rita; Garrigue-Antar, Laure; Papy-Garcia, Dulce; Morin, Christophe

    2015-01-01

    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. PMID:25617759

  7. 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.

  8. Model for external influences on cellular signal transduction pathways including cytosolic calcium oscillations

    Energy Technology Data Exchange (ETDEWEB)

    Eichwald, C.; Kaiser, F. [Technical Univ. of Darmstadt (Germany)

    1995-06-01

    Experiments on the effects of extremely-low-frequency (ELF) electric and magnetic fields on cells of the immune system, T-lymphocytes in particular, suggest that the external field interacts with the cell at the level of intracellular signal transduction pathways. These are directly connected with changes in the calcium-signaling processes of the cell. Based on these findings, a theoretical model for receptor-controlled cytosolic calcium oscillations and for external influences on the signal transduction pathway is presented. The authors discuss the possibility that the external field acts on the kinetics of the signal transduction between the activated receptors at the cell membrane and the G-proteins. It is shown that, depending on the specific combination of cell internal biochemical and external physical parameters, entirely different responses of the cell can occur. The authors compare the effects of a coherent (periodic) modulation and of incoherent perturbations (noise). The model and the calculations are based on the theory of self-sustained, nonlinear oscillators. It is argued that these systems form an ideal basis for information-encoding processes in biological systems.

  9. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans.

    Science.gov (United States)

    Gullón, Sonia; Marín, Silvia; Mellado, Rafael P

    2015-01-01

    Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein (agarase) in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients' depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.

  10. A Novel Protocol to Differentiate Induced Pluripotent Stem Cells by Neuronal microRNAs to Provide a Suitable Cellular Model.

    Science.gov (United States)

    Zare, Mehrak; Soleimani, Masoud; Akbarzadeh, Abolfazl; Bakhshandeh, Behnaz; Aghaee-Bakhtiari, Seyed Hamid; Zarghami, Nosratollah

    2015-08-01

    Neurodegenerative diseases are one of the most challenging subjects in medicine. Investigation of their underlying genetic or epigenetic factors is hampered by lack of suitable models. Patient-specific induced pluripotent stem cells (iPS cells) represent a valuable approach to provide a proper model for poorly understood mechanisms of neuronal diseases and the related drug screenings. miR-124 and miR-128 are the two brain-enriched miRNAs with different time-points of expression during neuronal development. Herein, we transduced human iPS cells with miR-124 and miR-128 harboring lentiviruses sequentially. The transduced plasmids contained GFP and puromycin antibiotic-resistant genes for easier selection and identification. Morphological assessment and immunocytochemistry (overexpressions of beta-tubulin and neuron-specific enolase) confirmed that induced hiPS cells by miR-124 and miR-128 represent similar characteristics to those of mature neurons. In addition, the upregulation of neuron-specific enolase, beta-tubulin, Map2, GFAP, and BDNF was detected by quantitative real-time PCR. In conclusion, it seems that our novel protocol remarks the combinatorial effect of miR-124 and miR-128 on neural differentiation in the absence of any extrinsic factor. Moreover, such cellular models could be used in personalized drug screening and applied for more effective therapies.

  11. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans

    Science.gov (United States)

    Gullón, Sonia; Marín, Silvia; Mellado, Rafael P.

    2015-01-01

    Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein (agarase) in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients’ depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host. PMID:26200356

  12. On the spatial dynamics and oscillatory behavior of a predator-prey model based on cellular automata and local particle swarm optimization.

    Science.gov (United States)

    Molina, Mario Martínez; Moreno-Armendáriz, Marco A; Carlos Seck Tuoh Mora, Juan

    2013-11-07

    A two-dimensional lattice model based on Cellular Automata theory and swarm intelligence is used to study the spatial and population dynamics of a theoretical ecosystem. It is found that the social interactions among predators provoke the formation of clusters, and that by increasing the mobility of predators the model enters into an oscillatory behavior.

  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. Cellular recovery from electroporation using synchronisation modulation as a rescue model for electrically injured cells.

    Science.gov (United States)

    Dando, Robin; Chen, Wei

    2008-12-01

    Electroporation of the plasma membrane resulting in a decrement in transmembrane potential is offered as a model in the study of the rescuing effects of the synchronisation modulation technique by electrically activating sodium potassium adenosine triphosphatase. Living cells were first electrically damaged by a pulsed intensive electric field, resulting in cell membrane electroporation, ion leakages and membrane potential depolarisation. Their recovery rate in natural conditions was compared with that of cells in a synchronisation modulation electric field. Fluorescence readings were taken using confocal microscopy and a potentiometric dye. Significantly more rapid recovery was observed after synchronisation modulation, with cell membranes actually polarised to levels higher than the original resting potential, a feature never seen in naturally recovering cells.

  15. 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.

  16. Iron deposition is independent of cellular inflammation in a cerebral model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lee Phil

    2011-06-01

    Full Text Available Abstract Background Perivenular inflammation is a common early pathological feature in multiple sclerosis (MS. A recent hypothesis stated that CNS inflammation is induced by perivenular iron deposits that occur in response to altered blood flow in MS subjects. In order to evaluate this hypothesis, an animal model was developed, called cerebral experimental autoimmune encephalomyelitis (cEAE, which presents with CNS perivascular iron deposits. This model was used to investigate the relationship of iron deposition to inflammation. Methods In order to generate cEAE, mice were given an encephalitogen injection followed by a stereotactic intracerebral injection of TNF-α and IFN-γ. Control animals received encephalitogen followed by an intracerebral injection of saline, or no encephalitogen plus an intracerebral injection of saline or cytokines. Laser Doppler was used to measure cerebral blood flow. MRI and iron histochemistry were used to localize iron deposits. Additional histological procedures were used to localize inflammatory cell infiltrates, microgliosis and astrogliosis. Results Doppler analysis revealed that cEAE mice had a reduction in cerebral blood flow compared to controls. MRI revealed T2 hypointense areas in cEAE animals that spatially correlated with iron deposition around vessels and at some sites of inflammation as detected by iron histochemistry. Vessels with associated iron deposits were distributed across both hemispheres. Mice with cEAE had more iron-labeled vessels compared to controls, but these vessels were not commonly associated with inflammatory cell infiltrates. Some iron-laden vessels had associated microgliosis that was above the background microglial response, and iron deposits were observed within reactive microglia. Vessels with associated astrogliosis were more commonly observed without colocalization of iron deposits. Conclusion The findings indicate that iron deposition around vessels can occur independently of

  17. 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.

  18. 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.)

  19. Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Sylvie Maubant

    Full Text Available The canonical Wnt/β-catenin pathway is activated in triple-negative breast cancer (TNBC. The activation of this pathway leads to the expression of specific target genes depending on the cell/tissue context. Here, we analyzed the transcriptome of two different TNBC cell lines to define a comprehensive list of Wnt target genes. The treatment of cells with Wnt3a for 6h up-regulated the expression (fold change > 1.3 of 59 genes in MDA-MB-468 cells and 241 genes in HCC38 cells. Thirty genes were common to both cell lines. Beta-catenin may also be a transcriptional repressor and we found that 18 and 166 genes were down-regulated in response to Wnt3a treatment for 6h in MDA-MB-468 and HCC38 cells, respectively, of which six were common to both cell lines. Only half of the activated and the repressed transcripts have been previously described as Wnt target genes. Therefore, our study reveals 137 novel genes that may be positively regulated by Wnt3a and 104 novel genes that may be negatively regulated by Wnt3a. These genes are involved in the Wnt pathway itself, and also in TGFβ, p53 and Hedgehog pathways. Thorough characterization of these novel potential Wnt target genes may reveal new regulators of the canonical Wnt pathway. The comparison of our list of Wnt target genes with those published in other cellular contexts confirms the notion that Wnt target genes are tissue-, cell line- and treatment-specific. Genes up-regulated in Wnt3a-stimulated cell lines were more strongly expressed in TNBC than in luminal A breast cancer samples. These genes were also overexpressed, but to a much lesser extent, in HER2+ and luminal B tumors. We identified 72 Wnt target genes higher expressed in TNBCs (17 with a fold change >1.3 which may reflect the chronic activation of the canonical Wnt pathway that occurs in TNBC tumors.

  20. Different Reactive Oxygen Species Lead to Distinct Changes of Cellular Metal Ions in the Eukaryotic Model Organism Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Peter J. Rogers

    2011-11-01

    Full Text Available Elemental uptake and export of the cell are tightly regulated thereby maintaining the ionomic homeostasis. This equilibrium can be disrupted upon exposure to exogenous reactive oxygen species (ROS, leading to reduction or elevation of the intracellular metal ions. In this study, the ionomic composition in the eukaryotic model organism Saccharomyces cerevisiae was profiled using the inductively-coupled plasma optical emission spectrometer (ICP-OES following the treatment with individual ROS, including hydrogen peroxide, cumen hydroperoxide, linoleic acid hydroperoxide (LAH, the superoxide-generating agent menadione, the thiol-oxidising agent diamide [diazine-dicarboxylic acid-bis(dimethylamide], dimedone and peroxynitrite. The findings demonstrated that different ROS resulted in distinct changes in cellular metal ions. Aluminium (Al3+ level rose up to 50-fold after the diamide treatment. Cellular potassium (K+ in LAH-treated cells was 26-fold less compared to the non-treated controls. The diamide-induced Al3+ accumulation was further validated by the enhanced Al3+ uptake along the time course and diamide doses. Pre-incubation of yeast with individual elements including iron, copper, manganese and magnesium failed to block diamide-induced Al3+ uptake, suggesting Al3+-specific transporters could be involved in Al3+ uptake. Furthermore, LAH-induced potassium depletion was validated by a rescue experiment in which addition of potassium increased yeast growth in LAH-containing media by 26% compared to LAH alone. Taken together, the data, for the first time, demonstrated the linkage between ionomic profiles and individual oxidative conditions.

  1. Quantitative cellular uptake of double fluorescent core-shelled model submicronic particles

    Energy Technology Data Exchange (ETDEWEB)

    Leclerc, Lara, E-mail: leclerc@emse.fr [Ecole Nationale Superieure des Mines, CIS-EMSE, LINA (France); Boudard, Delphine [LINA (France); Pourchez, Jeremie; Forest, Valerie [Ecole Nationale Superieure des Mines, CIS-EMSE, LINA (France); Marmuse, Laurence; Louis, Cedric [NANO-H S.A.S (France); Bin, Valerie [LINA (France); Palle, Sabine [Universite Jean Monnet, Centre de Microscopie Confocale Multiphotonique (France); Grosseau, Philippe; Bernache-Assollant, Didier [Ecole Nationale Superieure des Mines, CIS-EMSE, LINA (France); Cottier, Michele [LINA (France)

    2012-11-15

    The relationship between particles' physicochemical parameters, their uptake by cells and their degree of biological toxicity represent a crucial issue, especially for the development of new technologies such as fabrication of micro- and nanoparticles in the promising field of drug delivery systems. This work was aimed at developing a proof-of-concept for a novel model of double fluorescence submicronic particles that could be spotted inside phagolysosomes. Fluorescein isothiocyanate (FITC) particles were synthesized and then conjugated with a fluorescent pHrodo Trade-Mark-Sign probe, red fluorescence of which increases in acidic conditions such as within lysosomes. After validation in acellular conditions by spectral analysis with confocal microscopy and dynamic light scattering, quantification of phagocytosis was conducted on a macrophage cell line in vitro. The biological impact of pHrodo functionalization (cytotoxicity, inflammatory response, and oxidative stress) was also investigated. Results validate the proof-of-concept of double fluorescent particles (FITC + pHrodo), allowing detection of entirely engulfed pHrodo particles (green and red labeling). Moreover incorporation of pHrodo had no major effects on cytotoxicity compared to particles without pHrodo, making them a powerful tool for micro- and nanotechnologies.

  2. 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.

  3. Dissecting systems-wide data using mixture models: application to identify affected cellular processes

    Directory of Open Access Journals (Sweden)

    Giphart-Gassler Micheline

    2005-07-01

    Full Text Available Abstract Background Functional analysis of data from genome-scale experiments, such as microarrays, requires an extensive selection of differentially expressed genes. Under many conditions, the proportion of differentially expressed genes is considerable, making the selection criteria a balance between the inclusion of false positives and the exclusion of false negatives. Results We developed an analytical method to determine a p-value threshold from a microarray experiment that is dependent on the quality and design of the data set. To this aim, populations of p-values are modeled as mathematical functions in which the parameters to describe these functions are estimated in an unsupervised manner. The strength of the method is exemplified by its application to a published gene expression data set of sporadic and familial breast tumors with BRCA1 or BRCA2 mutations. Conclusion We present an objective and unsupervised way to set thresholds adapted to the quality and design of the experiment. The resulting mathematical description of the data sets of genome-scale experiments enables a probabilistic approach in systems biology.

  4. Dct::lacZ ES cells: a novel cellular model to study melanocyte determination and differentiation.

    Science.gov (United States)

    Pla, Patrick; Solov'eva, Olga; Moore, Robert; Alberti, Christophe; Kunisada, Takahiro; Larue, Lionel

    2004-04-01

    Embryonic stem (ES) cells differentiate into various cell lineages in vitro. A procedure was previously designed to promote the differentiation of ES cells towards the melanocyte lineage and to obtain large and reproducible amounts of melanocytes. To elucidate the main events that lead to the development of melanocytes in vitro, we used transgenic Dct::lacZ mouse blastocysts to establish ES cell lines expressing the lacZ reporter gene under the control of the Dct promoter. Dct, a melanoblast marker, is expressed just after melanoblast determination in vivo. We evaluated the importance of recruitment, proliferation and differentiation during melanocyte ontogeny after the in vitro differentiation of Dct::lacZ ES cells into melanocytes. We showed that bFGF and cholera toxin induce precocious melanoblast determination, associated with early melanocyte differentiation. Edn3 induced melanoblast proliferation and long-term melanoblast recruitment, but not precocious determination. The lack of basic Fibroblast Growth Factor (bFGF) and cholera toxin can be partially compensated by Edn3. Thus, Dct::lacZ ES cells can be used as a model to study determination, proliferation and differentiation in the melanocyte lineage in vitro.

  5. Interaction of non-aqueous dispersions of silver nanoparticles with cellular membrane models.

    Science.gov (United States)

    Soriano, Gustavo Bonomi; da Silva Oliveira, Roselaine; Camilo, Fernanda Ferraz; Caseli, Luciano

    2017-02-13

    In this work, silver nanoparticles (AgNPs) dispersed in non-aqueous media and stabilized with polyether block polymers amide (PEBA) were incorporated in Langmuir monolayers of dipalmitoylphosphatidylcholine (DPPC), which served as a cell membrane model. The AgNPs presented surface activity, disturbing the viscoelastic properties of the floating film. They expanded the monolayers decreasing their surface elasticity as observed with surface pressure-area isotherms. Polarization modulation reflection-absorption spectroscopy showed that the permanence of AgNPs at the air-water interface is favored by PEBA, affecting both the hydrophilic and the hydrophobic groups of the phospholipid. Brewster angle microscopy showed that the AgNPs lead to the formation of aggregates at the air-water interface, establishing domains that shear with each other due to the low lateral viscosity of irregular and non-monomolecular domains. These data can be correlated to the possible toxicity and microbicide effect of AgNPs in lipidic surfaces such as in mammalian and microbial membranes.

  6. Modeling land use and land cover changes in a vulnerable coastal region using artificial neural networks and cellular automata.

    Science.gov (United States)

    Qiang, Yi; Lam, Nina S N

    2015-03-01

    As one of the most vulnerable coasts in the continental USA, the Lower Mississippi River Basin (LMRB) region has endured numerous hazards over the past decades. The sustainability of this region has drawn great attention from the international, national, and local communities, wanting to understand how the region as a system develops under intense interplay between the natural and human factors. A major problem in this deltaic region is significant land loss over the years due to a combination of natural and human factors. The main scientific and management questions are what factors contribute to the land use land cover (LULC) changes in this region, can we model the changes, and how would the LULC look like in the future given the current factors? This study analyzed the LULC changes of the region between 1996 and 2006 by utilizing an artificial neural network (ANN) to derive the LULC change rules from 15 human and natural variables. The rules were then used to simulate future scenarios in a cellular automation model. A stochastic element was added in the model to represent factors that were not included in the current model. The analysis was conducted for two sub-regions in the study area for comparison. The results show that the derived ANN models could simulate the LULC changes with a high degree of accuracy (above 92 % on average). A total loss of 263 km(2) in wetlands from 2006 to 2016 was projected, whereas the trend of forest loss will cease. These scenarios provide useful information to decision makers for better planning and management of the region.

  7. 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

  8. 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.

  9. 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.

  10. A BABCOCK–LEIGHTON SOLAR DYNAMO MODEL WITH MULTI-CELLULAR MERIDIONAL CIRCULATION IN ADVECTION- AND DIFFUSION-DOMINATED REGIMES

    Energy Technology Data Exchange (ETDEWEB)

    Belucz, Bernadett; Forgács-Dajka, Emese [Eötvös University, Department of Astronomy, 1518 Budapest, Pf. 32 (Hungary); Dikpati, Mausumi, E-mail: bbelucz@astro.elte.hu, E-mail: dikpati@ucar.edu [High Altitude Observatory, National Center for Atmospheric Research, 3080 Center Green, Boulder, CO 80307-3000 (United States)

    2015-06-20

    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 the presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in the butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of the butterfly wing to an antisolar type. A butterfly diagram constructed from the 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 latitude behaves distinctly differently in the two regimes, producing solar-like butterfly diagrams with fast cycles in the higher diffusivity regime, and complex branches in butterfly diagrams in the lower diffusivity regime. We also find that dynamo solutions for a four-celled pattern, two in radius and two in latitude, prefer to quickly relax to quadrupolar parity if the bottom flow speed is strong enough, of similar order of magnitude as the surface flow speed.

  11. 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...

  12. A cellular automaton model examining the effects of oxygen, hydrogen ions and lactate on early tumour growth.

    Science.gov (United States)

    Al-Husari, Maymona; Murdoch, Craig; Webb, Steven D

    2014-10-01

    Some tumours are known to exhibit an extracellular pH that is more acidic than the intracellular, creating a 'reversed pH gradient' across the cell membrane and this has been shown to affect their invasive and metastatic potential. Tumour hypoxia also plays an important role in tumour development and has been directly linked to both tumour morphology and aggressiveness. In this paper, we present a hybrid mathematical model of intracellular pH regulation that examines the effect of oxygen and pH on tumour growth and morphology. In particular, we investigate the impact of pH regulatory mechanisms on the cellular pH gradient and tumour morphology. Analysis of the model shows that: low activity of the Na+/H+ exchanger or a high rate of anaerobic glycolysis can give rise to a "fingering" tumour morphology; and a high activity of the lactate/H+ symporter can result in a reversed transmembrane pH gradient across a large portion of the tumour mass. Also, the reversed pH gradient is spatially heterogeneous within the tumour, with a normal pH gradient observed within an intermediate growth layer within the spheroid. We also include a fractal dimension analysis of the simulated tumour contours, in which we compare the fractal dimensions of the simulated tumour surfaces with those found experimentally via photomicrographs.

  13. The farnesyltransferase inhibitors tipifarnib and lonafarnib inhibit cytokines secretion in a cellular model of mevalonate kinase deficiency.

    Science.gov (United States)

    Marcuzzi, Annalisa; De Leo, Luigina; Decorti, Giuliana; Crovella, Sergio; Tommasini, Alberto; Pontillo, Alessandra

    2011-07-01

    The shortage of geranylgeranyl-pyrophosphate (GGPP) was associated to an increased IL-1β release in the autoinflammatory syndrome mevalonate kinase deficiency (MKD), a rare inherited disease that has no specific therapy. Farnesyltransferase inhibitors (FTIs) act at the end of mevalonate pathway. Two FTIs, tipifarnib (Tip) and lonafarnib (Lon), were therefore evaluated as possible therapeutical choices for the treatment of MKD. FTIs could lead to a redirection of the limited available number of mevalonate intermediates preferentially to GGPP synthesis, eventually preventing the uncontrolled inflammatory response. The effect of Tip and Lon on intracellular cholesterol level (ICL) and on proinflammatory cytokines secretion was evaluated in a cellular model of MKD, chemically obtained treating RAW 264.7 cells with lovastatin (Lova) and alendronate (Ald). The combination of FTIs with the isoprenoid geraniol (GOH) was also tested both in this model and in monocytes isolated from MKD patients. Tip and Lon proved to revert the ICL lowering and to significantly reduce the lipopolysaccharide-induced cytokines secretion in Ald-Lova -RAW 264.7 cells. This anti-inflammatory effect was amplified combining the use of GOH with FTIs. The effect of GOH and Tip was successfully replicated in MKD patients' monocytes. Tip and Lon showed a dramatic anti-inflammatory effect in monocytes where mevalonate pathway was chemically or genetically impaired.

  14. New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models.

    Science.gov (United States)

    Le Douaron, Gael; Ferrié, Laurent; Sepulveda-Diaz, Julia E; Amar, Majid; Harfouche, Abha; Séon-Méniel, Blandine; Raisman-Vozari, Rita; Michel, Patrick P; Figadère, Bruno

    2016-07-14

    Parkinson's disease (PD) is a neurodegenerative disorder of aging characterized by motor symptoms that result from the loss of midbrain dopamine neurons and the disruption of dopamine-mediated neurotransmission. There is currently no curative treatment for this disorder. To discover druggable neuroprotective compounds for dopamine neurons, we have designed and synthesized a second-generation of quinoxaline-derived molecules based on structure-activity relationship studies, which led previously to the discovery of our first neuroprotective brain penetrant hit compound MPAQ (5c). Neuroprotection assessment in PD cellular models of our newly synthesized quinoxaline-derived compounds has led to the selection of a better hit compound, PAQ (4c). Extensive in vitro characterization of 4c showed that its neuroprotective action is partially attributable to the activation of reticulum endoplasmic ryanodine receptor channels. Most interestingly, 4c was able to attenuate neurodegeneration in a mouse model of PD, making this compound an interesting drug candidate for the treatment of this disorder.

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

    Science.gov (United States)

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

    2016-10-21

    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 (i.e. time elapsed since they were born). The age-dependent (oxygen-regulated) birth rate is given by a stochastic model of oxygen-dependent cell cycle progression. Once the birth rate is determined, we 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 (carrying capacity): cells consume oxygen which in turn 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 three main results. First, we have shown that the age to the G1/S transition, which essentially determines the birth rate, exhibits a remarkably simple scaling behaviour. Besides the fact that this simple behaviour emerges from a rather complex model, this allows for a huge simplification of our numerical methodology. A further result is the observation that heterogeneous populations undergo an internal process of quasi-neutral competition. Finally, we investigated the effects of cell-cycle-phase dependent therapies (such as radiation therapy) on heterogeneous populations. In particular, we have studied the case in which the population contains a quiescent sub-population. Our mean-field analysis and numerical simulations confirm that, if the survival fraction of the therapy is too high, rescue of the quiescent population occurs. This gives rise to emergence of resistance

  16. 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.

  17. 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.

  18. 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.

  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. Topographical Analysis of Spatial Patterns Generated by a Cellular Automaton Model of the Proliferation of a Cancer Cell Line In Vitro

    Directory of Open Access Journals (Sweden)

    Jacqueline Palmari

    1997-01-01

    Full Text Available A well‐suited model to simulate cellular population dynamics is the two‐dimensional cellular automaton model, which consists of a lattice of sites, the value ai,j of each site being updated in discrete time steps according to an identical deterministic rule depending on a neighbourhood of sites around it. A cellular automaton is described which mimics cell population proliferation by replacing the site values by the age and the cycle phase of cells. The model takes into account the size of the cells. It is used to simulate the proliferation of the human breast cancer cell line MCF‐7 and the results of the simulation are compared with experimental data obtained from a light microscopic image analysis of the proliferation process. The initial configuration of the cellular automaton is obtained from the discretization of the results of the initial stage of the image processing. After each day of proliferation the pattern obtained from the simulation is compared to the experimental result of the corresponding image analysis. The comparison is made from a topographical point of view through the concept of the minimal spanning tree graph. The agreement between experiment and model is a good starting point to complex models such as cell proliferation under growth effectors or drugs.

  1. A Modified Cellular Automaton Model for Traffic Flow%一种改进的交通流元胞自动机模型

    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.

  2. Antioxidant Treatment and Induction of Autophagy Cooperate to Reduce Desmin Aggregation in a Cellular Model of Desminopathy.

    Directory of Open Access Journals (Sweden)

    Eva Cabet

    Full Text Available Desminopathies, a subgroup of myofibrillar myopathies (MFMs, the progressive muscular diseases characterized by the accumulation of granulofilamentous desmin-positive aggregates, result from mutations in the desmin gene (DES, encoding a muscle-specific intermediate filament. Desminopathies often lead to severe disability and premature death from cardiac and/or respiratory failure; no specific treatment is currently available. To identify drug-targetable pathophysiological pathways, we performed pharmacological studies in C2C12 myoblastic cells expressing mutant DES. We found that inhibition of the Rac1 pathway (a G protein signaling pathway involved in diverse cellular processes, antioxidant treatment, and stimulation of macroautophagy reduced protein aggregation by up to 75% in this model. Further, a combination of two or three of these treatments was more effective than any of them alone. These results pave the way towards the development of the first treatments for desminopathies and are potentially applicable to other muscle or brain diseases associated with abnormal protein aggregation.

  3. Kinin Peptides Enhance Inflammatory and Oxidative Responses Promoting Apoptosis in a Parkinson’s Disease Cellular Model

    Directory of Open Access Journals (Sweden)

    Anna Niewiarowska-Sendo

    2016-01-01

    Full Text Available Kinin peptides ubiquitously occur in nervous tissue and participate in inflammatory processes associated with distinct neurological disorders. These substances have also been demonstrated to promote the oxidative stress. On the other hand, the importance of oxidative stress and inflammation has been emphasized in disorders that involve the neurodegenerative processes such as Parkinson’s disease (PD. A growing number of reports have demonstrated the increased expression of kinin receptors in neurodegenerative diseases. In this study, the effect of bradykinin and des-Arg10-kallidin, two representative kinin peptides, was analyzed with respect to inflammatory response and induction of oxidative stress in a PD cellular model, obtained after stimulation of differentiated SK-N-SH cells with a neurotoxin, 1-methyl-4-phenylpyridinium. Kinin peptides caused an increased cytokine release and enhanced production of reactive oxygen species and NO by cells. These changes were accompanied by a loss of cell viability and a greater activation of caspases involved in apoptosis progression. Moreover, the neurotoxin and kinin peptides altered the dopamine receptor 2 expression. Kinin receptor expression was also changed by the neurotoxin. These results suggest a mediatory role of kinin peptides in the development of neurodegeneration and may offer new possibilities for its regulation by using specific antagonists of kinin receptors.

  4. Faithful SGCE imprinting in iPSC-derived cortical neurons: an endogenous cellular model of myoclonus-dystonia

    Science.gov (United States)

    Grütz, Karen; Seibler, Philip; Weissbach, Anne; Lohmann, Katja; Carlisle, Francesca A.; Blake, Derek J.; Westenberger, Ana; Klein, Christine; Grünewald, Anne

    2017-01-01

    In neuropathology research, induced pluripotent stem cell (iPSC)-derived neurons are considered a tool closely resembling the patient brain. Albeit in respect to epigenetics, this concept has been challenged. We generated iPSC-derived cortical neurons from myoclonus-dystonia patients with mutations (W100G and R102X) in the maternally imprinted ε-sarcoglycan (SGCE) gene and analysed properties such as imprinting, mRNA and protein expression. Comparison of the promoter during reprogramming and differentiation showed tissue-independent differential methylation. DNA sequencing with methylation-specific primers and cDNA analysis in patient neurons indicated selective expression of the mutated paternal SGCE allele. While fibroblasts only expressed the ubiquitous mRNA isoform, brain-specific SGCE mRNA and ε-sarcoglycan protein were detected in iPSC-derived control neurons. However, neuronal protein levels were reduced in both mutants. Our phenotypic characterization highlights the suitability of iPSC-derived cortical neurons with SGCE mutations for myoclonus-dystonia research and, in more general terms, prompts the use of iPSC-derived cellular models to study epigenetic mechanisms impacting on health and disease. PMID:28155872

  5. Analysis and simulation of land use spatial pattern in Harbin prefecture based on trajectories and cellular automata-Markov modelling

    Science.gov (United States)

    Gong, Wenfeng; Yuan, Li; Fan, Wenyi; Stott, Philip

    2015-02-01

    There have been rapid population and accelerating urban growth with associated changes in land use and soil degradation in northeast China, an important grain-producing region. The development of integrated use of remote sensing, geographic information systems, and combined cellular automata- Markov models has provided new means of assessing changes in land use and land cover, and has enabled projection of trajectories into the future. We applied such techniques to the prefecture-level city of Harbin, the tenth largest city in China. We found that there had been significant losses of the land uses termed "cropland", "grassland", "wetland", and "floodplain" in favour of "built-up land" and lesser transformations from "floodplain" to "forestland" and "water body" over the 18-year period. However, the transition was not a simple process but a complex network of changes, interchanges, and multiple transitions. In the absence of effective land use policies, projection of past trajectories into a balance state in the future would result in the decline of cropland from 65.6% to 46.9% and the increase of built-up area from 7.7% to 23.0% relative to the total area of the prefecture in 1989. It also led to the virtual elimination of land use types such as unused wetland and floodplain.

  6. Modeling mechanical behaviors of composites with various ratios of matrix–inclusion properties using movable cellular automaton method

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    A.Yu. Smolin

    2015-03-01

    Full Text Available Two classes of composite materials are considered: classical metal–ceramic 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 metal–ceramic 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.

  7. Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma.

    Science.gov (United States)

    Roth, Udo; Razawi, Hanieh; Hommer, Julia; Engelmann, Katja; Schwientek, Tilo; Müller, Stefan; Baldus, Stephan E; Patsos, Georgios; Corfield, Anthony P; Paraskeva, Christos; Hanisch, Franz-Georg

    2010-01-01

    This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS. Progression-associated proteins belong to the functional complexes of anaerobic glycolysis/gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintenance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.

  8. Role of LIMP-2 in the intracellular trafficking of β-glucosidase in different human cellular models.

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    Malini, Erika; Zampieri, Stefania; Deganuto, Marta; Romanello, Milena; Sechi, Annalisa; Bembi, Bruno; Dardis, Andrea

    2015-09-01

    Acid β-glucosidase (GCase), the enzyme deficient in Gaucher disease (GD), is transported to lysosomes by the lysosomal integral membrane protein (LIMP)-2. In humans, LIMP-2 deficiency leads to action myoclonus-renal failure (AMRF) syndrome. GD and AMRF syndrome share some clinical features. However, they are different from clinical and biochemical points of view, suggesting that the role of LIMP-2 in the targeting of GCase would be different in different tissues. Besides, the role of LIMP-2 in the uptake and trafficking of the human recombinant (hr)GCase used in the treatment of GD is unknown. Thus, we compared GCase activity and intracellular localization in immortalized lymphocytes, fibroblasts, and a neuronal model derived from multipotent adult stem cells, from a patient with AMRF syndrome, patients with GD, and control subjects. In fibroblasts and neuronlike cells, GCase targeting to the lysosomes is completely dependent on LIMP-2, whereas in blood cells, GCase is partially targeted to lysosomes by a LIMP-2-independent mechanism. Although hrGCase cellular uptake is independent of LIMP-2, its trafficking to the lysosomes is mediated by this receptor. These data provide new insights into the mechanisms involved in the intracellular trafficking of GCase and in the pathogeneses of GD and AMRF syndrome.

  9. Simulation of Regionally Ecological Land Based on a Cellular Automation Model: A Case Study of Beijing, China

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    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.

  10. Modeling the shrub and juniper encroachment in the western north America grasslands with a Cellular Automata model

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    Caracciolo, D.; Istanbulluoglu, E.; Noto, L. V.

    2013-12-01

    Arid and semiarid grasslands of western North America have experienced dramatic changes over the last 150 years as a result of woody plant encroachment (WPE). WPE is characterized as increase in density, cover and biomass of indigenous tree or shrubby plants in grasslands. In this study we examine the environmental factors that trigger and further the progress of WPE at two semiarid sites using the CATGraSS ecohydrologic plant coexistence model. CATGraSS is a spatially distributed model driven by spatially explicit irradiance and runs on a fine-resolution gridded domain. In CATGraSS each cell can hold a single plant type or can remain empty. Plant competition is modeled by keeping track of mortality and establishment of plants, both calculated probabilistically based on soil moisture stress. For this study CATGraSS is improved with a stochastic fire and a grazing function, and its plant establishment algorithm is modified. Using CATGraSS shrub encroachment is studied in the Sevilleta National Wildlife Refuge (SNWR), New Mexico, located in the northern Chihuahuan desert. The area shows a dramatic encroachment front of Larrea tridentata (shrub) into native desert grassland. The model is implemented in a small area (7.3 km2) in SNWR. The second study site is a small catchment (11.8 km2) located within the Ochoco National Forest, Crook County, OR, where Juniper encroachment has been observed since the mid 1800s. The outcome of the changes in observed climate, fire frequency, and grazing intensity are investigated through numerical modeling scenarios. While in the Ochoco National Forest basin, the Western Juniper encroaches all the study area and the shrub disappears. In the SNWR basin, the model is able to reproduce the encroachment, simulating an increasing of the shrub from 2% in 1860 to 42% in 2010 (actual shrub percentage) highlighting as more influent factors the reduced fire frequency and the increased grazing intensity.

  11. Protective effect of probiotics on Salmonella infectivity assessed with combined in vitro gut fermentation-cellular models

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    Zihler Annina

    2011-12-01

    epithelial integrity compared to previous E. coli L1000 periods, as reflected by a significant mean increase of TER by 58% in all reactors. Inulin addition enhanced Salmonella growth and invasion when tested with distal and proximal reactor samples, respectively, but induced a limited decrease of TER (minus 18% in all reactors. Conclusions Our results highlight the benefits of combining suitable cellular and colonic fermentation models to assess strain-specific first-level host protection properties of probiotics during Salmonella infection, providing an efficient system biology tool for preclinical development of new antimicrobials.

  12. Expression of matrix metalloproteinases (MMPs in primary human breast cancer and breast cancer cell lines: New findings and review of the literature

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    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