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Sample records for cancer cellular model

  1. 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.

  2. Lobular breast cancer : molecular basis, mouse and cellular models

    NARCIS (Netherlands)

    Christgen, Matthias; Derksen, Patrick W B

    2015-01-01

    Infiltrating lobular breast cancer (ILC) is the most common special breast cancer subtype. With mutational or epigenetic inactivation of the cell adhesion molecule E-cadherin (CDH1) being confined almost exclusively to ILC, this tumor entity stands out from all other types of breast cancers. The mol

  3. 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.

  4. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

  6. Aging, cellular senescence, and cancer.

    Science.gov (United States)

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

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

    International Nuclear Information System (INIS)

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

  8. 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

  9. A medaka model of cancer allowing direct observation of transplanted tumor cells in vivo at a cellular-level resolution.

    Science.gov (United States)

    Hasegawa, Sumitaka; Maruyama, Kouichi; Takenaka, Hikaru; Furukawa, Takako; Saga, Tsuneo

    2009-08-18

    The recent success with small fish as an animal model of cancer with the aid of fluorescence technique has attracted cancer modelers' attention because it would be possible to directly visualize tumor cells in vivo in real time. Here, we report a medaka model capable of allowing the observation of various cell behaviors of transplanted tumor cells, such as cell proliferation and metastasis, which were visualized easily in vivo. We established medaka melanoma (MM) cells stably expressing GFP and transplanted them into nonirradiated and irradiated medaka. The tumor cells were grown at the injection sites in medaka, and the spatiotemporal changes were visualized under a fluorescence stereoscopic microscope at a cellular-level resolution, and even at a single-cell level. Tumor dormancy and metastasis were also observed. Interestingly, in irradiated medaka, accelerated tumor growth and metastasis of the transplanted tumor cells were directly visualized. Our medaka model provides an opportunity to visualize in vivo tumor cells "as seen in a culture dish" and would be useful for in vivo tumor cell biology. PMID:19666513

  10. Cellular characterization of ultrasound-stimulated microbubble radiation enhancement in a prostate cancer xenograft model

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    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.

  11. Cigarette smoke effects on TSPO and VDAC expression in a cellular lung cancer model.

    Science.gov (United States)

    Gavish, Moshe; Cohen, Shiri; Nagler, Rafael

    2016-09-01

    As redox iron and copper ions are found in lung pleural fluid and parenchyma, we aimed to examine the effect of cigarette smoke (CS) alone and the combined effects of CS and redox metals, iron and copper ions, containing medium (saliva), on epithelial H1299 lung cancer cells. We also examined the expression levels of the anticarcinogenic and proapoptotic 18 kDa translocator protein (TSPO) and its closely associated protein voltage-dependent anion channel (VDAC). H1299 cells were subjected to western blot analysis using anti-TSPO and anti-VDAC antibodies. With the former, the 18 kDa band appeared as expected and a 72 kDa band also appeared. It may be assumed that in H1299 lung cancer cells, an additional form of TSPO protein appears as a four-unit tetrameric complex, which is affected by CS exposure. A significant decrease in the expression level of the 72 kDa protein occurred following only 60 min of CS exposure, whereas VDAC protein levels were increased following only 30 min of CS exposure. These results, together with our previous related studies, suggest a comprehensive two-arm novel paradigm for lung cancer induced by CS, and mediated by an altered TSPO protein, possibly resulting from both the 72 kDa TSPO degradation and redox metal ion-induced enhancement of free radical attack. We suggest that both of the most important proapoptotic and anticancer proteins, p53 and TSPO, are damaged by CS, paving the way for lung cancer initiation and progression. PMID:26378498

  12. Modelling cellular behaviour

    Science.gov (United States)

    Endy, Drew; Brent, Roger

    2001-01-01

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

  13. Fate of PLA and PCL-Based Polymeric Nanocarriers in Cellular and Animal Models of Triple-Negative Breast Cancer.

    Science.gov (United States)

    Sitia, Leopoldo; Ferrari, Raffaele; Violatto, Martina B; Talamini, Laura; Dragoni, Luca; Colombo, Claudio; Colombo, Laura; Lupi, Monica; Ubezio, Paolo; D'Incalci, Maurizio; Morbidelli, Massimo; Salmona, Mario; Moscatelli, Davide; Bigini, Paolo

    2016-03-14

    An integrated platform to assess the interaction between nanocarriers and biological matrices has been developed by our group using poly methyl-methacrylate nanoparticles. In this study, we exploited this platform to evaluate the behavior of two biodegradable formulations, poly-ε-caprolactone (PCL3) and poly lactic-acid (PLA8), respectively, in cellular and animal models of triple-negative breast cancer (TNBC). Both NPs shared the main physicochemical parameters (size, shape, ζ-potential) and exclusively differentiated on the material on which they are composed. Our results showed that (1) PLA8 NPs, systemically injected in mice, underwent rapid degradation without penetration into tumors; (2) PLA8 NPs were not internalized in the human TNBC cell line (MDA-MB-231); (3) PCL3 NPs had a longer bioavailability, reached the tumor parenchyma, and efficiently penetrated in MDA-MB-231 cells. Our data highlight the relevance of the material selection to both improve bioavailability and target tropism, and make PCL3 NPs an interesting tool for the development of nanodrugs against TNBC. PMID:26791775

  14. Cellular telephone use and cancer risk

    DEFF Research Database (Denmark)

    2006-01-01

    expected in the Danish population. RESULTS: A total of 14,249 cancers were observed (SIR = 0.95; 95% confidence interval [CI] = 0.93 to 0.97) for men and women combined. Cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.97), acoustic neuromas (SIR = 0.73), salivary...

  15. Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model

    Directory of Open Access Journals (Sweden)

    Mirmiranpour Hossein

    2010-11-01

    Full Text Available Abstract Background/Aims Matrix Metalloproteinases 2 is a key molecule in cellular invasion and metastasis. Mitochondrial ROS has been established as a mediator of MMP activity. Coenzyme Q10 contributes to intracellular ROS regulation. Coenzyme Q10 beneficial effects on cancer are still in controversy but there are indications of Coenzyme Q10 complementing effect on tamoxifen receiving breast cancer patients. Methods In this study we aimed to investigate the correlation of the effects of co-incubation of coenzyme Q10 and N-acetyl-L-cysteine (NAC on intracellular H2O2 content and Matrix Metalloproteinase 2 (MMP-2 activity in MCF-7 cell line. Results and Discussion Our experiment was designed to assess the effect in a time and dose related manner. Gelatin zymography and Flowcytometric measurement of H2O2 by 2'7',-dichlorofluorescin-diacetate probe were employed. The results showed that both coenzyme Q10 and N-acetyl-L-cysteine reduce MMP-2 activity along with the pro-oxidant capacity of the MCF-7 cell in a dose proportionate manner. Conclusions Collectively, the present study highlights the significance of Coenzyme Q10 effect on the cell invasion/metastasis effecter molecules.

  16. Mathematical Modeling of Cellular Metabolism.

    Science.gov (United States)

    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.

  17. A Mathematical Model for Cisplatin Cellular Pharmacodynamics

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    Ardith W. El-Kareh

    2003-03-01

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

  18. Cellular and molecular aspects of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Malcolm G Smith; Georgina L Hold; Eiichi Tahara; Emad M El-Omar

    2006-01-01

    Gastric cancer remains a global killer with a shifting burden from the developed to the developing world.The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori (H pylori) as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie H pyloriinduced gastric cancer.

  19. 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

  20. New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

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    Stroncek David F

    2012-03-01

    Full Text Available Abstract A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL, are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs, chimeric antibody-T cell receptors (CARs and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies.

  1. 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.

  2. 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.

  3. Using cancer to make cellular reproduction rigorous and relevant

    Science.gov (United States)

    Duncan, Cynthia F.

    The 1983 report Nation at Risk highlighted the fact that test scores of American students were far below that of competing nations and educational standards were being lowered. This trend has continued and studies have also shown that students are not entering college ready for success. This trend can be reversed. Students can better understand and retain biology content expectations if they are taught in a way that is both rigorous and relevant. In the past, students have learned the details of cellular reproduction with little knowledge of why it is important to their everyday lives. This material is learned only for the test. Knowing the details of cellular reproduction is crucial for understanding cancer. Cancer is a topic that will likely affect all of my students at some point in their lives. Students used hands on activities, including simulations, labs, and models to learn about cellular reproduction with cancer as a theme throughout. Students were challenged to learn how to use the rigorous biology content expectations to think about cancer, including stem cell research. Students that will some day be college students, voting citizens, and parents, will become better learners. Students were assessed before and after the completion of the unit to determine if learning occurs. Students did learn the material and became more critical thinkers. Statistical analysis was completed to insure confidence in the results.

  4. 'P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model'.

    Science.gov (United States)

    2016-05-01

    This article corrects: P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model Volume 229, Issue 5, 705–718, Article first published online: 24 January 2013. By Ana Sofia Ribeiro, Bárbara Sousa, Laura Carreto, Nuno Mendes, Ana Rita Nobre, Sara Ricardo, André Albergaria, Jorge F Cameselle-Teijeiro, Rene Gerhard, Ola Söderberg, Raquel Seruca, Manuel A Santos, Fernando Schmitt and Joana Paredes, J Pathol 2013; 229: 708–718. DOI: 10.1002/path.4143. The above article, published online on 24 January 2013 on Wiley Online Library (wileyonlinelibrary.com). The funding information, “This work was also funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE (FCOMP-01-0124-FEDER-021209).” was omitted from the Acknowledgements section. We apologise for any inconvenience caused.

  5. 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.

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

    Science.gov (United States)

    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.

  7. Cellular automata modelling of biomolecular networks dynamics.

    Science.gov (United States)

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

    2010-01-01

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

  8. Cellular Hyperproliferation and Cancer as Evolutionary Variables

    OpenAIRE

    Alvarado, Alejandro Sánchez

    2012-01-01

    Technological advances in biology have begun to dramatically change the way we think about evolution, development, health and disease. The ability to sequence the genomes of many individuals within a population, and across multiple species, has opened the door to the possibility of answering some long-standing and perplexing questions about our own genetic heritage. One such question revolves around the nature of cellular hyperproliferation. This cellular behavior is used to effect wound heal...

  9. Understanding cisplatin resistance using cellular models.

    OpenAIRE

    STORDAL, BRITTA KRISTINA

    2007-01-01

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

  10. Understanding cisplatin resistance using cellular models

    OpenAIRE

    Stordal, Britta; Davey, Mary

    2007-01-01

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

  11. Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

    OpenAIRE

    Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

    2013-01-01

    There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol...

  12. Commercialization of cellular immunotherapies for cancer.

    Science.gov (United States)

    Walker, Anthony; Johnson, Robert

    2016-04-15

    Successful commercialization of a cell therapy requires more than proving safety and efficacy to the regulators. The inherent complexity of cellular products delivers particular manufacturing, logistical and reimbursement hurdles that threaten commercial viability for any therapy with a less than spectacular clinical profile that truly changes the standard of care. This is particularly acute for autologous cell therapies where patients receive bespoke treatments manufactured from a sample of their own cells and where economies of scale, which play an important role in containing the production costs for small molecule and antibody therapeutics, are highly limited. Nevertheless, the promise of 'game-changing' efficacy, as exemplified by very high levels of complete responses in refractory haematological malignancies, has attracted capital investments on a vast scale, and the attendant pace of technology development provides promising indicators for future clinical and commercial success. PMID:27068936

  13. Animal and cellular models of human disease

    OpenAIRE

    Arends, Mark; White, Eric; Whitelaw, Christopher

    2016-01-01

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

  14. 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.

  15. A Health Services Research Agenda for Cellular, Molecular and Genomic Technologies in Cancer Care

    Science.gov (United States)

    Wideroff, Louise; Phillips, Kathryn A.; Randhawa, Gurvaneet; Ambs, Anita; Armstrong, Katrina; Bennett, Charles L.; Brown, Martin L.; Donaldson, Molla S.; Follen, Michele; Goldie, Sue J.; Hiatt, Robert A.; Khoury, Muin J.; Lewis, Graham; McLeod, Howard L.; Piper, Margaret; Powell, Isaac; Schrag, Deborah; Schulman, Kevin A.; Scott, Joan

    2009-01-01

    Background In recent decades, extensive resources have been invested to develop cellular, molecular and genomic technologies with clinical applications that span the continuum of cancer care. Methods In December 2006, the National Cancer Institute sponsored the first workshop to uniquely examine the state of health services research on cancer-related cellular, molecular and genomic technologies and identify challenges and priorities for expanding the evidence base on their effectiveness in routine care. Results This article summarizes the workshop outcomes, which included development of a comprehensive research agenda that incorporates health and safety endpoints, utilization patterns, patient and provider preferences, quality of care and access, disparities, economics and decision modeling, trends in cancer outcomes, and health-related quality of life among target populations. Conclusions Ultimately, the successful adoption of useful technologies will depend on understanding and influencing the patient, provider, health care system and societal factors that contribute to their uptake and effectiveness in ‘real-world’ settings. PMID:19367091

  16. 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.

  17. Sub-cellular force microscopy in single normal and cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Babahosseini, H. [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States); Carmichael, B. [Nonlinear Intelligent Structures Laboratory, Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487-0276 (United States); Strobl, J.S. [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States); Mahmoodi, S.N., E-mail: nmahmoodi@eng.ua.edu [Nonlinear Intelligent Structures Laboratory, Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487-0276 (United States); Agah, M., E-mail: agah@vt.edu [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States)

    2015-08-07

    This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. - Highlights: • The cells are modeled as a triple-layered structure using Generalized Maxwell model. • The sub-domains include membrane/cortex, cytoplasm/nucleus, and nuclear/integrin. • Biomechanics of corresponding sub-domains are compared among normal and cancer cells. • Viscoelasticity of sub-domains show a decreasing trend from normal to cancer cells. • The decreasing trend becomes most significant in the deeper sub-domain.

  18. The Convergent Cancer Evolution toward a Single Cellular Destination.

    Science.gov (United States)

    Chen, Han; He, Xionglei

    2016-01-01

    The essence of Darwin's theory is that evolution is driven by purposeless mutations that are subsequently selected by natural environments, so there is often no predefined destination in organismal evolution. Using gene expressions of 107 cell types, we built a functional space of human cells to trace the evolutionary trajectory of 18 types of solid tumor cancers. We detected a dominant evolving trend toward the functional status of embryonic stem cells (ESC) for approximately 3,000 tumors growing in distinct tissue environments. This pattern remained the same after excluding known cancer/ESC signature genes (∼ 3,000 genes) or excluding all oncogenic gene sets (∼ 12,000 genes) annotated in MSigDB, suggesting a convergent evolution of the overall functional status in cancers. In support of this, the functional distance to ESC served as a common prognostic indicator for cancers of various types, with shorter distance corresponding to poor prognosis, which was true even when randomly selected gene sets were considered. Thus, regardless of the external environments, cancer evolution is a directional process toward a defined cellular destination, a finding reconciling development and evolution, the two seemingly incompatible philosophies both adopted by the cancer research community, and also raising new questions to evolutionary biology.

  19. 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.

  20. Cellular radiosensitivity of small-cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Krarup, M; Poulsen, H S; Spang-Thomsen, M

    1997-01-01

    . The multitarget single hit model was applied to calculate the cellular radiosensitivity (D0), the capacity for sublethal damage repair (Dq), and the extrapolation number (n). Values for alpha and beta were determined from best-fit curves according to the linear-quadratic model and these values were applied...... to calculate the surviving fraction after 2-Gy irradiation (SF2). RESULTS: In our investigation, the extrapolation method proved to be inappropriate for the study of in vitro cellular radiosensitivity due to lack of reproducibility. The results obtained by the clonogenic assay showed that the cell lines...

  1. 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.

  2. 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).

  3. 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.

  4. P53 family and cellular stress responses in cancer

    Directory of Open Access Journals (Sweden)

    Johanna ePflaum

    2014-10-01

    Full Text Available p53 is an important tumor suppressor gene, which is stimulated by cellular stress like ionizing radiation, hypoxia, carcinogens and oxidative stress. Upon activation p53 leads to cell cycle arrest and promotes DNA repair or induces apoptosis via several pathways. p63 and p73 are structural homologs of p53 that can act similarly to the protein but also hold functions distinct from p53. Today more than forty different isoforms of the p53 family members are known. They result from transcription via different promoters and alternative splicing. Some isoforms have carcinogenic properties and mediate resistance to chemotherapy. Therefore, expression patterns of the p53 family genes can offer prognostic information in several malignant tumors. Furthermore, the p53 family constitutes a potential target for cancer therapy. Small molecules (e.g. Nutlins, RITA, PRIMA-1, and MIRA-1 among others have been objects of intense research interest in recent years. They restore pro-apoptotic wild-type p53 function and were shown to break chemotherapeutic resistance. Due to p53 family interactions small molecules also influence p63 and p73 activity. Thus, the members of the p53 family are key players in the cellular stress response in cancer and are expected to grow in importance as therapeutic targets.

  5. Modeling the topological organization of cellular processes.

    Science.gov (United States)

    Giavitto, Jean-Louis; Michel, Olivier

    2003-07-01

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

  6. Cellular automata modeling of cooperative eutectic growth

    Directory of Open Access Journals (Sweden)

    E. Olejnik

    2010-01-01

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

  7. Modeling cellular effects of coal pollutants

    International Nuclear Information System (INIS)

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

  8. 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...

  9. Hyperthermia versus Oncothermia: Cellular Effects in Complementary Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Gabriella Hegyi

    2013-01-01

    Full Text Available Hyperthermia means overheating of the living object completely or partly. Hyperthermia, the procedure of raising the temperature of a part of or the whole body above normal for a defined period of time, is applied alone or as an adjunctive with various established cancer treatment modalities such as radiotherapy and chemotherapy. However, hyperthermia is not generally accepted as conventional therapy. The problem is its controversial performance. The controversy is originated from the complications of the deep heating and the focusing of the heat effect. The idea of oncothermia solves the selective deep action on nearly cellular resolution. We would like to demonstrate the force and perspectives of oncothermia, as a highly specialized hyperthermia in clinical oncology. Our aim is to prove the ability of oncothermia to be a candidate to become a widely accepted modality of the standard cancer care. We would like to show the proofs and the challenges of the hyperthermia and oncothermia applications to provide the presently available data and summarize the knowledge in the topic. Like many early stage therapies, oncothermia lacks adequate treatment experience and long-range, comprehensive statistics that can help us optimize its use for all indications.

  10. Mouse models of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  11. Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2013-01-01

    Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

  12. The impact of cellular senescence in cancer therapy:is it true or not?

    Institute of Scientific and Technical Information of China (English)

    Yi ZHANG; Jin-ming YANG

    2011-01-01

    Cellular senescence is defined as the physiological program of terminal growth arrest,which can be triggered by various endogenous or exogenous stress signals.Cellular senescence can be induced in response to oncogenic activation and acts as a barrier to tumorigenesis.Moreover,tumor cells can undergo senescence when exposed to chemotherapeutic agents.In addition to suppressing tumorigenesis,senescent cells remain metabolically active and may contribute to tumor formation and to therapy resistance.In the current review,we discuss the molecular regulation of cellular senescence,the potential implications of senescence in human cancers,and the possibility of exploiting cellular senescence for the treatment of cancers.

  13. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

    DEFF Research Database (Denmark)

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P;

    2015-01-01

    and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted...... using unconditional logistic regression under a log-additive model, and the FDR qcancers combined and for the serous subtype was observed for SNP rs17216603 in the iron......BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes...

  14. Matrix rigidity regulates cancer cell growth and cellular phenotype.

    Directory of Open Access Journals (Sweden)

    Robert W Tilghman

    Full Text Available BACKGROUND: The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness of the microenvironment and how this response varies among cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: "rigidity dependent" (those which show an increase in cell growth as extracellular rigidity is increased, and "rigidity independent" (those which grow equally on both soft and stiff substrates. Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug. CONCLUSIONS/SIGNIFICANCE: These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models.

  15. Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

    OpenAIRE

    Grant, Stephen G.; Melan, Melissa A.; Latimer, Jean J.; Witt-Enderby, Paula A.

    2009-01-01

    Recent studies have suggested that the pineal hormone melatonin may protect against breast cancer, and the mechanisms underlying its actions are becoming clearer. Melatonin works through receptors and distinct second messenger pathways to reduce cellular proliferation and to induce cellular differentiation. In addition, independently of receptors melatonin can modulate oestrogen-dependent pathways and reduce free-radical formation, thus preventing mutation and cellular toxicity. The fact that...

  16. Cellular origin and procoagulant activity of tissue factor-exposing microparticles in cancer patients

    NARCIS (Netherlands)

    Kleinjan, A.; Berckmans, R.J.; Böing, A.N.; Sturk, A.; Büller, H.R.; Kamphuisen, P.W.; Nieuwland, R.

    2012-01-01

    Background: In patients with cancer, tissue factor-exposing microparticles (TF-exposing MP) have been associated with disease progression and thrombosis. The cellular origin and coagulant activity of TF-exposing MP, however, remain disputed. Therefore, we investigated the cellular origin of the TF-e

  17. 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.

  18. 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.

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

    OpenAIRE

    Shinkarev, A. A.

    2016-01-01

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

  20. 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.

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

    OpenAIRE

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

    2008-01-01

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

  2. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

    Science.gov (United States)

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K.; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S. L.; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A. T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kelemen, Linda E.; Kellar, Mellissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F. A. G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Hasmad, Hanis N.; Berchuck, Andrew; Iversen, Edwin S.; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N. A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2015-01-01

    Background Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). Conclusion These results, generated on a large cohort of women, revealed associations

  3. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC Risk.

    Directory of Open Access Journals (Sweden)

    Ganna Chornokur

    Full Text Available Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC, we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC. Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS. SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020; this SNP was also associated with the borderline/low malignant potential (LMP tumors (P = 0.021. Other genes significantly associated with EOC histological subtypes (p<0.05 included the UGT1A (endometrioid, SLC25A45 (mucinous, SLC39A11 (low malignant potential, and SERPINA7 (clear cell carcinoma. In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4.These results, generated on a large cohort of women, revealed associations between inherited cellular

  4. 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...

  5. Computational model of cellular metabolic dynamics

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  6. Cellular automata modeling of cooperative eutectic growth

    OpenAIRE

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

    2010-01-01

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

  7. Modeling cellular deformations using the level set formalism

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2008-07-01

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

  8. Modeling cellular deformations using the level set formalism

    OpenAIRE

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

    2008-01-01

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

  9. 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.

  10. The cellular cancer resistance of the SR/CR mouse

    DEFF Research Database (Denmark)

    Koch, Janne; Hau, Jann; Jensen, Henrik Elvang;

    2012-01-01

    injection showed formations of immune cells morphologically resembling polymorphonuclear granulocytes and macrophages adjoining the cancer cells. The results point to the potential involvement of innate immune cells in cancer immunology. Our data support migration of polymorphonuclear granulocytes......The SR/CR mouse phenotype, first described in 1999 in BALB/c and later bred into C57BL/6 mice, is resistant to cancer formation following high doses of cancer cells administered intraperitoneally. The tumor cell targeting and destruction mechanisms have not been identified. By fluorescence......-activated cell sorting analysis, the immune response of SR/CR mice after intraperitoneal injection of cancer cells was investigated and compared with parent strain mice. A massive influx of leukocytes into the peritoneal cavity was found. A large fraction of these leukocytes were polymorphonuclear granulocytes...

  11. Lipid Droplets: A Key Cellular Organelle Associated with Cancer Cell Survival under Normoxia and Hypoxia

    Science.gov (United States)

    Koizume, Shiro; Miyagi, Yohei

    2016-01-01

    The Warburg effect describes the phenomenon by which cancer cells obtain energy from glycolysis even under normoxic (O2-sufficient) conditions. Tumor tissues are generally exposed to hypoxia owing to inefficient and aberrant vasculature. Cancer cells have multiple molecular mechanisms to adapt to such stress conditions by reprogramming the cellular metabolism. Hypoxia-inducible factors are major transcription factors induced in cancer cells in response to hypoxia that contribute to the metabolic changes. In addition, cancer cells within hypoxic tumor areas have reduced access to serum components such as nutrients and lipids. However, the effect of such serum factor deprivation on cancer cell biology in the context of tumor hypoxia is not fully understood. Cancer cells are lipid-rich under normoxia and hypoxia, leading to the increased generation of a cellular organelle, the lipid droplet (LD). In recent years, the LD-mediated stress response mechanisms of cancer cells have been revealed. This review focuses on the production and functions of LDs in various types of cancer cells in relation to the associated cellular environment factors including tissue oxygenation status and metabolic mechanisms. This information will contribute to the current understanding of how cancer cells adapt to diverse tumor environments to promote their survival. PMID:27589734

  12. 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.

  13. Cellular Automaton Model for Immunology of Tumor Growth

    CERN Document Server

    Voitikova, M

    1998-01-01

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

  14. A cellular automata evacuation model considering friction and repulsion

    Institute of Scientific and Technical Information of China (English)

    SONG Weiguo; YU Yanfei; FAN Weicheng; Zhang Heping

    2005-01-01

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

  15. Cellular spectroscopy: applications to cancer stem cell characterization

    Science.gov (United States)

    Wiegand, G.; Xin, H.; Anderson, A.; Mullinax, J.; Jaiswal, K.; Wiegand, A.; Avital, Itzhak

    2011-02-01

    Spectroscopic and light scattering methods were used to gain insight into the existence and characterization of the cancer stem cell. Fundamental technical description of devices used have been reported elsewhere. We included alterations and implementation of these biophotonic instruments as applied to our objectives. We disassociated human tumor and submitted the cells to optical characterization to support our working hypothesis of stem cell origins to cancer and mechanisms. Single cell combined with population based analysis within the Pancreatic cancer system led us to information regarding the polarization state of cells possessing anchor proteins and drug influx pumps. Multispectral imaging combined with flow cytometry enabled us to target rare cells that appear to retain template DNA. rendering them resistant to anti-cancer drug therapy. In this study we describe an optical method that combines high-throughput population pattern and correlates each cell with an individual fluorescent and bright-field image.

  16. 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.

  17. A Versatile Dependent Model for Heterogeneous Cellular Networks

    OpenAIRE

    Haenggi, Martin

    2013-01-01

    We propose a new model for heterogeneous cellular networks that incorporates dependencies between the layers. In particular, it places lower-tier base stations at locations that are poorly covered by the macrocells, and it includes a small-cell model for the case where the goal is to enhance network capacity.

  18. 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

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

    CERN Document Server

    Wolf-Gladrow, Dieter A

    2000-01-01

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

  20. 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.

  1. The molecular and cellular origin of human prostate cancer.

    Science.gov (United States)

    Packer, John R; Maitland, Norman J

    2016-06-01

    Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs.

  2. 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.

  3. Modeling evolution and immune system by cellular automata

    International Nuclear Information System (INIS)

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

  4. Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

    Directory of Open Access Journals (Sweden)

    Anna E. Maciag

    2013-01-01

    Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

  5. 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

  6. 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.

  7. 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.

  8. Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

    OpenAIRE

    Mario Orozco-Morales; Giovanny Soca-Chafre; Pedro Barrios-Bernal; Norma Hernández-Pedro; Oscar Arrieta

    2016-01-01

    Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical ...

  9. Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer.

    Science.gov (United States)

    Orozco-Morales, Mario; Soca-Chafre, Giovanny; Barrios-Bernal, Pedro; Hernández-Pedro, Norma; Arrieta, Oscar

    2016-01-01

    Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use. PMID:26941482

  10. Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mario Orozco-Morales

    2016-01-01

    Full Text Available Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs, the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs. Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use.

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

    OpenAIRE

    H Couclelis

    1985-01-01

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

  12. 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.

  13. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy.

    Science.gov (United States)

    Marengo, Barbara; Nitti, Mariapaola; Furfaro, Anna Lisa; Colla, Renata; Ciucis, Chiara De; Marinari, Umberto Maria; Pronzato, Maria Adelaide; Traverso, Nicola; Domenicotti, Cinzia

    2016-01-01

    Reactive oxygen species (ROS) and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy.

  14. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

    Directory of Open Access Journals (Sweden)

    Barbara Marengo

    2016-01-01

    Full Text Available Reactive oxygen species (ROS and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  16. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Soo Mi Kim

    2016-07-01

    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  17. Cellular and Molecular Mechanisms of 3,3'-Diindolylmethane in Gastrointestinal Cancer.

    Science.gov (United States)

    Kim, Soo Mi

    2016-01-01

    Studies in humans have shown that 3,3'-diindolylmethane (DIM), which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER) stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers. PMID:27447608

  18. Mouse models of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yunguang Tong; Wancai Yang; H. Phillip Koeffler

    2011-01-01

    Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer.

  19. Colon Cancer-associated DNA Polymerase β Variant Induces Genomic Instability and Cellular Transformation*

    Science.gov (United States)

    Nemec, Antonia A.; Donigan, Katherine A.; Murphy, Drew L.; Jaeger, Joachim; Sweasy, Joann B.

    2012-01-01

    Rapidly advancing technology has resulted in the generation of the genomic sequences of several human tumors. We have identified several mutations of the DNA polymerase β (pol β) gene in human colorectal cancer. We have demonstrated that the expression of the pol β G231D variant increased chromosomal aberrations and induced cellular transformation. The transformed phenotype persisted in the cells even once the expression of G231D was extinguished, suggesting that it resulted as a consequence of genomic instability. Biochemical analysis revealed that its catalytic rate was 140-fold slower than WT pol β, and this was a result of the decreased binding affinity of nucleotides by G231D. Residue 231 of pol β lies in close proximity to the template strand of the DNA. Molecular modeling demonstrated that the change from a small and nonpolar glycine to a negatively charged aspartate resulted in a repulsion between the template and residue 231 leading to the distortion of the dNTP binding pocket. In addition, expression of G231D was insufficient to rescue pol β-deficient cells treated with chemotherapeutic agents suggesting that these agents may be effectively used to treat tumors harboring this mutation. More importantly, this suggests that the G231D variant has impaired base excision repair. Together, these data indicate that the G231D variant plays a role in driving cancer. PMID:22573322

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. A New Cellular Automaton Model for Traffic Flow

    Institute of Scientific and Technical Information of China (English)

    YongtaoHU

    1999-01-01

    Establishment of effective traffic models to reveal fundamental traffic characteristics is an essential requirement in the design,planning and operation of transportation systems .In 1992 Nagel and Schreckenberg presented a cellular automaton model describing traffic flow of N cars on a single lane and applied it in the famous project TRANSIMS on transportation simulation.In this paper,the author proposes a new model for the same problem and gives a comparison of simulation results with the former ones.The comparison shows that the new model works better under the condition of high traffic density.

  6. 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.  

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

    Institute of Scientific and Technical Information of China (English)

    LI Ke-Ping

    2006-01-01

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

  8. Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Hall John C

    2008-09-01

    Full Text Available Abstract Background The regulatory subunit of cAMP-dependent protein kinase (PKA exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I and type II (PKA-II. Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8. Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600 was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression.

  9. Advance of Cellular Immunotherapy in Clinical and Translational Medicine of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Fei; YU Shao-rong; FENG Ji-feng

    2016-01-01

    Lung cancer is one of the most common cancers and ranks the ifrst in the mortality worldwide. The core of immunotherapy, especially cellular immunotherapy, is to activate the T cell-mediated tumor-killing effect in patients with tumors, so as to increase their anti-tumor effect. Surgery and radio- and chemotherapy cannot radically eliminate cancerous cells, but immunotherapy is an important supplementary method in killing tumor stem cells and non-proliferating cells. Cellular immunotherapy contains dendritic cells (DC), cytokine-induced killer (CIK), DC-CIK, natural killer T cells (NKT) and γδ T cells, which provides new techniques for the comprehensive treatment of lung cancer. Using CIK combined with DC, radiochemotherapy, radiofrequency ablation and monomers of Chinese medicine to induce CIK cells that directionally migrate to cancerous nest can increase tumor-killing ability and immunoregulatory ability of CIK cells, reduce adverse and toxic reactions and increase patients’ quality of life, and NKT cell and γδ T cell therapies have also been gradually perfected and promoted in clinical translation. This study mainly introduced the clinical translation of DC vaccines, CIK cells and DC-CIK treatment for lung cancer, hoping to provide new pathways and reference for the clinical treatment of lung cancer.

  10. Autophagy and cellular senescence mediated by Sox2 suppress malignancy of cancer cells.

    Directory of Open Access Journals (Sweden)

    Yong-Yeon Cho

    Full Text Available Autophagy is a critical cellular process required for maintaining cellular homeostasis in health and disease states, but the molecular mechanisms and impact of autophagy on cancer is not fully understood. Here, we found that Sox2, a key transcription factor in the regulation of the "stemness" of embryonic stem cells and induced-pluripotent stem cells, strongly induced autophagic phenomena, including intracellular vacuole formation and lysosomal activation in colon cancer cells. The activation occurred through Sox2-mediated ATG10 gene expression and resulted in the inhibition of cell proliferation and anchorage-independent colony growth ex vivo and tumor growth in vivo. Further, we found that Sox2-induced-autophagy enhanced cellular senescence by up-regulating tumor suppressors or senescence factors, including p16(INK4a, p21 and phosphorylated p53 (Ser15. Notably, knockdown of ATG10 in Sox2-expressing colon cancer cells restored cancer cell properties. Taken together, our results demonstrated that regulation of autophagy mediated by Sox2 is a mechanism-driven novel strategy to treat human colon cancers.

  11. Mathematical model for flood routing based on cellular automaton

    Directory of Open Access Journals (Sweden)

    Xin CAI

    2014-04-01

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

  12. Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis

    Institute of Scientific and Technical Information of China (English)

    Guocan Wang; Chia-Hsin Chan; Yuan Gao; Hui-Kuan Lin

    2012-01-01

    S-phase kinase-associated protein 2 (Skp2) belongs to the F-box protein family.It is a component of the SCF E3 ubiquitin ligase complex.Skp2 has been shown to regulate cellular proliferation by targeting several cell cycle-regulated proteins for ubiquitination and degradation,including cyclin-dependent kinase inhibitor p27.Skp2 has also been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers.This review discusses the recent discoveries on the novel roles of Skp2 in regulating cellular senescence,cancer progression,and metastasis,as well as the therapeutic potential of targeting Skp2 for human cancer treatment.

  13. Functional and genetic deconstruction of the cellular origin in liver cancer

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S

    2015-01-01

    During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...

  14. Interaction of cellular-localized signature modules in response to prostate cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Rapid progress in high-throughput biotechnologies (e. g. microarrays) and exponential accumulation of gene functional knowledge makes it promising for systematic understanding of complex human diseases at the functional modules level. Current modular categorizations can be defined and selected more specifically and precisely in terms of both biological processes and cellular locations, aiming at uncovering the modular molecular networks highly relevant to cancers. Based on Gene Ontology, we identifed the functional modules enriched with differentially expressed genes and characterized by biological processes and specific cellular locations. Then, according to the ranking of the disease discriminating abilities of the pre-selected functional modules, we further defined and filtered signature modules which have higher relevance to the cancer under study. Applications of the proposed method to the analysis of a prostate cancer dataset revealed insightful biological modules.

  15. Facile Synthesis of Biocompatible Fluorescent Nanoparticles for Cellular Imaging and Targeted Detection of Cancer Cells.

    Science.gov (United States)

    Tang, Fu; Wang, Chun; Wang, Xiaoyu; Li, Lidong

    2015-11-18

    In this work, we report the facile synthesis of functional core-shell structured nanoparticles with fluorescence enhancement, which show specific targeting of cancer cells. Biopolymer poly-l-lysine was used to coat the silver core with various shell thicknesses. Then, the nanoparticles were functionalized with folic acid as a targeting agent for folic acid receptor. The metal-enhanced fluorescence effect was observed when the fluorophore (5-(and-6)-carboxyfluorescein-succinimidyl ester) was conjugated to the modified nanoparticle surface. Cellular imaging assay of the nanoparticles in folic acid receptor-positive cancer cells showed their excellent biocompatibility and selectivity. The as-prepared functional nanoparticles demonstrate the efficiency of the metal-enhanced fluorescence effect and provide an alternative approach for the cellular imaging and targeting of cancer cells.

  16. 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.

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

    OpenAIRE

    Fang, Jianguo; Silverman, Richard B.

    2009-01-01

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

  18. Cellular-Based Statistical Model for Mobile Dispersion

    OpenAIRE

    Abdulla, Mouhamed; Shayan, Yousef R.

    2013-01-01

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

  19. 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.

  20. Animal Models of Colorectal Cancer

    Science.gov (United States)

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650

  1. Organoids as Models for Neoplastic Transformation | Office of Cancer Genomics

    Science.gov (United States)

    Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines.

  2. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-12-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  3. 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.

  4. 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.

  5. Modelling of detonation cellular structure in aluminium suspensions

    Science.gov (United States)

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

    2010-12-01

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

  6. 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.

  7. Cellular automata model of magnetospheric-ionospheric coupling

    OpenAIRE

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

    2003-01-01

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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Optical quantification of cellular mass, volume and density of circulating tumor cells identified in an ovarian cancer patient

    Directory of Open Access Journals (Sweden)

    Kevin Gregory Phillips

    2012-07-01

    Full Text Available Clinical studies have demonstrated that circulating tumor cells (CTCs are present in the blood of cancer patients with known metastatic disease across the major types of epithelial malignancies. Recent studies have shown that the concentration of CTCs in the blood is prognostic of overall survival in breast, prostate, colorectal and non-small cell lung cancer. This study characterizes CTCs identified using the high-definition (HD-CTC assay in an ovarian cancer patient with stage IIIC disease. We characterized the physical properties of 31 HD-CTCs and 50 normal leukocytes from a single blood draw taken just prior to the initial debulking surgery. We utilized a non-interferometric quantitative phase microscopy technique using brightfield imagery to measure cellular dry mass. Next we used a quantitative differential interference contrast microscopy technique to measure cellular volume. These techniques were combined to determine cellular dry mass density. We found that HD-CTCs were more massive than leukocytes: 33.6 ± 3.2 pg (HD-CTC compared to 18.7 ± 0.6 pg (leukocytes, p < 0.001; had greater volumes: 518.3 ± 24.5 fL (HD-CTC compared to 230.9 ± 78.5 fL (leukocyte, p<0.001; and possessed a decreased dry mass density with respect to leukocytes: 0.065 ± 0.006 pg/fL (HD-CTC compared to 0.085 ± 0.004 pg/fL (leukocyte, p < 0.006. Quantification of HD-CTC dry mass content and volume provide key insights into the fluid dynamics of cancer, and may provide the rationale for strategies to isolate, monitor or target CTCs based on their physical properties. The parameters reported here can also be incorporated into blood cell flow models to better understand metastasis.

  14. Engineered Swine Models of Cancer

    Directory of Open Access Journals (Sweden)

    Adrienne L. Watson

    2016-05-01

    Full Text Available Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs in cancer modeling are immense. In this review, we discuss how pigs have been and can be used as a biomedical models for cancer research, with an emphasis on current technologies. We have focused on applications of precision genetics that can provide models that mimic human cancer predisposition syndromes. In particular, we describe the advantages of targeted gene-editing using custom endonucleases, specifically TALENs and CRISPRs, and transposon systems, to make novel pig models of cancer with broad preclinical applications.

  15. Engineered Swine Models of Cancer.

    Science.gov (United States)

    Watson, Adrienne L; Carlson, Daniel F; Largaespada, David A; Hackett, Perry B; Fahrenkrug, Scott C

    2016-01-01

    Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs in cancer modeling are immense. In this review, we discuss how pigs have been and can be used as a biomedical models for cancer research, with an emphasis on current technologies. We have focused on applications of precision genetics that can provide models that mimic human cancer predisposition syndromes. In particular, we describe the advantages of targeted gene-editing using custom endonucleases, specifically TALENs and CRISPRs, and transposon systems, to make novel pig models of cancer with broad preclinical applications. PMID:27242889

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Antiatherogenic and antitumoral properties of Opuntia cladodes: inhibition of low density lipoprotein oxidation by vascular cells, and protection against the cytotoxicity of lipid oxidation product 4-hydroxynonenal in a colorectal cancer cellular model.

    Science.gov (United States)

    Keller, Julia; Camaré, Caroline; Bernis, Corinne; Astello-García, Marizel; de la Rosa, Ana-Paulina Barba; Rossignol, Michel; del Socorro Santos Díaz, María; Salvayre, Robert; Negre-Salvayre, Anne; Guéraud, Françoise

    2015-09-01

    Opuntia species have been used for thousands of years as a folk medicine in the treatment of diseases. However, the components and protective mechanisms are still unclear. We make the hypothesis that Opuntia species may protect the development of oxidative stress-associated diseases, such as atherosclerosis or colon cancer, via their antioxidant properties. We investigated the protective effect of Opuntia cladode powder against the oxidation of low-density lipoprotein (LDL) evoked by vascular endothelial cells, an important risk factor for atherosclerosis development, and the toxicity of 4-hydroxynonenal (a major lipid peroxidation product) on normal (Apc +/+) and preneoplastic (Apc min/+) immortalized epithelial colon cells. Various Opuntia species classified according to their degree of domestication, from the wildest (Opuntia streptacantha, Opuntia hyptiacantha, Opuntia megacantha), medium (Opuntia albicarpa), to the most domesticated (Opuntia ficus-indica) were tested. Cladode powders prepared from these Opuntia species significantly inhibited LDL oxidation induced by incubation with murine endothelial cells and the subsequent foam cell formation of RAW 264.7 murine macrophages and cytotoxicity on murine endothelial cells. Moreover, Opuntia cladode powder blocked the promotion of colon cancer development on an in vitro model of colonocytes. It may be noted that the phenolic acid and flavonoids content, the antioxidant capacity, and the protective effect were relatively similar in all the cladode powders from wild (O. streptacantha) and domesticated Opuntia. Altogether, these data confirm the therapeutic potential of Opuntia cladodes in diseases associated with oxidative stress. PMID:25840808

  1. 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...

  2. Models of breast cancer: quo vadis, animal modeling?

    International Nuclear Information System (INIS)

    Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease

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

    Science.gov (United States)

    Gao, Yuying; Beni, Gerardo

    2005-05-01

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

  4. Mouse models for cancer research

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Lynette Moore; Ping Ji

    2011-01-01

    Mouse models of cancer enable researchers to leamn about tumor biology in complicated and dynamic physiological systems. Since the development of gene targeting in mice, cancer biologists have been among the most frequent users of transgenic mouse models, which have dramatically increased knowledge about how cancers form and grow. The Chinese Joumnal of Cancer will publish a series of papers reporting the use of mouse models in studying genetic events in cancer cases. This editorial is an overview of the development and applications of mouse models of cancer and directs the reader to upcoming papers describing the use of these models to be published in coming issues, beginning with three articles in the current issue.

  5. A MULTISCALE, CELL-BASED FRAMEWORK FOR MODELING CANCER DEVELOPMENT

    Energy Technology Data Exchange (ETDEWEB)

    JIANG, YI [Los Alamos National Laboratory

    2007-01-16

    Cancer remains to be one of the leading causes of death due to diseases. We use a systems approach that combines mathematical modeling, numerical simulation, in vivo and in vitro experiments, to develop a predictive model that medical researchers can use to study and treat cancerous tumors. The multiscale, cell-based model includes intracellular regulations, cellular level dynamics and intercellular interactions, and extracellular level chemical dynamics. The intracellular level protein regulations and signaling pathways are described by Boolean networks. The cellular level growth and division dynamics, cellular adhesion and interaction with the extracellular matrix is described by a lattice Monte Carlo model (the Cellular Potts Model). The extracellular dynamics of the signaling molecules and metabolites are described by a system of reaction-diffusion equations. All three levels of the model are integrated through a hybrid parallel scheme into a high-performance simulation tool. The simulation results reproduce experimental data in both avasular tumors and tumor angiogenesis. By combining the model with experimental data to construct biologically accurate simulations of tumors and their vascular systems, this model will enable medical researchers to gain a deeper understanding of the cellular and molecular interactions associated with cancer progression and treatment.

  6. 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.

  7. 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}).

  8. Simulation of root forms using cellular automata model

    International Nuclear Information System (INIS)

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

  9. 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.

  10. Intrinsic Radiosensitivity and Cellular Characterization of 27 Canine Cancer Cell Lines.

    Science.gov (United States)

    Maeda, Junko; Froning, Coral E; Brents, Colleen A; Rose, Barbara J; Thamm, Douglas H; Kato, Takamitsu A

    2016-01-01

    Canine cancer cell lines have progressively been developed, but are still underused resources for radiation biology research. Measurement of the cellular intrinsic radiosensitivity is important because understanding the difference may provide a framework for further elucidating profiles for prediction of radiation therapy response. Our studies have focused on characterizing diverse canine cancer cell lines in vitro and understanding parameters that might contribute to intrinsic radiosensitivity. First, intrinsic radiosensitivity of 27 canine cancer cell lines derived from ten tumor types was determined using a clonogenic assay. The 27 cell lines had varying radiosensitivities regardless tumor type (survival fraction at 2 Gy, SF2 = 0.19-0.93). In order to understand parameters that might contribute to intrinsic radiosensitivity, we evaluated the relationships of cellular radiosensitivity with basic cellular characteristics of the cell lines. There was no significant correlation of SF2 with S-phase fraction, doubling time, chromosome number, ploidy, or number of metacentric chromosomes, while there was a statistically significant correlation between SF2 and plating efficiency. Next, we selected the five most radiosensitive cell lines as the radiosensitive group and the five most radioresistant cell lines as the radioresistant group. Then, we evaluated known parameters for cell killing by ionizing radiation, including radiation-induced DNA double strand break (DSB) repair and apoptosis, in the radiosensitive group as compared to the radioresistant group. High levels of residual γ-H2AX foci at the sites of DSBs were present in the four out of the five radiosensitive canine cancer cell lines. Our studies suggested that substantial differences in intrinsic radiosensitivity exist in canine cancer cell lines, and radiation-induced DSB repair was related to radiosensitivity, which is consistent with previous human studies. These data may assist further investigations

  11. Global Network Model based on Earth Grid and Cellular

    Directory of Open Access Journals (Sweden)

    Dongqi Lu

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Hallan Souza-e-Silva

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

  13. The effect of strength training on muscle cellular stress in prostate cancer patients on ADT

    Directory of Open Access Journals (Sweden)

    T S Nilsen

    2016-05-01

    Full Text Available Background Androgen deprivation therapy (ADT for prostate cancer (PCa is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT. Methods Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG (n=16 or a control group (CG (n=15 for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV, HSP60 and indicators of muscle cellular stress (heat shock protein (HSP 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins using Western blot and ELISA. Results No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups. Conclusion Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.

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

    Directory of Open Access Journals (Sweden)

    Hui Guo

    2016-07-01

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

  15. Viral and Cellular Biomarkers in the Diagnosis of Cervical Intraepithelial Neoplasia and Cancer

    Directory of Open Access Journals (Sweden)

    Maria Lina Tornesello

    2013-01-01

    Full Text Available Cervical cancer arises from cells localized in the ectoendocervical squamocolumnar junction of the cervix persistently infected with one of about 13 human papillomavirus (HPV genotypes. The majority of HPV infections induces low grade squamous epithelial lesions that in more than 90% of cases spontaneously regress and in about 10% eventually progress to high grade lesions and even less frequently evolve to invasive cancer. Tumor progression is characterized by (1 increased expression of E6 and E7 genes of high risk HPVs, known to bind to and inactivate p53 and pRb oncosuppressors, respectively; (2 integration of viral DNA into host genome, with disruption of E2 viral genes and host chromosomal loci; and (3 molecular alterations of key regulators of cell cycle. Molecular markers with high sensitivity and specificity in differentiating viral infections associated with cellular abnormalities with high risk of progression are strongly needed for cervical cancer screening and triage. This review will focus on the analysis of clinical validated or candidate biomarkers, such as HPV DNA, HPV E6/E7 mRNA, HPV proteins, p16(INK4a and Ki67, TOP2A and MCM2 cellular factors, and DNA methylation profiles, which will likely improve the identification of premalignant lesions that have a high risk to evolve into invasive cervical cancer.

  16. PRC2 mediated H3K27 methylations in cellular identity and cancer.

    Science.gov (United States)

    Conway, Eric; Healy, Evan; Bracken, Adrian P

    2015-12-01

    The Polycomb Repressive Complex 2 (PRC2) is a multiprotein chromatin modifying complex that is essential for vertebrate development and differentiation. It is composed of a trimeric core of SUZ12, EED and EZH1/2 and is responsible for catalysing both di-methylation and tri-methylation of Histone H3 at lysine 27 (H3K27me2/3). Both H3K27 methylations contribute to the role of PRC2 in maintaining cellular identity. In all cell types, the H3K27me3 modification is associated with repression of genes encoding regulators of alternative lineages. The less well-characterised H3K27me2 modification is ubiquitous throughout the genome and is thought to act like a protective blanket to maintain the repression of non-H3K27me3 associated genes and cell-type-specific enhancers of alternative lineages. Recent cancer genome sequencing studies highlighted that several genes encoding PRC2 components as well as Histone H3 are mutated in multiple cancer types. Intriguingly, these cancers have changes in the global levels of the H3K27me2 and H3K27me3 modifications as well as genome-wide redistributions. Exciting new studies suggest that these changes confer context dependent blocks in cellular differentiation and increased vulnerability to aberrant cancer signalling pathways. PMID:26497635

  17. Multifocal Breast Cancer in Young Women with Prolonged Contact between Their Breasts and Their Cellular Phones.

    Science.gov (United States)

    West, John G; Kapoor, Nimmi S; Liao, Shu-Yuan; Chen, June W; Bailey, Lisa; Nagourney, Robert A

    2013-01-01

    Breast cancer occurring in women under the age of 40 is uncommon in the absence of family history or genetic predisposition, and prompts the exploration of other possible exposures or environmental risks. We report a case series of four young women-ages from 21 to 39-with multifocal invasive breast cancer that raises the concern of a possible association with nonionizing radiation of electromagnetic field exposures from cellular phones. All patients regularly carried their smartphones directly against their breasts in their brassieres for up to 10 hours a day, for several years, and developed tumors in areas of their breasts immediately underlying the phones. All patients had no family history of breast cancer, tested negative for BRCA1 and BRCA2, and had no other known breast cancer risks. Their breast imaging is reviewed, showing clustering of multiple tumor foci in the breast directly under the area of phone contact. Pathology of all four cases shows striking similarity; all tumors are hormone-positive, low-intermediate grade, having an extensive intraductal component, and all tumors have near identical morphology. These cases raise awareness to the lack of safety data of prolonged direct contact with cellular phones.

  18. Multifocal Breast Cancer in Young Women with Prolonged Contact between Their Breasts and Their Cellular Phones

    Directory of Open Access Journals (Sweden)

    John G. West

    2013-01-01

    Full Text Available Breast cancer occurring in women under the age of 40 is uncommon in the absence of family history or genetic predisposition, and prompts the exploration of other possible exposures or environmental risks. We report a case series of four young women—ages from 21 to 39—with multifocal invasive breast cancer that raises the concern of a possible association with nonionizing radiation of electromagnetic field exposures from cellular phones. All patients regularly carried their smartphones directly against their breasts in their brassieres for up to 10 hours a day, for several years, and developed tumors in areas of their breasts immediately underlying the phones. All patients had no family history of breast cancer, tested negative for BRCA1 and BRCA2, and had no other known breast cancer risks. Their breast imaging is reviewed, showing clustering of multiple tumor foci in the breast directly under the area of phone contact. Pathology of all four cases shows striking similarity; all tumors are hormone-positive, low-intermediate grade, having an extensive intraductal component, and all tumors have near identical morphology. These cases raise awareness to the lack of safety data of prolonged direct contact with cellular phones.

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

    KAUST Repository

    Li, YZ

    2014-08-01

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

  20. p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer

    DEFF Research Database (Denmark)

    Tschaharganeh, Darjus F; Xue, Wen; Calvisi, Diego F;

    2014-01-01

    The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protei...... by p53 restricts cellular plasticity and tumorigenesis in liver cancer.......The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protein...

  1. Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance

    DEFF Research Database (Denmark)

    D’Andrea, Filippo P.; Safwat, Akmal; Kassem, Moustapha;

    2011-01-01

    found the genes involved in cancer, proliferation, DNA repair and cell death. ConclusionsThe higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide...... that could explain cancer stem cell radiation resistance. MethodsTumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2Gy was assessed by Affymetric exon chip analysis and further...... validated with q-RT-PCR using TaqMan probes. ResultsThe CE8 clone was more radiation resistant than the BB3 clone. From a pool of 15 validated genes with altered expression in the CE8 clone, we found the enzyme nicotinamide N-methyltransferase (NNMT) more than 5-fold upregulated. In-depth pathway analysis...

  2. The cellular functions of RASSF1A and its inactivation in prostate cancer

    Directory of Open Access Journals (Sweden)

    Karishma S Amin

    2012-01-01

    Full Text Available Epigenetic events significantly impact the transcriptome of cells and often contribute to the onset and progression of human cancers. RASSF1A (Ras-association domain family 1 isoform A, a well-known tumor suppressor gene, is frequently silenced by epigenetic mechanisms such as promoter hypermethylation in a wide range of cancers. In the past decade a vast body of literature has emerged describing the silencing of RASSF1A expression in various cancers and demonstrating its ability to reverse the cancerous phenotype when re-expressed in cancer cells. However, the mechanisms by which RASSF1A exerts its tumor suppressive properties have not been entirely defined. RASSF1A appears to mediate three important cellular processes: microtubule stability, cell cycle progression, and the induction of apoptosis through specific molecular interactions with key factors involved in these processes. Loss of function of RASSF1A leads to accelerated cell cycle progression and resistance to apoptotic signals, resulting in increased cell proliferation. In this review, we attempt to summarize the current understanding of the biological functions of RASSF1A and provide insight that the development of targeted drugs to restore RASSF1A function holds promise for the treatment of prostate cancer.

  3. 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.

  4. 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...

  5. Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy

    OpenAIRE

    Lee, Kye-Sung; Zhao, Huimin; Ibrahim, Sherrif F; Meemon, Natthani; Khoudeir, Laura; Rolland, Jannick P.

    2012-01-01

    Abstract. We investigate morphological differences in three-dimensional (3-D) images with cellular resolution between nonmelanoma skin cancer and normal skin using Gabor domain optical coherence microscopy. As a result, we show for the first time cellular optical coherence images of 3-D features differentiating cancerous skin from normal skin. In addition, in vivo volumetric images of normal skin from different anatomic locations are shown and compared.

  6. Computer Modeling of the Earliest Cellular Structures and Functions

    Science.gov (United States)

    Pohorille, Andrew

    2000-03-01

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

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

    International Nuclear Information System (INIS)

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

  8. Correlating two-photon excited fluorescence imaging of breast cancer cellular redox state with seahorse flux analysis of normalized cellular oxygen consumption

    Science.gov (United States)

    Hou, Jue; Wright, Heather J.; Chan, Nicole; Tran, Richard; Razorenova, Olga V.; Potma, Eric O.; Tromberg, Bruce J.

    2016-06-01

    Two-photon excited fluorescence (TPEF) imaging of the cellular cofactors nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide is widely used to measure cellular metabolism, both in normal and pathological cells and tissues. When dual-wavelength excitation is used, ratiometric TPEF imaging of the intrinsic cofactor fluorescence provides a metabolic index of cells-the "optical redox ratio" (ORR). With increased interest in understanding and controlling cellular metabolism in cancer, there is a need to evaluate the performance of ORR in malignant cells. We compare TPEF metabolic imaging with seahorse flux analysis of cellular oxygen consumption in two different breast cancer cell lines (MCF-7 and MDA-MB-231). We monitor metabolic index in living cells under both normal culture conditions and, for MCF-7, in response to cell respiration inhibitors and uncouplers. We observe a significant correlation between the TPEF-derived ORR and the flux analyzer measurements (R=0.7901, p<0.001). Our results confirm that the ORR is a valid dynamic index of cell metabolism under a range of oxygen consumption conditions relevant for cancer imaging.

  9. Helicobacter pylori eradication to prevent gastric cancer:underlying molecular and cellular mechanisms

    Institute of Scientific and Technical Information of China (English)

    Shingo Tsuji; Norio Hayashi; Masahiko Tsujii; Hiroaki Murata; Tsutomu Nishida; Masato Komori; Masakazu Yasumaru; Shuji Ishii; Yoshiaki Sasayama; Sunao Kawano

    2006-01-01

    Numerous cellular and molecular events have been described in development of gastric cancer. In this article,we overviewed roles of Helicobacter pylori(H pylori) infection on some of the important events in gastric carcinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carcinogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phenotype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H pylori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However,some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population,and warrant further investigation.

  10. Extracellular vesicles – biomarkers and effectors of the cellular interactome in cancer

    Directory of Open Access Journals (Sweden)

    Janusz eRak

    2013-03-01

    Full Text Available In multicellular organisms both health and disease are defined by patterns of communications between the constituent cells. In addition to networks of soluble mediators, cells are also programmed to exchange complex messages pre-assembled as multimolecular cargo of membraneous structures known extracellular vesicles (EV. Several biogenetic pathways produce EVs with different properties and known as exosomes, ectosomes and apoptotic bodies. In cancer, EVs carry molecular signatures and effectors of the disease, such as mutant oncoproteins, oncogenic transcripts, microRNA and DNA sequences. Intercellular trafficking of such EVs (oncosomes may contribute to horizontal cellular transformation, phenotypic reprogramming and functional re-education of recipient cells, both locally and systemically. The EV-mediated, reciprocal molecular exchange also includes tumor suppressors, phosphoproteins, proteases, growth factors and bioactive lipids, all of which participate in the functional integration of multiple cells and their collective involved in tumor angiogenesis, inflammation, immunity, coagulopathy, mobilization of bone marrow derived effectors, metastasis, drug resistance or cellular stemness. In cases where the EV involvement is rate limiting their production and uptake may represent and unexplored anticancer therapy target. Moreover, oncosomes circulating in biofluids of cancer patients offer an unprecedented, remote and non-invasive access to crucial molecular information about cancer cells, including their driver mutations, classifiers, molecular subtypes, therapeutic targets and biomarkers of drug resistance. New nanotechnologies are being developed to exploit this unique biomarker platform. Indeed, embracing the notion that human cancers are defined not only by processes occurring within cancer cells, but also between them, and amidst the altered tumor and systemic microenvironment may open new diagnostic and therapeutic opportunities.

  11. 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.

  12. Discovering the cellular-localized functional modules and modular interactions in response to liver cancer

    Institute of Scientific and Technical Information of China (English)

    Zhu Jing; Guo Zheng; Yang Da; Zhang Min; Wang Jing; Wang Chenguang

    2008-01-01

    In this paper, we firstly identify the functional modules enriched with differentially expressed genes (DEGs) and characterized by biological processes in specific cellular locations, based on gene ontology (GO) and microarray data. Then, we further define and filter disease relevant signature modules according to the ranking of the disease discriminating abilities of the pre-selected functional modules. At last, we analyze the potential way by which they cooperate towards human disease. Application of the proposed method to the analysis of a liver cancer dataset shows that, using the same false discovery rate (FDR) threshold, we can find more biologically meaningful and detailed processes by using the cellular localization information. Some biological evidences support the relevancy of our biological modules to the disease mechanism.

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

    Directory of Open Access Journals (Sweden)

    Falade A. J

    2015-08-01

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

  14. 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.

  15. Cellular automaton model of mass transport with chemical reactions

    International Nuclear Information System (INIS)

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

  16. A node-based version of the cellular Potts model.

    Science.gov (United States)

    Scianna, Marco; Preziosi, Luigi

    2016-09-01

    The cellular Potts model (CPM) is a lattice-based Monte Carlo method that uses an energetic formalism to describe the phenomenological mechanisms underlying the biophysical problem of interest. We here propose a CPM-derived framework that relies on a node-based representation of cell-scale elements. This feature has relevant consequences on the overall simulation environment. First, our model can be implemented on any given domain, provided a proper discretization (which can be regular or irregular, fixed or time evolving). Then, it allowed an explicit representation of cell membranes, whose displacements realistically result in cell movement. Finally, our node-based approach can be easily interfaced with continuous mechanics or fluid dynamics models. The proposed computational environment is here applied to some simple biological phenomena, such as cell sorting and chemotactic migration, also in order to achieve an analysis of the performance of the underlying algorithm. This work is finally equipped with a critical comparison between the advantages and disadvantages of our model with respect to the traditional CPM and to some similar vertex-based approaches. PMID:27416549

  17. Downregulation of microRNA-498 in colorectal cancers and its cellular effects

    Energy Technology Data Exchange (ETDEWEB)

    Gopalan, Vinod; Smith, Robert A.; Lam, Alfred K.-Y., E-mail: a.lam@griffith.edu.au

    2015-01-15

    miR-498 is a non-coding RNA located intergenically in 19q13.41. Due to its predicted targeting of several genes involved in control of cellular growth, we examined the expression of miR-498 in colon cancer cell lines and a large cohort of patients with colorectal adenocarcinoma. Two colon cancer cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The expression of miR-498 was tested in these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). Tissues from 80 patients with surgical resection of colorectum (60 adenocarcinomas and 20 non-neoplastic tissues) were tested for miR-498 expression by qRT-PCR. In addition, an exogenous miR-498 (mimic) was used to detect the miRNA's effects on cell proliferation and cell cycle events in SW480 using MTT calorimetric assay and flow cytometry respectively. The colon cancer cell lines showed reduced expression of miR-498 compared to a normal colonic epithelial cell line. Mimic driven over expression of miR-498 in the SW480 cell line resulted in reduced cell proliferation and increased proportions of G2-M phase cells. In tissues, miR-498 expression was too low to be detected in all colorectal adenocarcinoma compared to non-neoplastic tissues. This suggests that the down regulation of miR-498 in colorectal cancer tissues and the direct suppressive cellular effect noted in cancer cell lines implies that miR-498 has some direct or indirect role in the pathogenesis of colorectal adenocarcinomas. - Highlights: • miR-498 is a non-coding RNA located in 19q13.41. • Colon cancer cell lines showed reduced expression of miR-498. • Mimic driven over expression of miR-498 in colon cancer cells resulted in lower cell proliferation. • miR-498 expression was down regulated in all colorectal adenocarcinoma tissues.

  18. 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

  19. 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.

  20. Liver Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  1. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  3. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  4. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  6. Esophageal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Cervical Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Testicular Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  10. Lung Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. A Computational model for compressed sensing RNAi cellular screening

    Directory of Open Access Journals (Sweden)

    Tan Hua

    2012-12-01

    Full Text Available Abstract 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

  12. 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

  13. Three-dimensional in vitro cancer models: a short review

    International Nuclear Information System (INIS)

    The re-creation of the tumor microenvironment including tumor–stromal interactions, cell–cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell–cell and cell–matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies. (topical review)

  14. New trends in molecular and cellular biomarker discovery for colorectal cancer.

    Science.gov (United States)

    Aghagolzadeh, Parisa; Radpour, Ramin

    2016-07-01

    Colorectal cancer (CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches, selection of appropriate therapeutic strategies and efficient follow-up programs are essential to reduce CRC mortalities. Biomarker discovery for CRC based on the personalized genotype and clinical information could facilitate the classification of patients with certain types and stages of cancer to tailor preventive and therapeutic approaches. These cancer-related biomarkers should be highly sensitive and specific in a wide range of specimen(s) (including tumor tissues, patients' fluids or stool). Reliable biomarkers which enable the early detection of CRC, can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Advances in our understanding of the natural history of CRC have led to the development of different CRC associated molecular and cellular biomarkers. This review highlights the new trends and approaches in CRC biomarker discovery, which could be potentially used for early diagnosis, development of new therapeutic approaches and follow-up of patients. PMID:27433083

  15. New trends in molecular and cellular biomarker discovery for colorectal cancer

    Science.gov (United States)

    Aghagolzadeh, Parisa; Radpour, Ramin

    2016-01-01

    Colorectal cancer (CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches, selection of appropriate therapeutic strategies and efficient follow-up programs are essential to reduce CRC mortalities. Biomarker discovery for CRC based on the personalized genotype and clinical information could facilitate the classification of patients with certain types and stages of cancer to tailor preventive and therapeutic approaches. These cancer-related biomarkers should be highly sensitive and specific in a wide range of specimen(s) (including tumor tissues, patients’ fluids or stool). Reliable biomarkers which enable the early detection of CRC, can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Advances in our understanding of the natural history of CRC have led to the development of different CRC associated molecular and cellular biomarkers. This review highlights the new trends and approaches in CRC biomarker discovery, which could be potentially used for early diagnosis, development of new therapeutic approaches and follow-up of patients. PMID:27433083

  16. Cellular, Molecular Consequences of Peroxisome Proliferator- Activated Receptor-δ Activation in Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sara Vignati

    2006-10-01

    Full Text Available Peroxisome proliferator-activated receptor-δ (PPAR-δ is a ligand-activated transcription factor. In addition to its canonical role in lipid, glucose metabolism, PPAR-δ controls cell proliferation, death, differentiation in several tissues. Here we have examined the expression of PPAR-δ in ovarian tumors, the cellular, molecular consequences of its activation in ovarian cancer cells. PPAR-δ was expressed in a large number of epithelial ovarian tumors, cell lines. The PPAR-δ lig, ciglitazone inhibited the growth, clonogenic survival of ovarian cancer cells, inducing cell cycle arrest, cell death. Growth inhibition by ciglitazone was reversed by the PPAR-δ antagonist GW9662, indicating the involvement of PPAR-δ- dependent mechanisms. Microarray-based gene profiling revealed complex changes in the transcriptional program of ovarian cancer cells on treatment with ciglitazone, identified multiple pathways that may contribute to PPAR-δ ligands' antitumor activity. Genes upregulated by ciglitazone were predominantly associated with metabolic, differentiation, tumorsuppressor pathways, whereas downregulated genes were involved in cell proliferation, cell cycle, cell organization, steroid biosynthesis. Collectively, our data indicate that PPAR-δ activation by selective agonists is a valid strategy for ovarian cancer therapy, prevention, should be tested alone, in combination with other anticancer drugs.

  17. Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology.

    Science.gov (United States)

    Hou, Tim Y; Davidson, Laurie A; Kim, Eunjoo; Fan, Yang-Yi; Fuentes, Natividad R; Triff, Karen; Chapkin, Robert S

    2016-07-17

    The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as "carcinogenic to humans" on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer. PMID:27431370

  18. Biology of cancer and aging: a complex association with cellular senescence.

    Science.gov (United States)

    Falandry, Claire; Bonnefoy, Marc; Freyer, Gilles; Gilson, Eric

    2014-08-20

    Over the last 50 years, major improvements have been made in our understanding of the driving forces, both parallel and opposing, that lead to aging and cancer. Many theories on aging first proposed in the 1950s, including those associated with telomere biology, senescence, and adult stem-cell regulation, have since gained support from cumulative experimental evidence. These views suggest that the accumulation of mutations might be a common driver of both aging and cancer. Moreover, some tumor suppressor pathways lead to aging in line with the theory of antagonist pleiotropy. According to the evolutionary-selected disposable soma theory, aging should affect primarily somatic cells. At the cellular level, both intrinsic and extrinsic pathways regulate aging and senescence. However, increasing lines of evidence support the hypothesis that these driving forces might be regulated by evolutionary-conserved pathways that modulate energy balance. According to the hyperfunction theory, aging is a quasi-program favoring both age-related diseases and cancer that could be inhibited by the regulation of longevity pathways. This review summarizes these hypotheses, as well as the experimental data that have accumulated over the last 60 years linking aging and cancer.

  19. Critical Behavior in Cellular Automata Animal Disease Transmission Model

    Science.gov (United States)

    Morley, P. D.; Chang, Julius

    Using 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 in a farm, there is mandatory slaughter (culling) of all livestock in an infected premise (IP). Those farms in the neighboring of 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 interactions 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 nonlocal disease transport probability can be as low as 0.01% 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 fission cascade. Finally, we calculate that the percentage of culled animals that are actually healthy is ≈30%.

  20. 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.

  1. Engineered Swine Models of Cancer

    OpenAIRE

    Watson, Adrienne L; Carlson, Daniel F.; Largaespada, David A; Hackett, Perry B; Fahrenkrug, Scott C.

    2016-01-01

    Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs...

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

    CERN Document Server

    Kier, Lemont B; Cheng, Chao-Kun

    2006-01-01

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

  3. Effect of verapamil on cellular uptake of Tc-99m MIBI and tetrofosmin on several cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Hyun; Yoo, Jung Ah; Bae, Jin Ho; Jeong, Shin Young; Suh, Myung Rang; Ahn, Byeong Cheol; Lee, Kyu Bo; Lee, Jae Tae [School of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)

    2004-02-01

    Cellular uptake of {sup 99}mTc-sestamibi (MIBI) and {sup 99}mTc-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Cellular uptakes of Tc-99m MIBI and TF were measured in erythroleukemia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto 200 {mu}M at 1*10{sup 6} cells/{sup m}l at 37.deg.C. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of 100 {mu}M and the maximal increase at 50 {mu}M was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7m SK-OV3 cells were decreased with verapamil treatment at a concentration over 1 {mu}M. With a concentration of 200 {mu}M verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with 10{mu}M, but were also decreased with verapamil higher than 10{mu}M, resulting 40% and 5% of baseline at 50 {mu}M. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at 200 {mu}M. Although verapamil increases uptake of MIBI and TF in MDR cancer cells

  4. miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in ovarian cancer

    Science.gov (United States)

    Pedersen, Lykke; Lim, Emilia; Hernandez-Herrera, Anadulce; Rowat, Amy C.; Patil, Sagar L.; Chan, Clara K.; Wen, Yunfei; Zhang, Xinna; Basu-Roy, Upal; Mansukhani, Alka; Chu, Andy; Sipahimalani, Payal; Bowlby, Reanne; Brooks, Denise; Thiessen, Nina; Coarfa, Cristian; Ma, Yussanne; Moore, Richard A.; Schein, Jacquie E.; Mungall, Andrew J.; Liu, Jinsong; Pecot, Chad V.; Sood, Anil K.; Jones, Steven J.M.; Marra, Marco A.; Gunaratne, Preethi H.

    2016-01-01

    Ovarian cancer presents as an aggressive, advanced stage cancer with widespread metastases that depend primarily on multicellular spheroids in the peritoneal fluid. To identify new druggable pathways related to metastatic progression and spheroid formation, we integrated microRNA and mRNA sequencing data from 293 tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified miR-509-3p as a clinically significant microRNA that is more abundant in patients with favorable survival in both the TCGA cohort (P = 2.3E–3), and, by in situ hybridization (ISH), in an independent cohort of 157 tumors (P migration and disrupted multi-cellular spheroids in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti-correlated predicted targets were enriched in components of the extracellular matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but not in the other cell lines, in which levels of this protein were moderate to low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target in cancers with high YAP1, and we propose that therapeutically targeting the miR-509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid formation, and so inhibit metastasis in epithelial ovarian cancer and potentially in other cancers. PMID:27036018

  5. Magnolol Affects Cellular Proliferation, Polyamine Biosynthesis and Catabolism-Linked Protein Expression and Associated Cellular Signaling Pathways in Human Prostate Cancer Cells in vitro

    Directory of Open Access Journals (Sweden)

    Brendan T. McKeown

    2015-01-01

    Full Text Available Background: Prostate cancer is the most commonly diagnosed form of cancer in men in Canada and the United States. Both genetic and environmental factors contribute to the development and progression of many cancers, including prostate cancer. Context and purpose of this study: This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on cellular proliferation and proliferation-linked activities of PC3 human prostate cancer cells in vitro. Results: PC3 cells exposed to magnolol at a concentration of 80 μM for 6 hours exhibited decreased protein expression of ornithine decarboxylase, a key regulator in polyamine biosynthesis, as well as affecting the expression of other proteins involved in polyamine biosynthesis and catabolism. Furthermore, protein expression of the R2 subunit of ribonucleotide reductase, a key regulatory protein associated with DNA synthesis, was significantly decreased. Finally, the MAPK (mitogen-activated protein kinase, PI3K (phosphatidylinositol 3-kinase, NFκB (nuclear factor of kappa-light-chain-enhancer of activated B cells and AP-1 (activator protein 1 cellular signaling pathways were assayed to determine which, if any, of these pathways magnolol exposure would alter. Protein expressions of p-JNK-1 and c-jun were significantly increased while p-p38, JNK-1/2, PI3Kp85, p-PI3Kp85, p-Akt, NFκBp65, p-IκBα and IκBα protein expressions were significantly decreased. Conclusions: These alterations further support the anti-proliferative effects of magnolol on PC3 human prostate cancer cells in vitro and suggest that magnolol may have potential as a novel anti-prostate cancer agent.

  6. Laparoscopic and open resection for colorectal cancer: an evaluation of cellular immunity

    Directory of Open Access Journals (Sweden)

    Cao Jun

    2010-10-01

    Full Text Available Abstract Background Colorectal cancer is one kind of frequent malignant tumors of the digestive tract which gets high morbidity and mortality allover the world. Despite the promising clinical results recently, less information is available regarding the perioperative immunological effects of laparoscopic surgery when compared with the open surgery. This study aimed to compare the cellular immune responses of patients who underwent laparoscopic(LCR and open resections(OCR for colorectal cancer. Methods Between Mar 2009 and Sep 2009, 35 patients with colorectal carcinoma underwent LCR by laparoscopic surgeon. These patients were compared with 33 cases underwent conventional OCR by colorectal surgeon. Clinical data about the patients were collected prospectively. Comparison of the operative details and postoperative outcomes between laparoscopic and open resection was performed. Peripheral venous blood samples from these 68 patients were taken prior to surgery as well as on postoperative days(POD 1, 4 and 7. Cell counts of total white blood cells, neutrophils, lymphocyte subpopulations, natural killer(NK cells as well as CRP were determined by blood counting instrument, flow cytometry and hematology analyzer. Results There was no difference in the age, gender and tumor status between the two groups. The operating time was a little longer in the laparoscopic group (P > 0.05, but the blood loss was less (P = 0.039. Patients with laparoscopic resection had earlier return of bowel function and earlier resumption of diet as well as shorter median hospital stay (P +T cells and CD8+T cells were significant more in LCR group (P +T or NK cell numbers between the two groups. Cellular immune responds were similar between the two groups on POD1 and POD7. Conclusions Laparoscopic colorectal resection gets less surgery stress and short-term advantages compared with open resection. Cellular immune respond appears to be less affected by laparoscopic colorectal

  7. Relationship between cellular response models and biochemical mechanisms

    International Nuclear Information System (INIS)

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

  8. Progression to metastatic stage in a cellular model of prostate cancer is associated with methylation of the androgen receptor gene and transcriptional suppression of the insulin-like growth factor-I receptor gene

    OpenAIRE

    Schayek, Hagit; Bentov, Itay; Sun, Shihua; Plymate, Stephen R; Werner, Haim

    2010-01-01

    The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)-regulated target genes and with a decrease in insulin-like growth factor-I receptor (IGF1R) expression. DNA methylation of CpG islands is an epigenetic mechanism associated with gene silencing. Recent studies have demonstrated that methylation occurs early in prostate carcinogenesis and, furthermore, may contribute to androgen ind...

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

    Science.gov (United States)

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

    2012-02-01

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

  10. Preparation of bufalin-loaded pluronic polyetherimide nanoparticles, cellular uptake, distribution, and effect on colorectal cancer

    Directory of Open Access Journals (Sweden)

    Hu Q

    2014-08-01

    Full Text Available Qiang Hu,1,3,* Bo Liang,2,* Ying Sun,4 Xiao-Ling Guo,2,* Yi-Jie Bao,2 Dong-Hao Xie,3 Ming Zhou,3 You-Rong Duan,4 Pei-Hao Yin,2 Zhi-Hai Peng11Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan, 2Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 3Department of General Surgery, Dahua Hospital, 4State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: A large number of studies have shown that bufalin can have a significant antitumor effect in a variety of tumors. However, because of toxicity, insolubility in water, fast metabolism, short half-life, and other shortcomings, its application is limited in cancer therapy. In this study, we explored the anti-metastatic role of bufalin-loaded pluronic polyetherimide nanoparticles on HCT116 colon cancer-bearing mice. Nanoparticle size, shape, drug loading, encapsulation efficiency, and in vitro drug release were studied. Also, cellular uptake of nanoparticles, in vivo tumor targeting, and tumor metastasis were studied. The nanoparticles had a particle size of about 60 nm and an encapsulation efficiency of 75.71%, by weight. The in vitro release data showed that free bufalin was released faster than bufalin-loaded pluronic polyetherimide nanoparticles, and almost 80% of free bufalin was released after 32 hours. Nanoparticles had an even size distribution, were stable, and had a slow release and a tumor-targeting effect. Bufalin-loaded pluronic polyetherimide nanoparticles can significantly inhibit the growth and metastasis of colorectal cancer.Keywords: colon cancer, nanoparticles, tumor target, bufalin

  11. Cellular automata model of magnetospheric-ionospheric coupling

    Directory of Open Access Journals (Sweden)

    B. V. Kozelov

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

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

    CERN Document Server

    Jiao, Yang

    2011-01-01

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

  13. Androgen Receptor Expression and Cellular Proliferation During Transition from Androgen-Dependent to Recurrent Growth after Castration in the CWR22 Prostate Cancer Xenograft

    OpenAIRE

    Kim, Desok; Gregory, Christopher W.; French, Frank S.; Smith, Gary J.; Mohler, James L.

    2002-01-01

    Androgen receptor expression was analyzed in the CWR22 human prostate cancer xenograft model to better understand its role in prostate cancer recurrence after castration. In androgen-dependent tumors, 98.5% of tumor cell nuclei expressed androgen receptor with a mean optical density of 0.26 ± 0.01. On day 2 after castration androgen deprivation decreased immunostained cells to 2% that stained weakly (mean optical density, 0.16 ± 0.08). Cellular proliferation measured using Ki-67 revealed

  14. 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

  15. 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

  16. A Cellular Automata Model for the Study of Landslides

    Science.gov (United States)

    Liucci, Luisa; Suteanu, Cristian; Melelli, Laura

    2016-04-01

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

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

    Science.gov (United States)

    Liucci, Luisa; Melelli, Laura; Suteanu, Cristian

    2015-04-01

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

  18. Chromatin remodeling system, cancer stem-like attractors, and cellular reprogramming.

    Science.gov (United States)

    Zhang, Yue; Moriguchi, Hisashi

    2011-11-01

    The cancer cell attractors theory provides a next-generation understanding of carcinogenesis and natural explanation of punctuated clonal expansions of tumor progression. The impressive notion of atavism of cancer is now updated but more evidence is awaited. Besides, the mechanisms that the ectopic expression of some germline genes result in somatic tumors such as melanoma and brain tumors are emerging but are not well understood. Cancer could be triggered by cells undergoing abnormal cell attractor transitions, and may be reversible with "cyto-education". From mammals to model organisms like Caenorhabditis elegans and Drosophila melanogaster, the versatile Mi-2β/nucleosome remodeling and histone deacetylation complexes along with their functionally related chromatin remodeling complexes (CRCs), i.e., the dREAM/Myb-MuvB complex and Polycomb group complex are likely master regulators of cell attractors. The trajectory that benign cells switch to cancerous could be the reverse of navigation of embryonic cells converging from a series of intermediate transcriptional states to a final adult state, which is supported by gene expression dynamics inspector assays and some cross-species genetic evidence. The involvement of CRCs in locking cancer attractors may help find the recipes of perturbing genes to achieve successful reprogramming such that the reprogrammed cancer cell function in the same way as the normal cells. PMID:21909785

  19. Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.

    Science.gov (United States)

    Dong, Shuping; Cho, Hyung Joon; Lee, Yong Woo; Roman, Maren

    2014-05-12

    Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis. PMID:24716601

  20. 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.

  1. Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer

    NARCIS (Netherlands)

    Dow, Lukas E; O'Rourke, Kevin P; Simon, Janelle; Tschaharganeh, Darjus F; van Es, Johan H; Clevers, Hans; Lowe, Scott W

    2015-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally su

  2. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert B. Sims

    2011-01-01

    Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  3. 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.

  4. 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...

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

    OpenAIRE

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

    2015-01-01

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

  6. Particle acceleration in a complex solar active region modelled by a Cellular automata model

    Science.gov (United States)

    Dauphin, C.; Vilmer, N.; Anastasiadis, A.

    2004-12-01

    The models of cellular automat allowed to reproduce successfully several statistical properties of the solar flares. We use a cellular automat model based on the concept of self-organised critical system to model the evolution of the magnetic energy released in an eruptive active area. Each burst of magnetic energy released is assimilated to a process of magnetic reconnection. We will thus generate several current layers (RCS) where the particles are accelerated by a direct electric field. We calculate the energy gain of the particles (ions and electrons) for various types of magnetic configuration. We calculate the distribution function of the kinetic energy of the particles after their interactions with a given number of RCS for each type of configurations. We show that the relative efficiency of the acceleration of the electrons and the ions depends on the selected configuration.

  7. 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.

  8. Cellular Telephones, Magnetic Field Exposure, Risk of Brain Tumours and Cancer at Other Sites: A Cohort Study (invited paper)

    International Nuclear Information System (INIS)

    The purpose of the study is to investigate whether exposure to electromagnetic fields from cellular telephones is associated with brain tumours and cancer at other sites. Key information has been obtained on all cellular telephone subscribers in Denmark from 1 January 1982 to 31 December 1995. The overall subscriber cohort will include approximately 500,000 individuals. Collected information includes name of subscriber, address, telephone number, system used (analogue or digital), and annual use of the telephone. The name and address of the subscribers will be linked to the Central Population Register, and the personal identification number will be supplied in addition to information on vital status and migration. Finally, all members of the cohort will be linked to the Danish Cancer Registry, and the observed number of tumours will be compared with those expected on the basis of national cancer incidence rates stratified by sex, age, and calendar time. (author)

  9. ANIMAL MODELS OF CANCER: A REVIEW

    OpenAIRE

    Archana M Navale

    2013-01-01

    Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primi...

  10. Multi-color fluorescence imaging of sub-cellular dynamics of cancer cells in live mice

    Science.gov (United States)

    Hoffman, Robert M.

    2006-02-01

    We have genetically engineered dual-color fluorescent cells with one color in the nucleus and the other in the cytoplasm that enables real-time nuclear-cytoplasmic dynamics to be visualized in living cells in the cytoplasm in vivo as well as in vitro. To obtain the dual-color cells, red fluorescent protein (RFP) was expressed of the cancer cells, and green fluorescent protein (GFP) linked to histone H2B was expressed in the nucleus. Mitotic cells were visualized by whole-body imaging after injection in the mouse ear. Common carotid artery or heart injection of dual-color cells and a reversible skin flap enabled the external visualization of the dual-color cells in microvessels in the mouse where extreme elongation of the cell body as well as the nucleus occurred. The migration velocities of the dual-color cancer cells in the capillaries were measured by capturing individual images of the dual-color fluorescent cells over time. Human HCT-116-GFP-RFP colon cancer and mouse mammary tumor (MMT)-GFP-RFP cells were injected in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the HCT-116-GFP-RFP cells occurred within 6 hours. The data suggest rapid death of HCT-116-GFP-RFP cells in the portal vein. In contrast, MMT-GFP-RFP cells injected into the portal vein mostly survived and formed colonies in the liver. However, when the host mice were pretreated with cyclophosphamide, the HCT-116-GFP-RFP cells also survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the HCT-116-GFP-RFP cells but could not effectively kill the MMT-GFP-RFP cells. With the ability to continuously image cancer cells at the subcellular level in the live animal, our understanding of the complex steps of metastasis will significantly increase. In addition, new drugs can be developed to target these newly visible steps of metastasis.

  11. 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.

  12. 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

  13. 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...

  14. Effect of morphology on water sorption in cellular solid foods. Part I: Pore scale network model

    NARCIS (Netherlands)

    Esveld, D.C.; Sman, van der R.G.M.; Dalen, van G.; Duynhoven, van J.P.M.; Meinders, M.B.J.

    2012-01-01

    A pore scale network model is developed to predict the dynamics of moisture diffusion into complex cellular solid foods like bread, crackers, and cereals. The morphological characteristics of the sample, including the characteristics of each cellular void and the open pore connections between them a

  15. 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

  16. DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer.

    Science.gov (United States)

    Terracina, Krista P; Graham, Laura J; Payne, Kyle K; Manjili, Masoud H; Baek, Annabel; Damle, Sheela R; Bear, Harry D

    2016-09-01

    Adoptive T cell immunotherapy is a promising approach to cancer treatment that currently has limited clinical applications. DNA methyltransferase inhibitors (DNAMTi) have known potential to affect the immune system through multiple mechanisms that could enhance the cytotoxic T cell responses, including: upregulation of tumor antigen expression, increased MHC class I expression, and blunting of myeloid derived suppressor cells (MDSCs) expansion. In this study, we have investigated the effect of combining the DNAMTi, decitabine, with adoptive T cell immunotherapy in the murine 4T1 mammary carcinoma model. We found that expression of neu, MHC class I molecules, and several murine cancer testis antigens (CTA) was increased by decitabine treatment of 4T1 cells in vitro. Decitabine also increased expression of multiple CTA in two human breast cancer cell lines. Decitabine-treated 4T1 cells stimulated greater IFN-gamma release from tumor-sensitized lymphocytes, implying increased immunogenicity. Expansion of CD11b + Gr1 + MDSC in 4T1 tumor-bearing mice was significantly diminished by decitabine treatment. Decitabine treatment improved the efficacy of adoptive T cell immunotherapy in mice with established 4T1 tumors, with greater inhibition of tumor growth and an increased cure rate. Decitabine may have a role in combination with existing and emerging immunotherapies for breast cancer. PMID:27416831

  17. 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.

  18. 13A. Integrative Cancer Care: The Life Over Cancer Model

    OpenAIRE

    Block, Keith; Block, Penny; Gyllenhaal, Charlotte; Shoham, Jacob

    2013-01-01

    Focus Areas: Integrative Algorithms of Care Integrative cancer treatment fully blends conventional cancer treatment with integrative therapies such as diet, supplements, exercise and biobehavioral approaches. The Life Over Cancer model comprises three spheres of intervention: improving lifestyle, improving biochemical environment (terrain), and improving tolerance of conventional treatment. These levels are applied within the context of a life-affirming approach to cancer patients and treatme...

  19. Genomic instability and cellular stress in organ biopsies and peripheral blood lymphocytes from patients with colorectal cancer and predisposing pathologies

    Science.gov (United States)

    Lombardi, Sara; Fuoco, Ilenia; di Fluri, Giorgia; Costa, Francesco; Ricchiuti, Angelo; Biondi, Graziano; Nardini, Vincenzo; Scarpato, Roberto

    2015-01-01

    Inflammatory bowel disease (IBD) and polyps, are common colorectal pathologies in western society and are risk factors for development of colorectal cancer (CRC). Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy. Cellular stress, may contribute to genomic instability. In colorectal biopsies and peripheral blood lymphocytes of patients with IBD, polyps and CRC, we evaluated 1) genomic instability using the γH2AX assay as marker of DSB and micronuclei in mononuclear lymphocytes kept under cytodieresis inhibition, and 2) cellular stress through expression and cellular localization of glutathione-S-transferase omega 1 (GSTO1). Colon biopsies showed γH2AX increase starting from polyps, while lymphocytes already from IBD. Micronuclei frequency began to rise in lymphocytes of subjects with polyps, suggesting a systemic genomic instability condition. Colorectal tissues lost GSTO1 expression but increased nuclear localization with pathology progression. Lymphocytes did not change GSTO1 expression and localization until CRC formation, where enzyme expression was increased. We propose that the growing genomic instability found in our patients is connected with the alteration of cellular environment. Evaluation of genomic damage and cellular stress in colorectal pathologies may facilitate prevention and management of CRC. PMID:26046795

  20. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

    Science.gov (United States)

    Stites, Edward C.

    2013-04-01

    Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients.

  1. Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells.

    Science.gov (United States)

    Price, D J; Miralem, T; Jiang, S; Steinberg, R; Avraham, H

    2001-03-01

    The expression of vascular endothelial growth factor (VEGF) by breast tumors has been previously correlated with a poor prognosis in the pathogenesis of breast cancer. Furthermore, VEGF secretion is a prerequisite for tumor development. Although most of the effects of VEGF have been shown to be attributable to the stimulation of endothelial cells, we present evidence here that breast tumor cells are capable of responding to VEGF. We show that VEGF stimulation of T-47D breast cancer cells leads to changes in cellular signaling and invasion. VEGF increases the cellular invasion of T-47D breast cancer cells on Matrigel/ fibronectin-coated transwell membranes by a factor of two. Northern analysis for the expression of the known VEGF receptors shows the presence of moderate levels of Flt-1 and low levels of Flk-1/KDR mRNAs in a variety of breast cancer cell lines. T-47D breast cancer cells bind 125I-labeled VEGF with a Kd of 13 x 10(-9) M. VEGF induces the activation of the extracellular regulated kinases 1,2 as well as activation of phosphatidylinositol 3'-kinase, Akt, and Forkhead receptor L1. These findings in T-47D breast cancer cells strongly suggest an autocrine role for VEGF contributing to the tumorigenic phenotype.

  2. CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling

    Directory of Open Access Journals (Sweden)

    Raul Torres-Ruiz

    2015-09-01

    Full Text Available The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers.

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

    KAUST Repository

    ElSawy, Hesham

    2016-03-22

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

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

    OpenAIRE

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

    2016-01-01

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

  5. Vanderbilt University Study Creates New Roadmap for Cellular Activity - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Scientists studying cellular processes have long sought to measure redox modifications because they provide one of the normal layers of cell control. But redox disruption or oxidative stress at the cellular level can also create a pathway to diseases like

  6. 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.

  7. 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.

  8. 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.

  9. Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

    Science.gov (United States)

    Chaplain, Mark A. J.; Powathil, Gibin G.

    Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.

  10. 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.

  11. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  13. Cellular cardiac electrophysiology modelling with Chaste and CellML

    Directory of Open Access Journals (Sweden)

    Jonathan eCooper

    2015-01-01

    Full Text Available 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 Generalised 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 generalised in our functional curation framework, which uses a domain-specific language for defining complex experiments as a basis for comparison of model behaviour.

  14. Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells.

    Science.gov (United States)

    Guo, Jianfeng; O'Driscoll, Caitriona M; Holmes, Justin D; Rahme, Kamil

    2016-07-25

    The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer. PMID:27188645

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

    Science.gov (United States)

    Bianca, Carlo; Dogbe, Christian; Lemarchand, Annie

    2016-02-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  17. 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.

  18. 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...

  19. Stem cell-like ALDHbright cellular states in EGFR-mutant non-small cell lung cancer

    Science.gov (United States)

    Corominas-Faja, Bruna; Oliveras-Ferraros, Cristina; Cuyàs, Elisabet; Segura-Carretero, Antonio; Joven, Jorge; Martin-Castillo, Begoña; Barrajón-Catalán, Enrique; Micol, Vicente; Bosch-Barrera, Joaquim; Menendez, Javier A

    2013-01-01

    The enrichment of cancer stem cell (CSC)-like cellular states has not previously been considered to be a causative mechanism in the generalized progression of EGFR-mutant non-small cell lung carcinomas (NSCLC) after an initial response to the EGFR tyrosine kinase inhibitor erlotinib. To explore this possibility, we utilized a pre-clinical model of acquired erlotinib resistance established by growing NSCLC cells containing a TKI-sensitizing EGFR exon 19 deletion (ΔE746-A750) in the continuous presence of high doses of erlotinib. Genome-wide analyses using Agilent 44K Whole Human Genome Arrays were evaluated via bioinformatics analyses through GSEA-based screening of the KEGG pathway database to identify the molecular circuitries that were over-represented in the transcriptomic signatures of erlotinib-refractory cells. The genomic spaces related to erlotinib resistance included a preponderance of cell cycle genes (E2F1, -2, CDC2, -6) and DNA replication-related genes (MCM4, -5, -6, -7), most of which are associated with early lung development and poor prognosis. In addition, metabolic genes such as ALDH1A3 (a candidate marker for lung cancer cells with CSC-like properties) were identified. Thus, we measured the proportion of erlotinib-resistant cells expressing very high levels of aldehyde dehydrogenase (ALDH) activity attributed to ALDH1/3 isoforms. Using flow cytometry and the ALDEFLUOR® reagent, we confirmed that erlotinib-refractory cell populations contained drastically higher percentages (>4500%) of ALDHbright cells than the parental erlotinib-responsive cells. Notably, strong decreases in the percentages of ALDHbright cells were observed following incubation with silibinin, a bioactive flavonolignan that can circumvent erlotinib resistance in vivo. The number of lung cancer spheres was drastically suppressed by silibinin in a dose-dependent manner, thus confirming the ability of this agent to inhibit the self-renewal of erlotinib-refractory CSC-like cells

  20. Specific cellular accumulation of photofrin-II in EC cells promotes photodynamic treatment efficacy in esophageal cancer.

    Science.gov (United States)

    Gao, Shegan; Liang, Shuo; Ding, Kaili; Qu, Zhifeng; Wang, Ying; Feng, Xiaoshan

    2016-06-01

    Photodynamic therapy (PDT), which uses a light-sensitive compound and laser irradiation, is a light-based oncological treatment modality. PDT offers an alternative, less invasive treatment for various malignant tumors, such as esophageal cancer (EC), through a photochemical reaction induced by photofrin-II or other oncotropic photosensitizers without severe complications. Previous studies has shown that cancerous tissues accumulated more photosensitizers than paired normal tissues, however, whether it is cellular or vascular mechanisms remains unknown. Herein, in vivo and in vitro examinations were performed to study the mechanisms by which photofrin-II effectively and specifically killed EC cells. In this study, EC tissue of patients treated with photofrin-II, human ESCC cellline SHEEC and parental normal cellline SHEE, primary culture cells of EC tissue were used. The concentration of photofrin-II in cells were evaluated by high-performance liquid chromatography (HPLC). The results exhibited that accumulation of photofrin-II in cancerous cells were significantly higher than that in non-cancerous cells (p<0.05) under certain dose and time period of incubation of photofrin-II. In summary, our study showed that, photofrin-II specifically accumulated in EC cells in vivo and in vitro after controlling for vascular factors, which provided strong evidence that maybe the cellular factor is the main mechanism by which photofrin-II-mediated PDT selectively caused EC cells death. PMID:26829562

  1. 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.

  2. Markov Model Based CAC algorithms for Cellular Networks

    Directory of Open Access Journals (Sweden)

    PATLEVIČ Peter

    2010-05-01

    Full Text Available In this paper, we investigate using ofthe Hidden Markov Model philosophy for solvingconnection admission control (CAC problem incellular networks. For more effective bandwidthutilization and Quality of Service (QoS support itis necessary to solve the connection admissioncontrol with respect to minimizing blockingprobability of handoff and newly arrivedconnections. This paper looks into an thresholdoriented CAC scheme for operation with twoclasses of connections with a Markov model usedfor computation of the threshold value based oncurrent conditions in the network and so makesthe operation of the mobile network cell moreeffectively. In article we extrapolate Markov chainmodel based CAC for three classes of connectionsand sketch how to generalize problem for n classesof connections.

  3. An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype.

    Directory of Open Access Journals (Sweden)

    Irina M Shapiro

    2011-08-01

    Full Text Available Epithelial-mesenchymal transition (EMT, a mechanism important for embryonic development, plays a critical role during malignant transformation. While much is known about transcriptional regulation of EMT, alternative splicing of several genes has also been correlated with EMT progression, but the extent of splicing changes and their contributions to the morphological conversion accompanying EMT have not been investigated comprehensively. Using an established cell culture model and RNA-Seq analyses, we determined an alternative splicing signature for EMT. Genes encoding key drivers of EMT-dependent changes in cell phenotype, such as actin cytoskeleton remodeling, regulation of cell-cell junction formation, and regulation of cell migration, were enriched among EMT-associated alternatively splicing events. Our analysis suggested that most EMT-associated alternative splicing events are regulated by one or more members of the RBFOX, MBNL, CELF, hnRNP, or ESRP classes of splicing factors. The EMT alternative splicing signature was confirmed in human breast cancer cell lines, which could be classified into basal and luminal subtypes based exclusively on their EMT-associated splicing pattern. Expression of EMT-associated alternative mRNA transcripts was also observed in primary breast cancer samples, indicating that EMT-dependent splicing changes occur commonly in human tumors. The functional significance of EMT-associated alternative splicing was tested by expression of the epithelial-specific splicing factor ESRP1 or by depletion of RBFOX2 in mesenchymal cells, both of which elicited significant changes in cell morphology and motility towards an epithelial phenotype, suggesting that splicing regulation alone can drive critical aspects of EMT-associated phenotypic changes. The molecular description obtained here may aid in the development of new diagnostic and prognostic markers for analysis of breast cancer progression.

  4. One-pot synthesis of FePt/CNTs nanocomposites for efficient cellular imaging and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weihong; Zheng, Xiuwen, E-mail: xwzheng1976@163.com [Linyi University, School of Chemistry & Chemical Engineering, Shandong Provincial Key Laboratory of Detection Technology for Tumor Makers (China); Li, Shulian [Linyi Tumor Hospital (China); Zhang, Wei; Wen, Xin [Linyi University, School of Chemistry & Chemical Engineering, Shandong Provincial Key Laboratory of Detection Technology for Tumor Makers (China); Yue, Ludan [Shandong Normal University (China); Wang, Jinlong [Shandong University of Technology (China)

    2015-11-15

    Here, we developed a facile route to synthesize carbon nanotube-based FePt nanocomposites (FePt/CNTs) as a potential theranostic platform in the cancer treatment. FePt/CNTs were firstly synthesized via one-pot polyol route, and then functionalized with 6-arm-polyethylene glycol-amine polymer. The average size of FePt nanoparticles (NPs) is 3–4 nm, which is dispersed on the CNT surface (ca.50–150 nm). The as-prepared FePt NPs display high cytotoxicity by highly reactive oxygen species in cancer cells. Folic acid and fluorescein isothiocyanate are assembled onto the surface of FePt/CNTs for effective targeting of folate receptor-positive cancer cells and simultaneously for the visualization of cellular uptake. Therefore, the FePt/CNTs NPs capability of simultaneously performing diagnosis, therapy, and targeting is, therefore, promising for future potential widespread application in biomedicine.

  5. Distinct cellular properties of oncogenic KIT receptor tyrosine kinase mutants enable alternative courses of cancer cell inhibition.

    Science.gov (United States)

    Shi, Xiarong; Sousa, Leiliane P; Mandel-Bausch, Elizabeth M; Tome, Francisco; Reshetnyak, Andrey V; Hadari, Yaron; Schlessinger, Joseph; Lax, Irit

    2016-08-16

    Large genomic sequencing analysis as part of precision medicine efforts revealed numerous activating mutations in receptor tyrosine kinases, including KIT. Unfortunately, a single approach is not effective for inhibiting cancer cells or treating cancers driven by all known oncogenic KIT mutants. Here, we show that each of the six major KIT oncogenic mutants exhibits different enzymatic, cellular, and dynamic properties and responds distinctly to different KIT inhibitors. One class of KIT mutants responded well to anti-KIT antibody treatment alone or in combination with a low dose of tyrosine kinase inhibitors (TKIs). A second class of KIT mutants, including a mutant resistant to imatinib treatment, responded well to a combination of TKI with anti-KIT antibodies or to anti-KIT toxin conjugates, respectively. We conclude that the preferred choice of precision medicine treatments for cancers driven by activated KIT and other RTKs may rely on clear understanding of the dynamic properties of oncogenic mutants. PMID:27482095

  6. Retrotransposon-Encoded Reverse Transcriptase in the Genesis, Progression and Cellular Plasticity of Human Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sinibaldi-Vallebona, Paola; Matteucci, Claudia [Department of Experimental Medicine and Biochemical Sciences, University ‘Tor Vergata’, Rome (Italy); Spadafora, Corrado, E-mail: cspadaf@tin.it [Italian National Institute of Health (ISS), Rome (Italy)

    2011-03-07

    LINE-1 (Long Interspersed Nuclear Elements) and HERVs (Human Endogenous Retroviruses) are two families of autonomously replicating retrotransposons that together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly those encoding the reverse transcriptase (RT) enzyme, are generally expressed at low levels in differentiated cells, but their expression is upregulated in transformed cells and embryonic tissues. Here we discuss a recently discovered RT-dependent mechanism that operates in tumorigenesis and reversibly modulates phenotypic and functional variations associated with tumor progression. Downregulation of active LINE-1 elements drastically reduces the tumorigenic potential of cancer cells, paralleled by reduced proliferation and increased differentiation. Pharmacological RT inhibitors (e.g., nevirapine and efavirenz) exert similar effects on tumorigenic cell lines, both in culture and in animal models. The HERV-K family play a distinct complementary role in stress-dependent transition of melanoma cells from an adherent, non-aggressive, to a non-adherent, highly malignant, growth phenotype. In synthesis, the retrotransposon-encoded RT is increasingly emerging as a key regulator of tumor progression and a promising target in a novel anti-cancer therapy.

  7. Cellular automata cell structure for modeling heterogeneous traffic

    OpenAIRE

    Pal, Dibyendu; C.Mallikarjuna

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    David L. Forest

    2015-05-01

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

  9. 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.

  10. Setup of IN VIVO Breast Cancer Models for Nanodrug Testing

    DEFF Research Database (Denmark)

    Schifter, Søren

    for detection of the primary tumor and metastasis and the efficacy of siRNA delivery is measured by reporter gene-targeting siRNAs and in vivo imaging. The use of a uniform siRNA not affecting cellular processes would allow for standardized assessment of siRNA delivery to cancer cells without interferences via......RNA/aptamer conjugates, or carriers such as liposome/chitosan/micelle spheres. As a first step towards testing of the efficacy of siRNA delivery in vivo via different conjugates and complexes, we aimed at developing a standardized breast cancer model system in mice. In this conception, a reporter gene is used...... differential knockdown efficacies and the readout can directly be performed by quantitative imaging using a Caliper IVIS system. In one line of experiments, we engineered non-metastatic MCF-7 breast cancer cells to express the luminescent reporter firefly luciferase (Luc2) along with a pro-metastatic micro...

  11. The mathematics of cancer: integrating quantitative models.

    Science.gov (United States)

    Altrock, Philipp M; Liu, Lin L; Michor, Franziska

    2015-12-01

    Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.

  12. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

    OpenAIRE

    Xuanbin Wang; Yibin Feng; Ning Wang; Fan Cheung; Hor Yue Tan; Sen Zhong; Charlie Li; Seiichi Kobayashi

    2014-01-01

    Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and...

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Huang Xinyi

    2015-01-01

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

  15. Cellular calcium dynamics in lactation and breast cancer: From physiology to pathology

    Science.gov (United States)

    Breast cancer is the second leading cause of cancer mortality in women, estimated at nearly 40,000 deaths and more than 230,000 new cases diagnosed in the U.S. this year alone. One of the defining characteristics of breast cancer is the radiographic presence of microcalcifications. These palpable mi...

  16. Chemical genetics and drug screening in Drosophila cancer models

    Institute of Scientific and Technical Information of China (English)

    Mara Gladstone; Tin Tin Su

    2011-01-01

    Drug candidates often fail in preclinical and clinical testing because of reasons of efficacy and/or safety.It would be time- and cost-efficient to have screening models that reduce the rate of such false positive candidates that appear promising at first but fail later.In this regard,it would be particularly useful to have a rapid and inexpensive whole animal model that can pre-select hits from high-throughput screens but before testing in costly rodent assays.Drosophila melanogaster has emerged as a potential whole animal model for drug screening.Of particular interest have been drugs that must act in the context of multi-cellularity such as those for neurological disorders and cancer.A recent review provides a comprehensive summary of drug screening in Drosophila,but with an emphasis on neurodegenerative disorders.Here,we review Drosophila screens in the literature aimed at cancer therapeutics.

  17. 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

  18. 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.

  19. 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.

  20. Nuclear reprogramming of luminal-like breast cancer cells generates Sox2-overexpressing cancer stem-like cellular states harboring transcriptional activation of the mTOR pathway

    Science.gov (United States)

    Corominas-Faja, Bruna; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Cuyàs, Elisabet; López-Bonet, Eugeni; Lupu, Ruth; Alarcón, Tomás; Vellon, Luciano; Iglesias, Juan Manuel; Leis, Olatz; Martín, Ángel G; Vazquez-Martin, Alejandro; Menendez, Javier A

    2013-01-01

    Energy metabolism plasticity enables stemness programs during the reprogramming of somatic cells to an induced pluripotent stem cell (iPSC) state. This relationship may introduce a new era in the understanding of Warburg’s theory on the metabolic origin of cancer at the level of cancer stem cells (CSCs). Here, we used Yamanaka’s stem cell technology in an attempt to create stable CSC research lines in which to dissect the transcriptional control of mTOR—the master switch of cellular catabolism and anabolism—in CSC-like states. The rare colonies with iPSC-like morphology, obtained following the viral transduction of the Oct4, Sox2, Klf4, and c-Myc (OSKM) stemness factors into MCF-7 luminal-like breast cancer cells (MCF-7/Rep), demonstrated an intermediate state between cancer cells and bona fide iPSCs. MCF-7/Rep cells notably overexpressed SOX2 and stage-specific embryonic antigen (SSEA)-4 proteins; however, other stemness-related markers (OCT4, NANOG, SSEA-1, TRA-1–60, and TRA-1–81) were found at low to moderate levels. The transcriptional analyses of OSKM factors confirmed the strong but unique reactivation of the endogenous Sox2 stemness gene accompanied by the silencing of the exogenous Sox2 transgene in MCF-7/Rep cells. Some but not all MCF-7/Rep cells acquired strong alkaline phosphatase (AP) activity compared with MCF-7 parental cells. SOX2-overexpressing MCF-7/Rep cells contained drastically higher percentages of CD44+ and ALDEFLUOR-stained ALDHbright cells than MCF-7 parental cells. The overlap between differentially expressed mTOR signaling-related genes in 3 different SOX2-overexpressing CSC-like cell lines revealed a notable downregulation of 3 genes, PRKAA1 (which codes for the catalytic α 1 subunit of AMPK), DDIT4/REDD1 (a stress response gene that operates as a negative regulator of mTOR), and DEPTOR (a naturally occurring endogenous inhibitor of mTOR activity). The insulin-receptor gene (INSR) was differentially upregulated in MCF-7/Rep

  1. Ensemble Modeling of Cancer Metabolism

    Directory of Open Access Journals (Sweden)

    Tahmineh eKhazaei

    2012-05-01

    Full Text Available The metabolic behaviour of cancer cells is adapted to meet their proliferative needs, with notable changes such as enhanced lactate secretion and glucose uptake rates. In this work, we use the Ensemble Modeling (EM framework to gain insight and predict potential drug targets for tumour cells. EM generates a set of models which span the space of kinetic parameters that are constrained by thermodynamics. Perturbation data based on known targets are used to screen the entire ensemble of models to obtain a sub-set, which is increasingly predictive. EM allows for incorporation of regulatory information and captures the behaviour of enzymatic reactions at the molecular level by representing reactions in the elementary reaction form. In this study, a metabolic network consisting of 58 reactions is considered and accounts for glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, and includes allosteric regulation of key enzymes. Experimentally measured intracellular and extracellular metabolite concentrations are used for developing the ensemble of models along with information on established drug targets. The resulting models predicted transaldolase (TALA and succinyl-CoA ligase (SUCOAS1m to cause a significant reduction in growth rate when repressed, relative to currently known drug targets. Furthermore, the results suggest that the synergetic repression of transaldolase and glycine hydroxymethyltransferase (GHMT2r will lead to a three-fold decrease in growth rate compared to the repression of single enzyme targets.

  2. PLGA nanoparticles codeliver paclitaxel and Stat3 siRNA to overcome cellular resistance in lung cancer cells

    Directory of Open Access Journals (Sweden)

    Su WP

    2012-08-01

    Full Text Available Wen-Pin Su,1,2 Fong-Yu Cheng,3 Dar-Bin Shieh,3–6 Chen-Sheng Yeh,5–7 Wu-Chou Su1,2,81Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University; 2Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; 3Institute of Oral Medicine, College of Medicine, National Cheng Kung University; 4Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; 5Advanced Optoelectronic Technology Center; 6Center for Frontier Materials and Micro/Nano Science and Technology, and 7Department of Chemistry, National Cheng Kung University; 8Cancer Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Abstract: Background: Effective cancer chemotherapy remains an important issue in cancer treatment, and signal transducer and activator of transcription-3 (Stat3 activation leads to cellular resistance of anticancer agents. Polymers are ideal vectors to carry both chemotherapeutics and small interfering ribonucleic acid (siRNA to enhance antitumor efficacy. In this paper, poly(lactic-co-glycolic acid (PLGA nanoparticles loaded with paclitaxel and Stat3 siRNA were successfully synthesized, and their applications in cancer cells were investigated.Methods: Firstly, paclitaxel was enclosed by PLGA nanoparticles through solvent evaporation. They were then coated with cationic polyethylenimine polymer (PLGA-PEI-TAX, enabling it to carry Stat3 siRNA on its surface through electrostatic interactions (PLGA-PEI-TAX-S3SI. The size, zeta potential, deliver efficacy, and release profile of the PLGA nanocomplexes were characterized in vitro. The cellular uptake, intracellular nanoparticle trajectory, and subsequent cellular events were evaluated after treatment with various PLGA nanocomplexes in human lung cancer A549 cells and A549-derived paclitaxel

  3. Cancer progression modeling using static sample data.

    Science.gov (United States)

    Sun, Yijun; Yao, Jin; Nowak, Norma J; Goodison, Steve

    2014-01-01

    As molecular profiling data continues to accumulate, the design of integrative computational analyses that can provide insights into the dynamic aspects of cancer progression becomes feasible. Here, we present a novel computational method for the construction of cancer progression models based on the analysis of static tumor samples. We demonstrate the reliability of the method with simulated data, and describe the application to breast cancer data. Our findings support a linear, branching model for breast cancer progression. An interactive model facilitates the identification of key molecular events in the advance of disease to malignancy.

  4. 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].

  5. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

    Science.gov (United States)

    Ye, Jun; Xia, Xuejun; Dong, Wujun; Hao, Huazhen; Meng, Luhua; Yang, Yanfang; Wang, Renyun; Lyu, Yuanfeng; Liu, Yuling

    2016-01-01

    There is no effective clinical therapy for triple-negative breast cancers (TNBCs), which have high low-density lipoprotein (LDL) requirements and express relatively high levels of LDL receptors (LDLRs) on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul) was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231) and non-TNBC (MCF7) cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native LDL. The findings of this paper further confirm the therapeutic potential of PTX-CH Emul in clinical applications involving TNBC therapy. PMID:27601899

  6. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel-cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines.

    Science.gov (United States)

    Ye, Jun; Xia, Xuejun; Dong, Wujun; Hao, Huazhen; Meng, Luhua; Yang, Yanfang; Wang, Renyun; Lyu, Yuanfeng; Liu, Yuling

    2016-01-01

    There is no effective clinical therapy for triple-negative breast cancers (TNBCs), which have high low-density lipoprotein (LDL) requirements and express relatively high levels of LDL receptors (LDLRs) on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel-cholesterol complex (PTX-CH Emul) was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231) and non-TNBC (MCF7) cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native LDL. The findings of this paper further confirm the therapeutic potential of PTX-CH Emul in clinical applications involving TNBC therapy. PMID:27601899

  7. Novel water-soluble polyurethane nanomicelles for cancer chemotherapy: physicochemical characterization and cellular activities

    Directory of Open Access Journals (Sweden)

    Khosroushahi Ahmad

    2012-01-01

    Full Text Available Abstract Background Efficient delivery of anticancer chemotherapies such as paclitaxel (PTX can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Accordingly, researches on polymeric nanomicelles continue to find suitable delivery systems. However, due to biocompatibility concerns, a few micellar nanoformulations have exquisitely been translated into clinical uses. Here, we report the synthesis of novel water-soluble nanomicelles using bioactive polyurethane (PU polymer and efficient delivery of PTX in the human breast cancer MCF-7 cells. Results The amphiphilic polyurethane was prepared through formation of urethane bounds between hydroxyl groups in poly (tetramethylene ether glycol (PTMEG and dimethylol propionic acid with isocyanate groups in toluene diisocyanate (TDI. The free isocyanate groups were blocked with phenol, while the free carboxyl groups of dimethylol propionic acid were reacted with triethylamine to attain ionic centers in the polymer backbone. These hydrophobic PTMEG blocks displayed self-assembly forming polymeric nanomicelles in water. The PTX loaded PU nanomicelles showed suitable physical stability, negative zeta potential charge (-43 and high loading efficiency (80% with low level of critical micelle concentration (CMC. In vitro drug release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4, implying involvement of a pH-sensitive mechanism for drug release from the nanomicelles. The kinetic of release exquisitely obeyed the Higuchi model, confirming involvement of diffusion and somewhat erosion at pH 5.4. These nanomicelles significantly inhibited the growth and proliferation of the human breast cancer MCF-7 cells, leading them to apoptosis. The real time RT-PCR analysis confirmed the activation of apoptosis as result of liberation of cytochrome c in the cells treated with the PTX loaded PU nanomicelles. The comet assay analysis showed somewhat DNA

  8. pH effect on cellular uptake of Sn(IV) chlorine e6 dichloride trisodium salt by cancer cells in vitro

    OpenAIRE

    Al-Khaza’leh, Khaled A.; Omar, Khalid; M. S. Jaafar

    2010-01-01

    The effects of pH value and presence of serum in an incubation medium on photosensitizer drug cellular uptake in MCF7 cancer cells have been investigated. The results showed that the presence of serum in an incubation medium reduced the drug cellular uptake at all pH values. It has been found that decreasing on pH values of the incubation medium increased the cellular uptake of the drug, demonstrating selective uptake of the sensitizer. The HepG2 liver cancer cells exhibited more drug cellula...

  9. Animal models of ovarian cancer

    OpenAIRE

    Shaw Tanya J; Vanderhyden Barbara C; Ethier Jean-François

    2003-01-01

    Abstract Ovarian cancer is the most lethal of all of the gynecological cancers and can arise from any cell type of the ovary, including germ cells, granulosa or stromal cells. However, the majority of ovarian cancers arise from the surface epithelium, a single layer of cells that covers the surface of the ovary. The lack of a reliable and specific method for the early detection of epithelial ovarian cancer results in diagnosis occurring most commonly at late clinical stages, when treatment is...

  10. Dexamethasone reduces sensitivity to cisplatin by blunting p53-dependent cellular senescence in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Haiyan Ge

    Full Text Available INTRODUCTION: Dexamethasone (DEX co-treatment has proved beneficial in NSCLC patients, improving clinical symptoms by the reduction of side effects after chemotherapy. However, recent studies have shown that DEX could render cancer cells more insensitive to cytotoxic drug therapy, but it is not known whether DEX co-treatment could influence therapy-induced senescence (TIS, and unknown whether it is in a p53-dependent or p53-independent manner. METHODS: We examined in different human NSCLC cell lines and detected cellular senescence after cisplatin (DDP treatment in the presence or absence of DEX. The in vivo effect of the combination of DEX and DDP was assessed by tumor growth experiments using human lung cancer cell lines growing as xenograft tumors in nude mice. RESULTS: Co-treatment with DEX during chemotherapy in NSCLC resulted in increased tumor cell viability and inhibition of TIS compared with DDP treated group. DEX co-treatment cells exhibited the decrease of DNA damage signaling pathway proteins, the lower expression of p53 and p21(CIP1, the lower cellular secretory program and down-regulation of NF-κB and its signaling cascade. DEX also significantly reduced DDP sensitivity in vivo. CONCLUSIONS: Our results underscore that DEX reduces chemotherapy sensitivity by blunting therapy induced cellular senescence after chemotherapy in NSCLC, which may, at least in part, in a p53-dependent manner. These data therefore raise concerns about the widespread combined use of gluocorticoids (GCs with antineoplastic drugs in the clinical management of cancer patients.

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

    Directory of Open Access Journals (Sweden)

    Mondry Adrian

    2004-08-01

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

  12. 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...

  13. 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

  14. pH effect on cellular uptake of Sn(IV) chlorine e6 dichloride trisodium salt by cancer cells in vitro.

    Science.gov (United States)

    Al-Khaza'leh, Khaled A; Omar, Khalid; Jaafar, M S

    2011-01-01

    The effects of pH value and presence of serum in an incubation medium on photosensitizer drug cellular uptake in MCF7 cancer cells have been investigated. The results showed that the presence of serum in an incubation medium reduced the drug cellular uptake at all pH values. It has been found that decreasing on pH values of the incubation medium increased the cellular uptake of the drug, demonstrating selective uptake of the sensitizer. The HepG2 liver cancer cells exhibited more drug cellular uptake than CCD-18CO normal colon cells, which assessed the selectivity uptake of photosensitizer on cancerous cells. The concentration of photosensitizer measured in 10(6) cells showed a good correlation to the incubation time. Fluorescence and absorption spectroscopy been have used to examine the cells. PMID:22210969

  15. Cellular and Molecular Consequences of Peroxisome Proliferator-Activated Receptor-γ Activation in Ovarian Cancer Cells1*

    OpenAIRE

    Vignati, Sara; Albertini, Veronica; Rinaldi, Andrea; Kwee, Ivo; RIVA Cristina; Oldrini, Rita; Capella, Carlo; Bertoni, Francesco; Carbone, Giuseppina M; Catapano, Carlo V.

    2006-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor. In addition to its canonical role in lipid and glucose metabolism, PPAR-γ controls cell proliferation, death, and differentiation in several tissues. Here we have examined the expression of PPAR-γ in ovarian tumors and the cellular and molecular consequences of its activation in ovarian cancer cells. PPAR-γ was expressed in a large number of epithelial ovarian tumors and cell lines. The PPAR-γ li...

  16. Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer.

    Science.gov (United States)

    Cook, Leah M; Araujo, Arturo; Pow-Sang, Julio M; Budzevich, Mikalai M; Basanta, David; Lynch, Conor C

    2016-01-01

    The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFβ because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFβ inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFβ. Patient specific information was seeded into the HCA model to predict the effect of TGFβ inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer. PMID:27411810

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

    OpenAIRE

    Xiaonian Shan; Zhibin Li; Xiaohong Chen; Jianhong Ye

    2015-01-01

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

  18. 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.

  19. Liver cancer mortality rate model in Thailand

    Science.gov (United States)

    Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

    2013-09-01

    Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

  20. Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer

    Science.gov (United States)

    Simon, Janelle; Tschaharganeh, Darjus F; van Es, Johan H; Clevers, Hans; Lowe, Scott W

    2015-01-01

    The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally suppressed using a doxycycline-regulated shRNA. Apc suppression produces adenomas in both the small intestine and colon that, in the presence of Kras and p53 mutations, can progress to invasive carcinoma. In established tumors, Apc restoration drives rapid and widespread tumor-cell differentiation and sustained regression without relapse. Tumor regression is accompanied by the re-establishment of normal crypt-villus homeostasis, such that once aberrantly proliferating cells reacquire self-renewal and multi-lineage differentiation capability. Our study reveals that CRC cells can revert to functioning normal cells given appropriate signals, and provide compelling in vivo validation of the Wnt pathway as a therapeutic target for treatment of CRC. PMID:26091037

  1. 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.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  3. Mouse models of anemia of cancer.

    Directory of Open Access Journals (Sweden)

    Airie Kim

    Full Text Available Anemia of cancer (AC may contribute to cancer-related fatigue and impair quality of life. Improved understanding of the pathogenesis of AC could facilitate better treatment, but animal models to study AC are lacking. We characterized four syngeneic C57BL/6 mouse cancers that cause AC. Mice with two different rapidly-growing metastatic lung cancers developed the characteristic findings of anemia of inflammation (AI, with dramatically different degrees of anemia. Mice with rapidly-growing metastatic melanoma also developed a severe anemia by 14 days, with hematologic and inflammatory parameters similar to AI. Mice with a slow-growing peritoneal ovarian cancer developed an iron-deficiency anemia, likely secondary to chronically impaired nutrition and bleeding into the peritoneal cavity. Of the four models, hepcidin mRNA levels were increased only in the milder lung cancer model. Unlike in our model of systemic inflammation induced by heat-killed Brucella abortus, ablation of hepcidin in the ovarian cancer and the milder lung cancer mouse models did not affect the severity of anemia. Hepcidin-independent mechanisms play an important role in these murine models of AC.

  4. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    International Nuclear Information System (INIS)

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution

  5. 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.

  6. Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice.

    Science.gov (United States)

    Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

    2016-07-01

    The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5(+) stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5(+) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5(+) stem cells and their progeny with Cre-reporter Rosa26(tdTomato). Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5(+) stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5(+) chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5(+) cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5(+) stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression. PMID:27091432

  7. Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications

    Science.gov (United States)

    2016-01-01

    Lung cancer has a very high mortality-to-incidence ratio, representing one of the main causes of cancer mortality worldwide. Therefore, new treatment strategies are urgently needed. Several diseases including lung cancer have been associated with the action of reactive oxygen species (ROS) from which hydrogen peroxide (H2O2) is one of the most studied. Despite the fact that H2O2 may have opposite effects on cell proliferation depending on the concentration and cell type, it triggers several antiproliferative responses. H2O2 produces both nuclear and mitochondrial DNA lesions, increases the expression of cell adhesion molecules, and increases p53 activity and other transcription factors orchestrating cancer cell death. In addition, H2O2 facilitates the endocytosis of oligonucleotides, affects membrane proteins, induces calcium release, and decreases cancer cell migration and invasion. Furthermore, the MAPK pathway and the expression of genes related to inflammation including interleukins, TNF-α, and NF-κB are also affected by H2O2. Herein, we will summarize the main effects of hydrogen peroxide on human lung cancer leading to suggesting it as a potential therapeutic tool to fight this disease. Because of the multimechanistic nature of this molecule, novel therapeutic approaches for lung cancer based on the use of H2O2 may help to decrease the mortality from this malignancy. PMID:27375834

  8. Nuclear Factor-κB Modulates Cellular Glutathione and Prevents Oxidative Stress in Cancer Cells

    OpenAIRE

    Meng, Qinghang; Peng, Zhimin; CHEN Liang; Si, Jutong; Dong, Zhongyun; Xia, Ying

    2010-01-01

    The NF-κB is best known for its role in inflammation. Here we show that constitutive NF-κB activity in cancer cells promotes the biosynthesis of redox scavenger glutathione (GSH), which in turn confers resistance to oxidative stress. Inhibition of NF-κB significantly decreases GSH in several lines of human leukemia and prostate cancer cells possessing high or moderate NF-κB activities. Concomitantly, NF-κB inhibition by pharmacological and molecular means sensitizes “NF-κB positive” cancer ce...

  9. Animal Models of Cancer Pain

    OpenAIRE

    Pacharinsak, Cholawat; Beitz, Alvin

    2008-01-01

    Modern cancer therapies have significantly increased patient survival rates in both human and veterinary medicine. Since cancer patients live longer they now face new challenges resulting from severe, chronic tumor-induced pain. Unrelieved cancer pain significantly decreases the quality of life of such patients; thus the goal of pain management is to not only to alleviate pain, but also to maintain the patient's physiological and psychological well-being. The major impediment for developing n...

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    J. P. M. Whitty

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  13. Expression of cellular FLICE-inhibitory protein and its association with p53 mutation in colon cancer

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Zhou; Jie-Ping Yu; Hong-Xia Chen; Hong-Gang Yu; He-Sheng Luo

    2005-01-01

    AIM: To investigate the expression of cellular FLICE (Fas associated death domain-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) and its association with p53mutation in colon cancer.METHODS: Immunohistochemical staining of c-FLIP and mutant p53 by using specific antibodies was performed by the standard streptavidin-peroxidase technique for 45 colon cancer tissue samples with matched normal tissues. Semi-quantitative reverse transcriptional (RT)-PCR was used to measure c-FLIP mRNA levels. t-test statistical method was used in data analyses.RESULTS: c-FLIP mRNA was expressed in all colon cancer tissues and its level (0.63±0.12) was significantly higher than that in normal tissues (0.38±0.10, P<0.01). Immunohistochemically, c-FLIP protein was also expressed in all colon cancers (45/45) and 71.1% (32/45) showed an intense immunostaining, in contrast, 93.3% (42/45) of normal colonic mucosa showed positive staining and none of them immunostained intensely. The quantity of c-FLIP protein was significantly higher in cancer tissues than in normal mucosa (7.04±1.20 vs 5.21±0.86, P<0.01).Positive staining of mutant p53 protein was found in 60%(27/45) colon cancers. c-FLIP mRNA level was decreased in p53 positive group compared with p53 negative cancer tissues (0.59±0.13 vs 0.69±0.14, P<0.01), but c-FLIP protein had a significantly higher level in p53 positive cancer tissues than in negative ones (7.57±1.30 vs 6.25±1.27,P<0.01).CONCLUSION: c-FLIP is specially overexpressed in colon cancers and it might contribute to carcinogenesis of normal colonic mucosa. p53 may exert transcriptional upregulation effects on c-FLIP gene and more potent effects on promoting the degradation of c-FLIP protein.

  14. ANIMAL MODELS OF CANCER: A REVIEW

    Directory of Open Access Journals (Sweden)

    Archana M. Navale

    2013-01-01

    Full Text Available Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primitive models. Although these models show good resemblance to the natural disease in humans, they were not capable of keeping pace with developing experimental therapeutics programs. It has therefore been necessary to take a further step towards artificiality, away from the clinical problem in the search for satisfactory testing method. From this step, the journey of artificially induced tumor models started. It is possible to induce cancer reproducibly in animals by exposing them to various agents and now, by transplanting tumor cells or tissue. The development of Genetically Engineered Animal models has provided a great help in knowing the disease. This article takes a review of present animal models used in anti-cancer drug discovery.

  15. 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.

  16. Structural Aberrations of Cellular Sialic Acids and TheirFunctions in Cancer Metastases

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Sialic acids (neuraminic acids) are a special series of 9-carbon ring negatively charged carbohydrates, which has been found to be selectively changed in malignant cells from structures (both synthesis and structure modifications) to functions (up and down regulation in cells). Sialic acids, in single forms or conjugates, have been systematically studied both in lab and in clinics by GC, GCMS, NMR, HPTLC, HPLC and other modern analytical means. Sialic acids and related conjugates are predicted to be used in cancer diagnosis, cancer prognostic forecasting, designing of cancer chemotherapy regimens, uncovering carcinogenetic processes and neoplasm metastasis. Tumor cell regulative systems and pathways are correlated with sialic acids, which can be applied to prognostic evaluation of cancer patients, and antimetastatic chemotherapy by sialic acid derivatives and analogues. Searching for new biological characteristics of sialic acids in cells have also been extensively studied these days. In this paper, main stream discoveries and advancements are provided , also discussions of possible mechanisms and hypotheses are invoked.

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

    OpenAIRE

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

    2007-01-01

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

  18. 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.

  19. Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer

    OpenAIRE

    Gusterson, Barry A.; Ross, Douglas T.; Heath, Victoria J; Stein, Torsten

    2005-01-01

    Recent publications have classified breast cancers on the basis of expression of cytokeratin-5 and -17 at the RNA and protein levels, and demonstrated the importance of these markers in defining sporadic tumours with bad prognosis and an association with BRCA1-related breast cancers. These important observations using different technology platforms produce a new functional classification of breast carcinoma. However, it is important in developing hypotheses about the pathogenesis of this tumo...

  20. 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/

  1. Genetically engineered mouse models of prostate cancer

    NARCIS (Netherlands)

    Nawijn, Martijn C.; Bergman, Andreas M.; van der Poel, Henk G.

    2008-01-01

    Objectives: Mouse models of prostate cancer are used to test the contribution of individual genes to the transformation process, evaluate the collaboration between multiple genetic lesions observed in a single tumour, and perform preclinical intervention studies in prostate cancer research. Methods:

  2. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.

    Science.gov (United States)

    Ding, Lin; El Zaatari, Mohamad; Merchant, Juanita L

    2016-01-01

    This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, "humanized" versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model. PMID:27573785

  3. Cancer Metabolism: A Modeling Perspective

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome...... suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells....... Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival, and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation...

  4. No evident dose-response relationship between cellular ROS level and its cytotoxicity--a paradoxical issue in ROS-based cancer therapy.

    Science.gov (United States)

    Zhu, Chunpeng; Hu, Wei; Wu, Hao; Hu, Xun

    2014-01-01

    Targeting cancer via ROS-based mechanism has been proposed as a radical therapeutic approach. Cancer cells exhibit higher endogenous oxidative stress than normal cells and pharmacological ROS insults via either enhancing ROS production or inhibiting ROS-scavenging activity can selectively kill cancer cells. In this study, we randomly chose 4 cancer cell lines and primary colon or rectal cancer cells from 4 patients to test the hypothesis and obtained following paradoxical results: while piperlongumin (PL) and β-phenylethyl isothiocyanate (PEITC), 2 well-defined ROS-based anticancer agents, induced an increase of cellular ROS and killed effectively the tested cells, lactic acidosis (LA), a common tumor environmental factor that plays multifaceted roles in promoting cancer progression, induced a much higher ROS level in the tested cancer cells than PL and PEITC, but spared them; L-buthionine sulfoximine (L-BSO, 20 μM) depleted cellular GSH more effectively and increased higher ROS level than PL or PEITC but permitted progressive growth of the tested cancer cells. No evident dose-response relationship between cellular ROS level and cytotoxicity was observed. If ROS is the effecter, it should obey the fundamental therapeutic principle - the dose-response relationship. This is a major concern. PMID:24848642

  5. Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein.

    Science.gov (United States)

    Liang, Jie; Luo, Guanhong; Ning, Xiaoxuan; Shi, Yongquan; Zhai, Huihong; Sun, Shiren; Jin, Haifeng; Liu, Zhenxiong; Zhang, Faming; Lu, Yuanyuan; Zhao, Yunping; Chen, Xiong; Zhang, Hongbo; Guo, Xuegang; Wu, Kaichun; Fan, Daiming

    2007-06-01

    The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein. PMID:17612632

  6. Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer.

    Science.gov (United States)

    Kono, Koji; Takahashi, Akihiro; Ichihara, Fumiko; Sugai, Hidemitsu; Fujii, Hideki; Matsumoto, Yoshirou

    2002-10-15

    The humanized monoclonal antibody Herceptin, which specifically targets HER-2/neu, exhibits growth inhibitory activity against HER-2/neu-overexpressing tumors and is approved for therapeutic use with proved survival benefit in patients with HER-2/neu-positive breast cancer. In the present study, we investigated whether Herceptin could affect the HER-2/neu-overexpressing gastric cancer cells based on antibody-dependent cell-mediated cytotoxicity (ADCC) and compared immune effector cells from gastric cancer patients with normal individuals on ADCC. HER-2/neu-expressing gastric cancer cells could be killed by Herceptin-mediated ADCC and the Herceptin-induced ADCC correlated with the degree of HER-2/neu expression on the gastric cancer cells. However, the Herceptin-mediated ADCC was significantly impaired in peripheral blood mononuclear cells from advanced disease patients (n = 10) compared with that in early disease (n = 12; P = 0.04) or healthy individuals (n = 10, P = 0.02). Moreover, natural killer (NK) cells purified from patients with advanced disease indicated less Herceptin-mediated ADCC in comparison with that from healthy donors (P = 0.04), whereas monocytes purified from the patients showed an almost equal amount of Herceptin-mediated ADCC in comparison with that from healthy individuals, indicating that NK cell dysfunction contributed to the impaired Herceptin-mediated ADCC in gastric cancer patients. Furthermore, the NK-cell dysfunction on Herceptin-mediated ADCC correlated with the down-regulation of CD16zeta expression in the patients, and interleukin 2 ex vivo treatment of NK cells could restore the impairment of Herceptin-mediated ADCC, concomitant to the normalization of the expression of CD16zeta molecules. Thus, some modalities such as interleukin 2 treatment aimed at reversing NK dysfunction may be necessary for successful Herceptin treatment of gastric cancer. PMID:12384543

  7. 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

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

    Science.gov (United States)

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

    2012-04-01

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

  9. 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.

  10. Ratio of phosphorylated HSP27 to nonphosphorylated HSP27 biphasically acts as a determinant of cellular fate in gemcitabine-resistant pancreatic cancer cells.

    Science.gov (United States)

    Kang, Dongxu; Choi, Hye Jin; Kang, Sujin; Kim, So Young; Hwang, Yong-Sic; Je, Suyeon; Han, Zhezhu; Kim, Joo-Hang; Song, Jae J

    2015-04-01

    Gemcitabine has been used most commonly as an anticancer drug to treat advanced pancreatic cancer patients. However, intrinsic or acquired resistance of pancreatic cancer to gemcitabine was also developed, which leads to very low five-year survival rates. Here, we investigated whether cellular levels of HSP27 phosphorylation act as a determinant of cellular fate with gemcitabine. In addition we have demonstrated whether HSP27 downregulation effectively could overcome the acquisition of gemcitabine resistance by using transcriptomic analysis. We observed that gemcitabine induced p38/HSP27 phosphorylation and caused acquired resistance. After acquisition of gemcitabine resistance, cancer cells showed higher activity of NF-κB. NF-κB activity, as well as colony formation in gemcitabine-resistant pancreatic cancer cells, was significantly decreased by HSP27 downregulation and subsequent TRAIL treatment, showing that HSP27 was a common network mediator of gemcitabine/TRAIL-induced cell death. After transcriptomic analysis, gene fluctuation after HSP27 downregulation was very similar to that of pancreatic cancer cells susceptible to gemcitabine, and then in opposite position to that of acquired gemcitabine resistance, which makes it possible to downregulate HSP27 to overcome the acquired gemcitabine resistance to function as an overall survival network inhibitor. Most importantly, we demonstrated that the ratio of phosphorylated HSP27 to nonphosphorylated HSP27 rather than the cellular level of HSP27 itself acts biphasically as a determinant of cellular fate in gemcitabine-resistant pancreatic cancer cells.

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Mariagrazia Belfiore

    2014-01-01

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

  14. A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer.

    Science.gov (United States)

    Levy, Oren; Brennen, W Nathaniel; Han, Edward; Rosen, David Marc; Musabeyezu, Juliet; Safaee, Helia; Ranganath, Sudhir; Ngai, Jessica; Heinelt, Martina; Milton, Yuka; Wang, Hao; Bhagchandani, Sachin H; Joshi, Nitin; Bhowmick, Neil; Denmeade, Samuel R; Isaacs, John T; Karp, Jeffrey M

    2016-06-01

    Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-particles (∼950 nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic 'Trojan Horse' therapy for targeted delivery of therapeutic agents to sites of metastatic PCa.

  15. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Xuanbin Wang

    2014-01-01

    Full Text Available Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and Methods. Chinese medicines (including Chinese medicinal herbs, animal parts, and minerals were used in the study. The key words including “cancer”, “cell death”, “apoptosis”, “autophagy,” “necrosis,” and “Chinese medicine” were used in retrieval of related information from PubMed and other databases. Results. The cell death induced by Chinese medicines is described as apoptotic, autophagic, or necrotic cell death and other types with an emphasis on their mechanisms of anticancer action. The relationship among different types of cell death induced by Chinese medicines is critically reviewed and discussed. Conclusions. This review summarizes that CMs treatment could induce multiple pathways leading to cancer cell death, in which apoptosis is the dominant type. To apply these preclinical researches to clinic application will be a key issue in the future.

  16. A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer.

    Science.gov (United States)

    Levy, Oren; Brennen, W Nathaniel; Han, Edward; Rosen, David Marc; Musabeyezu, Juliet; Safaee, Helia; Ranganath, Sudhir; Ngai, Jessica; Heinelt, Martina; Milton, Yuka; Wang, Hao; Bhagchandani, Sachin H; Joshi, Nitin; Bhowmick, Neil; Denmeade, Samuel R; Isaacs, John T; Karp, Jeffrey M

    2016-06-01

    Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-particles (∼950 nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic 'Trojan Horse' therapy for targeted delivery of therapeutic agents to sites of metastatic PCa. PMID:27019026

  17. A literature mining-based approach for identification of cellular pathways associated with chemoresistance in cancer.

    Science.gov (United States)

    Oh, Jung Hun; Deasy, Joseph O

    2016-05-01

    Chemoresistance is a major obstacle to the successful treatment of many human cancer types. Increasing evidence has revealed that chemoresistance involves many genes and multiple complex biological mechanisms including cancer stem cells, drug efflux mechanism, autophagy and epithelial-mesenchymal transition. Many studies have been conducted to investigate the possible molecular mechanisms of chemoresistance. However, understanding of the biological mechanisms in chemoresistance still remains limited. We surveyed the literature on chemoresistance-related genes and pathways of multiple cancer types. We then used a curated pathway database to investigate significant chemoresistance-related biological pathways. In addition, to investigate the importance of chemoresistance-related markers in protein-protein interaction networks identified using the curated database, we used a gene-ranking algorithm designed based on a graph-based scoring function in our previous study. Our comprehensive survey and analysis provide a systems biology-based overview of the underlying mechanisms of chemoresistance. PMID:26220932

  18. AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study

    Directory of Open Access Journals (Sweden)

    Knight Robert A

    2009-03-01

    Full Text Available Abstract Background Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI. In this study, we used superparamagentic iron oxide (SPIO-labeled APCs to carry the human sodium iodide symporter (hNIS gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m scan. Results Three million human breast cancer (MDA-MB-231 cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor was significantly different between animals that received non-transduced and transduced cells (P Conclusion This study indicates that genetically transformed

  19. Preventing clonal evolutionary processes in cancer: Insights from mathematical models.

    Science.gov (United States)

    Rodriguez-Brenes, Ignacio A; Wodarz, Dominik

    2015-07-21

    Clonal evolutionary processes can drive pathogenesis in human diseases, with cancer being a prominent example. To prevent or treat cancer, mechanisms that can potentially interfere with clonal evolutionary processes need to be understood better. Mathematical modeling is an important research tool that plays an ever-increasing role in cancer research. This paper discusses how mathematical models can be useful to gain insights into mechanisms that can prevent disease initiation, help analyze treatment responses, and aid in the design of treatment strategies to combat the emergence of drug-resistant cells. The discussion will be done in the context of specific examples. Among defense mechanisms, we explore how replicative limits and cellular senescence induced by telomere shortening can influence the emergence and evolution of tumors. Among treatment approaches, we consider the targeted treatment of chronic lymphocytic leukemia (CLL) with tyrosine kinase inhibitors. We illustrate how basic evolutionary mathematical models have the potential to make patient-specific predictions about disease and treatment outcome, and argue that evolutionary models could become important clinical tools in the field of personalized medicine.

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

    Science.gov (United States)

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

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

  1. MicroRNA-124 inhibits cellular proliferation and invasion by targeting Ets-1 in breast cancer.

    Science.gov (United States)

    Li, Wentao; Zang, Wenqiao; Liu, Pei; Wang, Yuanyuan; Du, Yuwen; Chen, Xiaonan; Deng, Meng; Sun, Wencong; Wang, Lei; Zhao, Guoqiang; Zhai, Baoping

    2014-11-01

    MicroRNAs (miRNAs) are small non-coding RNAs that, by targeting certain messenger RNAs (mRNAs) for translational repression or cleavage, can regulate the expression of these genes. In addition, miRNAs may also function as oncogenes and tumor-suppressor genes, as the abnormal expression of miRNAs is associated with various human tumors. However, the effects of the expression of miR-124 in breast cancer remain unclear. The present study was conducted to study the expression of miR-124 in breast cancer, paying particular attention to miR-124's relation to the proliferation, invasion, and apoptosis in breast cancer cell MCF-7 and MDA-MB-231. Real-time quantitative RT-PCR (qRT-PCR) was performed to identify miR-124 that was down-regulated in breast cancer tissues. We also showed E26 transformation specific-1 (Ets-1) and miR-124 expression levels in breast cancer tissues that were associated with lymph node metastases. With transfected synthetic miR-124 agomir into MCF-7 and MDA-MB-231, a significant reduction (P Ets-1 as a potential major target gene of miR-124, and the result showed that miR-124 can bind to putative binding sites within the Ets-1 mRNA 3' untranslated region (UTR) to reduce its expression. Based on these findings, we propose that miR-124 and Ets-1 may serve as a therapeutic agent in breast cancer.

  2. Toward an Ising model of cancer and beyond

    Science.gov (United States)

    Torquato, Salvatore

    2011-02-01

    The holy grail of tumor modeling is to formulate theoretical and computational tools that can be utilized in the clinic to predict neoplastic progression and propose individualized optimal treatment strategies to control cancer growth. In order to develop such a predictive model, one must account for the numerous complex mechanisms involved in tumor growth. Here we review the research work that we have done toward the development of an 'Ising model' of cancer. The Ising model is an idealized statistical-mechanical model of ferromagnetism that is based on simple local-interaction rules, but nonetheless leads to basic insights and features of real magnets, such as phase transitions with a critical point. The review begins with a description of a minimalist four-dimensional (three dimensions in space and one in time) cellular automaton (CA) model of cancer in which cells transition between states (proliferative, hypoxic and necrotic) according to simple local rules and their present states, which can viewed as a stripped-down Ising model of cancer. This model is applied to study the growth of glioblastoma multiforme, the most malignant of brain cancers. This is followed by a discussion of the extension of the model to study the effect on the tumor dynamics and geometry of a mutated subpopulation. A discussion of how tumor growth is affected by chemotherapeutic treatment, including induced resistance, is then described. We then describe how to incorporate angiogenesis as well as the heterogeneous and confined environment in which a tumor grows in the CA model. The characterization of the level of organization of the invasive network around a solid tumor using spanning trees is subsequently discussed. Then, we describe open problems and future promising avenues for future research, including the need to develop better molecular-based models that incorporate the true heterogeneous environment over wide range of length and time scales (via imaging data), cell motility

  3. 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.

  4. 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.

  5. 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.

  6. Cellular contractility and extracellular matrix stiffness regulate matrix metalloproteinase activity in pancreatic cancer cells.

    Science.gov (United States)

    Haage, Amanda; Schneider, Ian C

    2014-08-01

    The pathogenesis of cancer is often driven by local invasion and metastasis. Recently, mechanical properties of the tumor microenvironment have been identified as potent regulators of invasion and metastasis, while matrix metalloproteinases (MMPs) are classically known as significant enhancers of cancer cell migration and invasion. Here we have been able to sensitively measure MMP activity changes in response to specific extracellular matrix (ECM) environments and cell contractility states. Cells of a pancreatic cancer cell line, Panc-1, up-regulate MMP activities between 3- and 10-fold with increased cell contractility. Conversely, they down-regulate MMP activities when contractility is blocked to levels seen with pan-MMP activity inhibitors. Similar, albeit attenuated, responses are seen in other pancreatic cancer cell lines, BxPC-3 and AsPC-1. In addition, MMP activity was modulated by substrate stiffness, collagen gel concentration, and the degree of collagen cross-linking, when cells were plated on collagen gels ranging from 0.5 to 5 mg/ml that span the physiological range of substrate stiffness (50-2000 Pa). Panc-1 cells showed enhanced MMP activity on stiffer substrates, whereas BxPC-3 and AsPC-1 cells showed diminished MMP activity. In addition, eliminating heparan sulfate proteoglycans using heparinase completely abrogated the mechanical induction of MMP activity. These results demonstrate the first functional link between MMP activity, contractility, and ECM stiffness and provide an explanation as to why stiffer environments result in enhanced cell migration and invasion.

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

    Directory of Open Access Journals (Sweden)

    Xiru Tang

    2013-06-01

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

  8. 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.

  9. Dynamic Computational Model Suggests That Cellular Citizenship Is Fundamental for Selective Tumor Apoptosis

    OpenAIRE

    Olsen, Megan; Siegelmann-Danieli, Nava; Siegelmann, Hava T.

    2010-01-01

    Computational models in the field of cancer research have focused primarily on estimates of biological events based on laboratory generated data. We introduce a novel in-silico technology that takes us to the next level of prediction models and facilitates innovative solutions through the mathematical system. The model's building blocks are cells defined phenotypically as normal or tumor, with biological processes translated into equations describing the life protocols of the cells in a quant...

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

    CERN Document Server

    Kelling, Jeffrey; Gemming, Sibylle

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  12. A Model of Redox Kinetics Implicates the Thiol Proteome in Cellular Hydrogen Peroxide Responses

    OpenAIRE

    Adimora, Nnenna J.; Jones, Dean P; Melissa L Kemp

    2010-01-01

    Hydrogen peroxide is appreciated as a cellular signaling molecule with second-messenger properties, yet the mechanisms by which the cell protects against intracellular H2O2 accumulation are not fully understood. We introduce a network model of H2O2 clearance that includes the pseudo-enzymatic oxidative turnover of protein thiols, the enzymatic actions of catalase, glutathione peroxidase, peroxiredoxin, and glutaredoxin, and the redox reactions of thioredoxin and glutathione. Simulations repro...

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

    OpenAIRE

    Abdulla, Mouhamed; Shayan, Yousef R.

    2013-01-01

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

  14. A model of redox kinetics implicates the thiol proteome in cellular hydrogen peroxide responses.

    Science.gov (United States)

    Adimora, Nnenna J; Jones, Dean P; Kemp, Melissa L

    2010-09-15

    Hydrogen peroxide is appreciated as a cellular signaling molecule with second-messenger properties, yet the mechanisms by which the cell protects against intracellular H(2)O(2) accumulation are not fully understood. We introduce a network model of H(2)O(2) clearance that includes the pseudo-enzymatic oxidative turnover of protein thiols, the enzymatic actions of catalase, glutathione peroxidase, peroxiredoxin, and glutaredoxin, and the redox reactions of thioredoxin and glutathione. Simulations reproduced experimental observations of the rapid and transient oxidation of glutathione and the rapid, sustained oxidation of thioredoxin on exposure to extracellular H(2)O(2). The model correctly predicted early oxidation profiles for the glutathione and thioredoxin redox couples across a range of initial extracellular [H(2)O(2)] and highlights the importance of cytoplasmic membrane permeability to the cellular defense against exogenous sources of H(2)O(2). The protein oxidation profile predicted by the model suggests that approximately 10% of intracellular protein thiols react with hydrogen peroxide at substantial rates, with a majority of these proteins forming protein disulfides as opposed to protein S-glutathionylated adducts. A steady-state flux analysis predicted an unequal distribution of the intracellular anti-oxidative burden between thioredoxin-dependent and glutathione-dependent antioxidant pathways, with the former contributing the majority of the cellular antioxidant defense due to peroxiredoxins and protein disulfides.

  15. 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.

  16. 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.

  17. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    NARCIS (Netherlands)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; Rye, Inga H; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-

  18. 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

  19. 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

  20. 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

  1. Bispecific antibodies and retargeted cellular cytotoxicity: novel approaches to cancer therapy.

    Science.gov (United States)

    Wunderlich, J R; Mezzanzanica, D; Garrido, M A; Neblock, D S; Daddona, P E; Andrew, S M; Zurawski, V R; Canevari, S; Colnaghi, M I; Segal, D M

    1992-01-01

    We have used a relatively new technology to increase the number of human lymphocytes that will react with human ovarian carcinoma cells. This technology, often called "retargeting of the immune system," can temporarily redirect the activity of immune cells that were originally committed to react with foreign substances other than cancer cells. In the example presented here, the antitumor effects of retargeted human T lymphocytes, collected from normal donors, were tested in immunodeficient mice with a human ovarian carcinoma line growing intraperitoneally. We retargeted T cells in vitro with a bispecific antibody that reacted with the T cell receptor complex and with a cell-surface antigen expressed by the ovarian carcinoma cells. Retargeted lymphocytes, injected intraperitoneally into mice 4 days after intraperitoneal injection of the tumor cells, impeded tumor growth and doubled the host survival time. These findings provide support for the concept that treatment of ovarian cancer patients with retargeted T cells could prove beneficial. PMID:1633315

  2. 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. PMID:6229999

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

    International Nuclear Information System (INIS)

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

  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. 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.

  7. Study of Cellular Experiment of Electric Pulse Imposed on Cancer Cell

    Institute of Scientific and Technical Information of China (English)

    XIONGLan; HUYa; 等

    2002-01-01

    The objective of the study is the cytocidal and inhibitory effect of energy-controllable pulse on ovarian cancer cell line SKOV3.Ovarian cancer cell suspension were treated by electric pulse with different parameters,.The inhibitory rate(IR) was assayed by modified colorimetric MTT methods,the growth curves of two test groups and one control group were also measured.and the ultrasturctureal changes were observed under electron microscopy(EM) and scan electron microscopy (SEM),It was found that the treated SKOV3 cell proliferated more slowly.IR was increased with the enhancement of pulse paramters,The ultrastructural study showed that morphological changes occured obviously.Swollen mitochondria,fracutured ridges,cytoplasmic vacuoles and membrane holes appeard in most of the processed cells,and a part of bilayer membrane was ruptured.It is indicated that irreversible electric breakdown occurred in some of the treated cells,and the electric pulse could kill cancer cell and inhibit its recovery and growth.

  8. Modeling the Aneuploidy Control of Cancer

    Directory of Open Access Journals (Sweden)

    Wang Zhong

    2010-07-01

    Full Text Available Abstract Background Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer. Methods We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm. Results Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model. Conclusions The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  11. Public Health Action Model for Cancer Survivorship.

    Science.gov (United States)

    Moore, Angela R; Buchanan, Natasha D; Fairley, Temeika L; Lee Smith, Judith

    2015-12-01

    Long-term objectives associated with cancer survivors have been suggested by Healthy People 2020, including increasing the proportion of survivors living beyond 5 years after diagnosis and improving survivors' mental and physical health-related quality of life. Prior to reaching these objectives, several intermediate steps must be taken to improve the physical, social, emotional, and financial well-being of cancer survivors. Public health has a role in developing strategic, actionable, and measurable approaches to facilitate change at multiple levels to improve the lives of survivors and their families. The social ecological model has been used by the public health community as the foundation of multilevel intervention design and implementation, encouraging researchers and practitioners to explore methods that promote internal and external changes at the individual, interpersonal, organizational, community, and policy levels. The survivorship community, including public health professionals, providers, policymakers, survivors, advocates, and caregivers, must work collaboratively to identify, develop, and implement interventions that benefit cancer survivors. The National Action Plan for Cancer Survivorship highlights public health domains and associated strategies that can be the impetus for collaboration between and among the levels in the social ecological model and are integral to improving survivor outcomes. This paper describes the Public Health Action Model for Cancer Survivorship, an integrative framework that combines the National Action Plan for Cancer Survivorship with the social ecological model to demonstrate how interaction among the various levels may promote better outcomes for survivors. PMID:26590641

  12. Evaluating biomarkers to model cancer risk post cosmic ray exposure.

    Science.gov (United States)

    Sridharan, Deepa M; Asaithamby, Aroumougame; Blattnig, Steve R; Costes, Sylvain V; Doetsch, Paul W; Dynan, William S; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D; Peterson, Leif E; Plante, Ianik; Ponomarev, Artem L; Saha, Janapriya; Snijders, Antoine M; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M

    2016-06-01

    Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing

  13. Evaluating biomarkers to model cancer risk post cosmic ray exposure

    Science.gov (United States)

    Sridharan, Deepa M.; Asaithamby, Aroumougame; Blattnig, Steve R.; Costes, Sylvain V.; Doetsch, Paul W.; Dynan, William S.; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D.; Peterson, Leif E.; Plante, Ianik; Ponomarev, Artem L.; Saha, Janapriya; Snijders, Antoine M.; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M.

    2016-06-01

    Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing

  14. 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.

  15. 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

    2016-01-01

    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 R(2) > 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. PMID:27624453

  16. 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.

  17. Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2011-04-01

    Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

  18. 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.

  19. 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

    The atmospheric conditions during an observed case of open cellular convection over the North Sea were simulated using the Weather Research and Forecasting (WRF) numerical model. Wind, temperature and water vapour mixing ratio profiles from the WRF simulation were used to initialize an idealized...... version of the model, which excluded the effects of topography, surface inhomogeneities and large-scale weather forcing. Cells with an average diameter of 17.4 km developed. Simulations both with and without a capping inversion were made, and the cell-scale kinetic energy budget was calculated for each...

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

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lin; ZHANG Cai-bei

    2006-01-01

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

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

    Science.gov (United States)

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

    2012-11-01

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

  2. Ovarian Cancer Pathogenesis: A Model in Evolution

    Directory of Open Access Journals (Sweden)

    Alison M. Karst

    2010-01-01

    Full Text Available Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease.

  3. 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.

  4. The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells.

    Science.gov (United States)

    Zhang, Jie; Liu, Dan; Zhang, Mengjun; Sun, Yuqi; Zhang, Xiaojun; Guan, Guannan; Zhao, Xiuli; Qiao, Mingxi; Chen, Dawei; Hu, Haiyang

    2016-01-01

    Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH2 was much lower and exocytosis of PAMAM-NH2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH2 as a drug and gene vector in resistant cells. PMID:27536106

  5. Physical and cellular radiobiological properties of heavy ions in relation to cancer therapy applications

    International Nuclear Information System (INIS)

    A variety of experiments have been carried out in vitro on several mammalian cell lines with carbon, neon, silicon and argon beams at 14 and 24 cm depth penetration. The results of these experiments substantiate the conceptual basis for physical and radiobiological advantages of accelerated heavy-ion beams in cancer therapy. The best biologically effective depth dose ratio for situations corresponding to therapy needs can be obtained with accelerated carbon beams. The depression of the oxygen effect with silicon or argon ion beams is greater than that achievable with neutrons or pions, or with heavy ions of lower atomic number

  6. Emerging and Evolving Ovarian Cancer Animal Models

    OpenAIRE

    Bobbs, Alexander S; Jennifer M. Cole; Cowden Dahl, Karen D.

    2015-01-01

    Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect ...

  7. 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.

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. Context Sensitive Modeling of Cancer Drug Sensitivity

    Science.gov (United States)

    Chen, Bo-Juen; Litvin, Oren; Ungar, Lyle; Pe’er, Dana

    2015-01-01

    Recent screening of drug sensitivity in large panels of cancer cell lines provides a valuable resource towards developing algorithms that predict drug response. Since more samples provide increased statistical power, most approaches to prediction of drug sensitivity pool multiple cancer types together without distinction. However, pan-cancer results can be misleading due to the confounding effects of tissues or cancer subtypes. On the other hand, independent analysis for each cancer-type is hampered by small sample size. To balance this trade-off, we present CHER (Contextual Heterogeneity Enabled Regression), an algorithm that builds predictive models for drug sensitivity by selecting predictive genomic features and deciding which ones should—and should not—be shared across different cancers, tissues and drugs. CHER provides significantly more accurate models of drug sensitivity than comparable elastic-net-based models. Moreover, CHER provides better insight into the underlying biological processes by finding a sparse set of shared and type-specific genomic features. PMID:26274927

  13. Context Sensitive Modeling of Cancer Drug Sensitivity.

    Directory of Open Access Journals (Sweden)

    Bo-Juen Chen

    Full Text Available Recent screening of drug sensitivity in large panels of cancer cell lines provides a valuable resource towards developing algorithms that predict drug response. Since more samples provide increased statistical power, most approaches to prediction of drug sensitivity pool multiple cancer types together without distinction. However, pan-cancer results can be misleading due to the confounding effects of tissues or cancer subtypes. On the other hand, independent analysis for each cancer-type is hampered by small sample size. To balance this trade-off, we present CHER (Contextual Heterogeneity Enabled Regression, an algorithm that builds predictive models for drug sensitivity by selecting predictive genomic features and deciding which ones should-and should not-be shared across different cancers, tissues and drugs. CHER provides significantly more accurate models of drug sensitivity than comparable elastic-net-based models. Moreover, CHER provides better insight into the underlying biological processes by finding a sparse set of shared and type-specific genomic features.

  14. The mannose receptor LY75 (DEC205/CD205) modulates cellular phenotype and metastatic potential of ovarian cancer cells.

    Science.gov (United States)

    Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Gobeil, Stephane; Morin, Chantale; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2016-03-22

    The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. Previously, we identified the mannose receptor LY75 gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. LY75 represents endocytic receptor expressed on dendritic cells and so far, has been primarily studied for its role in antigen processing and presentation. Here we demonstrate that LY75 is overexpressed in advanced EOC and that LY75 suppression induces mesenchymal-to-epithelial transition (MET) in EOC cell lines with mesenchymal morphology (SKOV3 and TOV112), accompanied by reduction of their migratory and invasive capacity in vitro and enhanced tumor cell colonization and metastatic growth in vivo. LY75 knockdown in SKOV3 cells also resulted in predominant upregulation of functional pathways implicated in cell proliferation and metabolism, while pathways associated with cell signaling and adhesion, complement activation and immune response were mostly suppressed. Moreover, LY75 suppression had an opposite effect on EOC cell lines with epithelial phenotype (A2780s and OV2008), by directing epithelial-to-mesenchymal transition (EMT) associated with reduced capacity for in vivo EOC cell colonization, as similar/identical signaling pathways were reversely regulated, when compared to mesenchymal LY75 knockdown EOC cells.To our knowledge, this is the first report of a gene displaying such pleiotropic effects in sustaining the cellular phenotype of EOC cells and points to novel functions of this receptor in modulating EOC dissemination. Our data also support previous findings regarding the superior capacity of epithelial cancer cells in metastatic colonization of distant sites, compared to cancer cells with mesenchymal-like morphology. PMID:26871602

  15. The mannose receptor LY75 (DEC205/CD205) modulates cellular phenotype and metastatic potential of ovarian cancer cells.

    Science.gov (United States)

    Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Gobeil, Stephane; Morin, Chantale; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2016-03-22

    The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. Previously, we identified the mannose receptor LY75 gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. LY75 represents endocytic receptor expressed on dendritic cells and so far, has been primarily studied for its role in antigen processing and presentation. Here we demonstrate that LY75 is overexpressed in advanced EOC and that LY75 suppression induces mesenchymal-to-epithelial transition (MET) in EOC cell lines with mesenchymal morphology (SKOV3 and TOV112), accompanied by reduction of their migratory and invasive capacity in vitro and enhanced tumor cell colonization and metastatic growth in vivo. LY75 knockdown in SKOV3 cells also resulted in predominant upregulation of functional pathways implicated in cell proliferation and metabolism, while pathways associated with cell signaling and adhesion, complement activation and immune response were mostly suppressed. Moreover, LY75 suppression had an opposite effect on EOC cell lines with epithelial phenotype (A2780s and OV2008), by directing epithelial-to-mesenchymal transition (EMT) associated with reduced capacity for in vivo EOC cell colonization, as similar/identical signaling pathways were reversely regulated, when compared to mesenchymal LY75 knockdown EOC cells.To our knowledge, this is the first report of a gene displaying such pleiotropic effects in sustaining the cellular phenotype of EOC cells and points to novel functions of this receptor in modulating EOC dissemination. Our data also support previous findings regarding the superior capacity of epithelial cancer cells in metastatic colonization of distant sites, compared to cancer cells with mesenchymal-like morphology.

  16. Influence of cellular ER alpha/ER beta ratio on the ER alpha-agonist induced proliferation of human T47D breast cancer cells

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Berg, van den H.; Vervoort, J.J.M.; Saag, van der P.; Strom, A.; Gustafsson, J.A.; Rietjens, I.M.C.M.; Murk, A.J.

    2008-01-01

    Breast cancer cells show overexpression of estrogen receptor (ER) relative to ERß compared to normal breast tissues. This observation has lead to the hypothesis that ERß may modulate the proliferative effect of ER. This study investigated how variable cellular expression ratios of the ER and ERß mod

  17. Branching process models of cancer

    CERN Document Server

    Durrett, Richard

    2015-01-01

    This volume develops results on continuous time branching processes and applies them to study rate of tumor growth, extending classic work on the Luria-Delbruck distribution. As a consequence, the authors calculate the probability that mutations that confer resistance to treatment are present at detection and quantify the extent of tumor heterogeneity. As applications, the authors evaluate ovarian cancer screening strategies and give rigorous proofs for results of Heano and Michor concerning tumor metastasis. These notes should be accessible to students who are familiar with Poisson processes and continuous time. Richard Durrett is mathematics professor at Duke University, USA. He is the author of 8 books, over 200 journal articles, and has supervised more than 40 Ph.D. students. Most of his current research concerns the applications of probability to biology: ecology, genetics, and most recently cancer.

  18. Mathematical models of breast and ovarian cancers.

    Science.gov (United States)

    Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

    2016-07-01

    Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review, we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, as answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. WIREs Syst Biol Med 2016, 8:337-362. doi: 10.1002/wsbm.1343 For further resources related to this article, please visit the WIREs website. PMID:27259061

  19. 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.

  20. 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).

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    M. Górny

    2012-12-01

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

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    A. S. Komarov

    2015-06-01

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

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

    Science.gov (United States)

    Mu, Fengyun; Zhang, Zengxiang

    2005-10-01

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

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

    Science.gov (United States)

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

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

  7. 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.

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

    OpenAIRE

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

    2006-01-01

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

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

    OpenAIRE

    Kohei Arai; Steven Ray Sentinuwo

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    This paper describes a computational model, based on inverse homogenization and topology design, for approximating energy bounds for two-phase composites under multiple load cases. The approach allows for the identification of possible single-scale cellular materials that give rise to the optimal...... bounds within this class of composites. A comparison of the computational results with the globally optimal bounds given via rank-N layered composites illustrates the behaviour for tension and shear load situations, as well as the importance of considering the shape of the basic unit cell as part...

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

    Institute of Scientific and Technical Information of China (English)

    Hua Wei; Liu Jun

    2006-01-01

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

  12. 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.

  13. 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...

  14. 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

  15. Restoration of the cellular secretory milieu overrides androgen dependence of in vivo generated castration resistant prostate cancer cells overexpressing the androgen receptor.

    Science.gov (United States)

    Patki, Mugdha; Huang, Yanfang; Ratnam, Manohar

    2016-07-22

    It is believed that growth of castration resistant prostate cancer (CRPC) cells is enabled by sensitization to minimal residual post-castrate androgen due to overexpression of the androgen receptor (AR). Evidence is derived from androgen-induced colony formation in the absence of cell-secreted factors or from studies involving forced AR overexpression in hormone-dependent cells. On the other hand, standard cell line models established from CRPC patient tumors (e.g., LNCaP and VCaP) are hormone-dependent and require selection pressure in castrated mice to re-emerge as CRPC cells and the resulting tumors then tend to be insensitive to the androgen antagonist enzalutamide. Therefore, we examined established CRPC model cells produced by castration of mice bearing hormone-dependent cell line xenografts including CRPC cells overexpressing full-length AR (C4-2) or co-expressing wtAR and splice-variant AR-V7 that is incapable of ligand binding (22Rv1). In standard colony formation assays, C4-2 cells were shown to be androgen-dependent and sensitive to enzalutamide whereas 22Rv1 cells were incapable of colony formation under identical conditions. However, both C4-2 and 22Rv1 cells formed colonies in conditioned media derived from the same cells or from HEK293 fibroblasts that were proven to lack androgenic activity. This effect was (i) not enhanced by androgen, (ii) insensitive to enzalutamide, (iii) dependent on AR (in C4-2) and on AR-V7 and wtAR (in 22Rv1) and (iv) sensitive to inhibitors of several signaling pathways, similar to androgen-stimulation. Therefore, during progression to CRPC in vivo, coordinate cellular changes accompanying overexpression of AR may enable cooperation between hormone-independent activity of AR and actions of cellular secretory factors to completely override androgen-dependence and sensitivity to drugs targeting hormonal factors. PMID:27179779

  16. In Silico Experimental Modeling of Cancer Treatment

    OpenAIRE

    Trisilowati; D. G. Mallet

    2012-01-01

    In silico experimental modeling of cancer involves combining findings from biological literature with computer-based models of biological systems in order to conduct investigations of hypotheses entirely in the computer laboratory. In this paper, we discuss the use of in silico modeling as a precursor to traditional clinical and laboratory research, allowing researchers to refine their experimental programs with an aim to reducing costs and increasing research efficiency. We explain the metho...

  17. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna;

    2015-01-01

    85 antimetabolites that can inhibit growth of, or even kill, any of the cell lines, while at the same time not being toxic for 83 different healthy human cell types. 60 of these antimetabolites were found to inhibit growth in all cell lines. Finally, we experimentally validated one of the predicted...... for inhibition of cell growth may provide leads for the development of efficient cancer treatment strategies.......Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...

  18. Beyond the antigen receptor: editing the genome of T-cells for cancer adoptive cellular therapies

    Directory of Open Access Journals (Sweden)

    Angharad eLloyd

    2013-08-01

    Full Text Available Recent early-stage clinical trials evaluating the adoptive transfer of patient CD8+ T-cells re-directed with antigen receptors recognising tumours have shown very encouraging results. These reports provide strong support for further development of the therapeutic concept as a curative cancer treatment. In this respect combining the adoptive transfer of tumour-specific T-cells with therapies that increase their anti-tumour capacity is viewed as a promising strategy to improve treatment outcome. The ex-vivo genetic engineering step that underlies T-cell re-direction offers a unique angle to combine antigen receptor delivery with the targeting of cell intrinsic pathways that restrict T-cell effector functions. Recent progress in genome editing technologies such as protein- and RNA-guided endonucleases raise the possibility of disrupting gene expression in T-cells in order to enhance effector functions or to bypass tumour immune suppression. This approach would avoid the systemic administration of compounds that disrupt immune homeostasis, potentially avoiding autoimmune adverse effects, and could improve the efficacy of T-cell based adoptive therapies.

  19. 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.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    Kamran Forghani

    2012-10-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Preclinical fluorescent mouse models of pancreatic cancer

    Science.gov (United States)

    Bouvet, Michael; Hoffman, Robert M.

    2007-02-01

    Here we describe our cumulative experience with the development and preclinical application of several highly fluorescent, clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of the bioluminescent green fluorescent (GFP) or red fluorescent protein (RFP). Fluorescent tumors are established subcutaneously in nude mice, and tumor fragments are then surgically transplanted onto the pancreas. Locoregional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdomen in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time visualization of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. We have shown a high correlation between florescent optical imaging and magnetic resonance imaging in these models. Alternatively, transplantation of RFP-expressing tumor fragments onto the pancreas of GFP-expressing transgenic mice may be used to facilitate visualization of tumor-host interaction between the pancreatic tumor fragments and host-derived stroma and vasculature. Such in vivo models have enabled us to serially visualize and acquire images of the progression of pancreatic cancer in the live animal, and to demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate human pancreatic cancer and therapeutic strategies directed against it.

  10. Impact of comorbid anxiety and depression on quality of life and cellular immunity changes in patients with digestive tract cancers

    Institute of Scientific and Technical Information of China (English)

    Fu-Ling Zhou; Wang-Gang Zhang; Yong-Chang Wei; Kang-Ling Xu; Ling-Yun Hui; Xu-Sheng Wang; Ming-Zhong Li

    2005-01-01

    AIM: A study was performed to investigate the impact of comorbid anxiety and depression (CAD) on quality of life (QOL) and cellular immunity changes in patients with digestive tract cancers.METHODS: One hundred and fifty-six cases of both sexes with cancers of the digestive tract admitted between March 2001 and February 2004 in the Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University were randomly enrolled in the study. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-Ⅳ. All adult patients were evaluated with the Hamilton depressive scale (HAMD, the 24-item version), the Hamilton anxiety scale (HAMA, a modified 14-item version), quality of life questionnaire-core 30 (QLQ-C30), social support rating scale (SSRS), simple coping style questionnaire (SCSQ), and other questionnaires, respectively. In terms of HAMD ≥ 20 and HAMA ≥ 14, the patients were categorized, including CAD (n = 31) in group A, anxiety disorder (n = 23) in group B,depressive disorder (n = 37) in group C, and non-disorder (n = 65) in group D. Immunological parameters such as T-lymphocyte subsets and natural killer (NK) cell activities in peripheral blood were determined and compared among the four groups.RESULTS: The incidence of CAD was 21.15% in patients with digestive tract cancers. The average scores of social support was 43.67±7.05 for 156 cases, active coping 20.34±7.33, and passive coping 9.55±5.51. Compared with group D, subjective support was enhanced slightly in group A, but social support, objective support, and utilization of support reduced, especially utilization of support with significance (6.16 vs 7.80, P<0.05); total scores of active coping decreased, while passive coping reversed; granulocytes proliferated, monocytes declined,and lymphocytes declined significantly (32.87 vs 34.00,P<0.05); moreover, the percentage of CD3, CD4, CD8and CD56 in T lymphocyte subsets was in lower

  11. Evaluation of Cellular Toxicity for Cisplatin, Arsenic And Acetaminophen in the Cancer and Normal Cell Line

    Directory of Open Access Journals (Sweden)

    S Saeedi Saravi

    2007-12-01

    Full Text Available Introduction: Cell culture is a process in which the cells ware isolated from original tissue, dispersed in liquid media and then placed in culture plate where the cells adhere together and propagate. Today, this method is used for assessment of cell toxicity, its mechanisms and effect of different compounds on intracellular components. Methods: Clonogenic assay was used for assessment of cell toxicity and amount of cell death after a specific time during which cells were exposed to different compounds. Thus, IC50 in caner cell lines (HePG2, SKOV3 and A549 and normal cell (LLCPK1, CHO and HGF1 was assessed after exposure to cisplatin, acetaminophen and arsenic. Results: Results showed that acetaminophen has maximum resistance and minimum sensitivity in CHO line with IC50=16.7±1.06 HePG2 with IC50=18.6±1.29. On the other hand, cisplatin showed minimum resistance and maximum sensitivity in HePG2 with IC50 = 0.87±0.07 and HGF1 with IC50 = 1.6±0.21 and lastly, arsenic showed minimum resistance and maximum sensitivity in A549 with IC50 = 4.59±0.29 and LLCPK1 with IC50= 1±0.37. Discussion: According to the evaluated IC50, there were differences between results of sensitivity of cell lines exposed to the three drugs (P<0.05. Entirely, resistance in cancer cell lines was lower than normal cells. The results showed the importance of cell defensive mechanisms encountering different substances like glutathione.

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

    Directory of Open Access Journals (Sweden)

    Drubin David

    2011-10-01

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

  13. 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.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Ahmad Zuhdi

    2011-05-01

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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. Microsatellite instability, KRAS mutations and cellular distribution of TRAIL-receptors in early stage colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Lydia Kriegl

    Full Text Available BACKGROUND: The fact that the receptors for the TNF-related apoptosis inducing ligand (TRAIL are almost invariably expressed in colorectal cancer (CRC represents the rationale for the employment of TRAIL-receptors targeting compounds for the therapy of patients affected by this tumor. Yet, first reports on the use of these bioactive agents provided disappointing results. We therefore hypothesized that loss of membrane-bound TRAIL-R might be a feature of some CRC and that the evaluation of membrane staining rather than that of the overall expression of TRAIL-R might predict the response to TRAIL-R targeting compounds in this tumor. AIM AND METHODS: Thus, we evaluated the immunofluorescence pattern of TRAIL-receptors and E-cadherin to assess the fraction of membrane-bound TRAIL-receptors in 231 selected patients with early-stage CRC undergoing surgical treatment only. Moreover, we investigated whether membrane staining for TRAIL-receptors as well as the presence of KRAS mutations or of microsatellite instability (MSI had an effect on survival and thus a prognostic effect. RESULTS: As expected, almost all CRC samples stained positive for TRAIL-R1 and 2. Instead, membrane staining for these receptors was positive in only 71% and 16% of samples respectively. No correlation between KRAS mutation status or MSI-phenotype and prognosis could be detected. TRAIL-R1 staining intensity correlated with survival in univariate analysis, but only membranous staining of TRAIL-R1 and TRAIL-R2 on cell membranes was an independent predictor of survival (cox multivariate analysis: TRAIL-R1: p = 0.019, RR 2.06[1.12-3.77]; TRAIL-R2: p = 0.033, RR 3.63[1.11-11.84]. CONCLUSIONS: In contrast to the current assumptions, loss of membrane staining for TRAIL-receptors is a common feature of early stage CRC which supersedes the prognostic significance of their staining intensity. Failure to achieve therapeutic effects in recent clinical trials using TRAIL-receptors targeting

  2. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the differ

  3. Mouse models of intestinal inflammation and cancer.

    Science.gov (United States)

    Westbrook, Aya M; Szakmary, Akos; Schiestl, Robert H

    2016-09-01

    Chronic inflammation is strongly associated with approximately one-fifth of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here, we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With

  4. Study of cellular and sub-cellular organelles targets on cancer therapy%肿瘤细胞和亚细胞器治疗靶标的研究

    Institute of Scientific and Technical Information of China (English)

    张百红; 综述岳红云; 审校

    2014-01-01

    Tumor cell type and sub-cellular organelle are potential targets for cancer therapy .These tar-gets have cell types including tumor -initiating cells ,cancer stem cells ,circulating tumor cells ,metastasis-initia-ting cells,bone marrow derived cells and stromal cells ,as well as sub-cellular organelles including mitochondri-a,lysosome,endoplasmic reticulum,extracellular vesicles,centrosome and nucleolus.New targets should provide more targeted therapy and personalized therapy for patients with human cancers .%各种细胞类型和亚细胞器都是肿瘤治疗的靶标,这些靶标包括肿瘤起始细胞、肿瘤干细胞、循环肿瘤细胞、转移起始细胞、骨髓来源细胞和基质细胞等细胞类型,以及线粒体、溶酶体、内质网、胞外膜泡、中心体和核仁等亚细胞器。靶向不同肿瘤细胞群和亚细胞器的治疗增加了肿瘤靶向治疗的内容,也使肿瘤个体化治疗成为可能。

  5. An event-driven model simulating fundamental seismic characteristics with the use of cellular automata

    Science.gov (United States)

    Pavlou, L.; Georgoudas, I. G.; Sirakoulis, G. Ch.; Scordilis, E. M.; Andreadis, I.

    This paper presents an extensive simulation tool based on a Cellular Automata (CA) system that models fundamental seismic characteristics of a region. The CA-based dynamic model consists of cells-charges and it is used for the simulation of the earthquake process. The simulation tool has remarkably accelerated the response of the model by incorporating principles of the High Performance Computing (HPC). Extensive programming features of parallel computing have been applied, thus improving its processing effectiveness. The tool implements an enhanced (or hyper-) 2-dimensional version of the proposed CA model. Regional characteristics that depend on the seismic background of the area under study are assigned to the model with the application of a user-friendly software environment. The model is evaluated with real data that correspond to a circular region around Skyros Island, Greece, for different time periods, as for example one of 45 years (1901-1945). The enhanced 2-dimensional version of the model incorporates all principal characteristics of the 2-dimensional one, also including groups of CA cells that interact with others, located to a considerable distance in an attempt to simulate long-range interaction. The advanced simulation tool has been thoroughly evaluated. Several measurements have been made for different critical states, as well as for various cascade (earthquake) sizes, cell activities and different neighbourhood sizes. Simulation results qualitatively approach the Gutenberg-Richter (GR) scaling law and reveal fundamental characteristics of the system.

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

    Directory of Open Access Journals (Sweden)

    Xiaonian Shan

    2015-01-01

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

  7. Antiangiogenic cancer drug using the zebrafish model.

    Science.gov (United States)

    Santoro, Massimo M

    2014-09-01

    The process of de novo vessel formation, called angiogenesis, is essential for tumor progression and spreading. Targeting of molecular pathways involved in such tumor angiogenetic processes by using specific drugs or inhibitors is important for developing new anticancer therapies. Drug discovery remains to be the main focus for biomedical research and represents the essence of antiangiogenesis cancer research. To pursue these molecular and pharmacological goals, researchers need to use animal models that facilitate the elucidation of tumor angiogenesis mechanisms and the testing of antiangiogenic therapies. The past few years have seen the zebrafish system emerge as a valid model organism to study developmental angiogenesis and, more recently, as an alternative vertebrate model for cancer research. In this review, we will discuss why the zebrafish model system has the advantage of being a vertebrate model equipped with easy and powerful transgenesis as well as imaging tools to investigate not only physiological angiogenesis but also tumor angiogenesis. We will also highlight the potential of zebrafish for identifying antitumor angiogenesis drugs to block tumor development and progression. We foresee the zebrafish model as an important system that can possibly complement well-established mouse models in cancer research to generate novel insights into the molecular mechanism of the tumor angiogenesis. PMID:24903092

  8. Modelling chronotaxicity of cellular energy metabolism to facilitate the identification of altered metabolic states

    Science.gov (United States)

    Lancaster, Gemma; Suprunenko, Yevhen F.; Jenkins, Kirsten; Stefanovska, Aneta

    2016-01-01

    Altered cellular energy metabolism is a hallmark of many diseases, one notable example being cancer. Here, we focus on the identification of the transition from healthy to abnormal metabolic states. To do this, we study the dynamics of energy production in a cell. Due to the thermodynamic openness of a living cell, the inability to instantaneously match fluctuating supply and demand in energy metabolism results in nonautonomous time-varying oscillatory dynamics. However, such oscillatory dynamics is often neglected and treated as stochastic. Based on experimental evidence of metabolic oscillations, we show that changes in metabolic state can be described robustly by alterations in the chronotaxicity of the corresponding metabolic oscillations, i.e. the ability of an oscillator to resist external perturbations. We also present a method for the identification of chronotaxicity, applicable to general oscillatory signals and, importantly, apply this to real experimental data. Evidence of chronotaxicity was found in glycolytic oscillations in real yeast cells, verifying that chronotaxicity could be used to study transitions between metabolic states. PMID:27483987

  9. The importance of cellular internalization of antibody-targeted carbon nanotubes in the photothermal ablation of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Marches, Radu; Vitetta, Ellen S [Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Mikoryak, Carole; Draper, Rockford K [Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75080 (United States); Wang, Ru-Hung; Pantano, Paul, E-mail: ellen.vitetta@utsouthwestern.edu [Department of Chemistry, University of Texas at Dallas, Richardson, TX 75080 (United States)

    2011-03-04

    Single-walled carbon nanotubes (CNTs) convert absorbed near infrared (NIR) light into heat. The use of CNTs in the NIR-mediated photothermal ablation of tumor cells is attractive because the penetration of NIR light through normal tissues is optimal and the side effects are minimal. Targeted thermal ablation with minimal collateral damage can be achieved by using CNTs attached to tumor-specific monoclonal antibodies (MAbs). However, the role that the cellular internalization of CNTs plays in the subsequent sensitivity of the target cells to NIR-mediated photothermal ablation remains undefined. To address this issue, we used CNTs covalently coupled to an anti-Her2 or a control MAb and tested their ability to bind, internalize, and photothermally ablate Her2{sup +} but not Her2{sup -} breast cancer cell lines. Using flow cytometry, immunofluorescence, and confocal Raman microscopy, we observed the gradual time-dependent receptor-mediated endocytosis of anti-Her2-CNTs whereas a control MAb-CNT conjugate did not bind to the cells. Most importantly, the Her2{sup +} cells that internalized the MAb-CNTs were more sensitive to NIR-mediated photothermal damage than cells that could bind to, but not internalize the MAb-CNTs. These results suggest that both the targeting and internalization of MAb-CNTs might result in the most effective thermal ablation of tumor cells following their exposure to NIR light.

  10. The conjugates of carbon nanodots and chlorin e6 for enhancing cellular internalization and photodynamic therapy of cancers

    Science.gov (United States)

    Wang, Jing; Wang, Xiongwei; Wang, Shimiao; Huang, Zheng; Liu, Jun

    2016-09-01

    Chlorin e6 (Ce6), a large heterocyclic aromatic molecule, is a promising photosensitizer for photodynamic therapy (PDT). We propose an efficient nano-photosensitizer delivery system based on covalent interactions between Ce6 and polyethylenimine (PEI) coated carbon nanodots (CDots). We observed  >50% Ce6 drug loading content for PEI, due to this compound’s unique ‘proton sponge effect.’ We found that the covalently incorporated Ce6 molecules retained their functional properties for near-infrared (NIR) fluorescence imaging and PDT. The chemical characteristics of CDot-PEI-Ce6 and Ce6 were evaluated using different analytical methods, including transmission electron microscopy and UV-Visible absorption spectra. Time-correlated single photon counting (TCSPC) and fluorescence spectra were used to demonstrate that Ce6 successfully conjugated to the CDots. The high cellular uptake of CDots-PEI-Ce6 was confirmed using flow cytometry and confocal laser scanning microscopy. According to the MTT assay, the CDots-PEI-Ce6 exhibited low dark toxicity and efficient PDT efficacy to HeLa cancer cells. These results indicate that CDot-PEI-Ce6 conjugates are potential photosensitizer delivery systems for PDT.

  11. The conjugates of carbon nanodots and chlorin e6 for enhancing cellular internalization and photodynamic therapy of cancers

    Science.gov (United States)

    Wang, Jing; Wang, Xiongwei; Wang, Shimiao; Huang, Zheng; Liu, Jun

    2016-09-01

    Chlorin e6 (Ce6), a large heterocyclic aromatic molecule, is a promising photosensitizer for photodynamic therapy (PDT). We propose an efficient nano-photosensitizer delivery system based on covalent interactions between Ce6 and polyethylenimine (PEI) coated carbon nanodots (CDots). We observed  >50% Ce6 drug loading content for PEI, due to this compound’s unique ‘proton sponge effect.’ We found that the covalently incorporated Ce6 molecules retained their functional properties for near-infrared (NIR) fluorescence imaging and PDT. The chemical characteristics of CDot-PEI-Ce6 and Ce6 were evaluated using different analytical methods, including transmission electron microscopy and UV–Visible absorption spectra. Time-correlated single photon counting (TCSPC) and fluorescence spectra were used to demonstrate that Ce6 successfully conjugated to the CDots. The high cellular uptake of CDots-PEI-Ce6 was confirmed using flow cytometry and confocal laser scanning microscopy. According to the MTT assay, the CDots-PEI-Ce6 exhibited low dark toxicity and efficient PDT efficacy to HeLa cancer cells. These results indicate that CDot-PEI-Ce6 conjugates are potential photosensitizer delivery systems for PDT.

  12. The use of cellular thermal shift assay (CETSA) to study Crizotinib resistance in ALK-expressing human cancers.

    Science.gov (United States)

    Alshareef, Abdulraheem; Zhang, Hai-Feng; Huang, Yung-Hsing; Wu, Chengsheng; Zhang, Jing Dong; Wang, Peng; El-Sehemy, Ahmed; Fares, Mohamed; Lai, Raymond

    2016-01-01

    Various forms of oncogenic ALK proteins have been identified in various types of human cancers. While Crizotinib, an ALK inhibitor, has been found to be therapeutically useful against a subset of ALK(+) tumours, clinical resistance to this drug has been well recognized and the mechanism of this phenomenon is incompletely understood. Using the cellular thermal shift assay (CETSA), we measured the Crizotinib-ALK binding in a panel of ALK(+) cell lines, and correlated the findings with the ALK structure and its interactions with specific binding proteins. The Crizotinib IC50 significantly correlated with Crizotinib-ALK binding. The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding. Interestingly, we found that the resistant cells expressed higher protein level of β-catenin and siRNA knockdown restored Crizotinib-ALK binding (correlated with a significant lowering of IC50). Computational analysis of the crystal structures suggests that β-catenin exerts steric hindrance to the Crizotinib-ALK binding. In conclusion, the Crizotinib-ALK binding measurable by CETSA is useful in predicting Crizotinib sensitivity, and Crizotinib-ALK binding is in turn dictated by the structure of ALK and some of its binding partners. PMID:27641368

  13. Evaluation of residual cellularity and proliferation on preoperatively treated breast cancer: a comparison between image analysis and light microscopy analysis.

    Science.gov (United States)

    Corletto, V; Verderio, P; Giardini, R; Cipriani, S; Di Palma, S; Rilke, F

    1998-01-01

    Histopathology has been suggested as a reliable method for tumour reduction evaluation of preoperatively treated breast cancer. Immunocytochemistry can be used to enhance the visibility of residual tumour cellularity and in the evaluation of its proliferative activity. We compared Image Analysis (IA) with Light Microscopy Analysis (LMA) on sections of breast carcinomas treated with preoperative chemo- or chemo/radiotherapy in the evaluation of the Neoplastic Cell Density (NCD) (69 cases) and the Proliferation Index (PI) (35 cases). NCD was expressed as the immunoreactive area to cytokeratin over the total original neoplastic area and PI was expressed as the number of immunostained tumoural nuclei with MIB 1 MoAb over the total of tumoural nuclei. The intraobserver agreement and that between IA and LMA for both indices were estimated by the common (kappa(w)) and the jackknife weighted kappa statistic (kappa(w)). The extent of agreement of each considered category was also assessed by means of the category-specific kappa statistics (kappa(cs)). The intraobserver agreement within LMA for NCD and PI and that between IA and LMA for PI were both satisfactory. Upon evaluation of the NCD, the agreement between IA and LMA showed unsatisfactory results, especially when the ratio between the residual tumour cells and the background was critical.

  14. Evaluation of Residual Cellularity and Proliferation on Preoperatively Treated Breast Cancer: A Comparison between Image Analysis and Light Microscopy Analysis

    Directory of Open Access Journals (Sweden)

    Valentina Corletto

    1998-01-01

    Full Text Available Histopathology has been suggested as a reliable method for tumour reduction evaluation of preoperatively treated breast cancer. Immunocytochemistry can be used to enhance the visibility of residual tumour cellularity and in the evaluation of its proliferative activity. We compared Image Analysis (IA with Light Microscopy Analysis (LMA on sections of breast carcinomas treated with preoperative chemo‐ or chemo/radiotherapy in the evaluation of the Neoplastic Cell Density (NCD (69 cases and the Proliferation Index (PI (35 cases. NCD was expressed as the immunoreactive area to cytokeratin over the total original neoplastic area and PI was expressed as the number of immunostained tumoural nuclei with MIB1 MoAb over the total of tumoural nuclei. The intraobserver agreement and that between IA and LMA for both indices were estimated by the common (Kw and the jackknife weighted kappa statistic (K˜w. The extent of agreement of each considered category was also assessed by means of the category‐specific kappa statistics (Kcs. The intraobserver agreement within LMA for NCD and PI and that between IA and LMA for PI were both satisfactory. Upon evaluation of the NCD, the agreement between IA and LMA showed unsatisfactory results, especially when the ratio between the residual tumour cells and the background was critical.

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

    International Nuclear Information System (INIS)

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

  16. 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.

  17. 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.

  18. Potential Field Cellular Automata Model for Pedestrian Evacuation in a Domain with a Ramp

    Directory of Open Access Journals (Sweden)

    Xiao-Xia Jian

    2014-01-01

    Full Text Available We propose a potential field cellular automata model with a pushing force field to simulate the pedestrian evacuation in a domain with a ramp. We construct a cost potential depending on the ramp angle and introduce a function to evaluate the pushing force, which is related to the cost and the desired direction of pedestrian. With increase of crowd density, there is no empty space for pedestrian moving forward; pedestrian will purposefully push another pedestrian on her or his desired location to arrive the destination quickly. We analyse the relationship between the slope of ramp and the pushing force and investigate the changing of injured situations with the changing of the slope of ramp. When the number of pedestrians and the ramp angle arrive at certain critical points, the Domino effect will be simulated by this proposed model.

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2015-08-01

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

  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. The expression of hTERT mRNA and cellular immunity in gastric cancer and precancerosis

    Institute of Scientific and Technical Information of China (English)

    Xi-Xian Yao; Lei Yin; Zhong-Cheng Sun

    2002-01-01

    AIM:To observe the expression of Human telomerasereverse transcriptase (hTERT) in gastric carcinomas andprecancerosis lesions, to evaluate the immune state ofsuch patients, and to then study the clinical significanceof hTERT and immune state for the diagnosis, treat-ment and prognosis of gastric cancer METHODS: In situ hybridization was used to detect theexpression of hTERT mRNA in 116 endoscopic of gas-tric mucosa. Analyzed tissue samples were as follows:30 cases of chronic superficial gastritis (CSG), 44 ofprecancerosis lesions (including 27 of chronic atrophicgastritis, 8 of adenomatous polyp and 9 of gastric ulcer)and 42 of gastric cancer (GC). In addition, the T lym-phocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ) andnatural killer cells (NK) in peripheral blood were deter-mined by flow cytometric analysis (FCM) in 30 cases ofCSG, 27 of precancorosis (chronic atrophic gastritis,CAG), and 42 of GC. The data were compared with thoseof normal control (NC).RESULTS:The detected positive rate of hTERT varied asfollows: 86 % (36/42) in GC, 36 % (16/44) inprecancerosis lesions and 0 % (0/30) in CSG. The ex-pression of hTERT mRNA was not associated with pa-tient gender, tumor location, macroscopic type, lymphnode metastasis, or degree of differentiation, It wasfound that the CD3+, CD4+ of the CSG group were lowerthan that of NC (P<0.05). Meanwhile, the T lympho-cyte subsets (CD3+,CD4+, CD4+/CD8+ ratio) and NK cellsof CAG were remarkably lower than that of NC and CSGgroups (P<0.05-0.01). Values ofT cells and NK cells ofthe GC group were significantly abnormal when com-pared with the CAG group (P<0.05-0.01). Furthermore,with tumor progression, the function of T cells wasweakened gradually.CONCLUSION: The expression of telomerase may be acrucial step in gastric carcinogenesis and increasedhTERT mRNA may serve as a novel marker for diagno-sis of GC. The immune state of patients with GC andprecancerosis was somewhat depressed, which indi-cates the importance of cellular

  5. Towards a multiscale model of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Ingeborg MM van Leeuwen; Carina M Edwards; Mohammad Ilyas; Helen M Byrne

    2007-01-01

    Colorectal cancer (CRC) is one of the best characterised cancers, with extensive data documenting the sequential gene mutations that underlie its development.Complementary datasets are also being generated describing changes in protein and RNA expression,tumour biology and clinical outcome. Both the quantity and the variety of information are inexorably increasing and there is now an accompanying need to integrate these highly disparate datasets. In this article we aim to explain why we believe that mathematical modelling represents a natural tool or language with which to integrate these data and, in so doing, to provide insight into CRC.

  6. 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.

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

    CERN Document Server

    Fuentes, Marcelo López

    2016-01-01

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

  8. 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.

  9. 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.

  10. A tunable cancer cell filter using magnetic beads: cellular and fluid dynamic simulations

    CERN Document Server

    Gusenbauer, Markus; Bance, Simon; Exl, Lukas; Reichel, Franz; Oezelt, Harald; Schrefl, Thomas

    2011-01-01

    In the field of biomedicine magnetic beads are used for drug delivery and to treat hyperthermia. Here we propose to use self-organized bead structures to isolate circulating tumor cells using lab-on-chip technologies. Typically blood flows past microposts functionalized with antibodies for circulating tumor cells. Creating these microposts with interacting magnetic beads makes it possible to tune the geometry in size, position and shape. We develop a simulation tool that combines micromagnetics, discrete particle dynamics and fluid dynamics, in order to design micropost arrays made of interacting beads. For the simulation of blood flow we use the Lattice-Boltzmann method with immersed elastic blood cell models. Parallelization distributes large fluid and particle dynamic simulations over available resources to reduce overall calculation time.

  11. Cancer chemoprevention by phytochemicals: potential molecular targets,biomarkers and animal models

    Institute of Scientific and Technical Information of China (English)

    Ki Han KWON; Avantika BARVE; Siwang YU; Mou-Tuan HUANG; Ah-Ng Tony KONG

    2007-01-01

    Recent studies have strongly indicated that certain daily-consumed dietary phytochemicals could have cancer protective effects against transgenic mice can-cer models and cancers mediated by carcinogens, irradiations and carcinogenic metabolites derived from exogenous or endogenous sources. The cancer-protec-tive effects elicited by these dietary compounds are believed to be due at least in part to the induction of cellular defense systems including the detoxifying and antioxidant enzymes system, as well as the inhibition of anti-inflammatory and anti-cell growth signaling pathways culminating in cell cycle arrest and/or cell-death. In this review, we summarize the potential mechanisms including the modu-lation of nuclear factor kappaB (NF-κB), cyclooxygenases-2 (COX-2), activator protein-1 (AP-1), mitogen-activated protein kinases (MAPKs) and the induction of phase Ⅱ cellular detoxifying and antioxidant enzymes mediated mainly by the antioxidant response elements (ARE) within the promoter regions of these genes through nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap 'n' collar (CNC) family of the basic region-leucine zipper transcription factor. In addition, we also review several animal models of carcinogenesis and cancer chemopreventive efficacy studies of these animal models using dietary chemopreventive compounds. Finally, we discuss the cellular signaling cascades mediated by Nrf2, NF-κB, AP-1, MAPKs and COX-2, which have been considered to play pivotal roles in tumor initiation, promotion and progression processes,and could be promising molecular targets for the design of drugs targeting cancer prevention and therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-26

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

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

    Science.gov (United States)

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

    2013-04-01

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

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    1998-12-01

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

  17. An empirical Bayesian approach for model-based inference of cellular signaling networks

    Directory of Open Access Journals (Sweden)

    Klinke David J

    2009-11-01

    Full Text Available Abstract Background A common challenge in systems biology is to infer mechanistic descriptions of biological process given limited observations of a biological system. Mathematical models are frequently used to represent a belief about the causal relationships among proteins within a signaling network. Bayesian methods provide an attractive framework for inferring the validity of those beliefs in the context of the available data. However, efficient sampling of high-dimensional parameter space and appropriate convergence criteria provide barriers for implementing an empirical Bayesian approach. The objective of this study was to apply an Adaptive Markov chain Monte Carlo technique to a typical study of cellular signaling pathways. Results As an illustrative example, a kinetic model for the early signaling events associated with the epidermal growth factor (EGF signaling network was calibrated against dynamic measurements observed in primary rat hepatocytes. A convergence criterion, based upon the Gelman-Rubin potential scale reduction factor, was applied to the model predictions. The posterior distributions of the parameters exhibited complicated structure, including significant covariance between specific parameters and a broad range of variance among the parameters. The model predictions, in contrast, were narrowly distributed and were used to identify areas of agreement among a collection of experimental studies. Conclusion In summary, an empirical Bayesian approach was developed for inferring the confidence that one can place in a particular model that describes signal transduction mechanisms and for inferring inconsistencies in experimental measurements.

  18. TAp73-mediated the activation of C-jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells

    OpenAIRE

    Pingde Zhang; Stephanie Si Liu; Hextan Yuen Sheung Ngan

    2012-01-01

    P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. ...

  19. Modeling pancreatic cancer with organoids

    NARCIS (Netherlands)

    Baker, Lindsey A; Tiriac, Hervé; Clevers, Hans; Tuveson, David A

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy for which new treatment and diagnostic approaches are urgently needed. In order for such breakthroughs to be discovered, researchers require systems that accurately model the development and biology of PDA. While cell lines, geneti

  20. 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.

  1. 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.

  2. 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...

  3. 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.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Tamaddon AM.

    2007-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Xin Zhao

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

  7. An Integrated Model for Production Planning and Cell Formation in Cellular Manufacturing Systems

    Directory of Open Access Journals (Sweden)

    Reza Raminfar

    2013-01-01

    Full Text Available Cellular manufacturing (CM is a production approach directed towards reducing costs, as well as increasing system's flexibility in today's small-to-medium lot production environment. Many structural and operational issues should be considered for a successful CM design and implementation such as cell formation (CF, production planning, and facility layout. Most researchers have addressed these issues sequentially or independently, instead of jointly optimizing a combination of these issues. In order to attain better results to ensure that the system will be capable of remaining efficient in unknown future situations, these issues should be addressed simultaneously. In this paper, a mathematical model is developed using an integrated approach for production planning and cell formation problems in a CM. A set of numerical examples are provided from existing the literature in order to test and illustrate the proposed model. In order to evaluate and verify the performance of the proposed model, it is compared with a well-known cell formation methods (rank order clustering and direct clustering analysis, using group capability index (GCI measure. The results and comparisons indicate that the proposed model has a significantly higher and satisfactory performance and it is reliable for the design and the analysis of CM systems.

  8. 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).

  9. An increase in galectin-3 causes cellular unresponsiveness to IFN-γ-induced signal transduction and growth inhibition in gastric cancer cells

    Science.gov (United States)

    Tseng, Po-Chun; Chen, Chia-Ling; Shan, Yan-Shen; Lin, Chiou-Feng

    2016-01-01

    Glycogen synthase kinase (GSK)-3β facilitates interferon (IFN)-γ signaling by inhibiting Src homology-2 domain-containing phosphatase (SHP) 2. Mutated phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) cause AKT activation and GSK-3β inactivation to induce SHP2-activated cellular unresponsiveness to IFN-γ in human gastric cancer AGS cells. This study investigated the potential role of galectin-3, which acts upstream of AKT/GSK-3β/SHP2, in gastric cancer cells. Increasing or decreasing galectin-3 altered IFN-γ signaling. Following cisplatin-induced galectin-3 upregulation, surviving cells showed cellular unresponsiveness to IFN-γ. Galectin-3 induced IFN-γ resistance independent of its extracellular β-galactoside-binding activity. Galectin-3 expression was not regulated by PI3K activation or by a decrease in PTEN. Increased galectin-3 may cause GSK-3β inactivation and SHP2 activation by promoting PDK1-induced AKT phosphorylation at a threonine residue. Overexpression of AKT, inactive GSK-3βR96A, SHP2, or active SHP2D61A caused cellular unresponsiveness to IFN-γ in IFN-γ-sensitive MKN45 cells. IFN-γ-induced growth inhibition and apoptosis in AGS cells were observed until galectin-3 expression was downregulated. These results demonstrate that an increase in galectin-3 facilitates AKT/GSK-3β/SHP2 signaling, causing cellular unresponsiveness to IFN-γ. PMID:26934444

  10. Tart cherry juice induces differential dose-dependent effects on apoptosis, but not cellular proliferation, in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Martin, Keith R; Wooden, Alissa

    2012-11-01

    Consumption of polyphenol-rich fruits, for example, tart cherries, is associated with a lower risk of cardiovascular disease and cancer. This is due, in large part, to the diverse myriad bioactive agents, that is, polyphenol anthocyanins, present in fruits. Anthocyanin-rich tart cherries purportedly modulate numerous cellular processes associated with oncogenesis such as apoptosis, cellular proliferation (CP), and cell cycle progression, although the effective concentrations eliciting these effects are unclear. We hypothesized that several dose-dependent effects over a large concentration range of 100% tart cherry juice (TCJ) would exist and affect these processes differentially with the potential for cellular protection and cellular death either by apoptosis or by necrosis. In this in vitro study, we tested the dose response of TCJ on CP and cell death in MCF-7 human breast cancer cells. TCJ was added at 0.03-30% (v/v) to cells and incubated overnight with the medium alone or with increasing TCJ. Bromodeoxyuridine incorporation was significantly reduced by 20% at ≥10% (v/v) TCJ and associated with necrosis, but was not different between the control and treatment groups at anthocyanins), yet significantly decreased (Panthocyanins. The data support a biphasic effect on apoptosis and no effect on proliferation. PMID:23057779

  11. Near-infrared dye loaded polymeric nanoparticles for cancer imaging and therapy and cellular response after laser-induced heating

    Directory of Open Access Journals (Sweden)

    Tingjun Lei

    2014-03-01

    Full Text Available Background: In the past decade, researchers have focused on developing new biomaterials for cancer therapy that combine imaging and therapeutic agents. In our study, we use a new biocompatible and biodegradable polymer, termed poly(glycerol malate co-dodecanedioate (PGMD, for the synthesis of nanoparticles (NPs and loading of near-infrared (NIR dyes. IR820 was chosen for the purpose of imaging and hyperthermia (HT. HT is currently used in clinical trials for cancer therapy in combination with radiotherapy and chemotherapy. One of the potential problems of HT is that it can up-regulate hypoxia-inducible factor-1 (HIF-1 expression and enhance vascular endothelial growth factor (VEGF secretion.Results: We explored cellular response after rapid, short-term and low thermal dose laser-IR820-PGMD NPs (laser/NPs induced-heating, and compared it to slow, long-term and high thermal dose heating by a cell incubator. The expression levels of the reactive oxygen species (ROS, HIF-1 and VEGF following the two different modes of heating. The cytotoxicity of NPs after laser/NP HT resulted in higher cell killing compared to incubator HT. The ROS level was highly elevated under incubator HT, but remained at the baseline level under the laser/NP HT. Our results show that elevated ROS expression inside the cells could result in the promotion of HIF-1 expression after incubator induced-HT. The VEGF secretion was also significantly enhanced compared to laser/NP HT, possibly due to the promotion of HIF-1. In vitro cell imaging and in vivo healthy mice imaging showed that IR820-PGMD NPs can be used for optical imaging.Conclusion: IR820-PGMD NPs were developed and used for both imaging and therapy purposes. Rapid and short-term laser/NP HT, with a low thermal dose, does not up-regulate HIF-1 and VEGF expression, whereas slow and long term incubator HT, with a high thermal dose, enhances the expression of both transcription factors.

  12. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  14. Modulation of early stress-related biomarkers in cytoplasm by the antioxidants silymarin and quercetin using a cellular model of acute arsenic poisoning.

    Science.gov (United States)

    Soria, Elio A; Eynard, Aldo R; Bongiovanni, Guillermina A

    2010-12-01

    Several pathologies (e.g. cancer and diabetes) are increased in arsenic-exposed populations, with oxidative stress being a major toxicological mechanism. Since the flavonoids silymarin (S) and quercetin (Q) are antioxidants and may protect cells, it would be valuable to develop a model which allows assessing the potential of xenobiotic against arsenic cytotoxicity in an efficient and rapid way. Thus, the oxidant production [e.g. reactive oxygen species and reactive nitrogen species (RNS)], the molecular parameters of biological response [e.g. plasma membrane composition, actin microfilaments and activated diphosphorilated c-Jun N-terminal kinase (JNK)] and cellular viability were determined in CHO-K1 cells treated with arsenite (As), S and Q. Arsenic caused loss of the cellular viability in a time-dependent manner. This effect was accompanied by a lipid hydroperoxide (LHP) formation, with no RNS induction or ganglioside content changes being found. Both flavonoids counteracted oxidative damage. Despite all treatments had unspecific responses on nitrite cellular release along the time, there was no relation between them and the cellular viability. Arsenic induced cytoplasmic microfilament rearrangement (tight perinuclear distribution with projections, stress fibres and pseudopodia) which was reversed by S. Also, activated JNK showed a similar distribution to actin. Contrarily, Q caused a dysmorphic granular pattern, thus behaving as a toxic agent. Summing up, toxic levels of arsenic disturb the redox homeostasis with LHP induction and early triggering of stress responses in cytoskeleton and cell signalling. Using the proposed model, only S showed to protect cells from arsenical cytotoxicity without own toxic properties. Thus, S might be considered for modulation of the human arsenic susceptibility.

  15. Mouse models for BRAF-induced cancers.

    Science.gov (United States)

    Pritchard, C; Carragher, L; Aldridge, V; Giblett, S; Jin, H; Foster, C; Andreadi, C; Kamata, T

    2007-11-01

    Oncogenic mutations in the BRAF gene are detected in approximately 7% of human cancer samples with a particularly high frequency of mutation in malignant melanomas. Over 40 different missense BRAF mutations have been found, but the vast majority (>90%) represent a single nucleotide change resulting in a valine-->glutamate mutation at residue 600 ((V600E)BRAF). In cells cultured in vitro, (V600E)BRAF is able to stimulate endogenous MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] and ERK phosphorylation leading to an increase in cell proliferation, cell survival, transformation, tumorigenicity, invasion and vascular development. Many of these hallmarks of cancer can be reversed by treatment of cells with siRNA (small interfering RNA) to BRAF or by inhibiting MEK, indicating that BRAF and MEK are attractive therapeutic targets in cancer samples with BRAF mutations. In order to fully understand the role of oncogenic BRAF in cancer development in vivo as well as to test the in vivo efficacy of anti-BRAF or anti-MEK therapies, GEMMs (genetically engineered mouse models) have been generated in which expression of oncogenic BRaf is conditionally dependent on the Cre recombinase. The delivery/activation of the Cre recombinase can be regulated in both a temporal and spatial manner and therefore these mouse models can be used to recapitulate the somatic mutation of BRAF that occurs in different tissues in the development of human cancer. The data so far obtained following Cre-mediated activation in haemopoietic tissue and the lung indicate that (V600E)BRAF mutation can drive tumour initiation and that its primary effect is to induce high levels of cyclin D1-mediated cell proliferation. However, hallmarks of OIS (oncogene-induced senescence) are evident that restrain further development of the tumour.

  16. Formal Modeling and Analysis of Pancreatic Cancer Microenvironment

    OpenAIRE

    Wang, Qinsi; Miskov-Zivanov, Natasa; Liu, Bing; Faeder, James R.; Lotze, Michael; Clarke, Edmund M

    2016-01-01

    The focus of pancreatic cancer research has been shifted from pancreatic cancer cells towards their microenvironment, involving pancreatic stellate cells that interact with cancer cells and influence tumor progression. To quantitatively understand the pancreatic cancer microenvironment, we construct a computational model for intracellular signaling networks of cancer cells and stellate cells as well as their intercellular communication. We extend the rule-based BioNetGen language to depict in...

  17. 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.

  18. 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.

  19. 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.

  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 < 0.05). This trans-well-based cellular model might be a useful pre-evaluation platform for the evaluation of TM repairing materials. The model is inexpensive, readily available, easy to create, and standardized for use. PMID:26335291