WorldWideScience

Sample records for cells model studies

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

    Science.gov (United States)

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

    2011-04-15

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

  2. Cell culture models for study of differentiated adipose cells

    OpenAIRE

    Clynes, Martin

    2014-01-01

    Adipose cells are an important source of mesenchymal stem cells and are important for direct use in research on lipid metabolism and obesity. In addition to use of primary cultures, there is increasing interest in other sources of larger numbers of cells, using approaches including induced pluripotent stem cell differentiation and viral immortalisation.

  3. Cell Line Modeling to Study Biomarker Panel in Prostate Cancer

    Science.gov (United States)

    NickKholgh, Bita; Fang, Xiaolan; Winters, Shira M.; Raina, Anvi; Pandya, Komal S.; Gyabaah, Kenneth; Fino, Nora; Balaji, K.C.

    2016-01-01

    BACKGROUND African–American men with prostate cancer (PCa) present with higher-grade and -stage tumors compared to Caucasians. While the disparity may result from multiple factors, a biological basis is often strongly suspected. Currently, few well-characterized experimental model systems are available to study the biological basis of racial disparity in PCa. We report a validated in vitro cell line model system that could be used for the purpose. METHODS We assembled a PCa cell line model that included currently available African–American PCa cell lines and LNCaP (androgen-dependent) and C4-2 (castration-resistant) Caucasian PCa cells. The utility of the cell lines in studying the biological basis of variance in a malignant phenotype was explored using a multiplex biomarker panel consisting of proteins that have been proven to play a role in the progression of PCa. The panel expression was evaluated by Western blot and RT-PCR in cell lines and validated in human PCa tissues by RT-PCR. As proof-of-principle to demonstrate the utility of our model in functional studies, we performed MTS viability assays and molecular studies. RESULTS The dysregulation of the multiplex biomarker panel in primary African–American cell line (E006AA) was similar to metastatic Caucasian cell lines, which would suggest that the cell line model could be used to study an inherent aggressive phenotype in African–American men with PCa. We had previously demonstrated that Protein kinase D1 (PKD1) is a novel kinase that is down regulated in advanced prostate cancer. We established the functional relevance by over expressing PKD1, which resulted in decreased proliferation and epithelial mesenchymal transition (EMT) in PCa cells. Moreover, we established the feasibility of studying the expression of the multiplex biomarker panel in archived human PCa tissue from African–Americans and Caucasians as a prelude to future translational studies. CONCLUSION We have characterized a novel in

  4. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

    Science.gov (United States)

    Drummond, Coyne G; Nickerson, Cheryl A; Coyne, Carolyn B

    2016-01-01

    Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the

  5. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells

    Science.gov (United States)

    Drummond, Coyne G.

    2015-01-01

    ABSTRACT Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and

  6. Transport Studies and Modeling in PEM Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Mittelsteadt, Cortney K. [Giner, Inc., Auburndale, MA (United States); Xu, Hui [Giner, Inc., Auburndale, MA (United States); Brawn, Shelly [Giner, Inc., Auburndale, MA (United States)

    2014-07-30

    This project’s aim was to develop fuel cell components (i.e. membranes, gas-diffusion media (GDM), bipolar plates and flow fields) that possess specific properties (i.e. water transport and conductivity). A computational fluid dynamics model was developed to elucidate the effect of certain parameters on these specific properties. Ultimately, the model will be used to determine sensitivity of fuel cell performance to component properties to determine limiting components and to guide research. We have successfully reached our objectives and achieved most of the milestones of this project. We have designed and synthesized a variety of hydrocarbon block polymer membranes with lower equivalent weight, structure, chemistry, phase separation and process conditions. These membranes provide a broad selection with optimized water transport properties. We have also designed and constructed a variety of devices that are capable of accurately measuring the water transport properties (water uptake, water diffusivity and electro-osmatic drag) of these membranes. These transport properties are correlated to the membranes’ structures derived from X-ray and microscopy techniques to determine the structure-property relationship. We successfully integrated hydrocarbon membrane MEAs with a current distribution board (CBD) to study the impact of hydrocarbon membrane on water transport in fuel cells. We have designed and fabricated various GDM with varying substrate, diffusivity and micro-porous layers (MPL) and characterized their pore structure, tortuosity and hydrophobicity. We have derived a universal chart (MacMullin number as function of wet proofing and porosity) that can be used to characterize various GDM. The abovementioned GDMs have been evaluated in operating fuel cells; their performance is correlated to various pore structure, tortuosity and hydrophobicity of the GDM. Unfortunately, determining a universal relationship between the MacMullin number and these properties

  7. Analytical modelling and experimental studies of SIS tunnel solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Cheknane, Ali [Laboratoire de Valorisation des Energies Renouvelables et Environnements Agressifs, Universite Amar Telidji de Laghouat, BP 37G route de Ghardaia, Laghouat (03000) Algerie (Algeria)], E-mail: cheknanali@yahoo.com

    2009-06-07

    This paper presents an experimental and computational study of semiconductor-insulator-semiconductor (SIS) tunnel solar cells. A transparent and conductive film of thallium trioxide Tl{sub 2}O{sub 3} has been deposited by anodic oxidation onto an n-Si(1 0 0) face to realize the SIS tunnel solar cells based on Si/SiO{sub x}/Tl{sub 2}O{sub 3}. An efficiency of 8.77% has been obtained under an incident power density of 33 mW cm{sup -2} illumination condition. A PSPICE model is implemented. The calculated results show that the theoretical values are in good agreement with experimental data. Moreover, the simulation clearly demonstrates that the performance of the tested device can be significantly improved.

  8. Epithelial Cell Culture from Human Adenoids: A Functional Study Model for Ciliated and Secretory Cells

    Directory of Open Access Journals (Sweden)

    Claudia González

    2013-01-01

    Full Text Available Background. Mucociliary transport (MCT is a defense mechanism of the airway. To study the underlying mechanisms of MCT, we have both developed an experimental model of cultures, from human adenoid tissue of ciliated and secretory cells, and characterized the response to local chemical signals that control ciliary activity and the secretion of respiratory mucins in vitro. Materials and Methods. In ciliated cell cultures, ciliary beat frequency (CBF and intracellular Ca2+ levels were measured in response to ATP, UTP, and adenosine. In secretory cultures, mucin synthesis and secretion were identified by using immunodetection. Mucin content was taken from conditioned medium and analyzed in the presence or absence of UTP. Results. Enriched ciliated cell monolayers and secretory cells were obtained. Ciliated cells showed a basal CBF of 10.7 Hz that increased significantly after exposure to ATP, UTP, or adenosine. Mature secretory cells showed active secretion of granules containing different glycoproteins, including MUC5AC. Conclusion. Culture of ciliated and secretory cells grown from adenoid epithelium is a reproducible and feasible experimental model, in which it is possible to observe ciliary and secretory activities, with a potential use as a model to understand mucociliary transport control mechanisms.

  9. Preliminary Modeling and Simulation Study on Olfactory Cell Sensation

    International Nuclear Information System (INIS)

    This paper introduced olfactory sensory neuron's whole-cell model with a concrete voltage-gated ionic channels and simulation. Though there are many models in olfactory sensory neuron and olfactory bulb, it remains uncertain how they express the logic of olfactory information processing. In this article, the olfactory neural network model is also introduced. This model specifies the connections among neural ensembles of the olfactory system. The simulation results of the neural network model are consistent with the observed olfactory biological characteristics such as 1/f-type power spectrum and oscillations.

  10. Model systems to study biochemical functions of rat sertoli cells

    NARCIS (Netherlands)

    J.M.W. Toebosch (Annemarie)

    1990-01-01

    textabstractDevelopment of roale genn cells (spermatogenesis) takes place in the testicular seminiferous tubules. The honrones follicle-stimulating honnone (FSH) and testosterone are essential for the initiation and maintenance of spermatogenesis. n>e genn cells in the tubules (spermatogonia, sperma

  11. THE STUDY OF VIRUSES REPRODUCTION IN CELL CULTURES BY THE METHOD OF MATHEMATICAL MODELING

    OpenAIRE

    N. A. Kontarov; S. A. Grishunina; N. V. Balaev; N. V. Yuminova; V. V. Zverev

    2014-01-01

    Abstract. In the study the mathematical analysis of viruses reproduction in cell culture using the Marchuk’ mathematical model to predict  reproduction of virus in one or another cell cultures has been conducted. The obtained theoretical results are corresponded to the experimental data on reproduction of rubella virus in cell cultures RK-13 and BHK-21. The sum of theoretical and experimental results can be used to select the optimal cell cultures for virus cumulation.

  12. Electrical activity of ON and OFF retinal ganglion cells: a modelling study

    Science.gov (United States)

    Guo, Tianruo; Tsai, David; Morley, John W.; Suaning, Gregg J.; Kameneva, Tatiana; Lovell, Nigel H.; Dokos, Socrates

    2016-04-01

    Objective. Retinal ganglion cells (RGCs) demonstrate a large range of variation in their ionic channel properties and morphologies. Cell-specific properties are responsible for the unique way RGCs process synaptic inputs, as well as artificial electrical signals such as that from a visual prosthesis. A cell-specific computational modelling approach allows us to examine the functional significance of regional membrane channel expression and cell morphology. Approach. In this study, an existing RGC ionic model was extended by including a hyperpolarization activated non-selective cationic current as well as a T-type calcium current identified in recent experimental findings. Biophysically-defined model parameters were simultaneously optimized against multiple experimental recordings from ON and OFF RGCs. Main results. With well-defined cell-specific model parameters and the incorporation of detailed cell morphologies, these models were able to closely reconstruct and predict ON and OFF RGC response properties recorded experimentally. Significance. The resulting models were used to study the contribution of different ion channel properties and spatial structure of neurons to RGC activation. The techniques of this study are generally applicable to other excitable cell models, increasing the utility of theoretical models in accurately predicting the response of real biological neurons.

  13. Comparative study of PEM fuel cell models for integration in propulsion systems of urban public transport

    OpenAIRE

    Garcia, Pablo; Fernandez, Luis; Garcia, Carlos A.; Jurado, Francisco

    2010-01-01

    International audience In this paper, a comparative study of three proton exchange membrane (PEM) fuel cell (FC) models is performed in order to choose the best model for its integration in the modelling of the hybrid propulsion system of a tramway. Two reduced models of PEM FC system are studied in this work: 1) a new reduced model obtained from a complete one is here presented (reduced model 1); and 2) a reduced model very used for hybrid vehicles and portable applications (reduced model...

  14. Comparative study of PEM fuel cell models for integration in propulsion systems of urban public transport

    OpenAIRE

    2010-01-01

    Abstract In this paper, a comparative study of three proton exchange membrane (PEM) fuel cell (FC) models is performed in order to choose the best model for its integration in the modelling of the hybrid propulsion system of a tramway. Two reduced models of PEM FC system are studied in this work: 1) a new reduced model obtained from a complete one is here presented (reduced model 1); and 2) a reduced model very used for hybrid vehicles and portable applications (reduced model 2). T...

  15. A review of multistate models in hematopoietic cell transplantation studies

    OpenAIRE

    Logan, Brent R.

    2012-01-01

    Multi-state models are used to describe how a patient’s clinical status evolves over time. They can be a useful tool for describing the complex post transplant recovery process. In this paper we review basic concepts of multistate models and describe how they are used to model transition rates or state probabilities. We also discuss the use of landmark analysis to summarize how a patient’s long-term prognosis changes as they transition to different health states. We illustrate these uses of m...

  16. Murine and Human Model Systems for the Study of Dendritic Cell Immunobiology.

    Science.gov (United States)

    Hargadon, Kristian M

    2016-03-01

    Dendritic cells are a population of innate immune cells that possess their own effector functions as well as numerous regulatory properties that shape the activity of other innate and adaptive cells of the immune system. Following their development from either lymphoid or myeloid progenitors, the function of dendritic cells is tightly linked to their maturation and activation status. Differentiation into specialized subsets of dendritic cells also contributes to the diverse immunologic functions of these cells. Because of the key role played by dendritic cells in the regulation of both immune tolerance and activation, significant efforts have been focused on understanding dendritic cell biology. This review highlights the model systems currently available to study dendritic cell immunobiology and emphasizes the advantages and disadvantages to each system in both murine and human settings. In particular, in vitro cell culture systems involving immortalized dendritic cell lines, ex vivo systems for differentiating and expanding dendritic cells from their precursor populations, and systems for expanding, ablating, and manipulating dendritic cells in vivo are discussed. Emphasis is placed on the contribution of these systems to our current understanding of the development, function, and immunotherapeutic applications of dendritic cells, and insights into how these models might be extended in the future to answer remaining questions in the field are discussed. PMID:25203775

  17. The study of MCF-7 cell aggregates encapsulated in alginate microbeads under the modeled weightlessness

    Science.gov (United States)

    Li, Yu; Zheng, Hongxia; Tian, Weiming; Yu, Lei; Zhang, Yao; Han, Fengtong

    Assessing the risks associated with exposure to the microgravity encountered in space is essential for the success of long-term space exploration. For understanding of the effects of microgravity, either traditional 2-dimensional (2D) cell cultures of adherent cell populations or animal models were typically used. The 2D in vitro systems do not allow assessment of the dynamic effects of intercellular interactions within tissues, whereas potentially confounding factors tend to be overlooked in animal models. Therefore novel cell culture model representative of the cellular interactions and with extracellular matrix present in tissues needs to be used. Toward this overall goal, 3D cell aggregates of breast cancer cell line MCF-7 was constructed by encapsu-lating in alginate microbeads. With this model we studied the simulated microgravity effects on MCF-7 by incubating the microbeads in NASA rotary cell culture system with a rate of 15rpm.We found MCF-7 showed higher proliferation rate than that of control group character-ized by up regulation of Ki-67. Further study showed that the effect was achieved by activating the MAPK intercellular signaling pathway. The result is inconsistent with previous conclusion obtained with 2D cell culture model which indicated that 3D cell culture model maybe better for elucidating the microgravity effects.

  18. Studying mast cells in peripheral tolerance by using a skin transplantation model.

    Science.gov (United States)

    de Vries, Victor C; Le Mercier, Isabelle; Nowak, Elizabeth C; Noelle, Randolph J

    2015-01-01

    Mast cells (MCs) play an important role in both inflammatory and immunosuppressive responses [1]. The importance of MCs in maintaining peripheral tolerance was discovered in a FoxP3(+) regulatory T-cell (Treg)-mediated skin transplant model [2]. MCs can directly mediate tolerance by releasing anti-inflammatory mediators (reviewed in ref. 3) or by interacting with other immune cells in the graft. Here we will present protocols used to study the role of MCs in peripheral tolerance with the emphasis on how MCs can regulate T-cell functionality. First we will introduce the skin transplant model followed by reconstitution of mast cell-deficient mice (B6.Cg-Kit (W-sh) ). This includes the preparation of MCs from the bone marrow. Finally the methods used to study the influence of MCs on T-cell responses and Treg functionality will be presented by modulating the balance between tolerance and inflammation. PMID:25388268

  19. Penium margaritaceum: A Unicellular Model Organism for Studying Plant Cell Wall Architecture and Dynamics

    OpenAIRE

    Domozych, David S

    2014-01-01

    Penium margaritaceum is a new and valuable unicellular model organism for studying plant cell wall structure and developmental dynamics. This charophyte has a cell wall composition remarkably similar to the primary cell wall of many higher plants and clearly-defined inclusive zones containing specific polymers. Penium has a simple cylindrical phenotype with a distinct region of focused wall synthesis. Specific polymers, particularly pectins, can be identified using monoclonal antibodies rais...

  20. Experimental and Computer Modelling Studies of Metastability of Amorphous Silicon Based Solar Cells

    OpenAIRE

    Munyeme, Geoffrey

    2003-01-01

    We present a combination of experimental and computer modelling studies of the light induced degradation in the performance of amorphous silicon based single junction solar cells. Of particular interest in this study is the degradation kinetics of different types of amorphous silicon single junction solar cells and the role of dangling bond states in mediating or driving the degradation mechanism. The approach taken in this study has enabled has to examine how light induced degradation is aff...

  1. Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review.

    Science.gov (United States)

    Ruiz-Ojeda, Francisco Javier; Rupérez, Azahara Iris; Gomez-Llorente, Carolina; Gil, Angel; Aguilera, Concepción María

    2016-01-01

    Over the last several years, the increasing prevalence of obesity has favored an intense study of adipose tissue biology and the precise mechanisms involved in adipocyte differentiation and adipogenesis. Adipocyte commitment and differentiation are complex processes, which can be investigated thanks to the development of diverse in vitro cell models and molecular biology techniques that allow for a better understanding of adipogenesis and adipocyte dysfunction associated with obesity. The aim of the present work was to update the different animal and human cell culture models available for studying the in vitro adipogenic differentiation process related to obesity and its co-morbidities. The main characteristics, new protocols, and applications of the cell models used to study the adipogenesis in the last five years have been extensively revised. Moreover, we depict co-cultures and three-dimensional cultures, given their utility to understand the connections between adipocytes and their surrounding cells in adipose tissue. PMID:27376273

  2. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Eder Zucconi

    2011-01-01

    Full Text Available Umbilical cord mesenchymal stromal cells (MSC have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs, independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1 human umbilical cord tissue (hUCT MSCs into the caudal vein of SJL mice; (2 hUCT and canine umbilical cord vein (cUCV MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies.

  3. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    Science.gov (United States)

    Zucconi, Eder; Vieira, Natassia Moreira; Bueno, Carlos Roberto; Secco, Mariane; Jazedje, Tatiana; Costa Valadares, Marcos; Fussae Suzuki, Miriam; Bartolini, Paolo; Vainzof, Mariz; Zatz, Mayana

    2011-01-01

    Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein of SJL mice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies. PMID:21785565

  4. Mixture models for single-cell assays with applications to vaccine studies.

    Science.gov (United States)

    Finak, Greg; McDavid, Andrew; Chattopadhyay, Pratip; Dominguez, Maria; De Rosa, Steve; Roederer, Mario; Gottardo, Raphael

    2014-01-01

    Blood and tissue are composed of many functionally distinct cell subsets. In immunological studies, these can be measured accurately only using single-cell assays. The characterization of these small cell subsets is crucial to decipher system-level biological changes. For this reason, an increasing number of studies rely on assays that provide single-cell measurements of multiple genes and proteins from bulk cell samples. A common problem in the analysis of such data is to identify biomarkers (or combinations of biomarkers) that are differentially expressed between two biological conditions (e.g. before/after stimulation), where expression is defined as the proportion of cells expressing that biomarker (or biomarker combination) in the cell subset(s) of interest. Here, we present a Bayesian hierarchical framework based on a beta-binomial mixture model for testing for differential biomarker expression using single-cell assays. Our model allows the inference to be subject specific, as is typically required when assessing vaccine responses, while borrowing strength across subjects through common prior distributions. We propose two approaches for parameter estimation: an empirical-Bayes approach using an Expectation-Maximization algorithm and a fully Bayesian one based on a Markov chain Monte Carlo algorithm. We compare our method against classical approaches for single-cell assays including Fisher's exact test, a likelihood ratio test, and basic log-fold changes. Using several experimental assays measuring proteins or genes at single-cell level and simulations, we show that our method has higher sensitivity and specificity than alternative methods. Additional simulations show that our framework is also robust to model misspecification. Finally, we demonstrate how our approach can be extended to testing multivariate differential expression across multiple biomarker combinations using a Dirichlet-multinomial model and illustrate this approach using single-cell gene

  5. Experimental and Computer Modelling Studies of Metastability of Amorphous Silicon Based Solar Cells

    NARCIS (Netherlands)

    Munyeme, Geoffrey

    2003-01-01

    We present a combination of experimental and computer modelling studies of the light induced degradation in the performance of amorphous silicon based single junction solar cells. Of particular interest in this study is the degradation kinetics of different types of amorphous silicon single junction

  6. Validation of Aedes aegypti Aag-2 cells as a model for insect immune studies

    OpenAIRE

    Barletta Ana; Silva Maria Clara L Nascimento; Sorgine Marcos

    2012-01-01

    Abstract Background The understanding of mosquito immune responses can provide valuable tools for development of novel mosquito control strategies. Aiming the study at insect innate immunity, continuous insect cell lines have been established and used as research tools due to the fact that they constitute more homogeneous, sensitive, and reproducible systems than the insects from which they originated. More recently, Aag-2, an Aedes aegypti cell lineage, began to be frequently used as a model...

  7. The SGBS cell strain as a model for the in vitro study of obesity and cancer.

    LENUS (Irish Health Repository)

    Allott, Emma H

    2012-10-01

    The murine adipocyte cell line 3T3-L1 is well characterised and used widely, while the human pre-adipocyte cell strain, Simpson-Golabi-Behmel Syndrome (SGBS), requires validation for use in human studies. Obesity is currently estimated to account for up to 41 % of the worldwide cancer burden. A human in vitro model system is required to elucidate the molecular mechanisms for this poorly understood association. This work investigates the relevance of the SGBS cell strain for obesity and cancer research in humans.

  8. The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Nurfatin Asyikhin Kamaruzaman

    2013-01-01

    Full Text Available No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

  9. Basis study on the model of hepatitis B-Vitro cell culture

    Institute of Scientific and Technical Information of China (English)

    Zheng-mingHUANG; Xin-boYANG; Wen-binCAO; Hong-yanCHEN; He-zhiLIU; ZhuangLI

    2004-01-01

    AIM: To explore and set up many kinds of experimental model of hepatitis B in order to provide varies methods for application study on drugs to prevent and to cure hepatitis B. METHODS: According to the disorder and characters of hepatitis B, we used the models of duck primary hepatocytes which were infected duck hepatitis B virus (DHBV), the human hepatocellular carcinoma (cell 2215, Hep G2) which was transferred with hepatitis Bvirus and rats primary hepatocytes cultured with CCl4 in vitro

  10. Proposing a Caco-2/HepG2 cell model for in vitro iron absorption studies.

    Science.gov (United States)

    Scheers, Nathalie M; Almgren, Annette B; Sandberg, Ann-Sofie

    2014-07-01

    The Caco-2 cell line is well established as an in vitro model for iron absorption. However, the model does not reflect the regulation of iron absorption by hepcidin produced in the liver. We aimed to develop the Caco-2 model by introducing human liver cells (HepG2) to Caco-2 cells. The Caco-2 and HepG2 epithelia were separated by a liquid compartment, which allowed for epithelial interaction. Ferritin levels in cocultured Caco-2 controls were 21.7±10.3 ng/mg protein compared to 7.7±5.8 ng/mg protein in monocultured Caco-2 cells. The iron transport across Caco-2 layers was increased when liver cells were present (8.1%±1.5% compared to 3.5%±2.5% at 120 μM Fe). Caco-2 cells were exposed to 0, 80 and 120 μM Fe and responded with increased hepcidin production at 120 μM Fe (3.6±0.3 ng/ml compared to 2.7±0.3 ng/ml). The expression of iron exporter ferroportin in Caco-2 cells was decreased at the hepcidin concentration of 3.6 ng/ml and undetectable at external addition of hepcidin (10 ng/ml). The apical transporter DMT1 was also undetectable at 10 ng/ml but was unchanged at the lower concentrations. In addition, we observed that sourdough bread, in comparison to heat-treated bread, increased the bioavailability of iron despite similar iron content (53% increase in ferritin formation, 97% increase in hepcidin release). This effect was not observed in monocultured Caco-2 cells. The Caco-2/HepG2 model provides an alternative approach to in vitro iron absorption studies in which the hepatic regulation of iron transport must be considered. PMID:24746839

  11. A kinetic-metabolic model based on cell energetic state: study of CHO cell behavior under Na-butyrate stimulation.

    Science.gov (United States)

    Ghorbaniaghdam, Atefeh; Henry, Olivier; Jolicoeur, Mario

    2013-04-01

    A kinetic-metabolic model approach describing and simulating Chinese hamster ovary (CHO) cell behavior is presented. The model includes glycolysis, pentose phosphate pathway, TCA cycle, respiratory chain, redox state and energetic metabolism. Growth kinetic is defined as a function of the major precursors for the synthesis of cell building blocks. Michaelis-Menten type kinetic is used for metabolic intermediates as well as for regulatory functions from energy shuttles (ATP/ADP) and cofactors (NAD/H and NADP/H). Model structure and parameters were first calibrated using results from bioreactor cultures of CHO cells expressing recombinant t-PA. It is shown that the model can simulate experimental data for all available experimental data, such as extracellular glucose, glutamine, lactate and ammonium concentration time profiles, as well as cell energetic state. A sensitivity analysis allowed identifying the most sensitive parameters. The model was then shown to be readily adaptable for studying the effect of sodium butyrate on CHO cells metabolism, where it was applied to the cases with sodium butyrate addition either at mid-exponential growth phase (48 h) or at the early plateau phase (74 h). In both cases, a global optimization routine was used for the simultaneous estimation of the most sensitive parameters, while the insensitive parameters were considered as constants. Finally, confidence intervals for the estimated parameters were calculated. Results presented here further substantiate our previous findings that butyrate treatment at mid-exponential phase may cause a shift in cellular metabolism toward a sustained and increased efficiency of glucose utilization channeled through the TCA cycle. PMID:22976819

  12. Development and validation of primary human myometrial cell culture models to study pregnancy and labour

    Directory of Open Access Journals (Sweden)

    Mosher Andrea A

    2013-01-01

    Full Text Available Abstract Background The development of the in vitro cell culture model has greatly facilitated the ability to study gene expression and regulation within human tissues. Within the human uterus, the upper (fundal segment and the lower segment may provide distinct functions throughout pregnancy and during labour. We have established primary cultured human myometrial cells, isolated from both upper and lower segment regions of the pregnant human uterus, and validated them for the purpose of studying human pregnancy and labour. The specific objectives of this study were to monitor the viability and characterize the expression profile using selected cellular, contractile and pregnancy associated markers in the primary cultured human myometrial cells. Labour has been described as an inflammatory process; therefore, the ability of these cells to respond to an inflammatory stimulus was also investigated. Methods Myometrial cells isolated from paired upper segment (US and lower segment (LS biopsies, obtained from women undergoing Caesarean section deliveries at term prior to the onset of labour, were used to identify expression of; α smooth muscle actin, calponin, caldesmon, connexin 43, cyclo-oxygenase-2 (COX-2, oxytocin receptor, tropomyosin and vimentin, by RT-PCR and/or immunocytochemistry. Interleukin (IL-1β was used to treat cells, subsequently expression of COX-2 mRNA and release of interleukin-8 (CXCL8, were measured. ANOVA followed by Bonferroni’s multiple comparisons test was performed. Results We demonstrate that US and LS human myometrial cells stably express all markers examined to at least passage ten (p10. Connexin 43, COX-2 and vimentin mRNA expression were significantly higher in LS cells compared to US cells. Both cell populations respond to IL-1β, demonstrated by a robust release of CXCL8 and increased expression of COX-2 mRNA from passage one (p1 through to p10. Conclusions Isolated primary myometrial cells maintain expression of

  13. Studying the function of dendritic cells in mouse models of asthma.

    Science.gov (United States)

    Pouliot, Philippe; Willart, Monique A; Hammad, Hamida; Lambrecht, Bart N

    2010-01-01

    Dendritic cells (DCs) are known to play a crucial role in the induction of allergic asthma in mouse models. Their antigen presentation capacity, linked to their capacity to prime naïve T cells and polarize them towards a Th1, Th2, Th17 or Treg profile, allows them to efficiently initiate an immune response to allergens. Airway dendritic cells also play a crucial role in the local restimulation of circulating effector T cells upon allergen challenge. Given their important implication in pathogenesis of asthma in mice models, the study of environmental and pharmacologic effects on DCs function is now a blooming field. There is therefore a critical need for a stable, yet flexible animal model to investigate the effects of various environmental factors (endotoxins, pollutants, etc.) or pharmacologic molecules on DCs and subsequently on their role in asthma pathogenesis. This chapter presents an approach using a reliable animal model of asthma that has the advantage to allow interventions on DCs before their use to induce allergic asthma. We also cover some of the endpoint techniques used to assess asthma and the immune reactions involved in its pathogenesis. PMID:19941123

  14. Mitochondrial alterations produced by misonidazole: a study using Amoeba proteus as a single cell model

    International Nuclear Information System (INIS)

    Misonidazole (MISO) is undergoing clinical trials because of its radiosensitizing and cytotoxic effects. Amoeba proteus was used as a single-cell model to study the mechanism of the action of MISO on aerobic and hypoxic cells. Preliminary ultrastructural findings with MISO treatment of aerobic amoebae are reported. Morphological changes to the mitochondria were noted, which included the generation of matrical inclusions. In earlier investigations similar changes of form have been correlated with a disruption of mitochondrial functioning, and the possible significance of the present results is discussed in the light of these. (author)

  15. A novel cell culture model for studying differentiation and apoptosis in the mouse mammary gland

    International Nuclear Information System (INIS)

    This paper describes the derivation and characterization of a novel, conditionally immortal mammary epithelial cell line named KIM-2. These cells were derived from mid-pregnant mammary glands of a mouse harbouring one to two copies of a transgene comprised of the ovine β-lactoglobulin milk protein gene promoter, driving expression of a temperature-sensitive variant of simian virus-40 (SV40) large T antigen (T-Ag). KIM-2 cells have a characteristic luminal epithelial cell morphology and a stable, nontransformed phenotype at the semipermissive temperature of 37°C. In contrast, at the permissive temperature of 33°C the cells have an elongated spindle-like morphology and become transformed after prolonged culture. Differentiation of KIM-2 cells at 37°C, in response to lactogenic hormones, results in the formation of polarized dome-like structures with tight junctions. This is accompanied by expression of the milk protein genes that encode β-casein and whey acidic protein (WAP), and activation of the prolactin signalling molecule, signal transducer and activator of transcription (STAT)5. Fully differentiated KIM-2 cultures at 37°C become dependent on lactogenic hormones for survival and undergo extensive apoptosis upon hormone withdrawal, as indicated by nuclear morphology and flow cytometric analysis. KIM-2 cells can be genetically modified by stable transfection and clonal lines isolated that retain the characteristics of untransfected cells. KIM-2 cells are a valuable addition, therefore, to currently available lines of mammary epithelial cells. Their capacity for extensive differentiation in the absence of exogenously added basement membrane, and ability to undergo apoptosis in response to physiological signals will provide an invaluable model system for the study of signal transduction pathways and transcriptional regulatory mechanisms that control differentiation and involution in the mammary gland

  16. Validation of Aedes aegypti Aag-2 cells as a model for insect immune studies

    Directory of Open Access Journals (Sweden)

    Barletta Ana

    2012-07-01

    Full Text Available Abstract Background The understanding of mosquito immune responses can provide valuable tools for development of novel mosquito control strategies. Aiming the study at insect innate immunity, continuous insect cell lines have been established and used as research tools due to the fact that they constitute more homogeneous, sensitive, and reproducible systems than the insects from which they originated. More recently, Aag-2, an Aedes aegypti cell lineage, began to be frequently used as a model for studies of mosquito immunity. Nevertheless, to our knowledge, no study has systematically characterized the responses of Aag-2 cell line against different kinds of pathogens and compared its response to those exhibited by whole mosquitoes. For this reason, in this study we characterized gene expression profiles of the Aag-2 cell line in response to different kinds of immune challenges, such as Gram negative and positive bacteria, fungi and viruses, comparing the obtained results with the ones already described in the literature for whole mosquitoes. Methods Aedes aegypti Aag-2 cells were exposed to different immune stimuli (gram-positive and gram negative heat inactivated bacteria, zymosan or Sindbis virus for 24 hours and the expression of selected marker genes from toll, IMD and Jak/STAT pathways was analyzed by qPCR. Also, cells were incubated with fluorescent latex beads for evaluation of its phagocytosis capacity. Results Aag-2 cells were stimulated with two concentrations of heat-killed Gram negative (Enterobacter cloacae or Gram positive (Micrococcus luteus bacteria, Zymosan or infected with Sindbis virus and the expression of key genes from the main immune related pathways, Toll, IMD and Jak/STAT, were investigated. Our results suggest that Toll and IMD pathways are activated in response to both Gram positive and negative bacteria and Zymosan in Aag-2 cells, displaying an immune profile similar to those described in the literature for whole

  17. A buccal cell model comet assay: Development and evaluation for human biomonitoring and nutritional studies

    International Nuclear Information System (INIS)

    The comet assay is a widely used biomonitoring tool for DNA damage. The most commonly used cells in human studies are lymphocytes. There is an urgent need to find an alternative target human cell that can be collected from normal subjects with minimal invasion. There are some reports of buccal cells, collected easily from the inside of the mouth, being used in studies of DNA damage and repair, and these were of interest. However, our preliminary studies following the published protocol showed that buccal cells sustained massive damage and disintegrated at the high pH [O. Ostling, K.J. Johanson. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem. Biophys. Res. Commun. 123 (1984) 291-298] used, but that at lower pH were extremely resistant to lysis, an essential step in the comet assay. Therefore, the aims of this study were to develop a protocol than enabled buccal cell lysis and DNA damage testing in the comet assay, and to use the model to evaluate the potential use of the buccal cell model in human biomonitoring and nutritional study. Specifically, we aimed to investigate intra- and inter-individual differences in buccal cell DNA damage (as strand breaks), the effect of in vitro exposure to both a standard oxidant challenge and antioxidant treatment, as well as in situ exposure to an antioxidant-rich beverage and supplementation-related effects using a carotenoid-rich food. Successful lysis was achieved using 0.25% trypsin for 30 min followed by proteinase K (1 mg/ml) treatment for 60 min. When this procedure was performed on cells pre-embedded in agarose on a microscope slide, followed by electrophoresis (in 0.01 M NaOH, 1 mM EDTA, pH 9.1, 18 min at 12 V), a satisfactory comet image was obtained, though inter-individual variation was quite wide. Pre-lysis exposure of cells to a standard oxidant challenge (induced by H2O2) increased DNA strand breaks in a dose related manner, and incubation of cells in Trolox

  18. Models of endometriosis and their utility in studying progression to ovarian clear cell carcinoma.

    Science.gov (United States)

    King, Claire M; Barbara, Cynthia; Prentice, Andrew; Brenton, James D; Charnock-Jones, D Stephen

    2016-01-01

    Endometriosis is a common benign gynaecological condition affecting at least 10% of women of childbearing age and is characterized by pain--frequently debilitating. Although the exact prevalence is unknown, the economic burden is substantial (∼$50 billion a year in the USA alone) and it is associated with considerable morbidity. The development of endometriosis is inextricably linked to the process of menstruation and thus the models that best recapitulate the human disease are in menstruating non-human primates. However, the use of these animals is ethically challenging and very expensive. A variety of models in laboratory animals have been developed and the most recent are based on generating menstrual-like endometrial tissue that can be transferred to a recipient animal. These models are genetically manipulable and facilitate precise mechanistic studies. In addition, these models can be used to study malignant transformation in epithelial ovarian carcinoma. Epidemiological and molecular evidence indicates that endometriosis is the most plausible precursor of both clear cell and endometrioid ovarian cancer (OCCA and OEA, respectively). While this progression is rare, understanding the underlying mechanisms of transformation may offer new strategies for prevention and therapy. Our ability to pursue this is highly dependent on improved animal models but the current transgenic models, which genetically modify the ovarian surface epithelium and oviduct, are poor models of ectopic endometrial tissue. In this review we describe the various models of endometriosis and discuss how they may be applicable to developing our mechanistic understanding of OCCA and OEA. PMID:26456077

  19. An analytical model and parametric study of electrical contact resistance in proton exchange membrane fuel cells

    Science.gov (United States)

    Wu, Zhiliang; Wang, Shuxin; Zhang, Lianhong; Hu, S. Jack

    This paper presents an analytical model of the electrical contact resistance between the carbon paper gas diffusion layers (GDLs) and the graphite bipolar plates (BPPs) in a proton exchange membrane (PEM) fuel cell. The model is developed based on the classical statistical contact theory for a PEM fuel cell, using the same probability distributions of the GDL structure and BPP surface profile as previously described in Wu et al. [Z. Wu, Y. Zhou, G. Lin, S. Wang, S.J. Hu, J. Power Sources 182 (2008) 265-269] and Zhou et al. [Y. Zhou, G. Lin, A.J. Shih, S.J. Hu, J. Power Sources 163 (2007) 777-783]. Results show that estimates of the contact resistance compare favorably with experimental data by Zhou et al. [Y. Zhou, G. Lin, A.J. Shih, S.J. Hu, J. Power Sources 163 (2007) 777-783]. Factors affecting the contact behavior are systematically studied using the analytical model, including the material properties of the two contact bodies and factors arising from the manufacturing processes. The transverse Young's modulus of chopped carbon fibers in the GDL and the surface profile of the BPP are found to be significant to the contact resistance. The factor study also sheds light on the manufacturing requirements of carbon fiber GDLs for a better contact performance in PEM fuel cells.

  20. An analytical model and parametric study of electrical contact resistance in proton exchange membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhiliang; Wang, Shuxin; Zhang, Lianhong [School of Mechanical Engineering, Tianjin University, Tianjin 300072 (China); Hu, S. Jack [Department of Mechanical Engineering, The University of Michigan, Ann Arbor, MI 48109-2125 (United States)

    2009-04-15

    This paper presents an analytical model of the electrical contact resistance between the carbon paper gas diffusion layers (GDLs) and the graphite bipolar plates (BPPs) in a proton exchange membrane (PEM) fuel cell. The model is developed based on the classical statistical contact theory for a PEM fuel cell, using the same probability distributions of the GDL structure and BPP surface profile as previously described in Wu et al. [Z. Wu, Y. Zhou, G. Lin, S. Wang, S.J. Hu, J. Power Sources 182 (2008) 265-269] and Zhou et al. [Y. Zhou, G. Lin, A.J. Shih, S.J. Hu, J. Power Sources 163 (2007) 777-783]. Results show that estimates of the contact resistance compare favorably with experimental data by Zhou et al. [Y. Zhou, G. Lin, A.J. Shih, S.J. Hu, J. Power Sources 163 (2007) 777-783]. Factors affecting the contact behavior are systematically studied using the analytical model, including the material properties of the two contact bodies and factors arising from the manufacturing processes. The transverse Young's modulus of chopped carbon fibers in the GDL and the surface profile of the BPP are found to be significant to the contact resistance. The factor study also sheds light on the manufacturing requirements of carbon fiber GDLs for a better contact performance in PEM fuel cells. (author)

  1. Study of pool-swell dynamics in a Mark II single-cell model. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Kiang, R.L.; Jeuck, P.R. III

    1980-03-01

    The dynamic response of a Mark II pressure-suppression system during the early air discharging phase of a postulated loss-of-coolant accident (LOCA) was studied via scale model experiments. Tests using a 13.3-scale single downcomer model yielded quantitative information on the vent-clearing process, the pool swell, the diaphragm floor differential pressure and many other dynamic responses of interest. Corresponding information for the reference plant from which the model is scaled can be obtained from the test results and the scaling laws which are given in the report. The single downcomer results were compared to multidowncomer results to determine the validity of single cell models. The comparison shows excellent agreement.

  2. Study of pool-swell dynamics in a Mark II single-cell model. Final report

    International Nuclear Information System (INIS)

    The dynamic response of a Mark II pressure-suppression system during the early air discharging phase of a postulated loss-of-coolant accident (LOCA) was studied via scale model experiments. Tests using a 13.3-scale single downcomer model yielded quantitative information on the vent-clearing process, the pool swell, the diaphragm floor differential pressure and many other dynamic responses of interest. Corresponding information for the reference plant from which the model is scaled can be obtained from the test results and the scaling laws which are given in the report. The single downcomer results were compared to multidowncomer results to determine the validity of single cell models. The comparison shows excellent agreement

  3. Intact brain cells: a novel model system for studying opioid receptor binding

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, N.F.; El-Fakahany, E.E.

    1985-07-29

    The use of a novel tissue preparation to study opioid receptor binding in viable, intact cells derived from whole brains of adult rats is presented. Mechanically dissociated and sieved cells, which were not homogenized at any stage of the experimental protocol, and iso-osmotic physiological buffer were used in these experiments. This system was adapted in order to avoid mechanical and chemical disruption of cell membranes, cytoskeletal ultrastructure or receptor topography by homogenization or by the use of nonphysiological buffers, and to mimic in vivo binding conditions as much as possible. Using (/sup 3/H)naloxone as the radioligand, the studies showed saturable and stereospecific high-affinity binding of this opioid antagonist in intact cells, which in turn showed consistently high viability. (/sup 3/H)Naloxone binding was also linear over a wide range of tissue concentrations. This technique provides a very promising model for future studies of the binding of opioids and of many other classes of drugs to brain tissue receptors in a more physiologically relevant system than those commonly used to date.

  4. Intact brain cells: a novel model system for studying opioid receptor binding

    International Nuclear Information System (INIS)

    The use of a novel tissue preparation to study opioid receptor binding in viable, intact cells derived from whole brains of adult rats is presented. Mechanically dissociated and sieved cells, which were not homogenized at any stage of the experimental protocol, and iso-osmotic physiological buffer were used in these experiments. This system was adapted in order to avoid mechanical and chemical disruption of cell membranes, cytoskeletal ultrastructure or receptor topography by homogenization or by the use of nonphysiological buffers, and to mimic in vivo binding conditions as much as possible. Using [3H]naloxone as the radioligand, the studies showed saturable and stereospecific high-affinity binding of this opioid antagonist in intact cells, which in turn showed consistently high viability. [3H]Naloxone binding was also linear over a wide range of tissue concentrations. This technique provides a very promising model for future studies of the binding of opioids and of many other classes of drugs to brain tissue receptors in a more physiologically relevant system than those commonly used to date

  5. Physiopathology of blood platelets: a model system for studies of cell-to-cell interaction. Progress report, November 1, 1979-October 31, 1980

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-01-01

    This report covers the studies on basic mechanisms of cellular interactions, utilizing platelets as a model system and, when possible, concentrating on the influence that environmental factors (nutritional, metabolic, cellular, immunologic and others) have on them. The four major sections include: platelet interaction with tumor cells; a model for the study of cell-to-cell interaction; interaction of platelets with vessel walls; and platelet interactions with immune proteins.

  6. Tungsten oxide in polymer electrolyte fuel cell electrodes-A thin-film model electrode study

    Energy Technology Data Exchange (ETDEWEB)

    Wickman, Bjoern, E-mail: bjorn.wickman@chalmers.s [Competence Centre for Catalysis, Department of Applied Physics, Chalmers University of Technology, SE-412 96 Goeteborg (Sweden); Wesselmark, Maria; Lagergren, Carina; Lindbergh, Goeran [Applied Electrochemistry, School of Chemical Science and Engineering, KTH, SE-100 44 Stockholm (Sweden)

    2011-10-30

    Highlights: > Platinum and tungsten oxide thin-film electrocatalysts. > Single cell fuel cell evaluation. > Hydrogen-tungsten bronze formation. > CO oxidation on platinum on tungsten oxide. - Abstract: Thin films of WO{sub x} and Pt on WO{sub x} were evaporated onto the microporous layer of a gas diffusion layer (GDL) and served as model electrodes in the polymer electrolyte fuel cell (PEFC) as well as in liquid electrolyte measurements. In order to study the effects of introducing WO{sub x} in PEFC electrodes, precise amounts of WO{sub x} (films ranging from 0 to 40 nm) with or without a top layer of Pt (3 nm) were prepared. The structure of the thin-film model electrodes was characterized by scanning electron microscopy and X-ray photoelectron spectroscopy prior to the electrochemical investigations. The electrodes were analyzed by cyclic voltammetry and the electrocatalytic activity for hydrogen oxidation reaction (HOR) and CO oxidation was examined. The impact of Nafion in the electrode structure was examined by comparing samples with and without Nafion solution sprayed onto the electrode. Fuel cell measurements showed an increased amount of hydrogen tungsten bronzes formed for increasing WO{sub x} thicknesses and that Pt affected the intercalation/deintercalation process, but not the total amount of bronzes. The oxidation of pre-adsorbed CO was shifted to lower potentials for WO{sub x} containing electrodes, suggesting that Pt-WO{sub x} is a more CO-tolerant catalyst than Pt. For the HOR, Pt on thicker films of WO{sub x} showed an increased limiting current, most likely originating from the increased electrochemically active surface area due to proton conductivity and hydrogen permeability in the WO{sub x} film. From measurements in liquid electrolyte it was seen that the system behaved very differently compared to the fuel cell measurements. This exemplifies the large differences between the liquid electrolyte and fuel cell systems. The thin-film model

  7. Model Membrane and Cell Studies of Antimicrobial Activity of Melittin Analogues.

    Science.gov (United States)

    Jamasbi, Elaheh; Mularski, Anna; Separovic, Frances

    2016-01-01

    Melittin is a 26 residue peptide and the major component of bee (Apis mellifera) venom. Although melittin has both anticancer and antimicrobial properties, utilization has been limited due to its high lytic activity against eukaryotic cells. The mechanism of this lytic activity remains unclear but several mechanisms have been proposed, including pore formation or a detergent like mechanism, which result in lysis of cell membranes. Several analogues of melittin have been synthesized to further understand the role of specific residues in its antimicrobial and lytic activity. Melittin analogues that have a proline residue substituted for an alanine, lysine or cysteine have been studied with both model membrane systems and living cells. These studies have revealed that the proline residue plays a critical role in antimicrobial activity and cytotoxicity. Analogues lacking the proline residue and dimers of these analogues displayed decreased cytotoxicity and minimum inhibition concentrations. Several mutant studies have shown that, when key substitutions are made, the resultant peptides have more activity in terms of pore formation than the native melittin. Designing analogues that retain antimicrobial and anticancer activity while minimizing haemolytic activity will be a promising way to utilize melittin as a potential therapeutic agent. PMID:26139117

  8. Human B-cell cancer cell lines as a preclinical model for studies of drug effect in diffuse large B-cell lymphoma and multiple myeloma.

    Science.gov (United States)

    Laursen, Maria Bach; Falgreen, Steffen; Bødker, Julie Støve; Schmitz, Alexander; Kjeldsen, Malene Krag; Sørensen, Suzette; Madsen, Jakob; El-Galaly, Tarec Christoffer; Bøgsted, Martin; Dybkær, Karen; Johnsen, Hans Erik

    2014-11-01

    Drug resistance in cancer refers to recurrent or primary refractory disease following drug therapy. At the cellular level, it is a consequence of molecular functions that ultimately enable the cell to resist cell death-one of the classical hallmarks of cancer. Thus, drug resistance is a fundamental aspect of the cancer cell phenotype, in parallel with sustained proliferation, immortality, angiogenesis, invasion, and metastasis. Here we present a preclinical model of human B-cell cancer cell lines used to identify genes involved in specific drug resistance. This process includes a standardized technical setup for specific drug screening, analysis of global gene expression, and the statistical considerations required to develop resistance gene signatures. The state of the art is illustrated by the first-step classical drug screen (including the CD20 antibody rituximab, the DNA intercalating topoisomerase II inhibitor doxorubicin, the mitotic inhibitor vincristine, and the alkylating agents cyclophosphamide and melphalan) along with the generation of gene lists predicting the chemotherapeutic outcome as validated retrospectively in clinical trial datasets. This B-cell lineage-specific preclinical model will allow us to initiate a range of laboratory studies, with focus on specific gene functions involved in molecular resistance mechanisms. PMID:25072621

  9. A bioengineered murine model using CD24+CD44+ pancreatic cancer stem cells for chemotherapy study

    International Nuclear Information System (INIS)

    In this work we first developed a murine pancreatic tumor model using CD24+CD44+ pancreatic cancer stem cells (CSC) supported by an electrospun scaffold. Unlike conventional models, the use of CSC and the scaffold, which were biologically and chemically defined, afforded scientists a reliable platform to evaluate novel chemotherapy regimens. CD24+CD44+ CSC successfully initiated tumorigenesis in vitro on the scaffold without suffering apoptosis, evidencing the lack of cytotoxicity of scaffolding materials. Also, the scaffold contributed to the acceleration of in vivo tumorigenesis and increased the likelihood of tumor formation. Using this model, we set out to explore the effectiveness of irinotecan/gemcitabine (IRIN-GEM), a chemotherapy regimen, for pancreatic cancer. Our study showed that IRIN-GEM induced a tumor regression whereas gemcitabine alone could only arrest the tumor growth. Further study suggested that the superior performance of IRIN-GEM could be attributed to its capacity to demolish the CD24+CD44+ CSC sub-population by inducing a large-scale apoptosis. The use of highly proliferative yet homogenous CD24+CD44+ CSC along with a chemically defined scaffold accelerated the tumor formation and significantly reduced the variability associated with conventional murine models. Armed with this new model, we discovered that IRIN-GEM would be a promising chemotherapy candidate for patients with advanced pancreatic cancer. (paper)

  10. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    OpenAIRE

    Eder Zucconi; Natassia Moreira Vieira; Carlos Roberto Bueno; Mariane Secco; Tatiana Jazedje; Marcos Costa Valadares; Miriam Fussae Suzuki; Paolo Bartolini; Mariz Vainzof; Mayana Zatz

    2011-01-01

    Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutati...

  11. Large animal induced pluripotent stem cells as pre-clinical models for studying human disease

    OpenAIRE

    Jordan R Plews; Gu, Mingxia; Longaker, Michael T.; Joseph C. Wu

    2012-01-01

    Abstract The derivation of human embryonic stem cells and subsequently human induced pluripotent stem cells (iPSCs) has energized regenerative medicine research and enabled seemingly limitless applications. Although small animal models, such as mouse models, have played an important role in the progression of the field, typically, they are poor representations of the human disease phenotype. As an alternative, large animal models should be explored as a potentially better approach for clinica...

  12. Laser Direct-Write Onto Live Tissues: A Novel Model for Studying Cancer Cell Migration.

    Science.gov (United States)

    Burks, Hope E; Phamduy, Theresa B; Azimi, Mohammad S; Saksena, Jayant; Burow, Matthew E; Collins-Burow, Bridgette M; Chrisey, Douglas B; Murfee, Walter L

    2016-11-01

    Investigation into the mechanisms driving cancer cell behavior and the subsequent development of novel targeted therapeutics requires comprehensive experimental models that mimic the complexity of the tumor microenvironment. Recently, our laboratories have combined a novel tissue culture model and laser direct-write, a form of bioprinting, to spatially position single or clustered cancer cells onto ex vivo microvascular networks containing blood vessels, lymphatic vessels, and interstitial cell populations. Herein, we highlight this new model as a tool for quantifying cancer cell motility and effects on angiogenesis and lymphangiogenesis in an intact network that matches the complexity of a real tissue. Application of our proposed methodology offers an innovative ex vivo tissue perspective for evaluating the effects of gene expression and targeted molecular therapies on cancer cell migration and invasion. J. Cell. Physiol. 231: 2333-2338, 2016. © 2016 Wiley Periodicals, Inc. PMID:26923437

  13. Construction of an allogenic chimeric mouse model for the study of the behaviors of donor stem cells in vivo

    Institute of Scientific and Technical Information of China (English)

    WANG Mo-lin; YAN Jing-bin; XIAO Yan-ping; HUANG Shu-zhen

    2005-01-01

    Background It is essential to establish an animal model for the elucidation of the biological behaviors of stem cells in vivo. We constructed a chimeric animal model by in utero transplantation for investigation of stem cell transplantation.Methods This chimerism was achieved by injecting the stem cells derived from the bone marrow of green fluorescence protein (GFP)-transgenic mice into fetal mice at 13.5 days of gestation. Several methods such as polymerase chain reaction (PCR), real-time PCR, fluorescence-assisted cell sorting (FACS) and fluorescence in situ hybridization (FISH) were used for the observation of donor cells.Results Under a fluorescence microscope, we observed the GFP cells of donor-origin in a recipient. PCR, FACS analysis and FISH indicated chimerism at various intervals. Real-time PCR indicated that some donor cells existed in chimera for more than 6 months.Conclusions Allogenic stem cells may exist in recipients for a long time and this allogenic animal model provides a useful tool for studying the behavior of hematopoietic stem cells and also offers an effective model system for the study of stem cells.

  14. Autologous Stem Cell Transplant Study in Lymphoma Patients: Statistical Analysis of Multi-State Models

    Czech Academy of Sciences Publication Activity Database

    Furstová, J.; Valenta, Zdeněk

    ISCB, 2012. s. 67-68. ISBN 978-82-8045-026-5. [Annual Conference of the International Society for Clinical Biostatistics /33./. 19.08.2012-23.08.2012, Bergen] Grant ostatní: ESF CZ.1.07/2.4.00/174.0117 Institutional support: RVO:67985807 Keywords : multi-state model * disability model * illness-death model * Markov model * autologous stem cell transplant Subject RIV: BB - Applied Statistics, Operational Research

  15. A Versatile Orthotopic Nude Mouse Model for Study of Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Joseph Chok Yan Ip

    2015-01-01

    Full Text Available Increasing evidence indicates tumor-stromal interactions play a crucial role in cancer. An in vivo esophageal squamous cell carcinoma (ESCC orthotopic animal model was developed with bioluminescence imaging established with a real-time monitoring platform for functional and signaling investigation of tumor-stromal interactions. The model was produced by injection of luciferase-labelled ESCC cells into the intraesophageal wall of nude mice. Histological examination indicates this orthotopic model is highly reproducible with 100% tumorigenesis among the four ESCC cell lines tested. This new model recapitulates many clinical and pathological properties of human ESCC, including esophageal luminal stricture by squamous cell carcinoma with nodular tumor growth, adventitia invasion, lymphovascular invasion, and perineural infiltration. It was tested using an AKT shRNA knockdown of ESCC cell lines and the in vivo tumor suppressive effects of AKT knockdown were observed. In conclusion, this ESCC orthotopic mouse model allows investigation of gene functions of cancer cells in a more natural tumor microenvironment and has advantages over previous established models. It provides a versatile platform with potential application for metastasis and therapeutic regimen testing.

  16. In CD4+ T-Cell-Induced Diabetes, Macrophages Are the Final Effector Cells that Mediate Islet β-Cell Killing : Studies from an Acute Model

    OpenAIRE

    Calderon, Boris; Suri, Anish; Unanue, Emil R.

    2006-01-01

    To understand better how diabetogenic CD4+ T cells induce islet β-cell death and cause diabetes, a transfer model of acute diabetes using the diabetogenic CD4+ BDC2.5 T-cell clone was established. Transfer of activated BDC T cells into NOD.scid mice resulted in diabetes within a week, characterized by strong inflammatory reaction. Electron micrographs of pancreas depicted macrophages in close contact with β cells that exhibited signs of apoptosis. Transfer into irradiated recipients inhibited...

  17. Study of beta-cell function (by HOMA model in metabolic syndrome

    Directory of Open Access Journals (Sweden)

    M K Garg

    2011-01-01

    Full Text Available Introduction: The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS, which strongly predict risk of diabetes and cardiovascular disease. Many studies implicate insulin resistance (IR in the development of diabetes, but ignore the contribution of beta-cell dysfunction. Hence, we studied beta-cell function, as assessed by HOMA model, in subjects with MS. Materials and Methods: We studied 50 subjects with MS diagnosed by IDF criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, biochemical, and insulin measurement. IR and secretion were calculated by HOMA model. Results: Subjects with MS had more IR (HOMA-IR than controls (3.35 ± 3.14 vs. 1.76 ± 0.53, P = 0.029 and secreted less insulin (HOMA-S than controls (66.80 ± 69.66 vs. 144.27 ± 101.61, P = 0.0003, although plasma insulin levels were comparable in both groups (10.7 ± 10.2 vs. 8.2 ± 2.38, P = 0.44. HOMA-IR and HOMA-S were related with number of metabolic abnormalities. HOMA-IR was positively associated with body mass index, waist hip ratio, body fat mass, and percent body fat. HOMA-S was negatively associated with waist hip ratio, fasting plasma glucose and total cholesterol and positively with basal metabolic rate. Percent body fat was an independent predictor of HOMA-IR and waist hip ratio of HOMA-S in multiple regression analysis. Conclusions: Subjects with MS have increased IR and decreased insulin secretion compared with healthy controls. Lifestyle measures have been shown to improve IR, insulin secretion, and various components and effects of MS. Hence, there is an urgent need for public health measures to prevent ongoing epidemic of diabetes and cardiovascular disease.

  18. Study of the selective effect on cells induced by nanosecond pulsed electric field with the resistor-capacitor circuit model

    Institute of Scientific and Technical Information of China (English)

    Xu Fei; Xiao Dengming; Li Zhaozhi

    2009-01-01

    A resistor-capacitor (RC) circuit model is proposed to study the effect of nanosecond pulsed electric field on cells according to the structure and electrical parameters of cells. After a nanosecond step field has been applied, the variation of voltages across cytomembrane and mitochondria membrane both in normal and in malignant cells are studied with this model. The time for selectively targeting the mitochondria membrane and malignant cell can be evaluated much easily with curves that show the variation of voltage across each membrane with time. Ramp field is the typical field applied in electrobiology. The voltages across each membrane induced by ramp field are analyzed with this model. To selectively target the mitochondria membrane, proper range of ramp slope is needed. It is relatively difficult to decide the range of a slope to selectively affect the malignant cell. Under some conditions, such a range even does not exist.

  19. Humanized mice as a model to study human hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tanner, Anne; Taylor, Stephen E; Decottignies, Wittnee; Berges, Bradford K

    2014-01-01

    Hematopoietic stem cell (HSC) transplantation has the potential to treat a variety of human diseases, including genetic deficiencies, immune disorders, and to restore immunity following cancer treatment. However, there are several obstacles that prevent effective HSC transplantation in humans. These include finding a matched donor, having a sufficient number of cells for the transplant, and the potency of the cells in the transplant. Ethical issues prevent effective research in humans that could provide insight into ways to overcome these obstacles. Highly immunodeficient mice can be transplanted with human HSCs and this process is accompanied by HSC homing to the murine bone marrow. This is followed by stem cell expansion, multilineage hematopoiesis, long-term engraftment, and functional human antibody and cellular immune responses. As such, humanized mice serve as a model for human HSC transplantation. A variety of conditions have been analyzed for their impact on HSC transplantation to produce humanized mice, including the type and source of cells used in the transplant, the number of cells transplanted, the expansion of cells with various protocols, and the route of introduction of cells into the mouse. In this review, we summarize what has been learned about HSC transplantation using humanized mice as a recipient model and we comment on how these models may be useful to future preclinical research to determine more effective ways to expand HSCs and to determine their repopulating potential in vivo. PMID:23962058

  20. A Human Espophageal Epithelial Cell Model for Study of Radiation Induced Cancer and DNA Damage Repair

    Science.gov (United States)

    Huff, Janice L.; Patel, Zarana S.; Hada, Megumi; Cucinotta, Francis A.

    2008-01-01

    For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma, a type of cancer found to have a significant enhancement in incidence in the survivors of the atomic bomb detonations in Japan. Here we present the results of our preliminary characterization of both normal and hTERT immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of - H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron).

  1. Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines.

    Science.gov (United States)

    Good, Michael F; Hawkes, Michael T; Yanow, Stephanie K

    2015-11-01

    Malaria vaccine development is hampered by the lack of small animal models that recapitulate human immune responses to Plasmodium falciparum. We review the burgeoning literature on humanized mice for P. falciparum infection, including challenges in engraftment of human immune cells, hepatocytes, and erythrocytes. Recent advances in immune-compromised mouse models and stem cell technology have already enabled proof of concept that the entire parasite life cycle can be sustained in a murine model and that adaptive human immune responses to several parasite stages can be measured. Nonetheless, optimization is needed to achieve a reproducible and relevant murine model for malaria vaccine development. This review is focused on the complexities of T cell development in a mouse humanized with both a lymphoid system and hepatocytes. An understanding of this will facilitate the use of humanized mice in the development of liver-stage vaccines. PMID:26458783

  2. Study on lipid droplet dynamics in live cells and fluidity changes in model bacterial membranes using optical microscopy techniques

    OpenAIRE

    Wong, Christine Shiang Yee

    2014-01-01

    In this thesis optical microscopy techniques are used to consider aspects of viral and bacterial infections. In part 1, the physical effects of cytomegalovirus on lipid droplet dynamics in live cells are studied; in part 2, the effects of an antimicrobial peptide on the fluidity of model bacterial membranes are studied. The optical microscopy techniques used to study the effects of murine-cytomegalovirus (mCMV) on lipid droplets in live NIH/3T3 fibroblast cells in real-time are...

  3. A human esophageal epithelial cell model for study of radiation induced cancer and DNA repair

    Science.gov (United States)

    Huff, Janice; Patel, Zarana; Hada, Megumi; Cucinotta, Francis A.

    For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma. Development of squamous cell carcinoma of the esophagus is associated with radiation exposure, as revealed by the significant enhanced in incidence rates for this type of cancer in the survivors of the atomic bomb detonations in Japan. It is also associated with poor nutritional status and micronutrient deficiencies, which are also important issues for long duration spaceflight. The possible synergies between nutritional issues and radiation exposure are unknown. Here we present the results of preliminary characterization of both normal and hTERT-immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of gamma-H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron.

  4. Study on Unit Cell Models and the Effective Thermal Conductivities of Silica Aerogel.

    Science.gov (United States)

    Liu, He; Li, Zeng-Yao; Zhao, Xin-Peng; Tao, Wen-Quan

    2015-04-01

    In this paper, two modified unit cell models, truncated octahedron and cubic array of intersecting square rods with 45-degree rotation, are developed in consideration of the tortuous path of heat conduction in solid skeleton of silica aerogel. The heat conduction is analyzed for each model and the expressions of effective thermal conductivity of the modified unit cell models are derived. Considering the random microstructure of silica aerogel, the probability model is presented. We also discuss the effect of the thermal conductivity of aerogel backbone. The effective thermal conductivities calculated by the proposed probability model are in good agreement with available experimental data when the density of the aerogel is 110 kg/m3. PMID:26353566

  5. Modeling and experimental studies to optimize the performance of a hydrogen - bromine fuel cell

    Science.gov (United States)

    Yarlagadda, Venkata Raviteja

    The regenerative Hydrogen-Bromine (H2-Br 2) fuel cells are considered to be one of the viable systems for large scale energy storage because of their high energy conversion efficiency, flexible operation, highly reversible reactions and low capital cost. The preliminary performance of a H2-Br2 fuel cell using both conventional as well as novel materials (Nafion and electrospun composite membranes along with platinum and rhodium sulfide electrocatalysts) was discussed. A maximum power density of 0.65 W/cm2 was obtained with a thicker Br 2 electrode (780 mum) and cell temperature of 45°C. The active area and wetting characteristics of Br2 electrodes were improved upon by either pre-treating with HBr or boiling them in de-ionized water. On the other hand, similar or better performances were obtained using dual fiber electrospun composite membranes (maximum power densities of 0.61 W/cm2 and 0.45 W/cm2 obtained with 25 mum and 65 mum electrospun membranes at 45°C) versus using Nafion membranes (maximum power densities of 0.52 W/cm 2 and 0.41 W/cm2 obtained with Nafion 212 and Nafion 115 membranes at 45°C). The rhodium sulfide (RhxSy) electrocatalyst proved to be more stable in the presence of HBr/Br2 than pure Pt. However, the H2 oxidation activity on RhxS y was quite low compared to that of Pt. In conclusion, a stable H 2 electrocatalyst that can match the hydrogen oxidation activity obtained with Pt and a membrane with low Br2/Br- permeability are essential to prolong the lifetime of a H2-Br2 fuel cell. A 1D mathematical model was developed to serve as a theoretical guiding tool for the experimental studies. The impact of convective and diffusive transport and kinetic rate on the performance of a H2-Br2 fuel cell is shown in this study. Of the two flow designs (flow-by and flow-through) incorporated in this study, the flow-through design demonstrated better performance, which can be attributed to the dominant convective transport inside the porous electrode. Both

  6. Ionic conductivity studies of solid oxide fuel cell electrolytes and theoretical modeling of an entire solid oxide fuel cell

    Science.gov (United States)

    Pornprasertsuk, Rojana

    Because of the steep increase in oil prices, the global warming effect and the drive for energy independence, alternative energy research has been encouraged worldwide. The sustainable fuels such as hydrogen, biofuel, natural gas, and solar energy have attracted the attention of researchers. To convert these fuels into a useful energy source, an energy conversion device is required. Fuel cells are one of the energy conversion devices which convert chemical potentials into electricity. Due to their high efficiency, the ease to scale from 1 W range to megawatts range, no recharging requirement and the lack of CO2 and NOx emission (if H2 and air/O 2 are used), fuel cells have become a potential candidate for both stationary power generators and portable applications. This thesis has been focused primarily on solid oxide fuel cell (SOFC) studies due to its high efficiency, varieties of fuel choices, and no water management problem. At the present, however, practical applications of SOFCs are limited by high operating temperatures that are needed to create the necessary oxide-ion vacancy mobility in the electrolyte and to create sufficient electrode reactivities. This thesis introduces several experimental and theoretical approaches to lower losses both in the electrolyte and the electrodes. Yttria stabilized zirconia (YSZ) is commonly used as a solid electrolyte for SOFCs due to its high oxygen-ion conductivity. To improve the ionic conductivity for low temperature applications, an approach that involves dilating the structure by irradiation and introducing edge dislocations into the electrolyte was studied. Secondly, to understand the activation loss in SOFC, the kinetic Monte Carlo (KMC) technique was implemented to model the SOFC operation to determining the rate-limiting step due to the electrodes on different sizes of Pt catalysts. The isotope exchange depth profiling technique was employed to investigate the irradiation effect on the ionic transport in different

  7. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity

    Directory of Open Access Journals (Sweden)

    Wu J

    2015-04-01

    Full Text Available Jinzi Wu, Liang-Jun Yan Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA Abstract: Chronic hyperglycemia and the corresponding glucotoxicity are the main pathogenic mechanisms of diabetes and its complications. Streptozotocin (STZ-induced diabetic animal models are useful platforms for the understanding of β cell glucotoxicity in diabetes. As diabetes induced by a single STZ injection is often referred to as type 1 diabetes that is caused by STZ’s partial destruction of pancreas, one question often being asked is whether the STZ type 1 diabetes animal model is a good model for studying the mitochondrial mechanisms of β cell glucotoxicity. In this mini review, we provide evidence garnered from the literature that the STZ type 1 diabetes is indeed a suitable model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity. Evidence presented includes: 1 continued β cell derangement is due to chronic hyperglycemia after STZ is completely eliminated out of the body; 2 STZ diabetes can be reversed by insulin treatment, which indicates that β cell responds to treatment and shows ability to regenerate; and 3 STZ diabetes can be ameliorated or alleviated by administration of phytochemicals. In addition, mechanisms of STZ action and fundamental gaps in understanding mitochondrial mechanisms of β cell dysfunction are also discussed. Keywords: diabetes, β cell, glucotoxicity, mitochondria, redox imbalance, streptozotocin

  8. Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

    Institute of Scientific and Technical Information of China (English)

    Claudia Gundacker; Helmut Dolznig; Mario Mikula; Margit Rosner; Oliver Brandau; Markus Hengstschl(a)ger

    2012-01-01

    Male infertility is a major public health issue predominantly caused by defects in germ cell development.In the past,studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo.Compared with model organisms including mice,there are fundamental differences in the molecular processes of human germ cell development.Therefore,an in vitro model mimicking human sperm formation would be an extremely valuable research tool.In the recent past,both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes.We here discuss the pessibility to use human amniotic fluid stem (AFS) cells as a biological model.Since their discovery in 2003,AFS cells have been characterized to differentiate into cells of all three germ layers,to be genomically stable,to have a high proliferative potential and to be non-tumourigenic.In addition,AFS cells are not subject of ethical concerns.In contrast to iPS cells,AFSs cells do not need ectopic induction of pluripotency,which is often associated with only imperfectly cleared epigenetic memory of the source cells.Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency,they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.

  9. Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies

    Czech Academy of Sciences Publication Activity Database

    Doležalová, D.; Hruška-Plocháň, M.; Bjarkam, C. R.; Sorensen, J. C. H.; Cunningham, M.; Weingarten, D.; Ciacci, J. D.; Juhás, Štefan; Juhásová, Jana; Motlík, Jan; Hefferan, M. P.; Hazel, T.; Johe, K.; Carromeu, C.; Muotri, A.; Bui, J. D.; Strnádel, J.; Marsala, M.

    2014-01-01

    Roč. 522, č. 12 (2014), s. 2784-2801. ISSN 0021-9967 R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : pig * neurodegenerative models * stem cells Subject RIV: FH - Neurology Impact factor: 3.225, year: 2014

  10. Modulation of monocytic leukemia cell function and survival by highgradient magnetic fields and mathematical modeling studies

    Czech Academy of Sciences Publication Activity Database

    Zablotskyy, Vitaliy A.; Syrovets, T.; Schmidt, Z.W.; Dejneka, Alexandr; Simmet, T.

    2014-01-01

    Roč. 35, č. 10 (2014), s. 3164-3171. ISSN 0142-9612 Grant ostatní: AV ČR(CZ) M100101219 Institutional support: RVO:68378271 Keywords : magnetic field * cell proliferation * leukemia * apoptosis * modeling Subject RIV: BO - Biophysics Impact factor: 8.557, year: 2014

  11. A murine model for study of anticryptococcal activity mediated by cytotoxic immune cells: Role in immunization and human vaccine strategies

    Directory of Open Access Journals (Sweden)

    Arsić-Arsenijević Valentina

    2011-01-01

    Full Text Available NK and T cells play a pivotal role in host defense to Cryptococcus neoformans (C. neoformans fungus which affects especially hosts with impaired cell mediated immunity. The vaccine against cryptococcosus is not developed yet, thus we established an animal BALB/c mice model to analyze anticryprococcal activity of immune cells. We detected that non-stimulated spleen mononuclear cells (MNC from non-immunized mice have the capacity to exhibit anticriptococcal activity on the incapsulated C. neoformans strain (ATCC 34873 and this activity can be enhanced by non-adherent cells (NAC. In order to obtained antigen-specific anticryprococcal activity, MNC and NAC were stimulated in vitro with corpuscular (Ag1 or soluble (Ag2 C. neoformans antigen prepared from the acapsular strain Cap67 (ATCC 52817. In vitro stimulation of immune cells with both C. neoformans antigens enhanced the anticryptococcal activity of MNC and NAC. NAC fraction expressed the highest anticryptococcal activity, also in the presence and in the absence of accessory cells (AC. The highest anticryptococcal activity of effector cells was detected after immunization of mice with the same C. neoformans antigens and after additional stimulation of immune cells in vitro with the some antigens. These data demonstrated that growth inhibition of C. neoformans mediated by mice effector cells can be enhanced with corpuscular, as well as soluble antigens. Thus designin an animal model which is simple and reproducible and can be used for further studies and development of immunization strategies against human cryptococcosis.

  12. Development of Hematopoietic and Endothelial Cells from Human Embryonic Stem Cells: Lessons from the Studies using Mouse as a Model

    OpenAIRE

    Anna Jezierski; Albert Swedani; Lisheng Wang

    2007-01-01

    The current progress using the human embryonic stem cell (hESC) model system has provided much insight into the early origins of the hematopoietic and endothelial lineages, particularly the elusive hemangioblast. Recently, the cellular hierarchy and molecular regulation controlling hematopoietic commitment have been further elucidated. These findings not only provide new insights into early human development, but also advance the knowledge required to develop techniques capable of generating ...

  13. Human ovarian tumor cell interactions with extracellular matrix: development of a model to study tumor cell invasion

    International Nuclear Information System (INIS)

    In order to investigate the mechanisms involved in ovarian carcinoma cell implantation and the associated tumor cell-host interactions, a model system was developed employing a mesothelial cell line grown on bovine corneal endothelial cell extracellular matrix (ECM), in an attempt to reconstruct the mesothelium in vitro. Morphologic alterations of the reconstructed mesothelium induced by OCC were observed using immunohistochemical staining, light and electron microscopy. A relationship was observed between extracellular β-N-acetylhexosaminidase activity and (1) the ability of OCC to morphologically degrade ECM; (2) the capacity of OCC to degrade [3H]-glucosamine radiolabelled ECM. The rate of accumulation of extracellular hexosaminidase in cell free-conditioned medium was progressive and closely paralleled the rate of OCC mediated release of [3H]-glucosamine from ECM. Purified hexosaminidase (placental and/or OCC) was observed to directly hydrolzye [3H]-glucosamine radiolabelled structurally intact ECM (up to 70% radiolabel) and resulted in the cumulative release of free [3H]-N-acetylglucosamine

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

    Directory of Open Access Journals (Sweden)

    Nathalie Boone

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

  15. New animal model to study epigenetic mechanisms mediating altered gravity effects upon cell growth and morphogenesis

    Science.gov (United States)

    Grigoryan, Eleonora N.; Dvorochkin, Natasha; Radugina, Elena A.; Poplinskaya, Valentina; Novikova, Julia; Almeida, Eduardo

    The gravitational field and its variations act as a major environmental factor that can impact morphogenesis developing through epigenetic molecular mechanisms. The mechanisms can be thoroughly investigated by using adequate animal models that reveal changes in the morpho-genesis of a growing organ as a function of gravitational effects. Two cooperative US/Russian experiments on Foton-M2 (2005) and Foton-M3 (2007) were the first to demonstrate differences in the shape of regenerating tails of space-flown and ground control newts. The space-flown and aquarium (simulated microgravity) animals developed lancet-shaped tails whereas 1 g con-trols (kept in space-type habitats) showed hook-like regenerates. These visual observations were supported by computer-aided processing of the images and statistical analysis of the results. Morphological examinations and cell proliferation measurements using BrdU demon-strated dorsal-ventral asymmetry as well as enhanced epithelial growth on the dorsal area of regenerating tails in 1 g newts. These findings were reproduced in laboratory tests on newts kept at 1 g and in large water tanks at cut g. The 1 g animals showed statistically significant deviations of the lancet-like tail shape typically seen in aquarium animals. Such modifications were found as early as regeneration stages III-IV and proved irreversible. The authors believe that the above phenomenon detected in newts used in many space experiments can serve as an adequate model for studying molecular mechanisms underlying gravitational effects upon animal morphogenesis.

  16. Development of a novel, physiologically relevant cytotoxicity model: Application to the study of chemotherapeutic damage to mesenchymal stromal cells

    International Nuclear Information System (INIS)

    There is an increasing need for development of physiologically relevant in-vitro models for testing toxicity, however determining toxic effects of agents which undergo extensive hepatic metabolism can be particularly challenging. If a source of such metabolic enzymes is inadequate within a model system, toxicity from prodrugs may be grossly underestimated. Conversely, the vast majority of agents are detoxified by the liver, consequently toxicity from such agents may be overestimated. In this study we describe the development of a novel in-vitro model, which could be adapted for any toxicology setting. The model utilises HepG2 liver spheroids as a source of metabolic enzymes, which have been shown to more closely resemble human liver than traditional monolayer cultures. A co-culture model has been developed enabling the effect of any metabolised agent on another cell type to be assessed. This has been optimised to enable the study of damaging effects of chemotherapy on mesenchymal stem cells (MSC), the supportive stem cells of the bone marrow. Several optimisation steps were undertaken, including determining optimal culture conditions, confirmation of hepatic P450 enzyme activity and ensuring physiologically relevant doses of chemotherapeutic agents were appropriate for use within the model. The developed model was subsequently validated using several chemotherapeutic agents, both prodrugs and active drugs, with resulting MSC damage closely resembling effects seen in patients following chemotherapy. Minimal modifications would enable this novel co-culture model to be utilised as a general toxicity model, contributing to the drive to reduce animal safety testing and enabling physiologically relevant in-vitro study. -- Highlights: ► An in vitro model was developed for study of drugs requiring hepatic metabolism ► HepG2 spheroids were utilised as a physiologically relevant source of liver enzymes ► The model was optimised to enable study of chemotherapeutic

  17. Development of a novel, physiologically relevant cytotoxicity model: Application to the study of chemotherapeutic damage to mesenchymal stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    May, Jennifer E., E-mail: Jennifer2.May@uwe.ac.uk; Morse, H. Ruth, E-mail: Ruth.Morse@uwe.ac.uk; Xu, Jinsheng, E-mail: Jinsheng.Xu@uwe.ac.uk; Donaldson, Craig, E-mail: Craig.Donaldson@uwe.ac.uk

    2012-09-15

    There is an increasing need for development of physiologically relevant in-vitro models for testing toxicity, however determining toxic effects of agents which undergo extensive hepatic metabolism can be particularly challenging. If a source of such metabolic enzymes is inadequate within a model system, toxicity from prodrugs may be grossly underestimated. Conversely, the vast majority of agents are detoxified by the liver, consequently toxicity from such agents may be overestimated. In this study we describe the development of a novel in-vitro model, which could be adapted for any toxicology setting. The model utilises HepG2 liver spheroids as a source of metabolic enzymes, which have been shown to more closely resemble human liver than traditional monolayer cultures. A co-culture model has been developed enabling the effect of any metabolised agent on another cell type to be assessed. This has been optimised to enable the study of damaging effects of chemotherapy on mesenchymal stem cells (MSC), the supportive stem cells of the bone marrow. Several optimisation steps were undertaken, including determining optimal culture conditions, confirmation of hepatic P450 enzyme activity and ensuring physiologically relevant doses of chemotherapeutic agents were appropriate for use within the model. The developed model was subsequently validated using several chemotherapeutic agents, both prodrugs and active drugs, with resulting MSC damage closely resembling effects seen in patients following chemotherapy. Minimal modifications would enable this novel co-culture model to be utilised as a general toxicity model, contributing to the drive to reduce animal safety testing and enabling physiologically relevant in-vitro study. -- Highlights: ► An in vitro model was developed for study of drugs requiring hepatic metabolism ► HepG2 spheroids were utilised as a physiologically relevant source of liver enzymes ► The model was optimised to enable study of chemotherapeutic

  18. Modeling, simulation, and concept studies of a fuel cell hybrid electric vehicle powertrain

    Energy Technology Data Exchange (ETDEWEB)

    Oezbek, Markus

    2010-03-29

    This thesis focuses on the development of a fuel cell-based hybrid electric powertrain for smaller (2 kW) hybrid electric vehicles (HEVs). A Hardware-in-the-Loop test rig is designed and built with the possibility to simulate any load profile for HEVs in a realistic environment, whereby the environment is modeled. Detailed simulation models of the test rig are developed and validated to real physical components and control algorithms are designed for the DC/DC-converters and the fuel cell system. A state-feedback controller is developed for the DC/DC-converters where the state-space averaging method is used for the development. For the fuel cells, a gain-scheduling controller based on state feedback is developed and compared to two conventional methods. The design process of an HEV with regard to a given load profile is introduced with comparison between SuperCaps and batteries. The HEV is also evaluated with an introduction to different power management concepts with regard to fuel consumption, dynamics, and fuel cell deterioration rate. The power management methods are implemented in the test rig and compared. (orig.)

  19. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis.

    Science.gov (United States)

    Park, Youn-Hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG→TCG) at codon 47 and the codon 72 polymorphism (CGC→CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. PMID:26091798

  20. Parametric and optimization study of a PEM fuel cell performance using three-dimensional computational fluid dynamics model

    Energy Technology Data Exchange (ETDEWEB)

    Sadiq Al-Baghdadi, Maher A.R.; Shahad Al-Janabi, Haroun A.K. [Department of Mechanical Engineering, International Technological University, 289 Cricklewood Broadway, London NW2 6NX (United Kingdom)

    2007-06-15

    A full three-dimensional, non-isothermal computational fluid dynamics model of a proton exchange membrane (PEM) fuel cell with straight flow field channels has been developed. This comprehensive model accounts for the major transport phenomena in a PEM fuel cell: convective and diffusive heat and mass transfer, electrode kinetics, and potential fields. The new feature of the algorithm developed in this work is its capability for accurate calculation of the local activation overpotentials, which in turn results in improved prediction of the local current density distribution. The model is shown to be able to understand the many interacting, complex electrochemical, and transport phenomena that cannot be studied experimentally. This model is used to study the effects of several operating, design, and material parameters on fuel cell performance. Detailed analyses of the fuel cell performance under various operating conditions have been conducted and examined. The analysis helped identifying critical parameters and shed insight into the physical mechanisms leading to a fuel cell performance under various operating conditions. (author)

  1. Hierarchical Bayesian mixture modelling for antigen-specific T-cell subtyping in combinatorially encoded flow cytometry studies

    DEFF Research Database (Denmark)

    Lin, Lin; Chan, Cliburn; Hadrup, Sine R;

    2013-01-01

    Novel uses of automated flow cytometry technology for measuring levels of protein markers on thousands to millions of cells are promoting increasing need for relevant, customized Bayesian mixture modelling approaches in many areas of biomedical research and application. In studies of immune profi...

  2. A brain slice culture model for studies of endogenous and exogenous precursor cell migration in the rostral migratory stream

    DEFF Research Database (Denmark)

    Tanvig, Mette; Blaabjerg, Morten; Andersen, Rikke K;

    2009-01-01

    The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone (SVZ) cells reach the olfactory bulb (OB) in rodents. This migration has been well studied in vivo, but an organotypic in vitro model would facilitate more experimental investigations. Here we introduce...

  3. Stochastic models of cell motility

    DEFF Research Database (Denmark)

    Gradinaru, Cristian

    2012-01-01

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

  4. [Elaboration of the in vitro model system to study the interaction of phytopathogenic mollicutes with plant cells].

    Science.gov (United States)

    Korobkova, K S; Onyshchenko, A M; Panchenko, L P; Mamchur, O Ie; Dmytruk, O O; Red'ko, V I

    2009-01-01

    The model system based on the sugar beet calluses infected by mycoplasms (mollicutes) was elaborated, and changes in the callus cells morphology under the effect of these microorganisms were also studied. The calluses of sugar beet 3K51 cultivated on the Gamborg medium were infected by phytopathogenic mollicute Acholaplasma laidlawii var. granulum str.118. Under the effect of mollicute infection one could observe changes in the cell morphology of sugar beet calluses: the plant cells were transformed from round to lengthened, the intensity of polyploids forming was increased, their grouping and their total destruction were observed. Data of electron microscopy confirm the presence of the mollicute in the sugar beet calluses: acholeplasma cells were localized between and within undifferentiated plant cells. PMID:19938618

  5. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    International Nuclear Information System (INIS)

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  6. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  7. Mathematical Model for Photovoltaic Cells

    OpenAIRE

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

    2013-01-01

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

  8. Modeling and cellular studies

    International Nuclear Information System (INIS)

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

  9. Use of intact rat brain cells as a model to study regulation of muscarinic acetylcholine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J.H.; El-Fakahany, E.E.

    1985-08-12

    Intact rat brain cells were dissociated and used to study the regulation of muscarinic acetylcholine receptors upon exposure to muscarinic receptor agonists. Incubation of cells with carbamylcholine resulted in a time-dependent decrease in subsequent (/sup 3/H)N-methylscopolamine specific binding, an effect which reached a steady state after 3 hr at 37/sup 0/C. This effect of carbamylcholine was dependent on the concentration of the agonist in the incubation medium and was due to a reduction in the maximal binding capacity of the receptor with no decrease in the affinity of the remaining receptors. This preparation might be useful in future studies to elucidate the mechanisms underlying the regulation of muscarinic acetylcholine receptors in the central nervous system. 20 references, 3 tables.

  10. Nanofibers Support Oligodendrocyte Precursor Cell Growth and Function as a Neuron-Free Model for Myelination Study

    OpenAIRE

    Li, Yongchao; CEYLAN, Muhammet; Shrestha, Bikesh; Wang, Haibo; Lu, Q. Richard; Asmatulu, Ramazan; Yao, Li

    2013-01-01

    Nanofiber-based scaffolds may simultaneously provide immediate contact guidance for neural regeneration and act as a vehicle for therapeutic cell delivery to enhance axonal myelination. Additionally, nanofibers can serve as a neuron-free model to study myelination of oligodendrocytes. In this study, we fabricated nanofibers using a polycaprolactone and gelatin co-polymer. The ratio of the gelatin component in the fibers was confirmed by energy dispersive x-ray spectroscopy. The addition of ge...

  11. A Multilayered Cell Culture Model for Transport Study in Solid Tumors: Evaluation of Tissue Penetration of Polyethyleneimine Based Cationic Micelles

    OpenAIRE

    Miura, Seiji; Suzuki, Hidenori; Bae, You Han

    2014-01-01

    Limited drug distribution is partially responsible for the efficacy gap between preclinical and clinical studies of nano-sized drug carriers for cancer therapy. In this study, we examined the transport behavior of cationic micelles formed from a triblock copolymer of poly(D,L-lactide-co-glycolide)-block-branched polyethyleneimine-block-poly(D,L-lactide-co-glycolide) using a unique in vitro tumor model composed of a multilayered cell culture (MCC) and an Ussing chamber system. The Cy3-labeled ...

  12. Bi facial silicon solar cell study in modelling in frequency dynamic regime under multispectral illumination: Recombination parameters determination methods

    International Nuclear Information System (INIS)

    A bibliographic study on the techniques of characterization of silicon solar cell, diodes, massifs and silicon wafer are presented. The influence of the modulation frequency and recombination in volume and in surface phenomena of on the profiles of carriers' densities, photocurrent and photovoltage has been put in evidence. The study of surface recombination velocities permitted to show that the bi facial silicon solar cell of Back Surface Field type behaves like an ohmic contacts solar cell for modulation frequencies above 40 khz. pplicability in frequency dynamic regime in the frequency range [0 - 40 khz] of three techniques of steady state recombination parameters determination is shown. A technique of diffusion length determination, in the range of (200 Hz - 40 khz] is proposed. It rests on the measurement of the short circuit current phase that is compared with the theoretical curve of short circuit current phase. The intersection of the experimental short circuit current phase and the theoretical curve of short circuit current phase permits to get the minority carriers effective diffusion length. An equivalent electric model of a solar cell in frequency dynamic regime is proposed. A study in modelling of the bi facial solar cell shunt resistance and space charge zone capacity is led from a determination method of these parameters proposed in steady state. (Author

  13. Comparative SAXS and DSC study on stratum corneum structural organization in an epidermal cell culture model (ROC)

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Herre, Angela; Fahr, Alfred;

    2013-01-01

    SC barrier properties and high structural and organizational similarity to that of native human SC, ROC presents a promising alternative for in vitro studies, particularly as it can be obtained under overall rather straightforward cell culture conditions and thus low assay costs.......Cell cultured skin equivalents present an alternative for dermatological in vitro evaluations of drugs and excipients as they provide the advantage of availability, lower variability and higher assay robustness compared to native skin. For penetration/permeation studies, an adequate stratum corneum...... barrier similar to that of human stratum corneum is, however, a prerequisite. In this study, the stratum corneum lipid organization in an epidermal cell culture model based on rat epidermal keratinocytes (REK organotypic culture, ROC) was investigated by small-angle X-ray scattering (SAXS) in dependence...

  14. Fuel Cell Power Model Version 2: Startup Guide, System Designs, and Case Studies. Modeling Electricity, Heat, and Hydrogen Generation from Fuel Cell-Based Distributed Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    Steward, D.; Penev, M.; Saur, G.; Becker, W.; Zuboy, J.

    2013-06-01

    This guide helps users get started with the U.S. Department of Energy/National Renewable Energy Laboratory Fuel Cell Power (FCPower) Model Version 2, which is a Microsoft Excel workbook that analyzes the technical and economic aspects of high-temperature fuel cell-based distributed energy systems with the aim of providing consistent, transparent, comparable results. This type of energy system would provide onsite-generated heat and electricity to large end users such as hospitals and office complexes. The hydrogen produced could be used for fueling vehicles or stored for later conversion to electricity.

  15. Histopathological and Behavioral Assessment of Toxin-Produced Cerebellar Lesion: A Potent Model for Cell Transplantation Studies in The Cerebellum

    Directory of Open Access Journals (Sweden)

    Mohammad Amin Edalatmanesh

    2014-04-01

    Full Text Available cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities. Materials and Methods: In this experimental study, slow administration of quinolinic acid (QA, 5 μl of 200 μmol, 1 μl/minute in the right cerebellar hemisphere (lobule VI caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student’s t test. Results: The QA treated group showed marked motor learning deficits on the rotating rod test (p≤0.0001, locomotor asymmetry on the cylinder test (p≤0.0001, dysmetria on the beam balance test (p≤0.0001, abnormalities in neuromuscular strength on the hang wire test (p≤0.0001, spatial memory deficits in the Morris water maze (MWM, p≤0.001 and fear conditioned memory on the passive avoidance test (p≤0.01 over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p≤0.001 and granular cell density (p≤0.0001 in the lesioned hemisphere of the cerebellum. Conclusion: Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies.

  16. Comparative study on the therapeutic potential of neurally differentiated stem cells in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Natalie L Payne

    Full Text Available BACKGROUND: Transplantation of neural stem cells (NSCs is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS. NSCs can be derived from primary central nervous system (CNS tissue or obtained by neural differentiation of embryonic stem (ES cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using a mouse model of MS, we evaluated the therapeutic potential of NSCs derived from ES cells by two different neural differentiation protocols that utilized adherent culture conditions and compared their effect to primary NSCs derived from the subventricular zone (SVZ. METHODOLOGY/PRINCIPAL FINDINGS: The proliferation and secretion of pro-inflammatory cytokines by antigen-stimulated splenocytes was reduced in the presence of SVZ-NSCs, while ES cell-derived NSCs exerted differential immunosuppressive effects. Surprisingly, intravenously injected NSCs displayed no significant therapeutic impact on clinical and pathological disease outcomes in mice with experimental autoimmune encephalomyelitis (EAE induced by recombinant myelin oligodendrocyte glycoprotein, independent of the cell source. Studies tracking the biodistribution of transplanted ES cell-derived NSCs revealed that these cells were unable to traffic to the CNS or peripheral lymphoid tissues, consistent with the lack of cell surface homing molecules. Attenuation of peripheral immune responses could only be achieved through multiple high doses of NSCs administered intraperitoneally, which led to some neuroprotective effects within the CNS. CONCLUSION/SIGNIFICANCE: Systemic transplantation of these NSCs does not have a major influence on the clinical course of rMOG-induced EAE. Improving the efficiency at which NSCs home to inflammatory sites may enhance their therapeutic potential in this model of CNS autoimmunity.

  17. Chorioallantoic Membrane Microtumor Model to Study the Mechanisms of Tumor Angiogenesis, Vascular Permeability, and Tumor Cell Intravasation.

    Science.gov (United States)

    Deryugina, Elena I

    2016-01-01

    The mechanisms governing the development of angiogenic blood vessels, which not only deliver the nutrients to growing tumors but also provide the conduits for tumor cell dissemination, are still not fully resolved. The model systems based on the grafting of human tumor cells onto the chorioallantoic membrane (CAM) of the chick embryo offer several advantages to study complex processes underlying tumor angiogenesis and tumor cell dissemination. In particular, the CAM model described here allows for investigation of multiple microtumors as independent entities, thereby greatly facilitating quantification and statistical analyses of tumor neovascularization and cancer spreading. This CAM microtumor system was designed specifically to measure the level of tumor cell intravasation in combination with quantitative analyses of the microarchitecture and permeability of the intratumoral angiogenic blood vessels. By using this newly established microtumor model we have demonstrated the functional involvement of tumor matrix metalloproteinase-1 (MMP-1) and epidermal growth factor receptor (EGFR) in regulating the development of a distinct angiogenic vasculature capable of sustaining tumor cell intravasation and metastasis. PMID:27172961

  18. The Potential Health Benefits of Polyphenol-Rich Extracts from Cichorium intybus L. Studied on Caco-2 Cells Model.

    Science.gov (United States)

    Azzini, Elena; Maiani, Giuseppe; Garaguso, Ivana; Polito, Angela; Foddai, Maria S; Venneria, Eugenia; Durazzo, Alessandra; Intorre, Federica; Palomba, Lara; Rauseo, Maria L; Lombardi-Boccia, Ginevra; Nobili, Fabio

    2016-01-01

    Phytochemicals can exert their bioactivity without reaching the systemic circulation; scarcely absorbed antioxidants might reach the large bowel contributing to protection from oxidative damage-induced gastrointestinal diseases. In the present work, we aimed to study the relationship between potential activity of polyphenol-rich extracts from Cichorium intybus L. and changes in morphological characteristics on Caco-2 cells. Phytochemicals content (carotenoids and flavonoids) and total antioxidant activity of Red Chicory of Treviso and Variegated Chicory of Castelfranco were evaluated. The bioactivity of polyphenol-rich extracts from chicories was studied in in vitro Caco-2 cell monolayers model. Morphological characteristics changes to test the antioxidant and/or prooxidant effect were verified by histological analysis and observed by Electronic Scansion Microscopy (SEM). On Caco-2 cell model, the polyphenols fractions from chicories have indicated a moderate antioxidant behavior until 17 μM concentration, while 70 μM and 34 μM exert cytotoxic effects for Treviso's and Castelfranco's Chicory, respectively, highlighted by TEER decreasing, increased permeability, and alteration of epithelium. Our findings support the beneficial effects of these products in counteracting the oxidative stress and cellular damage, induced in vitro on Caco-2 cell model, through interaction with the mucopolysaccharide complexes in the glycocalyx, maintaining in vivo a healthy and effective intestinal barrier. PMID:26843906

  19. The Potential Health Benefits of Polyphenol-Rich Extracts from Cichorium intybus L. Studied on Caco-2 Cells Model

    Directory of Open Access Journals (Sweden)

    Elena Azzini

    2016-01-01

    Full Text Available Phytochemicals can exert their bioactivity without reaching the systemic circulation; scarcely absorbed antioxidants might reach the large bowel contributing to protection from oxidative damage-induced gastrointestinal diseases. In the present work, we aimed to study the relationship between potential activity of polyphenol-rich extracts from Cichorium intybus L. and changes in morphological characteristics on Caco-2 cells. Phytochemicals content (carotenoids and flavonoids and total antioxidant activity of Red Chicory of Treviso and Variegated Chicory of Castelfranco were evaluated. The bioactivity of polyphenol-rich extracts from chicories was studied in in vitro Caco-2 cell monolayers model. Morphological characteristics changes to test the antioxidant and/or prooxidant effect were verified by histological analysis and observed by Electronic Scansion Microscopy (SEM. On Caco-2 cell model, the polyphenols fractions from chicories have indicated a moderate antioxidant behavior until 17 μM concentration, while 70 μM and 34 μM exert cytotoxic effects for Treviso’s and Castelfranco’s Chicory, respectively, highlighted by TEER decreasing, increased permeability, and alteration of epithelium. Our findings support the beneficial effects of these products in counteracting the oxidative stress and cellular damage, induced in vitro on Caco-2 cell model, through interaction with the mucopolysaccharide complexes in the glycocalyx, maintaining in vivo a healthy and effective intestinal barrier.

  20. Caenorhabditis elegans as a model system for studying non-cell-autonomous mechanisms in protein-misfolding diseases

    Directory of Open Access Journals (Sweden)

    Carmen I. Nussbaum-Krammer

    2014-01-01

    Full Text Available Caenorhabditis elegans has a number of distinct advantages that are useful for understanding the basis for cellular and organismal dysfunction underlying age-associated diseases of protein misfolding. Although protein aggregation, a key feature of human neurodegenerative diseases, has been typically explored in vivo at the single-cell level using cells in culture, there is now increasing evidence that proteotoxicity has a non-cell-autonomous component and is communicated between cells and tissues in a multicellular organism. These discoveries have opened up new avenues for the use of C. elegans as an ideal animal model system to study non-cell-autonomous proteotoxicity, prion-like propagation of aggregation-prone proteins, and the organismal regulation of stress responses and proteostasis. This Review focuses on recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism. These findings emphasize the potential of C. elegans to provide insights into non-cell-autonomous proteotoxic mechanisms underlying age-related protein-misfolding diseases.

  1. A novel cell model to study the function of the adrenoleukodystrophy-related protein

    International Nuclear Information System (INIS)

    X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder due to mutations in the ABCD1 (ALD) gene. ALDRP, the closest homolog of ALDP, has been shown to have partial functional redundancy with ALDP and, when overexpressed, can compensate for the loss-of-function of ALDP. In order to characterize the function of ALDRP and to understand the phenomenon of gene redundancy, we have developed a novel system that allows the controlled expression of the ALDRP-EGFP fusion protein (normal or non-functional mutated ALDRP) using the Tet-On system in H4IIEC3 rat hepatoma cells. The generated stable cell lines express negligible levels of endogenous ALDRP and doxycycline dosage-dependent levels of normal or mutated ALDRP. Importantly, the ALDRP-EGFP protein is targeted correctly to peroxisome and is functional. The obtained cell lines will be an indispensable tool in our further studies aimed at the resolution of the function of ALDRP to characterize its potential substrates in a natural context

  2. Development of an OP9 derived cell line as a robust model to rapidly study adipocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Jacqueline M Lane

    Full Text Available One hallmark of obesity is adipocyte hypertrophy and hyperplasia. To gain novel insights into adipose biology and therapeutics, there is a pressing need for a robust, rapid, and informative cell model of adipocyte differentiation for potential RNAi and drug screens. Current models are prohibitive for drug and RNAi screens due to a slow differentiation time course and resistance to transfection. We asked if we could create a rapid, robust model of adipogenesis to potentially enable rapid functional and obesity therapeutic screens. We generated the clonal population OP9-K, which differentiates rapidly and reproducibly, and displays classic adipocyte morphology: rounded cell shape, lipid accumulation, and coalescence of lipids into a large droplet. We further validate the OP9-K cells as an adipocyte model system by microarray analysis of the differentiating transcriptome. OP9-K differentiates via known adipogenic pathways, involving the transcriptional activation and repression of common adipose markers Plin1, Gata2, C/Ebpα and C/Ebpβ and biological pathways, such as lipid metabolism, PPARγ signaling, and osteogenesis. We implemented a method to quantify lipid accumulation using automated microscopy and tested the ability of our model to detect alterations in lipid accumulation by reducing levels of the known master adipogenic regulator Pparγ. We further utilized our model to query the effects of a novel obesity therapeutic target, the transcription factor SPI1. We determine that reduction in levels of Spi1 leads to an increase in lipid accumulation. We demonstrate rapid, robust differentiation and efficient transfectability of the OP9-K cell model of adipogenesis. Together with our microscopy based lipid accumulation assay, adipogenesis assays can be achieved in just four days' time. The results of this study can contribute to the development of rapid screens with the potential to deepen our understanding of adipose biology and efficiently

  3. McCoy cell line as a possible model containing CD4+ receptors for the study of HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Nogueira Yeda L.

    2003-01-01

    Full Text Available Several studies have recently shown the use of recombinant rabies virus as potential vector-viral vaccine for HIV-1. The sequence homology between gp 120 and rabies virus glycoprotein has been reported. The McCoy cell line has therefore been used to show CD4+ or CD4+ like receptors. Samples of HIV-1 were isolated, when plasma of HIV-1 positive patients was inoculated in the McCoy cell line. The virus infection was then studied during successive virus passages. The proteins released in the extra cellular medium were checked for protein activity, by exposure to SDS Electrophoresis and blotting to nitro-cellulose filter, then reacting with sera of HIV positive and negative patients. Successive passages were performed, and showed viral replication, membrane permeabilization, the syncytium formation, and the cellular lysis (cytopathic effect. Flow cytometry analysis shows clear evidence that CD4+ receptors are present in this cell line, which enhances the likelihood of easy isolation and replication of HIV. The results observed allow the use of this cell line as a possible model for isolating HIV, as well as for carrying out studies of the dynamics of viral infection in several situations, including exposure to drugs in pharmacological studies, and possibly studies and analyses of the immune response in vaccine therapies.

  4. Renal mesangial cell cultures as a model for study of erythropoietin production.

    OpenAIRE

    Kurtz, Armin; Jelkmann, W; Sinowatz, F.; Bauer, Christian

    1983-01-01

    Mesangial cells derived from isolated glomeruli of rat kidney were grown as homogeneous cell lines in culture. They released, into the culture medium, erythropoietin that had free terminal galactosyl residues and was therefore not active in vivo. The production of erythropoietin by these cells was significantly enhanced by either lowering the PO2 in the incubation atmosphere or by adding cobalt chloride to the culture medium. Therefore, mesangial cells in culture may be considered as an in vi...

  5. In-situ X-ray studies of model electrode surfaces for solid oxide fuel cells

    OpenAIRE

    Khorshidi, Navid

    2010-01-01

    Fuel cells are considered as a promising way to produce clean energy. These cells convert the chemical energy created by the reaction of hydrogen and oxygen to water into electric energy. Regarding the difficulties connected with the production and more importantly storage of hydrogen, solid oxide fuel cells (SOFCs) play an outstanding role among the diverse fuel cell types. SOFCs are able to use not only pure hydrogen as a fuel, but also hydrocarbons. This ability leads to impressive efficie...

  6. ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

    Directory of Open Access Journals (Sweden)

    Chrisler William B

    2010-11-01

    g/mL basis and target cell doses on a particle surface area or number basis can be as high as three to six orders of magnitude. As a consequence, in vitro hazard assessments utilizing mass-based exposure metrics have inherently high errors where particle number or surface areas target cells doses are believed to drive response. The gold standard for particle dosimetry for in vitro nanotoxicology studies should be direct experimental measurement of the cellular content of the studied particle. However, where such measurements are impractical, unfeasible, and before such measurements become common, particle dosimetry models such as ISDD provide a valuable, immediately useful alternative, and eventually, an adjunct to such measurements.

  7. Modeling and Experimental Study of PEM Fuel Cell Transient Response for Automotive Applications

    Institute of Scientific and Technical Information of China (English)

    HUA Jianfeng; XU Liangfei; LIN Xinfan; LU Languang; OUYANG Minggao

    2009-01-01

    This paper presents an analysis of the dynamic response of a low pressure proton exchange membrane (PEM) fuel cell stack to step changes in load, which are characteristic of automotive fuel cell system applications. The goal is a better understanding of the electrical and electrochemical processes when accounting for the characteristic cell voltage response during transients. The analysis and experiment are based on a low pressure 5 kW proton exchange membrane fuel cell (PEMFC) stack, which is similar to those used in several of Tsinghua's fuel cell buses. The experimental results provide an effective improvement reference for the power train control scheme of the fuel cell buses in Olympic demonstration in Beijing 2008.

  8. Mitochondria-Rich Cells as Experimental Model in Studies of Epithelial Chloride Channels

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Amstrup, Jan; Møbjerg, Nadja;

    2002-01-01

    -actin localised in the submembrane domain in the neck region of the flask-shaped mr cell. (ii) The other identified Cl- pathway of mr cells is mediated by small-conductance apical CFTR chloride channels as concluded from its activation via ß-adrenergic receptors, ion selectivity, genistein stimulation and...... inhibition by glibenclamide. bbCFTR has been cloned, and immunostaining has shown that the gene product is selectively expressed in mr cells. There is cross-talk between the two pathways in the sense that activation of the conductance of the mr cell by voltage clamping excludes activation via receptor...

  9. OPTIMIZATION OF THE CATHODE LONG-TERM STABILITY IN MOLTEN CARBONATE FUEL CELLS: EXPERIMENTAL STUDY AND MATHEMATICAL MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Hector Colonmer; Prabhu Ganesan; Nalini Subramanian; Dr. Bala Haran; Dr. Ralph E. White; Dr. Branko N. Popov

    2002-09-01

    phase homogeneous model was developed to simulate the performance of the molten carbonate fuel cell cathode and the complete fuel cell. The homogeneous model is based on volume averaging of different variables in the three phases over a small volume element. This approach can be used to model porous electrodes as it represents the real system much better than the conventional agglomerate model. Using the homogeneous model the polarization characteristics of the MCFC cathode and fuel cell were studied under different operating conditions. Both the cathode and the full cell model give good fits to the experimental data.

  10. ISDD: A Computational Model of Particle Sedimentation, Diffusion and Target Cell Dosimetry for In Vitro Toxicity Studies

    Energy Technology Data Exchange (ETDEWEB)

    Hinderliter, Paul M.; Minard, Kevin R.; Orr, Galya; Chrisler, William B.; Thrall, Brian D.; Pounds, Joel G.; Teeguarden, Justin G.

    2010-11-30

    . As a consequence, in vitro hazard assessments utilizing mass-based exposure metrics have inherently high errors where particle number or surface areas target cells doses are believed to drive response. The gold standard for particle dosimetry for in vitro nanotoxicology studies should be direct experimental measurement of the cellular content of the studied particle. However, where such measurements are impractical, unfeasible, and before such measurements become common, particle dosimetry models such as ISDD provide a valuable, immediately useful alternative, and eventually an adjunct to such measurements.

  11. Plasma-treated polystyrene surfaces : model surfaces for studying cell-biomaterial interactions

    NARCIS (Netherlands)

    van Kooten, TG; Spijker, HT; Busscher, HJ

    2004-01-01

    Biocompatibility of biomaterials relates, amongst others, to the absence of adverse cellular reactions and modulation of cell adhesion and subsequent responses. With respect to tissue-engineering applications, most materials need to evoke cell adhesion and spreading, while potentially displaying dif

  12. 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

  13. Mathematical Model for Photovoltaic Cells

    Directory of Open Access Journals (Sweden)

    Wafaa ABD EL-BASIT

    2013-11-01

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

  14. Experimental study and modelling of degradation phenomena in HTPEM fuel cell stacks for use in CHP systems

    DEFF Research Database (Denmark)

    Andreasen, Søren Juhl

    2009-01-01

    Degradation phenomena in HTPEM fuel cells for use in CHP systems were investigated experimentally and by modelling. It was found that the two main degradation mechanisms in HTPEM fuel cells are carbon corrosion and Pt agglomeration. On basis of this conclusion a mechanistic model, describing the...

  15. Experimental study and modeling of degradation phenomena in HTPEM fuel cell stacks for use in CHP systems

    DEFF Research Database (Denmark)

    Nielsen, Mads Pagh; Andreasen, Søren Juhl; Rasmussen, Peder Lund;

    2009-01-01

    Degradation phenomena in HTPEM fuel cells for use in CHP systems were investigated experimentally and by modeling. It was found that the two main degradation mechanisms in HTPEM fuel cells are carbon corrosion and Pt agglomeration. On basis of this conclusion a mechanistic model, describing the...

  16. An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

    OpenAIRE

    Tang, Zhongshu; Zhang, Shuihua; Lee, Chunsik; Kumar, Anil; Arjunan, Pachiappan; LI Yang; Zhang, Fan; Li, Xuri

    2011-01-01

    Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness.

  17. A multiscale modeling study of loss processes in block-copolymer-based solar cell nanodevices

    Science.gov (United States)

    Donets, Sergii; Pershin, Anton; Christlmaier, Martin J. A.; Baeurle, Stephan A.

    2013-03-01

    Flexible photovoltaic devices possess promising perspectives in opto-electronic technologies, where high mobility and/or large-scale applicability are important. However, their usefulness in such applications is currently still limited due to the low level of optimization of their performance and durability. For the improvement of these properties, a better understanding and control of small-scale annihilation phenomena involved in the photovoltaic process, such as exciton loss and charge carrier loss, is necessary, which typically implicates multiple length- and time-scales. Here, we study the causes for their occurrence on the example of nanostructured diblock- and triblock-copolymer systems by making use of a novel solar-cell simulation algorithm and explore new routes to optimize their photovoltaic properties. A particular focus is set on the investigation of exciton and charge carrier loss phenomena and their dependence on the inter-monomeric interaction strength, chain architecture, and external mechanical loading. Our simulation results reveal that in the regime from low up to intermediate χ-parameters an increasing number of continuous percolation paths is created. In this parameter range, the internal quantum efficiency (IQE) increases up to a maximum, characterized by a minimum in the number of charge losses due to charge recombination. In the regime of high χ-parameters both block-copolymer systems form nanostructures with a large number of bottlenecks and dead ends. These lead to a large number of charge losses due to charge recombination, charge trapping, and a deteriorated exciton dissociation, resulting in a significant drop in the IQE. Moreover, we find that the photovoltaic performance of the triblock-copolymer material decreases with increasing mechanical loading, caused by a growing number of charge losses due to charge recombination and charge accumulation. Finally, we demonstrate that the process of charge trapping in defects can be reversed

  18. Low Dose Studies with Focused X-Rays in cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    Energy Technology Data Exchange (ETDEWEB)

    Kathy Held; Kevin Prise; Barry Michael; Melvyn Folkard

    2002-12-14

    the biological ha sis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in low-dose radiation risk. This project therefore also examines how cells are damaged by treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and therefore it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  19. Oogonial stem cells as a model to study age-associated infertility in women

    Science.gov (United States)

    Garg, Neha; Sinclair, David A.

    2016-01-01

    Fertility is the first biological process to break down during aging, thereby making it a useful tool to understand fundamental processes of aging. Reproductive aging in females is associated with a loss of ovarian function characterised by a reduction in the number and quality of oocytes. The central dogma, namely that females are born with a fixed pool of oocytes that progressively decline with increasing maternal age, has been challenged by evidence supporting postnatal oogenesis in mammals. Reports demonstrating formation of new oocytes from newly discovered germline stem cells, referred to as oogonial stem cells (OSCs), has opened new avenues for treatment of female infertility. In this review we discuss why the OSCs possibly lose their regenerative potential over time, and focus specifically on the aging process in germline stem cells as a possible mechanism for understanding female age-related infertility and how we can slow or delay ovarian aging. PMID:25897831

  20. Oogonial stem cells as a model to study age-associated infertility in women.

    Science.gov (United States)

    Garg, Neha; Sinclair, David A

    2015-07-01

    Fertility is the first biological process to break down during aging, thereby making it a useful tool to understand fundamental processes of aging. Reproductive aging in females is associated with a loss of ovarian function characterised by a reduction in the number and quality of oocytes. The central dogma, namely that females are born with a fixed pool of oocytes that progressively decline with increasing maternal age, has been challenged by evidence supporting postnatal oogenesis in mammals. Reports demonstrating formation of new oocytes from newly discovered germline stem cells, referred to as oogonial stem cells (OSCs), has opened new avenues for treatment of female infertility. In this review we discuss why the OSCs possibly lose their regenerative potential over time, and focus specifically on the aging process in germline stem cells as a possible mechanism for understanding female age-related infertility and how we can slow or delay ovarian aging. PMID:25897831

  1. Low Dose Studies with Focused X-rays in Cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    Energy Technology Data Exchange (ETDEWEB)

    Barry D. Michael; Kathryn Held; Kevin Prise

    2002-12-19

    study the biological basis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and there it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  2. Evaluation of eukaryotic cultured cells as a model to study extracellular DNA / D.L. Peters

    OpenAIRE

    Peters, Dimetrie Leslie

    2011-01-01

    The diagnostic value of extracellular occurring DNA (eoDNA) is limited by our lack of understanding its biological function. eoDNA exists in a number of forms, namely vesicle bound DNA, histone/DNA complexes or nucleosomes and virtosomes. These forms of DNA can also be categorized under the terms circulating DNA, cell free DNA, free DNA and extracellular DNA. The DNA can be released by means of form–specific mechanisms and seem to be governed by cell cycle phases and apoptosis....

  3. Fundamental studies of materials, designs, and models development for polymer electrolyte membrane fuel cell flow field distributors

    Science.gov (United States)

    Nikam, Vaibhav Vilas

    Fuel cells are becoming a popular source of energy due to their promising performance and availability. However, the high cost of fuel cell stack forbids its deployment to end user. Moreover, bipolar plate is one of the critical components in current polymer electrolyte membrane fuel cell (PEMFC) system, causing severe increase in manufacturing cost. The objective of this research work is to develop new materials, design and manufacturing process for bipolar plates. The materials proposed for use were tested for corrosion resistance in simulated fuel cell conditions. After corrosion studies copper alloy (C17200) and Low Temperature Carburized (LTC) SS 316 were selected as an alternative material for bipolar plate. It was observed that though the copper alloy offered good resistance in corrosive atmosphere, the major advantage of using the alloys was good conductivity even after formation of corrosion layer compared to SS 316. However, LTC SS 316 achieved the best corrosion resistance (ever reported in current open literature at relatively low cost) with decreased contact resistance, as compared to SS 316. Due to the expensive and tedious machining for bipolar plate manufacturing, the conventional machining process was not used. Bipolar plates were manufactured from thin corrugated sheets formed of the alloy. This research also proposed a novel single channel convoluted flow field design which was developed by increasing the tortuosity of conventional serpentine design. The CFD model for novel single channel convoluted design showed uniform distribution of velocity over the entire three dimensional domain. The novel design was further studied using pressure drop and permeability models. These modeling calculations showed substantial benefit in using corrugated sheet design and novel single channel convoluted flow field design. All the concepts of materials (except for LTC SS 316), manufacturing and design are validated using various tests like long term stability

  4. Novel Desaturation Cell to Quantify Gushing Intensity: A Preliminary Study on Model Solutions

    Czech Academy of Sciences Publication Activity Database

    Novák, Pavel; Poštulková, Michaela; Růžička, Marek; Brányik, T.

    2015-01-01

    Roč. 73, č. 2 (2015), s. 185-189. ISSN 0361-0470 R&D Projects: GA MŠk(CZ) LD13018 Institutional support: RVO:67985858 Keywords : gushing * desaturation cell * gushing matrix Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 0.886, year: 2014

  5. Biomass-powered Solid Oxide Fuel Cells: Experimental and Modeling Studies for System Integrations

    NARCIS (Netherlands)

    Liu, M.

    2013-01-01

    Biomass is a sustainable energy source which, through thermo-chemical processes of biomass gasification, is able to be converted from a solid biomass fuel into a gas mixture, known as syngas or biosyngas. A solid oxide fuel cell (SOFC) is a power generation device that directly converts the chemical

  6. Studying nanotube-based oscillators and their application as memory cells via nanoscale continuum modeling and simulation

    Directory of Open Access Journals (Sweden)

    Shaoping Xiao

    2015-12-01

    Full Text Available A nanoscale continuum model of carbon nanotube-based oscillators is proposed in this paper. In the continuum model, the nanotube is discretized via the meshfree particle method. The atomistic interlayer interaction between the outer and inner tubes is approximated by the interlayer interaction between particles. The mechanical behaviors of oscillators are studied and compared well with molecular dynamics simulation results. The nanotube-based oscillator can be employed to design a nanoelectromechanical system. In this system, two electrodes are attached on the top of the outer tube so that the induced electromagnetic force can overcome the interlayer friction. The mechanisms of such nanoelectromechanical systems as memory cells are also considered.

  7. Optimization of the output of a solar cell per theoretical and experimental study of the models to one and two exponential

    Directory of Open Access Journals (Sweden)

    Benyoucef B.

    2012-06-01

    Full Text Available The production of electricity based on the conversion of the sunlight by photovoltaic cells containing crystalline silicon is the way most used on the technological and industrial level Consequently, the development of the terrestrial applications for the energy production requires high-output cells and low cost.The aim of our work is to present a comparative study between both theoretical and experimental models of a solar cell based silicon type PHYWE (connecting four cells in series of 80 mm diameter to improve photovoltaic performance.This study led to the determination of the parameters of the cell starting from the current-voltage characteristic, the influence of luminous flow on this characteristic as well as the effect of the incidental photons on the solar cell. We justify the interest to use the model with two exponential for the optimization of the output by underlining the insufficiency of the model to one exponential.

  8. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    OpenAIRE

    Piya Prajumwongs; Oratai Weeranantanapan; Thiranut Jaroonwitchawan; Parinya Noisa

    2016-01-01

    Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs) recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in unders...

  9. Plant cell culture as a model for study of degradation of TNT

    Czech Academy of Sciences Publication Activity Database

    Podlipná, Radka; Nepovím, Aleš; Zeman, S.; Vágner, Martin; Vaněk, Tomáš

    Chania : Technical University of Crete, 2001, s. 540-542. [European Bioremediation Conference /1./. Chania (GR), 02.07.2001-05.07.2001] R&D Projects: GA ČR GA206/99/1252; GA ČR GA206/99/P034; GA MŠk OC 837.10 Institutional research plan: CEZ:AV0Z4055905 Keywords : plant cell culture Subject RIV: CE - Biochemistry

  10. AlgiMatrix™ based 3D cell culture system as an in-vitro tumor model for anticancer studies.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available BACKGROUND: Three-dimensional (3D in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening. METHODS: Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100-300 µm. Spheroids were grown in two weeks in cultures without compromising the growth characteristics. Different marketed anticancer drugs were screened by incubating them for 24 h at 7, 9 and 11 days in 3D cultures and cytotoxicity was measured by AlamarBlue® assay. Effectiveness of anticancer drug treatments were measured based on spheroid number and size distribution. Evaluation of apoptotic and anti-apoptotic markers was done by immunohistochemistry and RT-PCR. The 3D results were compared with the conventional 2D monolayer cultures. Cellular uptake studies for drug (Doxorubicin and nanoparticle (NLC were done using spheroids. RESULTS: IC(50 values for anticancer drugs were significantly higher in AlgiMatrix™ systems compared to 2D culture models. The cleaved caspase-3 expression was significantly decreased (2.09 and 2.47 folds respectively for 5-Fluorouracil and Camptothecin in H460 spheroid cultures compared to 2D culture system. The cytotoxicity, spheroid size distribution, immunohistochemistry, RT-PCR and nanoparticle penetration data suggested that in vitro tumor models show higher resistance to anticancer drugs and supporting the fact that 3D culture is a better model for the cytotoxic evaluation of anticancer drugs in vitro. CONCLUSION: The results from our studies are useful to develop a high throughput in vitro tumor model to study the effect of various anticancer agents and various molecular pathways affected by the anticancer drugs and formulations.

  11. Generation of human/rat xenograft animal model for the study of human donor stem cell behaviors in vivo

    OpenAIRE

    Sun, Yan; Xiao, Dong; Pan, Xing-hua; Zhang, Ruo-Shuang; Cui, Guang-Hui; Chen, Xi-Gu

    2007-01-01

    AIM: To accurately and realistically elucidate human stem cell behaviors in vivo and the fundamental mechanisms controlling human stem cell fates in vivo, which is urgently required in regenerative medicine and treatments for some human diseases, a surrogate human-rat chimera model was developed.

  12. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Piya Prajumwongs

    2016-01-01

    Full Text Available Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.

  13. Survivin as a potential mediator to support autoreactive cell survival in myasthenia gravis: a human and animal model study.

    Directory of Open Access Journals (Sweden)

    Linda L Kusner

    Full Text Available The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.

  14. X/XO or H2O2 induced IPEC-J2 cell as a new in vitro model for studying apoptosis in post-weaning piglets.

    Science.gov (United States)

    Cai, Xuan; Zhu, Lihui; Chen, Xiaolian; Sheng, Yongshuai; Guo, Qi; Bao, Jian; Xu, Jianxiong

    2016-08-01

    We previously demonstrated that intestinal epithelial cell apoptosis in weaned piglets is much more serious than that observed in sucking piglets and is related to oxidative stress during weaning. It is difficult to study the apoptosis mechanisms only using in vivo methods because of the limit of existing research technology. An in vitro cellular system is required for piglet intestinal epithelial cell apoptosis research. In this study, a non-tumorigenic epithelial cell line, IPEC-J2 cells, was employed as a cell model. Hydrogen peroxide and xanthine/xanthine oxidase (X/XO) were both used and compared for apoptosis modeling. The concentrations of hydrogen peroxide and XO were selected and verified using cell viability analysis, the comet assay and flow cytometry. Intracellular ROS were measured using fluorescent probes. Additionally, the expression levels of the apoptosis-related genes Fas, Bcl-2, P53, Caspase 3, Caspase 8, and Caspase 9 were analyzed using quantitative RT-PCR. The results indicated the optimal modeling method is a final concentration of 0.5 mM H2O2 incubated with IPEC-J2 cells for 1 h at 37 °C in 5 % CO2 for hydrogen peroxide-induced apoptosis modeling, and a final concentration of 250 μM X/50 U/L XO incubated with IPEC-J2 cells for 6 h at 37 °C in 5 % CO2 for X/XO-induced apoptosis modeling. For the apoptotic pathway, the X/XO modeling method is more similar to 21 days weaning piglets. Therefore, we suggest that X/XO modeling with IPEC-J2 cells be used as an in vitro cell culture model for weaning piglet intestinal epithelial cell apoptosis. PMID:25528136

  15. Model cell membranes

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  16. In vitro-differentiated embryonic stem cell macrophages: a model system for studying atherosclerosis-associated macrophage functions.

    Science.gov (United States)

    Moore, K J; Fabunmi, R P; Andersson, L P; Freeman, M W

    1998-10-01

    Monocytes/macrophages (Mo) appear to play a critical role in the initiation and progression of atherosclerotic lesions. In this study, we characterized in vitro-differentiated embryonic stem (ES) cell macrophages as a model system for studying atherosclerosis-associated Mo functions. Using immunofluorescence staining and Western analysis, we demonstrate that ES Mo express typical macrophage cell surface markers, as well as the known receptors for modified forms of low density lipoprotein (LDL), including the Mo scavenger receptors (SR-A type I and type II), CD36, and CD68. Differentiated ES Mo specifically bind and degrade 125I-labeled acetylated LDL with high affinity, and their incubation with acetylated LDL (15 microg/mL) for 48 hours produces characteristic "foamy" Mo, as visualized by oil red O staining. ES Mo also express matrix-degrading metalloproteinases (MMP-3, MMP-9), which have been implicated in collagen breakdown in the fibrous cap of atherosclerotic plaques, and secrete cytokines (tumor necrosis factor-alpha, interleukin-6) in response to inflammatory stimuli. Transfection experiments, using a green fluorescent protein reporter gene, driven by the myeloid-specific promoter, CD11b, demonstrated that ES Mo can also be used to study macrophage-restricted gene expression in vitro. Taken together, these data demonstrate that ES Mo exhibit many properties typical of arterial lesion macrophages. Its ease of genetic manipulation makes it an attractive system for investigations of macrophage functions in vitro. PMID:9763539

  17. Olfactory Stem Cells, a New Cellular Model for Studying Molecular Mechanisms Underlying Familial Dysautonomia

    OpenAIRE

    Nathalie Boone; Béatrice Loriod; Aurélie Bergon; Oualid Sbai; Christine Formisano-Tréziny; Jean Gabert; Michel Khrestchatisky; Catherine Nguyen; François Féron; Axelrod, Felicia B.; El Chérif Ibrahim

    2010-01-01

    BACKGROUND: Familial dysautonomia (FD) is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and mod...

  18. Modeling Stem Cell Induction Processes

    OpenAIRE

    Filipe Grácio; Joaquim Cabral; Bruce Tidor

    2012-01-01

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

  19. Loss of FADS2 Function Severely Impairs the Use of HeLa Cells as an In Vitro Model for Host Response Studies Involving Fatty Acid Effects

    OpenAIRE

    Jaudszus, Anke; Degen, Christian; Barth, Stephan W.; Klempt, Martin; Schlörmann, Wiebke; Roth, Alexander; Rohrer, Carsten; Sauerwein, Helga; Sachse, Konrad; Jahreis, Gerhard

    2014-01-01

    Scope Established epithelial cell lines equipped with pattern recognition receptors such as the Toll-like receptor (TLR)-2 are common tools for immune response studies on invading pathogens, e.g. the obligate intracellular species of Chlamydia. Moreover, such models are widely used to elucidate fatty acid-mediated immune effects. In several transformed cell lines, however, unusual loss of metabolic functions was described. The cell lines A549 and HeLa are poorly characterized in this respect....

  20. Simulation studies of statistical distributions of cell membrane capacities and an ellipse model to assess the frequency behaviour of biological tissues

    International Nuclear Information System (INIS)

    The frequency behaviour of biological tissues is commonly described by a Cole model reflecting a single-cell bio-impedance model extended with an exponent α. However, for this parameter α there is no physical or biological substrate, which impedes an interpretation. The present study confirms by computer simulations of tissue models that the factual frequency behaviour can be explained by assuming a distribution of the electrical impedance properties of cells and of the capacitive coupling between cells. This behaviour is modelled mathematically by an ellipse. A mathematical procedure is presented to estimate this ellipse from experimental data by a least square method. A model parameter β is introduced, representing the ratio of the axes of the ellipse. A higher value of β means a larger variation in cell properties, which makes a patho-physiological interpretation of changes possible.

  1. Modeling and CFD simulation of nutrient distribution in picoliter bioreactors for bacterial growth studies on single-cell level.

    Science.gov (United States)

    Westerwalbesloh, Christoph; Grünberger, Alexander; Stute, Birgit; Weber, Sophie; Wiechert, Wolfgang; Kohlheyer, Dietrich; von Lieres, Eric

    2015-11-01

    A microfluidic device for microbial single-cell cultivation of bacteria was modeled and simulated using COMSOL Multiphysics. The liquid velocity field and the mass transfer within the supply channels and cultivation chambers were calculated to gain insight in the distribution of supplied nutrients and metabolic products secreted by the cultivated bacteria. The goal was to identify potential substrate limitations or product accumulations within the cultivation device. The metabolic uptake and production rates, colony size, and growth medium composition were varied covering a wide range of operating conditions. Simulations with glucose as substrate did not show limitations within the typically used concentration range, but for alternative substrates limitations could not be ruled out. This lays the foundation for further studies and the optimization of existing picoliter bioreactor systems. PMID:26345659

  2. Activation and inhibition of retinal ganglion cells in response to epiretinal electrical stimulation: a computational modelling study

    Science.gov (United States)

    Abramian, Miganoosh; Lovell, Nigel H.; Morley, John W.; Suaning, Gregg J.; Dokos, Socrates

    2015-02-01

    Objective. Retinal prosthetic devices aim to restore sight in visually impaired people by means of electrical stimulation of surviving retinal ganglion cells (RGCs). This modelling study aims to demonstrate that RGC inhibition caused by high-intensity cathodic pulses greatly influences their responses to epiretinal electrical stimulation and to investigate the impact of this inhibition on spatial activation profiles as well as their implications for retinal prosthetic device design. Another aim is to take advantage of this inhibition to reduce axonal activation in the nerve fibre layer. Approach. A three-dimensional finite-element model of epiretinal electrical stimulation was utilized to obtain RGC activation and inhibition threshold profiles for a range of parameters. Main results. RGC activation and inhibition thresholds were highly dependent on cell and stimulus parameters. Activation thresholds were 1.5, 3.4 and 11.3 μA for monopolar electrodes with 5, 20 and 50 μm radii, respectively. Inhibition to activation threshold ratios were mostly within the range 2-10. Inhibition significantly altered spatial patterns of RGC activation. With concentric electrodes and appropriately high levels of stimulus amplitudes, activation of passing axons was greatly reduced. Significance. RGC inhibition significantly impacts their spatial activation profiles, and therefore it most likely influences patterns of perceived phosphenes induced by retinal prosthetic devices. Thus this inhibition should be taken into account in future studies concerning retinal prosthesis development. It might be possible to utilize this inhibitory effect to bypass activation of passing axons and selectively stimulate RGCs near their somas and dendrites to achieve more localized phosphenes.

  3. A Choroid Plexus Epithelial Cell-based Model of the Human Blood-Cerebrospinal Fluid Barrier to Study Bacterial Infection from the Basolateral Side.

    Science.gov (United States)

    Dinner, Stefanie; Borkowski, Julia; Stump-Guthier, Carolin; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

    2016-01-01

    The epithelial cells of the choroid plexus (CP), located in the ventricular system of the brain, form the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB functions in separating the cerebrospinal fluid (CSF) from the blood and restricting the molecular exchange to a minimum extent. An in vitro model of the BCSFB is based on cells derived from a human choroid plexus papilloma (HIBCPP). HIBCPP cells display typical barrier functions including formation of tight junctions (TJs), development of a transepithelial electrical resistance (TEER), as well as minor permeabilities for macromolecules. There are several pathogens that can enter the central nervous system (CNS) via the BCSFB and subsequently cause severe disease like meningitis. One of these pathogens is Neisseria meningitidis (N. meningitidis), a human-specific bacterium. Employing the HIBCPP cells in an inverted cell culture filter insert system enables to study interactions of pathogens with cells of the BCSFB from the basolateral cell side, which is relevant in vivo. In this article, we describe seeding and culturing of HIBCPP cells on cell culture inserts. Further, infection of the cells with N. meningitidis along with analysis of invaded and adhered bacteria via double immunofluorescence is demonstrated. As the cells of the CP are also involved in other diseases, including neurodegenerative disorders like Alzheimer`s disease and Multiple Sclerosis, as well as during the brain metastasis of tumor cells, the model system can also be applied in other fields of research. It provides the potential to decipher molecular mechanisms and to identify novel therapeutic targets. PMID:27213495

  4. A computational model of amoeboid cell migration.

    Science.gov (United States)

    Lim, Fong Yin; Koon, Yen Ling; Chiam, Keng-Hwee

    2013-10-01

    We present a two-dimensional computational model of amoeboid cell migration characterised by cell shape changes due to the formation and extension of protrusions known as blebs. Using this model, we numerically study the deformation of the cell membrane during blebbing, as well as the effects of obstacles, such as protein fibres in the extracellular matrix, on the motion of the blebbing cell. The model is established in the framework of Stokes flow. Cell membrane deformation is coupled to membrane tension, membrane bending, membrane-cortex adhesion and cortical activities via the intracellular and extracellular fluid field described by the Stokes equation. By assuming that actin monomers move at constant speed towards the membrane and polymerise when they approach the membrane, our model shows that the cell movement in unconfined space can be sustained. We also study how a migrating cell interacts with obstacles hydrodynamically, allowing us to model cell migration in confined environments and to investigate the effects of confinement on the cell migration speed. Our model can be used to further study how tumour cells move through the extracellular matrix during cancer metastasis. PMID:23342988

  5. TRANSFECTED MDCK CELL LINE WITH ENHANCED EXPRESSION OF CYP3A4 AND P-GLYCOPROTEIN AS A MODEL TO STUDY THEIR ROLE IN DRUG TRANSPORT AND METABOLISM

    OpenAIRE

    Kwatra, Deep; Budda, Balasubramanyam; Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Ashim K. Mitra

    2012-01-01

    The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drugs of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Simila...

  6. Spinal cord T-cell infiltration in the spared nerve injury model of neuropathic pain: a time course study

    OpenAIRE

    Clarke C.

    2012-01-01

    Background : Numerous studies have shown that immune cells infiltrate the spinal cord after peripheral nerve injury and that they play a major contribution to sensory hypersensitivity in rodents. In particular, the role of monocyte-derived cells and T lymphocytes seems to be prominent in this process. This exciting new perspective in research on neuropathic pain opens many different areas of work, including the understanding of the function of these cells and how they impact on neural functio...

  7. Relative contribution of target cell disturbances and immunosuppression in radiation leukemogenesis: model studies with exogenous virus

    International Nuclear Information System (INIS)

    The effects of preirradiation on the sensitivity of adult BALB/c mice to the leukemogenic and sarcomagenic effects of MSV/MLV have been studied. Chronic radiation (392 rad at 28 rad/day) induces a transient enhanced sensitivity to the leukemogenic effects of MLV, which disappears between 2 and 6 months after exposure. Acute irradiation (392 rad at 41 rad/min) decreases sensitivity to the leukemogenic effects of MSV/MLV below that of unirradiated mice and this decrease persists through 6 months' postexposure. Conversely, acute irradiation enhances sensitivity to the sarcomagenic effects of MSV/MLV. Both of these effects of acute irradiation can be reversed by addition of immunostimulants such as poly(Am). It is proposed that enhanced sensitivity to leukemogenesis is a reflection of lymphoid hyperplasia while decreased sensitivity reflects lymphoid depletion. In contrast, enhanced sensitivity to sarcomagenesis is a reflection of lymphoid depletion, while increased resistance reflects lymphoid hyperplasia

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

    Science.gov (United States)

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

    2011-10-01

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

  9. Effect of Stem Cell Therapy on Bone Mineral Density: A Meta-Analysis of Preclinical Studies in Animal Models of Osteoporosis

    Science.gov (United States)

    Li, Feng; Zhou, Changlin; Xu, Liang; Tao, Shuqing; Zhao, Jingyi; Gu, Qun

    2016-01-01

    Background Preclinical studies of the therapeutic role of stem cell based therapy in animal models of osteoporosis have largely yielded inconsistent results. We performed a meta-analysis to provide an overview of the currently available evidence. Methods Pubmed, Embase and Cochrane Library databases were systematically searched for relevant controlled studies. A random-effect model was used for pooled analysis of the effect of stem cell based therapy on bone mineral density (BMD). Stratified analyses were performed to explore the effect of study characteristics on the outcomes. Results Pooled results from 12 preclinical studies (110 animals in stem cell treatment groups, and 106 animals in control groups) indicated that stem cell based treatment was associated with significantly improved BMD (standardized mean difference [SMD] = 1.29, 95% Confidence Interval [CI]: 0.84–1.74, P 0.05). Egger’s test detected potential publication bias (P = 0.055); however, ‘trim and fill’ analysis yielded similar results after statistically incorporating the hypothetical studies in the analysis (SMD = 1.24, 95% CI: 0.32–2.16, P < 0.001). Conclusions Stem cell transplantation may improve BMD in animal models of osteoporosis. Our meta-analysis indicates a potential therapeutic role of stem cell based therapy for osteoporosis, and serves to augment the rationale for clinical studies. PMID:26882451

  10. Evolutionary aspects of non-cell-autonomous regulation in vascular plants: structural background and models to study

    OpenAIRE

    Anastasiia I. Evkaikina; Marina A. Romanova; Olga V. Voitsekhovskaja

    2014-01-01

    Plasmodesmata (PD) serve for the exchange of information in form of miRNA, proteins, and mRNA between adjacent cells in the course of plant development. This fundamental role of PD is well established in angiosperms but has not yet been traced back to the evolutionary ancient plant taxa where functional studies lag behind studies of PD structure and ontogenetic origin. There is convincing evidence that the ability to form secondary (post-cytokinesis) PD, which can connect any adjacent cells, ...

  11. Modeling: driving fuel cells

    Directory of Open Access Journals (Sweden)

    Michael Francis

    2002-05-01

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

  12. Artificial vesicles as an animal cell model for the study of biological application of non-thermal plasma

    Science.gov (United States)

    Ki, S. H.; Park, J. K.; Sung, C.; Lee, C. B.; Uhm, H.; Choi, E. H.; Baik, K. Y.

    2016-03-01

    Artificial cell-like model systems can provide information which is hard to obtain with real biological cells. Giant unilamellar vesicles (GUV) containing intra-membrane DNA or OH radical-binding molecules are used to visualize the cytolytic activity of OH radicals. Changes in the GUV membrane are observed by microscopy or flow cytometry as performed for animal cells after non-thermal plasma treatment. The experimental data shows that OH radicals can be detected inside the membrane, although the biological effects are not as significant as for H2O2. This artificial model system can provide a systemic means to elucidate the complex interactions between biological materials and non-thermal plasma.

  13. Artificial vesicles as an animal cell model for the study of biological application of non-thermal plasma

    International Nuclear Information System (INIS)

    Artificial cell-like model systems can provide information which is hard to obtain with real biological cells. Giant unilamellar vesicles (GUV) containing intra-membrane DNA or OH radical-binding molecules are used to visualize the cytolytic activity of OH radicals. Changes in the GUV membrane are observed by microscopy or flow cytometry as performed for animal cells after non-thermal plasma treatment. The experimental data shows that OH radicals can be detected inside the membrane, although the biological effects are not as significant as for H2O2. This artificial model system can provide a systemic means to elucidate the complex interactions between biological materials and non-thermal plasma. (paper)

  14. Evaluation of silicon nitride as a substrate for culture of PC12 cells: an interfacial model for functional studies in neurons.

    Directory of Open Access Journals (Sweden)

    Johan Jaime Medina Benavente

    Full Text Available Silicon nitride is a biocompatible material that is currently used as an interfacial surface between cells and large-scale integration devices incorporating ion-sensitive field-effect transistor technology. Here, we investigated whether a poly-L-lysine coated silicon nitride surface is suitable for the culture of PC12 cells, which are widely used as a model for neural differentiation, and we characterized their interaction based on cell behavior when seeded on the tested material. The coated surface was first examined in terms of wettability and topography using contact angle measurements and atomic force microscopy and then, conditioned silicon nitride surface was used as the substrate for the study of PC12 cell culture properties. We found that coating silicon nitride with poly-L-lysine increased surface hydrophilicity and that exposing this coated surface to an extracellular aqueous environment gradually decreased its roughness. When PC12 cells were cultured on a coated silicon nitride surface, adhesion and spreading were facilitated, and the cells showed enhanced morphological differentiation compared to those cultured on a plastic culture dish. A bromodeoxyuridine assay demonstrated that, on the coated silicon nitride surface, higher proportions of cells left the cell cycle, remained in a quiescent state and had longer survival times. Therefore, our study of the interaction of the silicon nitride surface with PC12 cells provides important information for the production of devices that need to have optimal cell culture-supporting properties in order to be used in the study of neuronal functions.

  15. PEM Fuel Cells with Bio-Ethanol Processor Systems A Multidisciplinary Study of Modelling, Simulation, Fault Diagnosis and Advanced Control

    CERN Document Server

    Feroldi, Diego; Outbib, Rachid

    2012-01-01

    An apparently appropriate control scheme for PEM fuel cells may actually lead to an inoperable plant when it is connected to other unit operations in a process with recycle streams and energy integration. PEM Fuel Cells with Bio-Ethanol Processor Systems presents a control system design that provides basic regulation of the hydrogen production process with PEM fuel cells. It then goes on to construct a fault diagnosis system to improve plant safety above this control structure. PEM Fuel Cells with Bio-Ethanol Processor Systems is divided into two parts: the first covers fuel cells and the second discusses plants for hydrogen production from bio-ethanol to feed PEM fuel cells. Both parts give detailed analyses of modeling, simulation, advanced control, and fault diagnosis. They give an extensive, in-depth discussion of the problems that can occur in fuel cell systems and propose a way to control these systems through advanced control algorithms. A significant part of the book is also given over to computer-aid...

  16. Generation of human/rat xenograft animal model for the study of human donor stem cell behaviors in vivo

    Institute of Scientific and Technical Information of China (English)

    Yan Sun; Dong Xiao; Xing-Hua Pan; Ruo-Shuang Zhang; Guang-Hui Cui; Xi-Gu Chen

    2007-01-01

    AIM: To accurately and realistically elucidate human stem cell behaviors In vivo and the fundamental mechanisms controlling human stem cell fates in vivo, which is urgently required in regenerative medicine and treatments for some human diseases, a surrogate human-rat chimera model was developed.METHODS: Human-rat chimeras were achieved by in utero transplanting low-density mononuclear cells from human umbilical cord blood into the fetal rats at 9-11 d of gestation, and subsequently, a variety of methods, including flow cytometry, PCR as well as immunohistochemical assay, were used to test the human donor contribution in the recipients.RESULTS: Of 29 live-born recipients, 19 had the presence of human CD45+ cells in peripheral blood (PB) detected by flow cytometry, while PCR analysis on genomic DNA from 11 different adult tissues showed that 14 selected from flow cytometry-positive 19 animals possessed of donor-derived human cell engraftment in multiple tissues (i.e. liver, spleen, thymus, heart, kidney, blood, lung, muscle, gut and skin) examined at the time of tissue collection, as confirmed by detecting human β2-microglobulin expression using immunohistochemistry.In this xenogeneic system, the engrafted donor-derived human cells persisted in multiple tissues for at least 6 mo after birth. Moreover, transplanted human donor cells underwent site-specific differentiation into CK18-positive human cells in chimeric liver and CD45-positive human cells in chimeric spleen and thymus of recipients.CONCLUSION: Taken together, these findings suggest that we successfully developed human-rat chimeras, in which xenogeneic human cells exist up to 6 mo later. This humanized small animal model, which offers an in vivo environment more closely resembling to the situations in human, provides an invaluable and effective approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the future

  17. Quantitative radiobiology: a method of in vivo study of germ cells exposed to gamma and neutron radiation, descriptive models

    International Nuclear Information System (INIS)

    A technique of quantitative analysis of in vivo cell survival of the germ cells of male rats was developed from the gonadal weight loss observed after irradiation. This technique - both global and functional - of quantifiying a cellular damage has several advantages: cell survival is completely studied in vivo; the dose range investigated is large; the results can be extended to man. The cell survival after γ and neutron exposure thus determined was investigated in the light of four cell survival theories: LEA's target theory; KELLERER and ROSSI's theory of dual action, CHADWICKS and LEENHOUT's molecular theory, and DELATTRE's general theory of transformation systems. The experimental results were well described by each theory. It was therefore concluded that the fundamental oneness of these theories should make it possible to include them all in a strict conceptual frame

  18. Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: a model system to study neurotoxicity in Alzheimer's disease.

    Science.gov (United States)

    Vazin, Tandis; Ball, K Aurelia; Lu, Hui; Park, Hyungju; Ataeijannati, Yasaman; Head-Gordon, Teresa; Poo, Mu-ming; Schaffer, David V

    2014-02-01

    Alzheimer's disease (AD) is among the most prevalent forms of dementia affecting the aging population, and pharmacological therapies to date have not been successful in preventing disease progression. Future therapeutic efforts may benefit from the development of models that enable basic investigation of early disease pathology. In particular, disease-relevant models based on human pluripotent stem cells (hPSCs) may be promising approaches to assess the impact of neurotoxic agents in AD on specific neuronal populations and thereby facilitate the development of novel interventions to avert early disease mechanisms. We implemented an efficient paradigm to convert hPSCs into enriched populations of cortical glutamatergic neurons emerging from dorsal forebrain neural progenitors, aided by modulating Sonic hedgehog (Shh) signaling. Since AD is generally known to be toxic to glutamatergic circuits, we exposed glutamatergic neurons derived from hESCs to an oligomeric pre-fibrillar forms of Aβ known as "globulomers", which have shown strong correlation with the level of cognitive deficits in AD. Administration of such Aβ oligomers yielded signs of the disease, including cell culture age-dependent binding of Aβ and cell death in the glutamatergic populations. Furthermore, consistent with previous findings in postmortem human AD brain, Aβ-induced toxicity was selective for glutamatergic rather than GABAeric neurons present in our cultures. This in vitro model of cortical glutamatergic neurons thus offers a system for future mechanistic investigation and therapeutic development for AD pathology using human cell types specifically affected by this disease. PMID:24055772

  19. A novel co-culture model of murine K12 osteosarcoma cells and S. aureus on common orthopedic implant materials: 'the race to the surface' studied in vitro.

    Science.gov (United States)

    McConda, David B; Karnes, Jonathan M; Hamza, Therwa; Lindsey, Brock A

    2016-07-01

    Infection is a major cause of orthopedic implant failure. There are few studies assessing both tissue cell and bacterial adherence on common orthopedic implant materials in a co-culture environment. An in vitro co-culture model was created using K12 osteosarcoma cells and Staphylococcus aureus in a medium incubated over metal disks for 48 h. The results showed that, in the presence of S. aureus, there were fewer osteosarcoma cells attached to the disks for all substrata tested. There were significantly more osteosarcoma cells adhering to the cobalt chrome than the stainless steel and titanium disks. Overall, in the presence of osteosarcoma cells, there were more bacteria adhering to the disks for all the substrata tested, with significantly more bacteria adhering to the stainless steel disks compared to cobalt chrome and titanium disks. Scanning electron microscopy verified that osteosarcoma cells and bacteria were adherent to the metal disks after incubation for 48 h. Furthermore, the observation that more bacteria were in the co-culture than in the control sample suggests that the osteosarcoma cells serve as a nutrient source for the bacteria. Future models assessing the interaction of osteogenic cells with bacteria on a substratum would be improved if the model accounted for the role of the immune system in secondary bone healing. PMID:27142312

  20. Adhesion of endometrial cells labeled with 111 Indium-tropolonate to peritoneum: a novel in vitro model to study endometriosis

    OpenAIRE

    Beliard, Aude; Noël, Agnès; Goffin, Frédéric; Frankenne, Francis; Foidart, Jean-Michel

    2003-01-01

    Objective: To evaluate, in a new original in vitro assay, putative factors that could modulate the adhesion of endometrial cells to peritoneum. Design: Prospective, controlled in vitro study. Setting: Academic research laboratory. Patient(s): Fourteen nonmenopausal women undergoing hysterectomy or laparoscopy for benign gynecologic indication. Intervention(s): Endometrial cells obtained from women with regular cycles without endometriosis were labeled with (111)Indium and confronted in vitro ...

  1. Models for Natural Killer Cell Repertoire Formation

    Directory of Open Access Journals (Sweden)

    Ramit Mehr

    2003-01-01

    Full Text Available Natural killer (NK cells lyse only cells that do not express sufficient levels of self class I MHC molecules. Inhibition of lysis is mediated by inhibitory receptors expressed by NK cells, such as the murine Ly49 receptors, that bind to MHC class I molecules. Since inhibitory receptor genes and MHC class I genes are located on different chromosomes, and are hence not automatically co-inherited, NK cells apparently adapt to the MHC environment during their development. Two models have been proposed to account for this “education” process of NK cells. The two-step selection model postulates that developing NK cells initiate the stable expression of a random set of Ly49 genes, and then undergo two selection steps, one for cells that express a sufficient number of self-MHC receptors, and one against cells that express too many inhibitory receptors. The sequential model postulates that a cell keeps initiating the stable expression of additional inhibitory receptors until a sufficient expression level of self-MHC specific receptors is reached, and the cell matures. In this study we implement both models in computer simulations, and compare simulation results to experimental data, in order to evaluate the relative plausibility of the two models.

  2. The construction of chimeric T-Cell receptor with spacer base of modeling study of VHH and MUC1 interaction.

    Science.gov (United States)

    Pirooznia, Nazanin; Hasannia, Sadegh; Taghdir, Majid; Rahbarizadeh, Fatemeh; Eskandani, Morteza

    2011-01-01

    Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, VHH and CD8α, and FcgIIα are used as signaling moieties, costimulating domain, antibody, and spacers, respectively. To investigate the influence of the ligation of spacers on the conformational structure of VHH, models of VHH were constructed. Molecular dynamics simulation was run to study the influence of the presence of spacers on the conformational changes in the binding sites of VHH. Root mean square deviation and root mean square fluctuation of critical segments in the binding site showed no noticeable differences with those in the native VHH. Results from molecular docking revealed that the presence of spacer FcgIIα causes an increasing effect on VHH with MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1. Expression analysis and evaluation of their functions were examined. The results showed good expression and function. PMID:21869862

  3. The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

    Directory of Open Access Journals (Sweden)

    Nazanin Pirooznia

    2011-01-01

    Full Text Available Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, VHH and CD8α, and FcgIIα are used as signaling moieties, costimulating domain, antibody, and spacers, respectively. To investigate the influence of the ligation of spacers on the conformational structure of VHH, models of VHH were constructed. Molecular dynamics simulation was run to study the influence of the presence of spacers on the conformational changes in the binding sites of VHH. Root mean square deviation and root mean square fluctuation of critical segments in the binding site showed no noticeable differences with those in the native VHH. Results from molecular docking revealed that the presence of spacer FcgIIα causes an increasing effect on VHH with MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1. Expression analysis and evaluation of their functions were examined. The results showed good expression and function.

  4. Characterization of mouse cell line IMA 2.1 as a potential model system to study astrocyte functions

    OpenAIRE

    Schildknecht, Stefan; Kirner, Susanne; Henn, Anja; Gasparic, Karlo; Pape, Regina; Efremova, Liudmila; Maier, Olaf; Fischer, Roman; Leist, Marcel

    2012-01-01

    Astrocytes are activated in most chronic neurodegenerative diseases associated with inflammatory events such as Parkinson’s disease or Alzheimer’s disease, but also in stroke. Due to an aging population worldwide, research efforts in these areas are likely to expand in the future. This will entail an increaseddemand for appropriate experimental models. We introduce here the new immortalized mouse astrocyte cell line IMA 2.1 as an alternative to currently used primary astrocyte cultures. IMA 2...

  5. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity

    OpenAIRE

    Wu J; Yan LJ

    2015-01-01

    Jinzi Wu, Liang-Jun Yan Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA Abstract: Chronic hyperglycemia and the corresponding glucotoxicity are the main pathogenic mechanisms of diabetes and its complications. Streptozotocin (STZ)-induced diabetic animal models are useful platforms for the understanding of β cell glucotoxicity in diabetes. As diabetes induced by a single STZ injection is often re...

  6. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity

    OpenAIRE

    Yan, Liang-Jun

    2015-01-01

    Jinzi Wu, Liang-Jun Yan Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA Abstract: Chronic hyperglycemia and the corresponding glucotoxicity are the main pathogenic mechanisms of diabetes and its complications. Streptozotocin (STZ)-induced diabetic animal models are useful platforms for the understanding of β cell glucotoxicity in diabetes. As diabetes induced by a single STZ injection is ofte...

  7. Establishment and Characterization of a New Muscle Cell Line of Zebrafish (Danio rerio) as an In Vitro Model for Gene Expression Studies.

    Science.gov (United States)

    Kumar, Amit; Singh, Neha; Goswami, Mukunda; Srivastava, J K; Mishra, Akhilesh K; Lakra, W S

    2016-07-01

    A new continuous fibroblast cell line was established from the muscle tissue of healthy juvenile Danio rerio (Zebrafish) through explant method. Fish cell lines serve as useful tool for investigating basic fish biology, as a model for bioassay of environmental toxicant, toxicity ranking, and for developing molecular biomarkers. The cell line was continuously subcultured for a period of 12 months (61 passages) and maintained at 28 °C in L-15 medium supplemented with 10% FBS and 10 ng/mL of basic fibroblastic growth factor (bFGF) without use of antibiotics. Its growth rate was proportional to the FBS concentration, with optimum growth at 15% FBS. DNA barcoding (16SrRNA and COX1) was used to authenticate the cell line. Cells were incubated with propidium iodide and sorted via flow cytometry to calculate the DNA content to confirm the genetic stability. Significant green fluorescent protein (GFP) signals confirmed the utility of cell line in transgenic and genetic manipulation studies. In vitro assay was performed with MTT to examine the growth potential of the cell line. The muscle cell line would provide a novel invaluable in vitro model to identify important genes to understand regulatory mechanisms that govern the molecular regulation of myogenesis and should be useful in biomedical research. PMID:26985868

  8. Engineered Models of Confined Cell Migration.

    Science.gov (United States)

    Paul, Colin D; Hung, Wei-Chien; Wirtz, Denis; Konstantopoulos, Konstantinos

    2016-07-11

    Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topographies found in the body. Therefore, a number of experimental in vitro models that confine and impose forces on cells in well-defined microenvironments have been engineered. We describe the design and use of microfluidic microchannel devices, grooved substrates, micropatterned lines, vertical confinement devices, patterned hydrogels, and micropipette aspiration assays for studying cell responses to confinement. Use of these devices has enabled the delineation of changes in cytoskeletal reorganization, cell-substrate adhesions, intracellular signaling, nuclear shape, and gene expression that result from physical confinement. These assays and the physiologically relevant signaling pathways that have been elucidated are beginning to have a translational and clinical impact. PMID:27420571

  9. The study of responses to 'model' DNA breaks induced by restriction endonucleases in cells and cell-free systems: achievements and difficulties

    International Nuclear Information System (INIS)

    The use of restriction endonucleases (RE) as a means of implicating DNA double-strand breaks (dsb) in cellular responses is reviewed. The introduction of RE into cells leads to many of the responses known to be characteristic of radiation damage -cell killing, chromosomal aberration, oncogenic transformation, gene mutation and amplification. Additionally, radiosensitive cell lines are hypersensitive to RE, including those from the human disorder ataxia-telangiectasia. However, quantitation of response and comparisons of the effectiveness of different RE are difficult, partly because of unknown activity and lifetime of RE in the cell. Re-induced dsb have also been used to reveal molecular mechanisms of repair and misrepair at specific sites in DNA. Dsb have been implicated in recombination processes including those leading to illegitimate rejoining (formation of deletions and rearrangements) at short sequence features in DNA. Also model dsb act as a signal to activate other cellular processes, which may influence or indirectly cause some responses, including cell death. In these signalling responses the detailed chemistry at the break site may not be very important, perhaps explaining why there is considerable overlap in responses to RE and to ionizing radiations. (author)

  10. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Karim Si-Tayeb

    2016-01-01

    Full Text Available Proprotein convertase subtilisin kexin type 9 (PCSK9 is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF mutations are associated with autosomal dominant hypercholesterolemia (ADH and premature atherosclerosis, PCSK9 loss-of-function (LOF mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL. However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs. Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R secreted less PCSK9 in the media (−38.5%; P=0.038 and had a 71% decrease (P<0.001 of low-density lipoprotein (LDL uptake, whereas cells originally derived from an individual with FHBL (HLC-R104C/V114A displayed a strong decrease in PCSK9 secretion (−89.7%; P<0.001 and had a 106% increase (P=0.0104 of LDL uptake. Pravastatin treatment significantly enhanced LDL receptor (LDLR and PCSK9 mRNA gene expression, as well as PCSK9 secretion and LDL uptake in both control and S127R HLCs. Pravastatin treatment of multiple clones led to an average increase of LDL uptake of 2.19±0.77-fold in HLC-S127R compared to 1.38±0.49 fold in control HLCs (P<0.01, in line with the good response to statin treatment of individuals carrying the S127R mutation (mean LDL cholesterol reduction=60.4%, n=5. In conclusion, urine samples provide an attractive and convenient source of somatic cells for reprogramming and hepatocyte differentiation, but also a powerful tool to further decipher PCSK9 mutations and function.

  11. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia

    Science.gov (United States)

    Si-Tayeb, Karim; Idriss, Salam; Champon, Benoite; Caillaud, Amandine; Pichelin, Matthieu; Arnaud, Lucie; Lemarchand, Patricia; Le May, Cédric; Zibara, Kazem; Cariou, Bertrand

    2016-01-01

    ABSTRACT Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs) as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs). Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R) secreted less PCSK9 in the media (−38.5%; P=0.038) and had a 71% decrease (P<0.001) of low-density lipoprotein (LDL) uptake, whereas cells originally derived from an individual with FHBL (HLC-R104C/V114A) displayed a strong decrease in PCSK9 secretion (−89.7%; P<0.001) and had a 106% increase (P=0.0104) of LDL uptake. Pravastatin treatment significantly enhanced LDL receptor (LDLR) and PCSK9 mRNA gene expression, as well as PCSK9 secretion and LDL uptake in both control and S127R HLCs. Pravastatin treatment of multiple clones led to an average increase of LDL uptake of 2.19±0.77-fold in HLC-S127R compared to 1.38±0.49 fold in control HLCs (P<0.01), in line with the good response to statin treatment of individuals carrying the S127R mutation (mean LDL cholesterol reduction=60.4%, n=5). In conclusion, urine samples provide an attractive and convenient source of somatic cells for reprogramming and hepatocyte differentiation, but also a powerful tool to further decipher PCSK9 mutations and function. PMID:26586530

  12. Physical models of cell motility

    CERN Document Server

    2016-01-01

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

  13. AlgiMatrix™ Based 3D Cell Culture System as an In-Vitro Tumor Model for Anticancer Studies

    OpenAIRE

    Godugu, Chandraiah; Patel, Apurva R.; Desai, Utkarsh; Andey, Terrick; Sams, Alexandria; Singh, Mandip

    2013-01-01

    Background Three-dimensional (3D) in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening. Methods Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100–300 µm. Spheroids were grown in two weeks in cultures without co...

  14. A study of V79 cell survival after for proton and carbon ion beams as represented by the parameters of Katz' track structure model

    DEFF Research Database (Denmark)

    Grzanka, Leszek; Waligórski, M. P. R.; Bassler, Niels

    Katz’s theory of cellular track structure (1) is an amorphous analytical model which applies a set of four cellular parameters representing survival of a given cell line after ion irradiation. Usually the values of these parameters are best fitted to a full set of experimentally measured survival...... curves available for a variety of ions. Once fitted, using these parameter values and the analytical formulae of the model calculations, cellular survival curves and RBE may be predicted for that cell line after irradiation by any ion, including mixed ion fields. While it is known that the Katz model...... parameters fitted to heavier ion data may yield unsatisfactory predictions of proton response, to our knowledge, no comprehensive data set which includes proton and heavier ion irradiations, measured in one laboratory, has been published. To study the consistency of evaluating parameters of this model from...

  15. A mathematical model to study the performance of a proton exchange membrane fuel cell in a dead-ended anode mode

    International Nuclear Information System (INIS)

    Highlights: • This model can predict the performance of a single cell in a dead-ended anode mode. • The hypothesis of how current density affects nitrogen accumulation is proposed. • The model was calibrated and validated by experiments. • Nitrogen concentration is regarded as a parameter for anode purge strategy. - Abstract: When a proton exchange membrane fuel cell (PEMFC) system is operated in the dead-ended anode mode, nitrogen will gradually permeate from the cathode to the anode. The accumulation of nitrogen in the anode causes a performance drop, which can be recovered by purging. The purge strategy depends on operating conditions of the PEMFC. To investigate the effect of operating conditions on the performance of a PEMFC with a dead-ended anode, a mathematical model is developed to estimate the nitrogen crossover and accumulation in the anode of the PEMFC, especially for varying-load operations. The effect of operating current density on nitrogen crossover is coupled in the model. Parameters in the model are calibrated according to experimental data. The experiments are designed to measure the voltage variations of the single cell with dead-ended anode at different operating current densities. The effect of current density on purge frequency and voltage variation is shown. Simulation results by this calibrated model agree well with experimental data. The transient of hydrogen concentration in the anode is investigated by the model. A purge strategy is suggested at the end of this study

  16. Development of representative models for the study of gastric cancer and evaluation of potential antitumor agents in primary gastric cancer cells and gastric metastasis in liver

    International Nuclear Information System (INIS)

    Gastric cancer has been the sixth most common malignancy worldwide and the leading cause of death by tumors in Costa Rica, the survival of patients is limited by difficulties in diagnosis and the lack of therapeutic options to improve life expectancy. The study has conducted a number of research models that will allow in the future to better understand the pathology of this tumor and it has evaluated the therapeutic action of naturally occurring in gastric cancer cells. A vivo model of carcinogenesis in stomachs of Wistar rats, has achieved to establish by means of chemical induction with MNNG, in which it has been possible to observe the appearance of tumors in the stratified epithelium flat keratinized starting from week 22 of experiment; while for the 40th week adenomas were observed in the simple cylindrical epithelium. Additionally, the role of Helicobacter pylori was inquired in the development of gastric cancer by inoculation of two strains of bacteria (CagA + and CagA-) in the stomach of Wistar rats, as well as the effect of his administration together with MNNG. However, the results of these models have been limited due to the lack of detection of the bacteria in the stomachs of rats inoculated. In addition, it has established an in vitro model of threedimensional cell culture, which has allowed to reproduce some of the characteristics observed in vivo in the tumors, in this case it was determined that the two gastric cancer cell lines have showed a different behavior, since the cells NCI-N87 from a in metastasis gastric liver were able to form steroids compact whereas AGS cells have been originate from a primary tumor that has formed easily dispersible structures and not compact spheroids. Finally, the effect of natural retinoids ATRA and retinoic acid 13-cis were evaluated, as well as retinamide synthetic retinoid on the viability of the cells AGS and NCI-N87. Cytotoxicity assays using MTT have allowed to observe the reduction of a variation in the

  17. The Potential Health Benefits of Polyphenol-Rich Extracts from Cichorium intybus L. Studied on Caco-2 Cells Model

    OpenAIRE

    Elena Azzini; Giuseppe Maiani; Ivana Garaguso; Angela Polito; Foddai, Maria S.; Eugenia Venneria; Alessandra Durazzo; Federica Intorre; Lara Palomba; Rauseo, Maria L.; Ginevra Lombardi-Boccia; Fabio Nobili

    2016-01-01

    Phytochemicals can exert their bioactivity without reaching the systemic circulation; scarcely absorbed antioxidants might reach the large bowel contributing to protection from oxidative damage-induced gastrointestinal diseases. In the present work, we aimed to study the relationship between potential activity of polyphenol-rich extracts from Cichorium intybus L. and changes in morphological characteristics on Caco-2 cells. Phytochemicals content (carotenoids and flavonoids) and total antioxi...

  18. The perfused isolated lung as a possible model for the study of lipid synthesis by type II cells in their natural environment

    International Nuclear Information System (INIS)

    The incorporation of radioactively labeled palmitate and acetate into total and disaturated phosphatidylcholines was studied in the perfused whole lung, in surfactant secreted during perfusion, and in isolated alveolar type II cells. Exogenously added palmitate was found to be incorporated preferentially into the 2-position of total and disaturated phosphatidylcholines in all cases. Acetate, when supplied at a high concentration, was incorporated preferentially into the 2-position in all cases. However, acetate supplied at a low concentration was incorporated preferentially into the 2-position in type II cells and in surfactant, but preferentially into the 1-position in the whole lung. The dissimilarity in incorporation of acetate between isolated type II cells and perfused whole lung and the similarity in this respect between isolated type II cells and surfactant indicate that the perfused isolated lung may only be a good model for studying the synthesis of surfactant components by the type II cells in their natural environment if the products of processes in type II cells are separated from products of other cells after the perfusion. Both in surfactant and in lavaged lung tissue, labeled palmitate and acetate incorporated mainly into the 2-position of phosphatidylglycerol. This indicates that remodeling reactions are involved in the synthesis of dipalmitoylphosphatidylglycerol

  19. Study of neuroprotective function of Ginkgo biloba extract (EGb761) derived-flavonoid monomers using a three-dimensional stem cell-derived neural model.

    Science.gov (United States)

    Wu, Yueting; Sun, Jiachen; George, Julian; Ye, Hua; Cui, Zhanfeng; Li, Zhaohui; Liu, Qingxi; Zhang, Yaozhou; Ge, Dan; Liu, Yang

    2016-05-01

    An in vitro three-dimensional (3D) cell culture system that can mimic organ and tissue structure and function in vivo will be of great benefit for drug discovery and toxicity testing. In this study, the neuroprotective properties of the three most prevalent flavonoid monomers extracted from EGb 761 (isorharmnetin, kaempferol, and quercetin) were investigated using the developed 3D stem cell-derived neural co-culture model. Rat neural stem cells were differentiated into co-culture of both neurons and astrocytes at an equal ratio in the developed 3D model and standard two-dimensional (2D) model using a two-step differentiation protocol for 14 days. The level of neuroprotective effect offered by each flavonoid was found to be aligned with its effect as an antioxidant and its ability to inhibit Caspase-3 activity in a dose-dependent manner. Cell exposure to quercetin (100 µM) following oxidative insult provided the highest levels of neuroprotection in both 2D and 3D models, comparable with exposure to 100 µM of Vitamin E, whilst exposure to isorhamnetin and kaempferol provided a reduced level of neuroprotection in both 2D and 3D models. At lower dosages (10 µM flavonoid concentration), the 3D model was more representative of results previously reported in vivo. The co-cultures of stem cell derived neurons and astrocytes in 3D hydrogel scaffolds as an in vitro neural model closely replicates in vivo results for routine neural drug toxicity and efficacy testing. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:735-744, 2016. PMID:26919031

  20. Studying nanotube-based oscillators and their application as memory cells via nanoscale continuum modeling and simulation

    OpenAIRE

    Shaoping Xiao; Weixuan Yang

    2015-01-01

    A nanoscale continuum model of carbon nanotube-based oscillators is proposed in this paper. In the continuum model, the nanotube is discretized via the meshfree particle method. The atomistic interlayer interaction between the outer and inner tubes is approximated by the interlayer interaction between particles. The mechanical behaviors of oscillators are studied and compared well with molecular dynamics simulation results. The nanotube-based oscillator can be employed to design a...

  1. Cooling of a Diesel Reformate Fuelled Solid Oxide Fuel Cell by Internal Reforming of Methane: A Modelling Study

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiaowei; Alexander Kromp

    2013-01-01

    In this paper a system combining a diesel reformer using catalytic partial oxidation (CPOX) with the Solid Oxide Fuel Cell (SOFC) for Auxiliary Power Unit (APU) applications is modeled with respect to the cooling effect provided by internal reforming of methane in anode gas channel.A model mixture consisting of 80% n-hexadecane and 20% 1-methylnaphthalin is used to simulate the commercial diesel.The modelling consists of several steps.First,equilibrium gas composition at the exit of CPOX reformer is modelled in terms oxygen to carbon (O/C) ratio,fuel utilization ratio and anode gas recirculation.Second,product composition,especially methane content,is determined for the methanation process at the operating temperatures ranging from 500 ℃ to 520 ℃.Finally,the cooling power provided by internal reforming of methane in SOFC fuel channel is calculated for two concepts to increase the methane content of the diesel reformate.The results show that the first concept,operating the diesel reformer at low O/C ratio and/or recirculation ratio,is not realizable due to high probability of coke formation,whereas the second concept,combining a methanation process with CPOX,can provide a significant cooling effect in addition to the conventional cooling concept which needs higher levels of excess air.

  2. Ultrastructural Islet Study of Early Fibrosis in the Ren2 Rat Model of Hypertension. Emerging Role of the Islet Pancreatic Pericyte-Stellate Cell

    Directory of Open Access Journals (Sweden)

    Melvin R Hayden

    2007-11-01

    Full Text Available Context Type 2 diabetes mellitus is a multifactorial disease with polygenic and environmental stressors resulting in multiple metabolic toxicities and islet oxidative stress. We have integrated the role of the islet reninangiotensin system (RAS in the pathogenesis of early islet fibrosis utilizing the transgenic (mRen227 rodent model of hypertension and tissue RAS overexpression. Objective The Ren2 pancreatic islet tissue was evaluated with transmission electron microscopy to study both early cellular and extracellular matrix remodeling. Animals Four 9- to 10-week-old male Ren2 untreated models and four Sprague Dawley sex and age matched controls were used. Design Ultrastructural study to compare pancreatic islet tissue. Main outcome measures Only qualitative and observational transmission electron microscopy findings are reported. Results Major remodeling differences in the Ren2 model were found to be located within the islet exocrine interface, including deposition of early fibrillar-banded collagen (fibrosis and cellular remodeling of the pericyte suggesting proliferation, migration, hypertrophy and activation as compared to the Sprague Dawley controls. Conclusion This study points to the possibility of the pericyte cell being one of many contributors to the fibrogenic pool of cells important for peri-islet fibrosis as a result of excess angiotensin II at the local tissue level in the Ren2 model. These findings suggest that the pericyte may be capable of differentiating into the pancreatic stellate cell. This islet ultrastructure study supports the notion that pericyte cells could be the link between islet vascular oxidative stress and peri-islet fibrosis. Pericyte-endothelialpancreatic stellate cell associations and morphology are discussed.

  3. The non-obese diabetic mouse strain as a model to study CD8+ T cell function in relapsing and progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Prenitha Mercy eIgnatius Arokia Doss

    2015-10-01

    Full Text Available Multiple sclerosis (MS is a neurodegenerative disease resulting from an autoimmune attack on central nervous system myelin. While CD4+ T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8+ T lymphocytes play a key role. Intriguingly, CD8+ T cells accumulate in great numbers in the CNS in progressive MS, a form of the disease that is refractory to current disease-modifying therapies which target the CD4+ T cell response. Here, we discuss the function of CD8+ T cells in experimental autoimmune encephalomyelitis (EAE, a mouse model of MS. In particular, we describe EAE in non-obese diabetic (NOD background mice, which develop a pattern of disease characterized by multiple attacks and remissions followed by a progressively worsening phase. This is highly reminiscent of the pattern of disease observed in nearly half of MS patients. Particular attention is paid to a newly described transgenic mouse strain (1C6 on the NOD background whose CD4+ and CD8+ T cells are directed against the encephalitogenic peptide MOG[35-55]. Use of this model will give us a more complete picture of the role(s played by distinct T cell subsets in CNS autoimmunity.

  4. Mathematical modeling of a thermovoltaic cell

    Science.gov (United States)

    White, Ralph E.; Kawanami, Makoto

    1992-01-01

    A new type of battery named 'Vaporvolt' cell is in the early stage of its development. A mathematical model of a CuO/Cu 'Vaporvolt' cell is presented that can be used to predict the potential and the transport behavior of the cell during discharge. A sensitivity analysis of the various transport and electrokinetic parameters indicates which parameters have the most influence on the predicted energy and power density of the 'Vaporvolt' cell. This information can be used to decide which parameters should be optimized or determined more accurately through further modeling or experimental studies. The optimal thicknesses of electrodes and separator, the concentration of the electrolyte, and the current density are determined by maximizing the power density. These parameter sensitivities and optimal design parameter values will help in the development of a better CuO/Cu 'Vaporvolt' cell.

  5. Study on the therapeutic role of transplantation of human umbilical cord mesenchymal stem cells in NOD-SCID mouse model of gastrointestinal radiation damage

    International Nuclear Information System (INIS)

    Objective: To explore the therapeutic role of transplantation of human umbilical cord mesenchymal stem cells (MSC) in NOD-SCID mouse model of gastrointestinal radiation damage and search for the reliable donator cell resource for the treatment of acute enter radiation disease. Methods: To observe the potential of multi-differentiation of huma umbilical cord MSC in vitro, transplant human umbilical cord MSC which were labeled with CM-DiI to the mouse model and study not only the pathological changed of entero-mucosa using histochemical stain but also the location of MSC in the entero-mucosa of mouse model using confocal microscopy. Results: The lesions in the mice treated with MSC were improved obviously compared with that of control mice.Many CM-DiI + MSCs derived cells were distributed in intestinal mucosa and submucosa of the recipient mice, which indicated that MSCs-derived cells were involved in regeneration of the gastrointestinal radiation damage. Conclusion: The data indicate that systemically administrated MSCs maybe accelerated tissue repair in mouse model and it is hopeful in the treatment of human acute enter radiation sickness in the future. (authors)

  6. Concise review: Preclinical studies on human cell-based therapy in rodent ischemic stroke models: where are we now after a decade?

    Science.gov (United States)

    Leong, Wai Khay; Lewis, Martin D; Koblar, Simon A

    2013-06-01

    Stroke, a debilitating brain insult, afflicts millions of individuals globally each year. In the last decade, researchers have investigated cell-based therapy as an alternative strategy to improve neurological outcome following stroke. This concise review critically examines preclinical reports using human adult and fetal stem/progenitor cells in rodent models of ischemic stroke. As we enter the second decade of study, we should aim to optimize our collective likelihood to translational success for stroke victims worldwide. We advocate international consensus recommendations be developed for future preclinical research. PMID:23390084

  7. In vitro and in vivo studies with [18F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to investigate (a) in vitro the relationship between [18F]fluorocholine ([18F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [18F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [18F]FCH and that of [18F]fluorodeoxyglucose ([18F]FDG) were measured before and after cytotoxic therapy. [18F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [18F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC50 values calculated with the [18F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [18F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [18F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [18F]FCH in liver metastases but there was a significant uptake of [18F]FDG. Conclusions: In vitro studies suggested that the incorporation of [18F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [18F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [18F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded

  8. Creating a Buzz about Macrophages: The Fly as an In Vivo Model for Studying Immune Cell Behavior.

    Science.gov (United States)

    Weavers, Helen; Wood, Will

    2016-07-25

    Drosophila macrophages exhibit functional parallels with their vertebrate counterparts in both their early developmental roles and later diverse roles in health and disease. This, together with the fly's genetic tractability and opportunities for live imaging, has recently established Drosophila as a powerful model to study macrophage behavior in vivo. PMID:27459064

  9. Effects of human milk on blood and bone marrow cells in a malnourished mice model: comparative study with cow milk

    Directory of Open Access Journals (Sweden)

    Isabel García

    2013-12-01

    Full Text Available Introduction: It has been demonstrated that the alterations caused by nutrient deficiency can be reverted by adequate nutritional repletion. Objective: To perform comparative studies between human and cow milks in order to evaluate the impact of both milks on the recovery of blood and bone marrow cells affected in malnourished mice. Method: Weaned mice were malnourished after consuming a protein free diet for 21 days. Malnourished mice received cow or human milk (CM or HM for 7 or 14 consecutive days. During the period of administration of milk, the mice consumed the protein free diet ad libitum. The malnourished control (MNC group received only protein free diet whereas the well-nourished control (WNC mice consumed the balanced conventional diet. Results and Discussion: Both milks normalized serum albumin levels and improved thymus weight. Human milk was less effective than cow milk to increase body weight and serum transferrin levels. In contrast, human milk was more effective than cow milk to increase the number of leukocytes (WNC: 6.90 ± 1.60ª; MNC: 2.80 ± 0.90b; CM 7d: 3.74 ± 1.10b; HM 7d: 7.16 ± 1.90ª; CM 14d: 4.35 ± 1.20b; HM 14d: 6.75 ± 1.20ª (10(9/L;p < 0.05 and lymphocytes (WNC: 5.80 ± 0.36ª; MNC: 1.80 ± 0.40b; CM 7d: 2.50 ± 0.30b; HM 7d: 4.20 ± 0.50c; CM 14d: 3.30 ± 0.31d; HM 14d: 4.70 ± 0.28c (10(9/L;p < 0.05 in peripheral blood. Both milks induced an increment in mitotic pool cells in bone marrow and α-naphthyl butyrate esterase positive cells in peripheral blood. They also normalized phagocytic function in blood neutrophils and oxidative burst in peritoneal cells. Conclusion: Both milks were equally effective to exert favorable effects on the number of the bone marrow cells and the functions of the blood and peritoneal cells involved in immune response. However, only human milk normalized the number of leukocytes and increased the number of neutrophils in peripheral blood.

  10. Modeling Light Trapping in Nanostructured Solar Cells

    OpenAIRE

    Ferry, Vivian E.; Polman, Albert; Atwater, Harry A.

    2011-01-01

    The integration of nanophotonic and plasmonic structures with solar cells offers the ability to control and confine light in nanoscale dimensions. These nanostructures can be used to couple incident sunlight into both localized and guided modes, enhancing absorption while reducing the quantity of material. Here we use electromagnetic modeling to study the resonances in a solar cell containing both plasmonic metal back contacts and nanostructured semiconductor top contacts, identify the local ...

  11. Fast-ignition transport studies: Realistic electron source, integrated particle-in-cell and hydrodynamic modeling, imposed magnetic fields

    International Nuclear Information System (INIS)

    Transport modeling of idealized, cone-guided fast ignition targets indicates the severe challenge posed by fast-electron source divergence. The hybrid particle-in-cell (PIC) code Zuma is run in tandem with the radiation-hydrodynamics code Hydra to model fast-electron propagation, fuel heating, and thermonuclear burn. The fast electron source is based on a 3D explicit-PIC laser-plasma simulation with the PSC code. This shows a quasi two-temperature energy spectrum and a divergent angle spectrum (average velocity-space polar angle of 52°). Transport simulations with the PIC-based divergence do not ignite for >1 MJ of fast-electron energy, for a modest (70 μm) standoff distance from fast-electron injection to the dense fuel. However, artificially collimating the source gives an ignition energy of 132 kJ. To mitigate the divergence, we consider imposed axial magnetic fields. Uniform fields ∼50 MG are sufficient to recover the artificially collimated ignition energy. Experiments at the Omega laser facility have generated fields of this magnitude by imploding a capsule in seed fields of 50-100 kG. Such imploded fields will likely be more compressed in the transport region than in the laser absorption region. When fast electrons encounter increasing field strength, magnetic mirroring can reflect a substantial fraction of them and reduce coupling to the fuel. A hollow magnetic pipe, which peaks at a finite radius, is presented as one field configuration which circumvents mirroring.

  12. Decellularized Extracellular Matrix as an In Vitro Model to Study the Comprehensive Roles of the ECM in Stem Cell Differentiation

    OpenAIRE

    Takashi Hoshiba; Guoping Chen; Chiho Endo; Hiroka Maruyama; Miyuki Wakui; Eri Nemoto; Naoki Kawazoe; Masaru Tanaka

    2016-01-01

    Stem cells are a promising cell source for regenerative medicine. Stem cell differentiation must be regulated for applications in regenerative medicine. Stem cells are surrounded by extracellular matrix (ECM) in vivo. The ECM is composed of many types of proteins and glycosaminoglycans that assemble into a complex structure. The assembly of ECM molecules influences stem cell differentiation through orchestrated intracellular signaling activated by many ECM molecules. Therefore, it is importan...

  13. PEM Fuel Cells - Fundamentals, Modeling and Applications

    OpenAIRE

    Maher A.R. Sadiq Al-Baghdadi

    2013-01-01

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

  14. PEM Fuel Cells - Fundamentals, Modeling and Applications

    Directory of Open Access Journals (Sweden)

    Maher A.R. Sadiq Al-Baghdadi

    2013-01-01

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

  15. Lower bounds in the quantum cell probe model

    OpenAIRE

    Sen, Pranab; Venkatesh, S.

    2001-01-01

    We introduce a new model for studying quantum data structure problems -- the "quantum cell probe model". We prove a lower bound for the static predecessor problem in the address-only version of this model where we allow quantum parallelism only over the `address lines' of the queries. The address-only quantum cell probe model subsumes the classical cell probe model, and many quantum query algorithms like Grover's algorithm fall into this framework. Our lower bound improves the previous known ...

  16. MATHEMATICAL MODELING AND NUMERICAL STUDY OF THE HYDRODYNAMICS OF THE EXPERIMENTAL ELECTROCHEMICAL CELL WITH ROTATING DISK MEMBRANE

    Directory of Open Access Journals (Sweden)

    Kovalenko A. V.

    2013-12-01

    Full Text Available This article investigates hydrodynamic of experimental electrochemical cell with rotating disk in the cation exchange membrane. We have also investigated the flow in open, with the free surface of the solution and in hermetically closed cells. The main regularities of the hydrodynamics of the experimental cell at its real size were set

  17. Fast-ignition transport studies: Realistic electron source, integrated particle-in-cell and hydrodynamic modeling, imposed magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Strozzi, D. J.; Tabak, M.; Larson, D. J.; Divol, L.; Kemp, A. J.; Bellei, C.; Marinak, M. M.; Key, M. H. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (United States)

    2012-07-15

    Transport modeling of idealized, cone-guided fast ignition targets indicates the severe challenge posed by fast-electron source divergence. The hybrid particle-in-cell (PIC) code Zuma is run in tandem with the radiation-hydrodynamics code Hydra to model fast-electron propagation, fuel heating, and thermonuclear burn. The fast electron source is based on a 3D explicit-PIC laser-plasma simulation with the PSC code. This shows a quasi two-temperature energy spectrum and a divergent angle spectrum (average velocity-space polar angle of 52 Degree-Sign ). Transport simulations with the PIC-based divergence do not ignite for >1 MJ of fast-electron energy, for a modest (70 {mu}m) standoff distance from fast-electron injection to the dense fuel. However, artificially collimating the source gives an ignition energy of 132 kJ. To mitigate the divergence, we consider imposed axial magnetic fields. Uniform fields {approx}50 MG are sufficient to recover the artificially collimated ignition energy. Experiments at the Omega laser facility have generated fields of this magnitude by imploding a capsule in seed fields of 50-100 kG. Such imploded fields will likely be more compressed in the transport region than in the laser absorption region. When fast electrons encounter increasing field strength, magnetic mirroring can reflect a substantial fraction of them and reduce coupling to the fuel. A hollow magnetic pipe, which peaks at a finite radius, is presented as one field configuration which circumvents mirroring.

  18. Study on the radiosensitivity of nude mice model transplanted lung adenocarcinoma cell treated by β-elemene

    International Nuclear Information System (INIS)

    Objective: To explore the effect of β-element on the radiosensitivity of transplanted tumor, and its relationship with the expression of surviving. Methods: The transplanted mice model was established through the cell suspension inoculation. The mice with transplanted tumor size of 0.8-1.0 cm3 were randomly divided into 8 groups as blank control, 25, 45 and 100 mg/kg group, irradiation group, 25 mg/kg + irradiation group, 45 mg/kg + irradiation group, 100 mg/kg + irradiation group. The tumor size was measured every other day until tumor size was double, and the growth curve was obtained. The average tumor growth inhibition rate of β-element and tumor size were attained at 2, 4, 6 and 8 d after β-element injection. The expression of surviving was detected with immunohistochemistry. Results: The nude mice model was successfully established and the growth curves were obtained according to the tumor size. Between 2 and 8 d after β-elemene injection, the variation tendency of the average tumor growth inhibition rate was consistent with the size in β-elemene treatment groups. The antitumor effect of β-elemene was in a dose-dependent manner. The values of radiosensitivity enhancement factor were 0.84, 1.24, 2.04 for 25, 45 and 100 mg/kg group, respectively, and the optimal dose was 45 mg/kg. β-element had little effect on the expression of surviving, and the expression of surviving significantly enhanced in irradiation group and decreased in β-element + irradiation groups. Conclusions: β-elemene could enhance the tumor radiosensitivity through inhibition the expression of surviving. (authors)

  19. Study of plasma meniscus and beam halo in negative ion sources using three dimension in real space and three dimension in velocity space particle in cell model

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, S., E-mail: nishioka@ppl.appi.keio.ac.jp; Goto, I.; Hatayama, A. [Graduate School of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522 (Japan); Miyamoto, K. [School of Natural and Living Sciences Education, Naruto University of Education, 748 Nakashima, Takashima, Naruto-cho, Naruto-shi, Tokushima 772-8502 (Japan); Okuda, S.; Fukano, A. [Toshiba, 33 Isogo-chou, Isogo-ku, Yokohama-shi, Kanagawa 235-001 (Japan)

    2014-02-15

    Our previous study by two dimension in real space and three dimension in velocity space-particle in cell model shows that the curvature of the plasma meniscus causes the beam halo in the negative ion sources. The negative ions extracted from the periphery of the meniscus are over-focused in the extractor due to the electrostatic lens effect, and consequently become the beam halo. The purpose of this study is to verify this mechanism with the full 3D model. It is shown that the above mechanism is essentially unchanged even in the 3D model, while the fraction of the beam halo is significantly reduced to 6%. This value reasonably agrees with the experimental result.

  20. Study of plasma meniscus and beam halo in negative ion sources using three dimension in real space and three dimension in velocity space particle in cell model

    International Nuclear Information System (INIS)

    Our previous study by two dimension in real space and three dimension in velocity space-particle in cell model shows that the curvature of the plasma meniscus causes the beam halo in the negative ion sources. The negative ions extracted from the periphery of the meniscus are over-focused in the extractor due to the electrostatic lens effect, and consequently become the beam halo. The purpose of this study is to verify this mechanism with the full 3D model. It is shown that the above mechanism is essentially unchanged even in the 3D model, while the fraction of the beam halo is significantly reduced to 6%. This value reasonably agrees with the experimental result

  1. Human pluripotent stem cells: an emerging model in developmental biology

    OpenAIRE

    Zhu, Zengrong; Huangfu, Danwei

    2013-01-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development ‘in a dish’. We also...

  2. Study of the cetuximab-ionizing radiation association on a model of in vitro endothelial cells; Etude de l'association cetuximab-radiations ionisantes sur un modele de cellules endotheliales in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Vautravers-Dewas, C.; Rebucci, M.; Lansiaux, A. [Centre Oscar-Lambret, Inserm U837, Lab. de Pharmacologie Antitumorale, 59 - Lille (France); Peixoto, P. [Inserm U837, 59 - Lille (France); Lartigau, E. [Centre Oscar-Lambret, Dept. Universitaire de Radiotherapie, 59 - Lille (France)

    2009-10-15

    These data support the existence of functional signalling tracks downstream epidermal growth factor receptor (E.G.F.R.) in endothelial cells. But our in vitro model, in two dimensional calculations, did not allow to show a radiosensitivity by cetuximab. The study of functional consequences of the association cetuximab-irradiation treatment will be relevant in an in vitro three dimensional model and on xenografts. (N.C.)

  3. Iron and cell death in Parkinson's disease: a nuclear microscopic study into iron-rich granules in the parkinsonian substantia nigra of primate models

    Science.gov (United States)

    Thong, P. S. P.; Watt, F.; Ponraj, D.; Leong, S. K.; He, Y.; Lee, T. K. Y.

    1999-10-01

    Parkinson's disease is a degenerative brain disease characterised by a loss of cells in the substantia nigra (SN) region of the brain and accompanying biochemical changes such as inhibition of mitochondrial function, increased iron concentrations and decreased glutathione levels in the parkinsonian SN. Though the aetiology of the disease is still unknown, the observed biochemical changes point to the involvement of oxidative stress. In particular, iron is suspected to play a role by promoting free radical production, leading to oxidative stress and cell death. The increase in iron in the parkinsonian SN has been confirmed by several research groups, both in human post-mortem brains and in brain tissue from parkinsonian animal models. However, the question remains as to whether the observed increase in iron is a cause or a consequence of the SN cell death process. Our previous study using unilaterally 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-lesioned monkeys in a time sequence experiment has shown that the increase in bulk iron concentrations follow rather than precede dopaminergic cell death. However, changes in the localised iron concentrations, which may play a more direct role in SN cell death, may not be reflected at the bulk level. Indeed, we have observed iron-rich granules in parkinsonian SNs. From this time sequence study into the iron content of iron-rich granules in the SNs of an untreated control and unilaterally MPTP-lesioned parkinsonian models, we present the following observations: (1) Iron-rich granules are found in both control and parkinsonian SNs and are variable in size and iron content in any one model. (2) These iron-rich granules may be associated with neuromelanin granules found in the SN and are known to accumulate transition metal ions such as iron. (3) The early onset of bulk SN cell loss (35%) was accompanied by a significant elevation of iron in granules found in the MPTP-injected SN compared to the contra-lateral SN. This

  4. Iron and cell death in Parkinson's disease: a nuclear microscopic study into iron-rich granules in the parkinsonian substantia nigra of primate models

    International Nuclear Information System (INIS)

    Parkinson's disease is a degenerative brain disease characterised by a loss of cells in the substantia nigra (SN) region of the brain and accompanying biochemical changes such as inhibition of mitochondrial function, increased iron concentrations and decreased glutathione levels in the parkinsonian SN. Though the aetiology of the disease is still unknown, the observed biochemical changes point to the involvement of oxidative stress. In particular, iron is suspected to play a role by promoting free radical production, leading to oxidative stress and cell death. The increase in iron in the parkinsonian SN has been confirmed by several research groups, both in human post-mortem brains and in brain tissue from parkinsonian animal models. However, the question remains as to whether the observed increase in iron is a cause or a consequence of the SN cell death process. Our previous study using unilaterally 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-lesioned monkeys in a time sequence experiment has shown that the increase in bulk iron concentrations follow rather than precede dopaminergic cell death. However, changes in the localised iron concentrations, which may play a more direct role in SN cell death, may not be reflected at the bulk level. Indeed, we have observed iron-rich granules in parkinsonian SNs. From this time sequence study into the iron content of iron-rich granules in the SNs of an untreated control and unilaterally MPTP-lesioned parkinsonian models, we present the following observations: (1) Iron-rich granules are found in both control and parkinsonian SNs and are variable in size and iron content in any one model. (2) These iron-rich granules may be associated with neuromelanin granules found in the SN and are known to accumulate transition metal ions such as iron. (3) The early onset of bulk SN cell loss (35%) was accompanied by a significant elevation of iron in granules found in the MPTP-injected SN compared to the contra-lateral SN. This

  5. Enantioselective endocrine disrupting effects of omeprazole studied in the H295R cell assay and by molecular modeling.

    Science.gov (United States)

    Sørensen, Amalie Møller; Hansen, Cecilie Hurup; Bonomo, Silvia; Olsen, Lars; Jørgensen, Flemming Steen; Weisser, Johan Juhl; Kretschmann, Andreas Christopher; Styrishave, Bjarne

    2016-08-01

    Enantiomers possess different pharmacokinetic and pharmacodynamic properties and this may not only influence the therapeutic effect of a drug but also its toxicological effects. In the present work we investigated the potential enantioselective endocrine disrupting effects of omeprazole (OME) and its two enantiomers on the human steroidogenesis using the H295R cell line. Differences in production of 16 steroid hormones were analyzed using LC-MS/MS. Additionally, to evaluate the differences in binding modes of these enantiomers, docking and molecular dynamics (MD) simulations of S-omeprazole (S-OME) and R-omeprazole (R-OME) in CYP17A1, CYP19A1 and CYP21A2 were carried out. Exposing H295R cells to OME and its enantiomers resulted in an increase of progesterone (PRO) and 17α-hydroxy-progesterone (OH-PRO) levels. At the same time, a decrease in the corticosteroid and androgen synthesis was observed, indicating inhibition of CYP21A2 and CYP17A1. In both cases, the effect of R-OME was smaller compared to that of the S-OME and a certain degree of enantioselectivity of CYP17A1 and CYP21A2 was suggested. Docking indicated that the N-containing rings of OME possibly could interact with the iron atom of the heme for S-OME in CYP17A1 and S- and R-OME in CYP21A2. However, density functional theory calculations suggest that the direct N-Fe interaction is weak. The study demonstrates enantioselective differences in the endocrine disrupting potential of chiral drugs such as omeprazole. These findings may have potential implications for drug safety and drug design. PMID:27002602

  6. Efficient definitive endoderm induction from mouse embryonic stem cell adherent cultures: A rapid screening model for differentiation studies

    Directory of Open Access Journals (Sweden)

    Josué Kunjom Mfopou

    2014-01-01

    Full Text Available Definitive endoderm (DE differentiation from mouse embryonic stem cell (mESC monolayer cultures has been limited by poor cell survival or low efficiency. Recently, a combination of TGFβ and Wnt activation with BMP inhibition improved DE induction in embryoid bodies cultured in suspension. Based on these observations we developed a protocol to efficiently induce DE cells in monolayer cultures of mESCs. We obtained a good cell yield with 54.92% DE induction as shown by Foxa2, Sox17, Cxcr4 and E-Cadherin expression. These DE-cells could be further differentiated into posterior foregut and pancreatic phenotypes using a culture protocol initially developed for human embryonic stem cell (hESC differentiation. In addition, this mESC-derived DE gave rise to hepatocyte-like cells after exposure to BMP and FGF ligands. Our data therefore indicate a substantial improvement of monolayer DE induction from mESCs and support the concept that differentiation conditions for mESC-derived DE are similar to those for hESCs. As mESCs are easier to maintain and manipulate in culture compared to hESCs, and considering the shorter duration of embryonic development in the mouse, this method of efficient DE induction on monolayer will promote the development of new differentiation protocols to obtain DE-derivatives, like pancreatic beta-cells, for future use in cell replacement therapies.

  7. Modeling the Control of Planar Cell Polarity

    Science.gov (United States)

    Axelrod, Jeffrey D.; Tomlin, Claire J.

    2016-01-01

    A growing list of medically important developmental defects and disease mechanisms can be traced to disruption of the Planar Cell Polarity (PCP) pathway. The PCP system polarizes cells in epithelial sheets along an axis orthogonal to their apical-basal axis. Studies in the fruitfly, Drosophila, have led to the concept of a modular system controlling PCP. The components of the PCP signaling modules, and the effector systems with which they interact, function together to produce emergent patterns. Experimental methods allow the manipulation of individual PCP signaling molecules in specified groups of cells; these interventions not only perturb the polarization of the targeted cells at a subcellular level, but also perturb patterns of polarity at the multicellular level, often affecting nearby cells in characteristic ways. These kinds of experiments should, in principle, allow one to infer the architecture within and between modules, but the relationships between molecular interactions and tissue-level pattern are sufficiently complex that they defy intuitive understanding. Mathematical modeling has been an important tool to address these problems. This review explores the emergence of a local signaling hypothesis, and describes how a local intercellular signal, coupled with a directional cue, can give rise to global pattern. We will discuss the critical role mathematical modeling has played in guiding and interpreting experimental results, and speculate about future roles for mathematical modeling of PCP. Mathematical models at varying levels of abstraction have and are expected to continue contributing in distinct ways to understanding the regulation of PCP signaling. PMID:21755606

  8. Comparison of manufactured and modeled solar cell

    OpenAIRE

    Strachala, D.; Hylský, J.

    2015-01-01

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

  9. Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light

    International Nuclear Information System (INIS)

    Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m2 and abolished at 50 J/m2. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus-host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m2 of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m2) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m2. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m2 survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m2 survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m2) and 2 of 9 (100 J/m2)

  10. Efficient Source of Cells in Proximal Oviduct for Testing Non-Viral Expression Constructs in the Chicken Bioreactor Model and for Other in Vitro Studies.

    Science.gov (United States)

    Stadnicka, Katarzyna; Bodnar, Magdalena; Marszałek, Andrzej; Bajek, Anna; Drewa, Tomasz; Płucienniczak, Grazyna; Chojnacka-Puchta, Luiza; Cecuda-Adamczewska, Violetta; Dunisławska, Aleksandra; Bednarczyk, Marek

    2016-01-01

    This work shows the usefulness of chicken oviduct epithelial cells (COEC) in evaluating the efficacy of non-viral expression vectors carrying human therapeutic genes. Secondly, an efficient source of progenitor COEC for in vitro studies is described. Within the distal part of the oviduct, weak to moderate expression of a trans membrane glycoprotein (CD44) was observed. Single cells presenting only weak expression of CD44 were found in magnum sections. in vitro cultured oviduct cells originating from the distal oviduct were suitable for subculturing and showed a stable proliferation potential up to the 2nd passage. However, the pavimentous epithelial-like morphology of COEC was progressively lost over time and mainly a fibroblast-like monolayer was established in consecutive passages. Moreover, various commercial transfection agents including FuGENE6 and XtremeGENE9 DNA were used to optimize delivery of human interferon alfa-2a, (IFNα2a) a therapeutic protein gene under an ovalbumin promoter. The transfection efficiency of adherent COEC was estimated for up to 40% at a ratio of 6:1 of transfectant to pOVA5EIFN + GFP plasmid. Expression of IFNα2a was confirmed by western blotting in transformed COEC. In conclusion, the population of epithelial progenitor cells sourced from the distal oviduct can significantly contribute to in vitro culture of COEC, representing an efficient model to develop the production of avian bioreactors and other in vitro studies related to oviduct tissue. PMID:27172711

  11. Physical modeling studies of electrolyte flow due to gas evolution and some aspects of bubble behavior in advanced hall cells: Part I. Flow in cells with a flat anode

    Science.gov (United States)

    Shekhar, R.; Evans, J. W.

    1994-06-01

    The need for energy reduction in the electrolytic production of aluminum led to the concept of advanced Hall cells that can be operated at lower interelectrode gaps compared to existing cells. However, gas bubbles generated by the anodic reaction increase the resistivity of electrolyte and cancel out part of the reduction in interelectrode resistance expected from bringing the electrodes closer together. Therefore, the primary objective of this work was to determine a cell design in which flow can be managed to promote the removal of anode gas bubbles from the interelectrode gap. In particular, this article focuses on advanced Hall cells equipped with “flat” anodes, similar to those used in existing cells. The principal experimental tool has been a “water” model consisting of a large tank in which simulated anodes can be suspended in either the horizontal or near-horizontal configurations. Gas was generated by forcing compressed air through porous graphite, and the fine bubbles characteristic of inert anodes used in advanced Hall cells were produced by adding butanol to water. Velocities were measured using a laser-Doppler velocimeter (LDV). This study indicates that the existing cell configuration might not be the optimum configuration for advanced Hall cells. The results also show that operation of an advanced Hall cell with a fully submerged anode should give rise to higher electrolyte velocities and thus rapid removal of bubbles. The bubble effect should be further lowered in a near-horizontal configuration; however, the flow pattern could have an adverse effect on current efficiency and alumina distribution in the cell. It has also been shown that the bubble size, and, therefore, the physical properties of the electrolyte, can have a significant effect on the electrolyte flow pattern in the interelectrode gap.

  12. Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

    Science.gov (United States)

    Globus, Ruth K.; Searby, Nancy D.; Almeida, Eduardo A. C.; Sutijono, Darrell; Yu, Joon-Ho; Malouvier, Alexander; Doty, Steven B.; Morey-Holton, Emily; Weinstein, Steven L.; Dalton, Bonnie P. (Technical Monitor)

    2000-01-01

    Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We

  13. Modeling and simulation of the motion of deformable interfaces in a confined geometry : application to the study of the flow of red blood cells in microcirculation

    OpenAIRE

    Aouane, Othmane

    2015-01-01

    Vesicles are extensively used as a model for understanding dynamics and deformation of red blood cells at the individual level but also regarding collective phenomena and rheology. Vesicles’ membranes withstand to bending but do not have a shear resistance, unlike red blood cells, but they still share several dynamical properties with red blood cells, like tank-treading and tumbling under linear shear flow, or parachute and slipper shapes under Poiseuille flow. The red blood cells are known t...

  14. Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies

    International Nuclear Information System (INIS)

    Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono‐L‐phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies.

  15. Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, T., E-mail: fujitaku@hp.pref.hyogo.jp [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Andoh, T. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Division of Pediatrics, University of Miyazaki, Miyazaki 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi Medical School, Nangoku 783-8505 (Japan); Sonobe, H. [Department of Pathology, Chugoku Central Hospital, Fukuyama 720-0001 (Japan); Epstein, Alan L. [Department of Pathology, Keck School of Medicine,University of Southern California, Los Angeles,CA 90033 (United States); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Fukumori, Y.; Ichikawa, H. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies.

  16. Modeling sarcomagenesis using multipotent mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Rene Rodriguez; Ruth Rubio; Pablo Menendez

    2012-01-01

    Because of their unique properties,multipotent mesenchymal stem cells (MSCs) represent one of the most promising adult stem cells being used worldwide in a wide array of clinical applications.Overall,compelling evidence supports the long-term safety of ex vivo expanded human MSCs,which do not seem to transform spontaneously.However,experimental data reveal a link between MSCs and cancer,and MSCs have been reported to inhibit or promote tumor growth depending on yet undefined conditions.Interestingly,solid evidence based on transgenic mice and genetic intervention of MSCs has placed these cells as the most likely cell of origin for certain sarcomas.This research area is being increasingly explored to develop accurate MSC-based models of sarcomagenesis,which will be undoubtedly valuable in providing a better understanding about the etiology and pathogenesis of mesenchymal cancer,eventually leading to the development of more specific therapies directed against the sarcoma-initiating cell.Unfortunately,still little is known about the mechanisms underlying MSC transformation and further studies are required to develop bona fide sarcoma models based on human MSCs.Here,we comprehensively review the existing MSC-based models of sarcoma and discuss the most common mechanisms leading to tumoral transformation of MSCs and sarcomagenesis.

  17. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

    Directory of Open Access Journals (Sweden)

    Victoria Kegel

    2015-01-01

    Full Text Available Drug induced liver injury (DILI is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2±0.9×106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay and cell activity (XTT assay. The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  18. Bifurcation structure of the special class of nonstationary regimes emerging in the 2D inertially coupled, unit-cell model: Analytical study

    Science.gov (United States)

    Vorotnikov, K.; Starosvetsky, Y.

    2016-09-01

    Present work is devoted to the analytical investigation of the bifurcation structure of special class of nonstationary low-energy regimes emerging in the locally resonant unit-cell model. System under consideration comprises an outer mass with internal rotator and subject to the 2D, nonlinear local potential. These regimes are characterized by the slow, purely rotational motion of the rotator synchronized with the periodic energy beats between the axial and the lateral vibrations of the outer element. Thus the angular speed of the rotator and the beating frequency of the outer element satisfy the 1:2 resonance condition. In the present study these regimes are referred to as regimes of synchronous nonlinear beats (RSNB). Using the regular muti-scale analysis in the limit of low energy excitation we derive the slow-flow model. To showcase the evolution of RSNBs we used the special Poincaré map technique applied on the slow-flow model. Results of the Poincaré sections unveiled some interesting local bifurcations undergone by these regimes. Further analysis of the slow-flow model enabled us to describe the RSNBs analytically as well as exposed their entire bifurcation structure. The bifurcation analysis has shown the coexistence of several branches of RSNBs corresponding to the regimes of weak and strong, two-dimensional, recurrent energy channeling. We substantiate the results of the analytical study with numerical simulations of the full model and find them to be in the very good agreement.

  19. Process modeling of fuel cell vehicle power system

    Institute of Scientific and Technical Information of China (English)

    CHEN LiMing; LIN ZhaoJia; MA ZiFeng

    2009-01-01

    Constructed here is a mathematic model of PEM Fuel Cell Vehicle Power System which is composed of fuel supply model, fuel cell stack model and water-heat management model. The model was developed by Matiab/Simulink to evaluate how the major operating variables affect the output performances. Itshows that the constructed model can represent characteristics of the power system closely by comparing modeling results with experimental data, and it can be used in the study and design of fuel cell vehicle power system.

  20. Modeling keratinocyte wound healing dynamics: Cell-cell adhesion promotes sustained collective migration.

    Science.gov (United States)

    Nardini, John T; Chapnick, Douglas A; Liu, Xuedong; Bortz, David M

    2016-07-01

    The in vitro migration of keratinocyte cell sheets displays behavioral and biochemical similarities to the in vivo wound healing response of keratinocytes in animal model systems. In both cases, ligand-dependent Epidermal Growth Factor Receptor (EGFR) activation is sufficient to elicit collective cell migration into the wound. Previous mathematical modeling studies of in vitro wound healing assays assume that physical connections between cells have a hindering effect on cell migration, but biological literature suggests a more complicated story. By combining mathematical modeling and experimental observations of collectively migrating sheets of keratinocytes, we investigate the role of cell-cell adhesion during in vitro keratinocyte wound healing assays. We develop and compare two nonlinear diffusion models of the wound healing process in which cell-cell adhesion either hinders or promotes migration. Both models can accurately fit the leading edge propagation of cell sheets during wound healing when using a time-dependent rate of cell-cell adhesion strength. The model that assumes a positive role of cell-cell adhesion on migration, however, is robust to changes in the leading edge definition and yields a qualitatively accurate density profile. Using RNAi for the critical adherens junction protein, α-catenin, we demonstrate that cell sheets with wild type cell-cell adhesion expression maintain migration into the wound longer than cell sheets with decreased cell-cell adhesion expression, which fails to exhibit collective migration. Our modeling and experimental data thus suggest that cell-cell adhesion promotes sustained migration as cells pull neighboring cells into the wound during wound healing. PMID:27105673

  1. Balance of Nanostructure and Bimetallic Interactions in Pt Model Fuel Cell Catalysts: An in Situ XAS and DFT Study

    Energy Technology Data Exchange (ETDEWEB)

    Friebel, Daniel; Viswanathan, Venkatasubramanian; Miller, Daniel James; Anniyev, Toyli; Ogasawara, Hirohito; Larsen, Ask Hjorth; O' Grady, Christopher P.; Norskov, Jens K.; Nilsson, Anders

    2012-05-31

    We have studied the effect of nanostructuring in Pt monolayer model electrocatalysts on a Rh(111) single-crystal substrate on the adsorption strength of chemisorbed species. In situ high energy resolution fluorescence detection X-ray absorption spectroscopy at the Pt L(3) edge reveals characteristic changes of the shape and intensity of the 'white-line' due to chemisorption of atomic hydrogen (H(ad)) at low potentials and oxygen-containing species (O/OH(ad)) at high potentials. On a uniform, two-dimensional Pt monolayer grown by Pt evaporation in ultrahigh vacuum, we observe a significant destabilization of both H(ad) and O/OH(ad) due to strain and ligand effects induced by the underlying Rh(111) substrate. When Pt is deposited via a wet-chemical route, by contrast, three-dimensional Pt islands are formed. In this case, strain and Rh ligand effects are balanced with higher local thickness of the Pt islands as well as higher defect density, shifting H and OH adsorption energies back toward pure Pt. Using density functional theory, we calculate O adsorption energies and corresponding local ORR activities for fcc 3-fold hollow sites with various local geometries that are present in the three-dimensional Pt islands.

  2. 'A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies'

    International Nuclear Information System (INIS)

    The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis. Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC). Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor α (ERα)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 × 103 cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples. Tumorspheres isolated under defined culture

  3. A critical stress model for cell motility

    OpenAIRE

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

    2012-01-01

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

  4. Creation and Reproduction of Model Cells with Semipermeable Membrane

    OpenAIRE

    Sakaguchi, Hidetsugu

    2008-01-01

    A high activity of reactions can be confined in a model cell with a semipermeable membrane in the Schl\\"ogl model. It is interpreted as a model of primitive metabolism in a cell. We study two generalized models to understand the creation of primitive cell systems conceptually from the view point of the nonlinear-nonequilibrium physics. In the first model, a single-cell system with a highly active state confined by a semipermeable membrane is spontaneously created from an inactive homogeneous ...

  5. Development of an in vitro cell culture model to study milk to plasma ratios of therapeutic drugs

    Directory of Open Access Journals (Sweden)

    Maithili A Athavale

    2013-01-01

    Conclusion: Our preliminary effort to develop an in vitro physiological model showed promising results. Transfer rate of the drugs using the developed model compared well with the transfer potential seen in vivo except for salicylic acid, which was transferred in far lower concentration in vitro. The model has a potential to be developed as a non-invasive alternative to the in vitro technique for determining the transfer of therapeutic drugs into breast milk.

  6. Modelling and characterization of the PEM fuel cell to study interactions with power converters; Modelisation et caracterisation de la pile pem pour l'etude des interactions avec les convertisseurs statiques

    Energy Technology Data Exchange (ETDEWEB)

    Fontes, G.

    2005-09-15

    The climatic and energy challenges were now clearly stated. The use of hydrogen is one of the best ways which gives many hopes. Fuel cells are an essential link in the chain of the use of hydrogen. Thus, a lot of studies have been undertaken throughout the world on fuel cells in many fields of physics. Concerning the field of power electronics, a lot of work on distributed generation technologies using fuel cells has been realised too and a great number of power converters dedicated to fuel cells have been studied. However, very few studies have been undertaken on the interactions between fuel cells and power converters. The goals of this work are to study interactions between fuel cells and power converters. Some requirements for the power electronic engineer can follow from this work. This work proposes high signal dynamic models of a H{sub 2}/O{sub 2} PEM fuel cell. These models include the different physical and chemical phenomena. Specific methods based on a limited number of original experiments (low frequency current sweeps) allow to extract the model parameters. These models are used to study the interactions between fuel cells and power converters which are the most used: buck chopper, boost chopper, inverters. The important part of the double layer capacitors has thus been underlined: they can filter the current harmonics created by the power converters. Finally, some choices of filtering elements to be connected to the fuel cell are proposed. (author)

  7. The Future of Whole-Cell Modeling

    OpenAIRE

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

    2014-01-01

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

  8. Modeling Rett Syndrome with Stem Cells

    OpenAIRE

    Walsh, Ryan M.; Hochedlinger, Konrad

    2010-01-01

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

  9. Non linear behaviour of cell tensegrity models

    Science.gov (United States)

    Alippi, A.; Bettucci, A.; Biagioni, A.; Conclusio, D.; D'Orazio, A.; Germano, M.; Passeri, D.

    2012-05-01

    Tensegrity models for the cytoskeleton structure of living cells is largely used nowadays for interpreting the biochemical response of living tissues to mechanical stresses. Microtubules, microfilaments and filaments are the microscopic cell counterparts of struts (microtubules) and cables (microfilaments and filaments) in the macroscopic world: the formers oppose to compression, the latters to tension, thus yielding an overall structure, light and highly deformable. Specific cell surface receptors, such as integrins, act as the coupling elements that transmit the outside mechanical stress state into the cell body. Reversible finite deformations of tensegrity structures have been widely demonstrated experimentally and in a number of living cell simulations. In the present paper, the bistability behaviour of two general models, the linear bar oscillator and the icosahedron, is studied, as they are both obtained from mathematical simulation, the former, and from larger scale experiments, the latter. The discontinuity in the frequency response of the oscillation amplitude and the lateral bending of the resonance curves are put in evidence, as it grows larger as the driving amplitude increases, respectively.

  10. Enantioselective endocrine disrupting effects of omeprazole studied in the H295R cell assay and by molecular modeling

    DEFF Research Database (Denmark)

    Sørensen, Amalie Møller; Hansen, Cecilie Hurup; Bonomo, Silvia;

    2016-01-01

    Enantiomers possess different pharmacokinetic and pharmacodynamic properties and this may not only influence the therapeutic effect of a drug but also its toxicological effects. In the present work we investigated the potential enantioselective endocrine disrupting effects of omeprazole (OME) and...... its two enantiomers on the human steroidogenesis using the H295R cell line. Differences in production of 16 steroid hormones were analyzed using LC-MS/MS. Additionally, to evaluate the differences in binding modes of these enantiomers, docking and molecular dynamics (MD) simulations of S-omeprazole (S......-OME) and R-omeprazole (R-OME) in CYP17A1, CYP19A1 and CYP21A2 were carried out. Exposing H295R cells to OME and its enantiomers resulted in an increase of progesterone (PRO) and 17α-hydroxy-progesterone (OH-PRO) levels. At the same time, a decrease in the corticosteroid and androgen synthesis was observed...

  11. The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

    OpenAIRE

    Nazanin Pirooznia; Sadegh Hasannia; Majid Taghdir; Fatemeh Rahbarizadeh; Morteza Eskandani

    2011-01-01

    Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, ...

  12. Motor neuron-like NSC-34 cells as a new model for the study of vitamin D metabolism in the brain.

    Science.gov (United States)

    Almokhtar, Mokhtar; Wikvall, Kjell; Ubhayasekera, S J Kumari A; Bergquist, Jonas; Norlin, Maria

    2016-04-01

    Vitamin D3 is a pro-hormone, which is sequentially activated by 25- and 1α-hydroxylation to form 25-hydroxyvitamin D3 [25(OH)D3] and 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], respectively. Subsequent inactivation is performed by 24-hydroxylation. These reactions are carried out by a series of CYP450 enzymes. The 25-hydroxylation involves mainly CYP2R1 and CYP27A1, whereas 1α-hydroxylation and 24-hydroxylation are catalyzed by CYP27B1 and CYP24A1, respectively, and are tightly regulated to maintain adequate levels of the active vitamin D hormone, 1α,25(OH)2D3. Altered circulating vitamin D levels, in particular 25(OH)D3, have been linked to several disorders of the nervous system, e.g., schizophrenia and Parkinson disease. However, little is known about the mechanisms of vitamin D actions in the neurons. In this study, we examined vitamin D metabolism and its regulation in a murine motor neuron-like hybrid cell line, NSC-34. We found that these cells express mRNAs for the four major CYP450 enzymes involved in vitamin D activation and inactivation, and vitamin D receptor (VDR) that mediates vitamin D actions. We also found high levels of CYP24A1-dependent 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] production, that was inhibited by the well-known CYP enzyme inhibitor ketoconazole and by several inhibitors that are more specific for CYP24A1. Furthermore, CYP24A1 mRNA levels in NSC-34 cells were up-regulated by 1α,25(OH)2D3 and its synthetic analogs, EB1089 and tacalcitol. Our results suggest that NSC-34 cells could be a novel model for the studies of neuronal vitamin D metabolism and its mechanism of actions. PMID:26704532

  13. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin

    1979-01-01

    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  14. Mathematical Model of an Inductive Measuring Cell for Contactless Conductometry

    CERN Document Server

    Semenov, Yury S

    2013-01-01

    A research of inductive conductometric cell is presented. An equivalent circuit and a mathematical model of inductive cell are given in the article. The model takes into account sample-coil capacity (i.e. capacity formed by the coil and the sample under study) and eddy currents. It is sample-coil capacity that makes inductive cell applicable for measurement of electrical conductivity of low conductive samples (specific conductance is less than 1S/m). The model can be used to calculate impedance of inductive cell for different characteristics of sample, materials and dimensions of cell without numerical solving of partial differential equations. Results of numerical simulation were verified by experiment for several devices with inductive cell. Some features that an engineer has to hold in mind while designing a conductometer based on inductive cell are discussed. Presented model can be useful for those who study inductively coupled plasma.

  15. IEEE 802.11 Networks: A Simple Model Geared Towards Offloading Studies and Considerations on Future Small Cells

    DEFF Research Database (Denmark)

    Garcia, Luis Guilherme Uzeda; Rodriguez, Ignacio; Catania, Davide;

    2013-01-01

    WiFi is the prevalent wireless access technology in local area deployments and is expected to play a major role in a mobile operator’s data offloading strategy. As a result, having simple tools that are able to assess the offloading potential of IEEE 802.11 networks is vital. In this paper, we...... propose a simple closed-form solution to calculate down- and uplink throughput values per user under full-buffer traffic when small WiFi cells are used to offload macrocells. Extensive measurement campaigns and simulation results demonstrate that there is an excellent quantitative match between analytical...

  16. Sulfur Tolerant Solid Oxide Fuel Cell for Coal Syngas Application: Experimental Study on Diverse Impurity Effects and Fundamental Modeling of Electrode Kinetics

    Science.gov (United States)

    Gong, Mingyang

    With demand over green energy economy, fuel cells have been developed as a promising energy conversion technology with higher efficiency and less emission. Solid oxide fuel cells (SOFC) can utilize various fuels in addition to hydrogen including coal derived sygas, and thus are favored for future power generation due to dependence on coal in electrical industry. However impurities such as sulfur and phosphorous present in coal syngas in parts per million (p.p.m.) levels can severely poison SOFC anode typically made of Ni/yttria-stabilized-zirconia (Ni-YSZ) and limit SOFC applicability in economically derivable fuels. The focus of the research is to develop strategy for application of high performance SOFC in coal syngas with tolerance against trace impurities such as H2S and PH3. To realize the research goal, the experimental study on sulfur tolerant anode materials and examination of various fuel impurity effects on SOFC anode are combined with electrochemical modeling of SOFC cathode kinetics in order to benefit design of direct-coal-syngas SOFC. Tolerant strategy for SOFC anode against sulfur is studied by using alternative materials which can both mitigate sulfur poisoning and function as active anode components. The Ni-YSZ anode was modified by incorporation of lanthanum doped ceria (LDC) nano-coatings via impregnation. Cell test in coal syngas containing 20 ppm H2S indicated the impregnated LDC coatings inhibited on-set of sulfur poisoning by over 10hrs. Cell analysis via X-ray photon spectroscopy (XPS), X-ray diffraction (XRD) and electrochemistry revealed LDC coatings reacted with H2S via chemisorptions, resulting in less sulfur blocking triple--phase-boundary and minimized performance loss. Meanwhile the effects of PH3 impurity on SOFC anode is examined by using Ni-YSZ anode supported SOFC. Degradation of cell is found to be irreversible due to adsorption of PH3 on TPB and further reaction with Ni to form secondary phases with low melting point. The

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

    Science.gov (United States)

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

    2015-03-01

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

  18. Critical Evaluation of Techniques to Detect and Measure Cell Death – Study in a Model of UV Radiation of the Leukaemic Cell Line HL60

    OpenAIRE

    Leite, Marina; Quinta‐Costa, Margarida; Leite, Pedro Simas; Guimarães, José Eduardo

    1999-01-01

    The reliability of eight distinct methods (Giemsa staining, trypan blue exclusion, acridine orange/ethidium bromide (AO/EB) double staining for fluorescence microscopy and flow cytometry, propidium iodide (PI) staining, annexin V assay, TUNEL assay and DNA ladder) for detection and quantification of cell death (apoptosis and necrosis) was evaluated and compared. Each of these methods detects different morphological or biochemical features of these two processes. The comparative analysis of th...

  19. Polymer electrolyte membrane fuel cell grade hydrogen production by methanol steam reforming: A comparative multiple reactor modeling study

    Science.gov (United States)

    Katiyar, Nisha; Kumar, Shashi; Kumar, Surendra

    2013-12-01

    Analysis of a fuel processor based on methanol steam reforming has been carried out to produce fuel cell grade H2. Six reactor configurations namely FBR1 (fixed bed reactor), MR1 (H2 selective membrane reactor with one reaction tube), MR2 (H2 selective membrane reactor with two reaction tubes), FBR2 (FBR1 + preferential CO oxidation (PROX) reactor), MR3 (MR1 + PROX), and MR4 (MR2 + PROX) are evaluated by simulation to identify the suitable processing scheme. The yield of H2 is significantly affected by H2 selective membrane, residence time, temperature, and pressure conditions at complete methanol conversion. The enhancement in residence time in MR2 by using two identical reaction tubes provides H2 yield of 2.96 with 91.25 mol% recovery at steam/methanol ratio of 1.5, pressure of 2 bar and 560 K temperature. The exit retentate gases from MR2 are further treated in PROX reactor of MR4 to reduce CO concentration to 4.1 ppm to ensure the safe discharge to the environment. The risk of carbon deposition on reforming catalyst is highly reduced in MR4, and MR4 reactor configuration generates 7.4 NL min-1 of CO free H2 from 0.12 mol min-1 of methanol which can provide 470 W PEMFC feedstock requirement. Hence, process scheme in MR4 provides a compact and innovative fuel cell grade H2 generating unit.

  20. Internal steam reforming in solid oxide fuel cells: Status and opportunities of kinetic studies and their impact on modelling

    DEFF Research Database (Denmark)

    Mogensen, David; Grunwaldt, J.-D.; Hendriksen, Peter Vang;

    2011-01-01

    operating conditions, catalyst support material and structure it is critical to transfer this knowledge directly to internal reforming in SOFCs, which is discussed in further detail in this article. There are big differences in the reported kinetic expression for steam reforming over both industrial Ni...... catalysts and SOFC anode materials. Surprisingly, there is a good agreement between measured rates pr. geometric anode area at high operating temperatures, even for very different anodes. Detailed experimental data on the intrinsic steam reforming kinetics of Ni-YSZ are necessary for micro structure SOFC......Solid oxide fuel cells (SOFC) systems with internal steam reforming have the potential to become an economically competitive technology for cogeneration power plants, exploiting its significantly higher electrical efficiency compared to existing technologies. Optimal design and operation of such a...

  1. MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPARγ expression: A rat fibrosis model study

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Le; Wang, Jinlong; Lu, Hongwei [Department of General Surgery, The Second Affiliated Hospital of Xi' an Jiaotong University, No.157, West 5th Road, Xi' an, Shaanxi 710004 (China); Zhang, Guoyu [West Hospital Ward 1, Shaanxi Provincial People' s Hospital, No.256, Youyi Road(west), Xi' an, Shaanxi 710068 (China); Liu, Yang; Wang, Jiazhong; Zhang, Yafei; Shang, Hao; Ji, Hong; Chen, Xi; Duan, Yanxia [Department of General Surgery, The Second Affiliated Hospital of Xi' an Jiaotong University, No.157, West 5th Road, Xi' an, Shaanxi 710004 (China); Li, Yiming, E-mail: yiminngli@163.com [Department of General Surgery, The Second Affiliated Hospital of Xi' an Jiaotong University, No.157, West 5th Road, Xi' an, Shaanxi 710004 (China)

    2015-09-25

    Hepatic stellate cells (HSCs) are the primary sources of extracellular matrix (ECM) in normal and fibrotic liver. Peroxisome proliferator-activated receptor gamma (PPARγ) maintains HSCs in a quiescent state, and its downregulation induces HSC activation. MicroRNAs (miRNAs) can induce PPARγ mRNA degradation, but the mechanism by which miRNAs regulate PPARγ in rat HSCs is unclear. This study aimed to investigate some miRNAs which putatively bind to the 3′-untranslated region (3′-UTR) of PPARγ mRNA, and increase expression of ECM genes in rat HSCs. In carbon tetrachloride injection (CCl{sub 4}) and common bile duct ligation (CBDL) liver fibrosis models, miRNAs miR-130a, miR-130b, miR-301a, miR-27b and miR-340 levels were found to be increased and PPARγ expression decreased. Overexpression of miR-130a and miR-130b enhanced cell proliferation by involving Runx3. MiR-130a and miR-130b decreased PPARγ expression by targeting the 3′-UTR of PPARγ mRNA in rat HSC-T6 cells. Transforming growth factor-β1 (TGF-β1) may mediate miR-130a and miR-130b overexpression, PPARγ downregulation, and ECM genes overexpression in cell culture. These findings suggest that miR-130a and miR-130b are involved in downregulation of PPARγ in liver fibrosis. - Highlights: • MiR-130a and miR-130b are increased and PPARγ is decreased in liver fibrosis models. • MiR-130a and miR-130b decreased PPARγ by targeting the 3′-UTR of PPARγ mRNA. • MiR-130a and miR-130b enhanced HSC cell proliferation by involving Runx3. • TGF-β1 may mediate miR-130a and miR-130b overexpression.

  2. MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPARγ expression: A rat fibrosis model study

    International Nuclear Information System (INIS)

    Hepatic stellate cells (HSCs) are the primary sources of extracellular matrix (ECM) in normal and fibrotic liver. Peroxisome proliferator-activated receptor gamma (PPARγ) maintains HSCs in a quiescent state, and its downregulation induces HSC activation. MicroRNAs (miRNAs) can induce PPARγ mRNA degradation, but the mechanism by which miRNAs regulate PPARγ in rat HSCs is unclear. This study aimed to investigate some miRNAs which putatively bind to the 3′-untranslated region (3′-UTR) of PPARγ mRNA, and increase expression of ECM genes in rat HSCs. In carbon tetrachloride injection (CCl4) and common bile duct ligation (CBDL) liver fibrosis models, miRNAs miR-130a, miR-130b, miR-301a, miR-27b and miR-340 levels were found to be increased and PPARγ expression decreased. Overexpression of miR-130a and miR-130b enhanced cell proliferation by involving Runx3. MiR-130a and miR-130b decreased PPARγ expression by targeting the 3′-UTR of PPARγ mRNA in rat HSC-T6 cells. Transforming growth factor-β1 (TGF-β1) may mediate miR-130a and miR-130b overexpression, PPARγ downregulation, and ECM genes overexpression in cell culture. These findings suggest that miR-130a and miR-130b are involved in downregulation of PPARγ in liver fibrosis. - Highlights: • MiR-130a and miR-130b are increased and PPARγ is decreased in liver fibrosis models. • MiR-130a and miR-130b decreased PPARγ by targeting the 3′-UTR of PPARγ mRNA. • MiR-130a and miR-130b enhanced HSC cell proliferation by involving Runx3. • TGF-β1 may mediate miR-130a and miR-130b overexpression

  3. Including excitons in semiconductor solar cell modelling

    OpenAIRE

    Burgelman, Marc; Minnaert, Ben

    2005-01-01

    Excitons are marginally important in classical semiconductor device physics, and their treatment is not included in standard solar cell modelling. However, in organic semiconductors and solar cells, the role of excitons is essential, as the primary effect of light absorption is exciton generation, and free electrons and holes are created by exciton dissociation. First steps to include excitons in solar cell modelling were presented by Green 1996 and Zhang 1998. Their model was restricted to a...

  4. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa J.

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  5. Bacterial kidney disease as a model for studies of cell mediated immunity in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Jansson, Eva; Hongslo, Thorbjörn; Johannisson, Anders; Pilström, Lars; Timmusk, Sirje; Norrgren, Leif

    2003-04-01

    A cell mediated immune (CMI) response was measured in vitro to heat-killed and to paraformaldehyde fixed Renibacterium salmoninarum (Rs) in rainbow trout (Oncorhynchus mykiss) experimentally challenged with live Rs. The mitogenic response to the T lymphocyte mitogen Concanavalin A (Con A) was reduced during samplings 4 to 6 weeks after immersion, but no effect of the response to the B lymphocyte mitogen lipopolysaccharide (LPS) was detected. The subpopulation of lymphocytes, detected by the monoclonal antibody 1C2, was decreased from the 4th week to the 5th week of infection, and remained at the decreased level up to 10 weeks post immersion. The proportion of Immunoglobulin (Ig) bearing lymphocytes was not affected during the Rs infection period. The humoral antibody level to heat-stable Rs-antigens was increased up to 10 weeks after immersion but after 27 weeks was reduced to a level similar to that of the non-challenged fish. An anamnestic response was demonstrated in challenged fish, as intraperitoneal injection of heat-treated Rs bacteria into Rs challenged fish elicited a stronger humoral antibody response compared with injection into non-challenged fish. PMID:12657537

  6. A novel mechanotactic 3D modeling of cell morphology

    International Nuclear Information System (INIS)

    Cell morphology plays a critical role in many biological processes, such as cell migration, tissue development, wound healing and tumor growth. Recent investigations demonstrate that, among other stimuli, cells adapt their shapes according to their substrate stiffness. Until now, the development of this process has not been clear. Therefore, in this work, a new three-dimensional (3D) computational model for cell morphology has been developed. This model is based on a previous cell migration model presented by the same authors. The new model considers that during cell–substrate interaction, cell shape is governed by internal cell deformation, which leads to an accurate prediction of the cell shape according to the mechanical characteristic of its surrounding micro-environment. To study this phenomenon, the model has been applied to different numerical cases. The obtained results, which are qualitatively consistent with well-known related experimental works, indicate that cell morphology not only depends on substrate stiffness but also on the substrate boundary conditions. A cell located within an unconstrained soft substrate (several kPa) with uniform stiffness is unable to adhere to its substrate or to send out pseudopodia. When the substrate stiffness increases to tens of kPa (intermediate and rigid substrates), the cell can adequately adhere to its substrate. Subsequently, as the traction forces exerted by the cell increase, the cell elongates and its shape changes. Within very stiff (hard) substrates, the cell cannot penetrate into its substrate or send out pseudopodia. On the other hand, a cell is found to be more elongated within substrates with a constrained surface. However, this elongation decreases when the cell approaches it. It can be concluded that the higher the net traction force, the greater the cell elongation, the larger the cell membrane area, and the less random the cell alignment. (paper)

  7. Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

    Energy Technology Data Exchange (ETDEWEB)

    Herodin, F.; Drouet, M. [Radiohematology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France)

    2002-07-01

    The sparing of viable hematopoietic stem and progenitor cells located in underexposed bone marrow territories associated with the relative radioresistance of certain stem cell populations is the rationale for autologous cell therapy consisting of ex vivo expansion of residual cells after collection postirradiation. The feasibility of this treatment mainly depends on time constraints and hematopoietic cell threshold. We showed in this study that in the absence of early-acting mobilizing agent administration, subliminar amounts of CD34{sup +} cells can be collected (1 x 10{sup 6} CD34{sup +} cells/100 mL bone marrow or for 1 L apheresis) from 6-Gy {gamma} globally irradiated baboons. Residual CD34{sup +} cells were successfully expanded in serum-free medium in the presence of antiapoptotic cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin 3, 50 ng/mL each, i.e., 4F): K{sub CD34{sup +}} = x2.8 and x13.7 (n=2). Moreover, we demonstrated the short-term neutrophil engraftment potential of a low-size mixed expanded graft (1.5 x 10{sup 6} final CD34{sup +}cells/kg) issued from the coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34{sup +} cells on an allogeneic stromal cell layer in the presence of 4F. Further preclinical research needs to be performed to clearly establish this therapeutic approach that could be optimized by the early administration of antiapoptotic cytokines. (author)

  8. On the relative relevance of subject-specific geometries and degeneration-specific mechanical properties for the study of cell death in human intervertebral disc models

    Directory of Open Access Journals (Sweden)

    Andrea eMalandrino

    2015-02-01

    Full Text Available Capturing patient- or condition-specific intervertebral disc (IVD properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disc degenerative changes are often modelled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disc geometries. Accordingly, we explored the ability of continuum tissue models to simulate disc degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disc cell nutrition, a potentially important actor in disc tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disc geometry on cell viability. While classic disc poromechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favoured by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disc degeneration.

  9. Active Gel Model of Amoeboid Cell Motility

    CERN Document Server

    Callan-Jones, A C

    2013-01-01

    We develop a model of amoeboid cell motility based on active gel theory. Modeling the motile apparatus of a eukaryotic cell as a confined layer of finite length of poroelastic active gel permeated by a solvent, we first show that, due to active stress and gel turnover, an initially static and homogeneous layer can undergo a contractile-type instability to a polarized moving state in which the rear is enriched in gel polymer. This agrees qualitatively with motile cells containing an actomyosin-rich uropod at their rear. We find that the gel layer settles into a steadily moving, inhomogeneous state at long times, sustained by a balance between contractility and filament turnover. In addition, our model predicts an optimal value of the gel-susbstrate adhesion leading to maximum layer speed, in agreement with cell motility assays. The model may be relevant to motility of cells translocating in complex, confining environments that can be mimicked experimentally by cell migration through microchannels.

  10. The future of whole-cell modeling.

    Science.gov (United States)

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

    2014-08-01

    Integrated whole-cell modeling is poised to make a dramatic impact on molecular and systems biology, bioengineering, and medicine--once certain obstacles are overcome. From our group's experience building a whole-cell model of Mycoplasma genitalium, we identified several significant challenges to building models of more complex cells. Here we review and discuss these challenges in seven areas: first, experimental interrogation; second, data curation; third, model building and integration; fourth, accelerated computation; fifth, analysis and visualization; sixth, model validation; and seventh, collaboration and community development. Surmounting these challenges will require the cooperation of an interdisciplinary group of researchers to create increasingly sophisticated whole-cell models and make data, models, and simulations more accessible to the wider community. PMID:24556244

  11. Minimal model for stem-cell differentiation

    Science.gov (United States)

    Goto, Yusuke; Kaneko, Kunihiko

    2013-09-01

    To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed.

  12. Minimal model for stem-cell differentiation.

    Science.gov (United States)

    Goto, Yusuke; Kaneko, Kunihiko

    2013-09-01

    To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed. PMID:24125305

  13. Studying cell-cell communication in co-culture

    OpenAIRE

    Bogdanowicz, Danielle R.; Lu, Helen H.

    2013-01-01

    Heterotypic and homotypic cellular interactions are essential for biological function, and co-culture models are versatile tools for investigating these cellular interactions in vitro. Physiologically relevant co-culture models have been used to elucidate the effects of cell-cell physical contact and/or secreted factors, as well as the influence of substrate geometry and interaction scale on cell response. Identifying the relative contribution of each cell population to co-culture is often ex...

  14. Cytoview: Development of a cell modelling framework

    Indian Academy of Sciences (India)

    Prashant Khodade; Samta Malhotra; Nirmal Kumar; M Sriram Iyengar; N Balakrishnan; Nagasuma Chandra

    2007-08-01

    The biological cell, a natural self-contained unit of prime biological importance, is an enormously complex machine that can be understood at many levels. A higher-level perspective of the entire cell requires integration of various features into coherent, biologically meaningful descriptions. There are some efforts to model cells based on their genome, proteome or metabolome descriptions. However, there are no established methods as yet to describe cell morphologies, capture similarities and differences between different cells or between healthy and disease states. Here we report a framework to model various aspects of a cell and integrate knowledge encoded at different levels of abstraction, with cell morphologies at one end to atomic structures at the other. The different issues that have been addressed are ontologies, feature description and model building. The framework describes dotted representations and tree data structures to integrate diverse pieces of data and parametric models enabling size, shape and location descriptions. The framework serves as a first step in integrating different levels of data available for a biological cell and has the potential to lead to development of computational models in our pursuit to model cell structure and function, from which several applications can flow out.

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

    International Nuclear Information System (INIS)

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

  16. Stochastic biophysical modeling of irradiated cells

    CERN Document Server

    Fornalski, Krzysztof Wojciech

    2014-01-01

    The paper presents a computational stochastic model of virtual cells irradiation, based on Quasi-Markov Chain Monte Carlo method and using biophysical input. The model is based on a stochastic tree of probabilities for each cell of the entire colony. Biophysics of the cells is described by probabilities and probability distributions provided as the input. The adaptation of nucleation and catastrophe theories, well known in physics, yields sigmoidal relationships for carcinogenic risk as a function of the irradiation. Adaptive response and bystander effect, incorporated into the model, improves its application. The results show that behavior of virtual cells can be successfully modeled, e.g. cancer transformation, creation of mutations, radioadaptation or radiotherapy. The used methodology makes the model universal and practical for simulations of general processes. Potential biophysical curves and relationships are also widely discussed in the paper. However, the presented theoretical model does not describe ...

  17. Los linfocitos: modelo de estudio en las enfermedades de Alzheimer y Parkinson Lymphocytes as a cell model to study Alzheimer’s and Parkinson’s diseases

    Directory of Open Access Journals (Sweden)

    Carlos Vélez Pardo

    2006-01-01

    therapeutic treatment aimed to reduce or retard the clinic and pathologic symptoms induced by both devastating diseases. Thus, the biochemical mechanism(s involved in neural loss has mainly been studied in biological models. In this article the authors, based on their own scientific experience and others, have proposed lymphocytes as a cellular model to study the molecular signalling mechanism induced by oxidative stress in AD and PD. Remarkably, lymphocytes and neurons are cellularly and biochemically alike. Indeed, lymphocytes express at least six different biological systems such as catecholaminergic, serotonergic, acetylcholinergic, glutamatergic, noradrenergic and GABAergic systems considered to be exclusively pertain to neural cells!. Given that lymphocytes are post-mitotic cells (i.e. Go cell cycle and possess the synthesis, transport and processing systems of amyloid-beta precursor protein (AβPP, presenilins and parkin proteins, these cells constitute not only an ideal bio-model to better understanding of the pathological signalling in those neurodegenerative processes, but also represent a meaningful tool to design innovative and rational therapeutic strategies focussed to arrest the neuronal death in Alzheimer’s and Parkinson’s patients from Antioquia.

  18. Comparison of immortalized bEnd5 and primary mouse brain microvascular endothelial cells as in vitro blood–brain barrier models for the study of T cell extravasation

    OpenAIRE

    Steiner, Oliver; Coisne, Caroline; Engelhardt, Britta; Lyck, Ruth

    2010-01-01

    Important insights into the molecular mechanism of T cell extravasation across the blood–brain barrier (BBB) have already been obtained using immortalized mouse brain endothelioma cell lines (bEnd). However, compared with bEnd, primary brain endothelial cells have been shown to establish better barrier characteristics, including complex tight junctions and low permeability. In this study, we asked whether bEnd5 and primary mouse brain microvascular endothelial cells (pMBMECs) were equally sui...

  19. Vital Autofluorescence: Application to the Study of Plant Living Cells

    OpenAIRE

    Roshchina, Victoria V.

    2012-01-01

    The application of various microscopy methods such as luminescence microscopy, microspectrofluorimetry and laser-scanning confocal microscopy has been considered as an approach to study the autofluorescence of plant living cells—from cell diagnostics up to modelling the cell-cell contacts and cell interactions with fluorescent biologically active substances. It bases on the direct observations of secretions released from allelopathic and medicinal species and the cell-donor interactions with ...

  20. Simulation Model Driven Engineering for Manufacturing Cell

    OpenAIRE

    Hibino, Hironori; Inukai, Toshihiro; Yoshida, Yukishige

    2010-01-01

    In our research, the simulation model driven engineering for manufacturing cell (SMDE-MC) is proposed. The purposes of SMDE-MC are to support the manufacturing engineering processes based on the simulation model and to extend the range of control applications and simulation applications using the PC based control. SMDE-MC provides the simulation model which controls and monitors the manufacturing cell directly using PC based control in the manufacturing system execution phase. Then when the s...

  1. Modeling human liver biology using stem cell-derived hepatocytes

    OpenAIRE

    Sun, Pingnan; Zhou, XiaoLing; Farnworth, Sarah; Arvind H Patel; Hay, David C.

    2013-01-01

    Stem cell-derived hepatocytes represent promising models to study human liver biology and disease. This concise review discusses the recent progresses in the field, with a focus on human liver disease, drug metabolism and virus infection.

  2. Modeling Human Liver Biology Using Stem Cell-Derived Hepatocytes

    OpenAIRE

    Arvind H Patel; Hay, David C.; Farnworth, Sarah L.; Pingnan Sun; Xiaoling Zhou

    2013-01-01

    Stem cell-derived hepatocytes represent promising models to study human liver biology and disease. This concise review discusses the recent progresses in the field, with a focus on human liver disease, drug metabolism and virus infection.

  3. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    OpenAIRE

    Qiao, Guanqun; Li, Qingquan; Peng, Gang; Ma, Jun; Fan, Hongwei; Li, Yingbin

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain t...

  4. Semi-solid tumor model in Xenopus laevis/gilli cloned tadpoles for intravital study of neovascularization, immune cells and melanophore infiltration.

    Science.gov (United States)

    Haynes-Gimore, Nikesha; Banach, Maureen; Brown, Edward; Dawes, Ryan; Edholm, Eva-Stina; Kim, Minsoo; Robert, Jacques

    2015-12-15

    Tumors have the ability to grow as a self-sustaining entity within the body. This autonomy is in part accomplished by the tumor cells ability to induce the formation of new blood vessels (angiogenesis) and by controlling cell trafficking inside the tumor mass. These abilities greatly reduce the efficacy of many cancer therapies and pose challenges for the development of more effective cancer treatments. Hence, there is a need for animal models suitable for direct microscopy observation of blood vessel formation and cell trafficking, especially during early stages of tumor establishment. Here, we have developed a reliable and cost effective tumor model system in tadpoles of the amphibian Xenopus laevis. Tadpoles are ideally suited for direct microscopy observation because of their small size and transparency. Using the thymic lymphoid tumor line 15/0 derived from, and transplantable into, the X. laevis/gilli isogenic clone LG-15, we have adapted a system that consists in transplanting 15/0 tumor cells embedded into rat collagen under the dorsal skin of LG-15 tadpole recipients. This system recapitulates many facets of mammalian tumorigenesis and permits real time visualization of the active formation of the tumor microenvironment induced by 15/0 tumor cells including neovascularization, collagen rearrangements as well as infiltration of immune cells and melanophores. PMID:25601449

  5. Entrainability of cell cycle oscillator models with exponential growth of cell mass.

    Science.gov (United States)

    Nakao, Mitsuyuki; Enkhkhudulmur, Tsog-Erdene; Katayama, Norihiro; Karashima, Akihiro

    2014-01-01

    Among various aspects of cell cycle, understanding synchronization mechanism of cell cycle is important because of the following reasons. (1)Cycles of cell assembly should synchronize to form an organ. (2) Synchronizing cell cycles are required to experimental analysis of regulatory mechanisms of cell cycles. (3) Cell cycle has a distinct phase relationship with the other biological rhythms such as circadian rhythm. However, forced as well as mutual entrainment mechanisms are not clearly known. In this study, we investigated entrainability of cell cycle models of yeast cell under the periodic forcing to both of the cell mass and molecular dynamics. Dynamics of models under study involve the cell mass growing exponentially. In our result, they are shown to allow only a limited frequency range for being entrained by the periodic forcing. In contrast, models with linear growth are shown to be entrained in a wider frequency range. It is concluded that if the cell mass is included in the cell cycle regulation, its entrainability is sensitive to a shape of growth curve assumed in the model. PMID:25571564

  6. Six-month angiographic study of immediate autologous bone marrow mononuclear cell implantation on acute anterior wall myocardial infarction using a mini-pig model.

    Science.gov (United States)

    Sheu, Jiunn-Jye; Yuen, Chun-Man; Sun, Cheuk-Kwan; Chang, Li-Teh; Yen, Chia-Hung; Chiang, Chiang-Hua; Ko, Sheung-Fat; Pei, Sung-Nan; Chua, Sarah; Bhasin, Anuj; Wu, Chiung-Jen; Yip, Hon-Kan

    2009-03-01

    This study investigated six-month angiographic results of autologous bone marrow mononuclear cell (BMMNC) transplantation immediately following acute myocardial infarction (AMI) in a mini-pig model.AMI was induced by left anterior descending artery ligation. Twenty-four mini-pigs were equally divided into group 1 [AMI plus saline injection in infarcted area (IA)], group 2 (AMI plus BMMNC transplantation into non-IA), group 3 (AMI plus BMMNC implantation into IA), and group 4 (sham control). One-week cultured BMMNCs (3.0 x 10(7)) were immediately transplanted following AMI induction. Angiographic studies over 6 months demonstrated that mitral regurgitation (MR) was lower in groups 3 and 4 than in groups 1 and 2 (all P < 0.01). Wall motion scores and left ventricular ejection fraction (LVEF) were higher in groups 3 and 4 than in groups 1 and 2 (all P < 0.05). Collateral circulation was higher in group 3 than in groups 1 and 2 ( P < 0.01). The wall thickness of the IA was higher, whereas the heart weight was lower in group 3 than in groups 1 and 2 (all P < 0.01).Immediate autologous BMMNC transplantation into IA is superior to saline-treated only or BMMNC transplantation into non-IA following AMI for reducing MR and improving LVEF. PMID:19367032

  7. Modeling cell behavior: moving beyond intuition

    Directory of Open Access Journals (Sweden)

    Mario Jolicoeur

    2014-04-01

    Full Text Available In the context of the launching of this new journal, we propose a forum to the community of researchers interested and involved in, or even simply questioning the why, what, how, and when of modeling cell or cell culture behavior. To start the discussion, we review some of the usual questions we are routinely asked on the pertinence of modeling cell behavior, and on who might benefit from conducting such work. To draw a global portrait, throughout this text we refer the reader to handbooks introducing the basics of modeling a biosystem, as well as to selected works that can help visualize the broad fields of applications.

  8. Predicting dynamics and rheology of blood flow: A comparative study of multiscale and low-dimensional models of red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Wenxiao; Fedosov, Dmitry A.; Caswell, Bruce; Karniadakis, George E.

    2011-05-27

    In this work we compare the predictive capability of two mathematical models for red blood cells (RBCs) focusing on blood flow in capillaries and arterioles. Both RBC models as well as their corresponding blood flows are based on the dissipative particle dynamics (DPD) method, a coarse-grained molecular dynamics approach. The first model employs a multiscale description of the RBC (MS-RBC), with its membrane represented by hundreds or even thousands of DPD-particles connected by springs into a triangular network in combination with out-of-plane elastic bending resistance. Extra dissipation within the network accounts for membrane viscosity, while the characteristic biconcave RBC shape is achieved by imposition of constraints for constant membrane area and constant cell volume. The second model is based on a low-dimensional description (LD-RBC) constructed as a closed torus-like ring of only 10 large DPD colloidal particles. They are connected into a ring by worm-like chain (WLC) springs combined with bending resistance. The LD-RBC model can be fitted to represent the entire range of nonlinear elastic deformations as measured by optical-tweezers for healthy and for infected RBCs in malaria. MS-RBCs suspensions model the dynamics and rheology of blood flow accurately for any size vessel but this approach is computationally expensive above 100 microns. Surprisingly, the much more economical suspensions of LD-RBCs also capture the blood flow dynamics and rheology accurately except for vessels with sizes comparable to RBC diameter. In particular, the LD-RBC suspensions are shown to properly capture the experimental data for the apparent viscosity of blood and its cell-free layer (CFL) in tube flow. Taken together, these findings suggest a hierarchical approach in modeling blood flow in the arterial tree, whereby the MS-RBC model should be employed for capillaries and arterioles below 100 microns, the LD-RBC model for arterioles, and the continuum description for

  9. Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

    Science.gov (United States)

    Hoffman, Andrew M; Dow, Steven W

    2016-07-01

    Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. PMID:27066769

  10. Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma

    Science.gov (United States)

    Anand, Sanjay; Thomas, Erik; Hasan, Tayyaba; Maytin, Edward V.

    2016-03-01

    Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor (pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25- dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol with oral cholecalciferol (D3), administered as a high (tenfold, "10K") diet over a ten-day period. Here, we ask whether VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks ("deficient"); controls were fed a normal 1,000 IU/kg diet ("1K"). Human A431 cells were implanted subcutaneously and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates. A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.

  11. Mechanical Response of Single Plant Cells to Cell Poking: A Numerical Simulation Model

    Institute of Scientific and Technical Information of China (English)

    Rong Wang; Qun-Ying Jiao; De-Qiang Wei

    2006-01-01

    Cell poking is an experimental technique that is widely used to study the mechanical properties of plant cells. A full understanding of the mechanical responses of plant cells to poking force is helpful for experimental work. The aim of this study was to numerically investigate the stress distribution of the cell wall,cell turgor, and deformation of plant cells in response to applied poking force. Furthermore, the locations damaged during poking were analyzed. The model simulates cell poking, with the cell treated as a spherical,homogeneous, isotropic elastic membrane, filled with incompressible, highly viscous liquid. Equilibrium equations for the contact region and the non-contact regions were determined by using membrane theory.The boundary conditions and continuity conditions for the solution of the problem were found. The forcedeformation curve, turgor pressure and tension of the cell wall under cell poking conditions were obtained.The tension of the cell wall circumference was larger than that of the meridian. In general, maximal stress occurred at the equator around. When cell deformation increased to a certain level, the tension at the poker tip exceeded that of the equator. Breakage of the cell wall may start from the equator or the poker tip,depending on the deformation. A nonlinear model is suitable for estimating turgor, stress, and stiffness,and numerical simulation is a powerful method for determining plant cell mechanical properties.

  12. In-cell PCR method for specific genotyping of genomic DNA from one individual in a mixture of cells from two individuals: a model study with specific relevance to prenatal diagnosis based on fetal cells in maternal blood

    DEFF Research Database (Denmark)

    Hviid, T Vauvert

    2002-01-01

    BACKGROUND: During recent years, much attention has been paid to the possibility of using fetal cells circulating in the pregnant woman's blood for prenatal diagnosis of genetic or chromosomal abnormalities. Although successes have been achieved in enrichment procedures for fetal cells from...... sequence only in the male cells, leading to the correct HLA-DPB1 genotyping of the male by DNA sequencing of a nested, linked TSPY-HLA-DPB1 PCR product. CONCLUSION: This approach might be usable on mixed cell populations of fetal and maternal cells obtained after conventional cell-sorting techniques on...

  13. Direct and inverse neural networks modelling applied to study the influence of the gas diffusion layer properties on PBI-based PEM fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Lobato, Justo; Canizares, Pablo; Rodrigo, Manuel A.; Linares, Jose J. [Chemical Engineering Department, University of Castilla-La Mancha, Campus Universitario s/n, 13004 Ciudad Real (Spain); Piuleac, Ciprian-George; Curteanu, Silvia [Faculty of Chemical Engineering and Environmental Protection, Department of Chemical Engineering, ' ' Gh. Asachi' ' Technical University Iasi Bd. D. Mangeron, No. 71A, 700050 IASI (Romania)

    2010-08-15

    This article shows the application of a very useful mathematical tool, artificial neural networks, to predict the fuel cells results (the value of the tortuosity and the cell voltage, at a given current density, and therefore, the power) on the basis of several properties that define a Gas Diffusion Layer: Teflon content, air permeability, porosity, mean pore size, hydrophobia level. Four neural networks types (multilayer perceptron, generalized feedforward network, modular neural network, and Jordan-Elman neural network) have been applied, with a good fitting between the predicted and the experimental values in the polarization curves. A simple feedforward neural network with one hidden layer proved to be an accurate model with good generalization capability (error about 1% in the validation phase). A procedure based on inverse neural network modelling was able to determine, with small errors, the initial conditions leading to imposed values for characteristics of the fuel cell. In addition, the use of this tool has been proved to be very attractive in order to predict the cell performance, and more interestingly, the influence of the properties of the gas diffusion layer on the cell performance, allowing possible enhancements of this material by changing some of its properties. (author)

  14. The Non-Obese Diabetic Mouse Strain as a Model to Study CD8+ T Cell Function in Relapsing and Progressive Multiple Sclerosis

    OpenAIRE

    Ignatius Arokia Doss, Prenitha Mercy; Roy, Andrée-Pascale; Wang, Aili; Anderson, Ana Carrizosa; Rangachari, Manu

    2015-01-01

    Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on central nervous system (CNS) myelin. Although CD4+ T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8+ T lymphocytes play a key role. Intriguingly, CD8+ T cells accumulate in great numbers in the CNS in progressive MS, a form of the disease that is refractory to current disease-modifying therapies that target the CD4+ T cell response. Here, we discuss...

  15. On a poroviscoelastic model for cell crawling

    KAUST Repository

    Kimpton, L. S.

    2014-02-08

    In this paper a minimal, one-dimensional, two-phase, viscoelastic, reactive, flow model for a crawling cell is presented. Two-phase models are used with a variety of constitutive assumptions in the literature to model cell motility. We use an upper-convected Maxwell model and demonstrate that even the simplest of two-phase, viscoelastic models displays features relevant to cell motility. We also show care must be exercised in choosing parameters for such models as a poor choice can lead to an ill-posed problem. A stability analysis reveals that the initially stationary, spatially uniform strip of cytoplasm starts to crawl in response to a perturbation which breaks the symmetry of the network volume fraction or network stress. We also demonstrate numerically that there is a steady travelling-wave solution in which the crawling velocity has a bell-shaped dependence on adhesion strength, in agreement with biological observation.

  16. A Coarse Estimation of Cell Size Region from a Mesoscopic Stochastic Cell Cycle Model

    Institute of Scientific and Technical Information of China (English)

    YI Ming; JIA Ya; LIU Quan; ZHU Chun-Lian; YANG Li-Jian

    2007-01-01

    Based on a deterministic cell cycle model of fission yeast, the effects of the finite cell size on the cell cycle regulation in wee1- cdc25△ double mutant type are numerically studied by using of the chemical Langevin equations. It is found that at a certain region of cell size, our numerical results from the chemical Langevin equations are in good qualitative agreement with the experimental observations. The two resettings to the G2 phase from early stages of mitosis can be induced under the moderate cell size. The quantized cycle times can be observed during such a cell size region. Therefore, a coarse estimation of cell size is obtained from the mesoscopic stochastic cell cycle model.

  17. The development of an OxyHb animal model in mice and the study on OxyHb-induced apoptosis of mouse brain cells in vivo

    Institute of Scientific and Technical Information of China (English)

    Shi Wei; Wang Ruizhi; Huang Liyong; Sun Jianjun; Wang Fangru; Liu Chongxiao; Zhou Le; Guo Zhenyu; John H Zhang

    2008-01-01

    Objective On the basis of developing a new animal model for oxyhemoglobin (OxyHb) injection into subarachnoid space in mice, this research was to explore the temporal dependence and spatial distribution of OxyHb- induced apoptosis in the mouse brain cells in vivo and the mechanism of neurocyte injury induced by OxyHb. Methods The animal model for OxyHb injection into subarachnoid space in mice was developed. Mice were divided randomly into the experimental group (n=40) and the control group (n= 35). The control group received saline injection (50 μL ) and the experimental group received OxyHb injection (50 μL ), both into the subarachnoid space. The mice of the two groups were subdivided according to different postoperative time (3 h, 6 h, 12 h, 24 h and 48 h). The apoptosis or necrosis of cells was distinguished with microscopy (HE staining), transmission electron microscopy and TUNEL method. Results The distribution of apoptosis was mainly in the ipsilateral neocortex and bilateral hippocampal gyrus. The apoptotic mouse brain cells showed morphological changes in the experimental group by HE staining and transmission electron microscopy. The count of TUNEL-positive cells showed substantial increase in the experimental group, and there was a significant difference between the control and experimental groups, and the number of OxyHb- induced apoptotic cells decreased with time. Conclusion OxyHb in subarachnoid space in mice can induce apoptasis, but not necrosis of mouse brain cells in viro. The apoptotic brain cells show the pattern of temporal dependence and spatial distribution. It is suggested that the early treatment should be the method of first choice for treating the hemorrhagic brain injury.

  18. Human normal bronchial epithelial cells: a novel in vitro cell model for toxicity evaluation.

    Directory of Open Access Journals (Sweden)

    Wenqiang Feng

    Full Text Available Human normal cell-based systems are needed for drug discovery and toxicity evaluation. hTERT or viral genes transduced human cells are currently widely used for these studies, while these cells exhibited abnormal differentiation potential or response to biological and chemical signals. In this study, we established human normal bronchial epithelial cells (HNBEC using a defined primary epithelial cell culture medium without transduction of exogenous genes. This system may involve decreased IL-1 signaling and enhanced Wnt signaling in cells. Our data demonstrated that HNBEC exhibited a normal diploid karyotype. They formed well-defined spheres in matrigel 3D culture while cancer cells (HeLa formed disorganized aggregates. HNBEC cells possessed a normal cellular response to DNA damage and did not induce tumor formation in vivo by xenograft assays. Importantly, we assessed the potential of these cells in toxicity evaluation of the common occupational toxicants that may affect human respiratory system. Our results demonstrated that HNBEC cells are more sensitive to exposure of 10~20 nm-sized SiO2, Cr(VI and B(aP compared to 16HBE cells (a SV40-immortalized human bronchial epithelial cells. This study provides a novel in vitro human cells-based model for toxicity evaluation, may also be facilitating studies in basic cell biology, cancer biology and drug discovery.

  19. A Structured Population Model of Cell Differentiation

    CERN Document Server

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

    2010-01-01

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

  20. Border Cell Migration: A Model System for Live Imaging and Genetic Analysis of Collective Cell Movement

    OpenAIRE

    M Prasad; Wang, X; He, L.; Cai, D.; Montell, DJ

    2015-01-01

    © 2015, Springer Science+Business Media New York. Border cell migration in the Drosophila ovary has emerged as a genetically tractable model for studying collective cell movement. Over many years border cell migration was exclusively studied in fixed samples due to the inability to culture stage 9 egg chambers in vitro. Although culturing late-stage egg chambers was long feasible, stage 9 egg chambers survived only briefl y outside the female body. We identifi ed culture conditions that suppo...

  1. Experimental Study of the Morphology and Dynamics of Gas-Laden Layers Under the Anodes in an Air-Water Model of Aluminum Reduction Cells

    Science.gov (United States)

    Vékony, Klára; Kiss, László I.

    2012-10-01

    The bubble layer formed under an anode and the bubble-induced flow play a significant role in the aluminum electrolysis process. The bubbles covering the anode bottom reduce the efficient surface that can carry current. In our experiments, we filmed and studied the bubble layer under the anode in a real-size air-water electrolysis cell model. Three different flow regimes were found depending on the gas generation rate. The covering factor was found to be proportional to the gas generation rate and inversely proportional to the angle of inclination. A correlation between the average height of the entire bubble layer and the position under the anode was determined. From this correlation and the measured contact sizes, the volume of the accumulated gas was calculated. The sweeping effect of large bubbles was observed. Moreover, the small bubbles under the inner edge of the anode were observed to move backward as a result of the escape of huge gas pockets, which means large momentum transport occurs in the bath.

  2. Cultured bovine brain capillary endothelial cells (BBCEC) - a blood-brain barrier model for studying the binding and internalization of insulin and insulin-like growth factor 1

    Energy Technology Data Exchange (ETDEWEB)

    Keller, B.T.; Borchardt, R.T.

    1987-05-01

    Cultured bovine brain capillary endothelial cells (BBCEC) have previously been reported by their laboratory as a working model for studying nutrient and drug transport and metabolism at the blood-brain barrier. In the present study, they have utilized this culture system to investigate the binding and internalization of (/sup 125/I)-labelled insulin (INS) and insulin-like growth factor 1(IGF-1) by BBCEC. After 2 hrs at 23/sup 0/C, the specific binding of INS and IGF-1 was 1.6% and 13.6%, respectively. At 37/sup 0/C, the maximum specific binding was 0.9% for INS and 5.8% for IGF-1. Using an acid-wash technique to assess peptide internalization, it was observed that, at 37/sup 0/C, approximately 60% of the bound INS rapidly became resistant to acid treatment, a value which was constant over 2 hr. With IGF-1, a similar proportion of the bound material, 62%, became resistant by 30 min, but subsequently decreased to 45% by 2 hr. Scatchard analysis of competitive binding studies indicated the presence of two binding sites for each protein, having K/sub d/'s of 0.82 nM and 19.2 nM for INS and 0.39 nM and 3.66 nM for IGF-1. Little change in the amount of INS binding was observed over a four-day interval as the cultures became a confluent monolayer. The present report of binding and internalization of these proteins suggests that the BBCEC may utilize a receptor-mediated process to internalize and/or transport (transcytosis) INS and IGF-1 from the circulation.

  3. Single-Molecule Studies in Live Cells

    Science.gov (United States)

    Yu, Ji

    2016-05-01

    Live-cell single-molecule experiments are now widely used to study complex biological processes such as signal transduction, self-assembly, active trafficking, and gene regulation. These experiments' increased popularity results in part from rapid methodological developments that have significantly lowered the technical barriers to performing them. Another important advance is the development of novel statistical algorithms, which, by modeling the stochastic behaviors of single molecules, can be used to extract systemic parameters describing the in vivo biochemistry or super-resolution localization of biological molecules within their physiological environment. This review discusses recent advances in experimental and computational strategies for live-cell single-molecule studies, as well as a selected subset of biological studies that have utilized these new technologies.

  4. A Human Breast Cell Model of Preinvasive to Invasive Transition

    OpenAIRE

    Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D; Jensen, Roy A; Idowu, Michael O.; Chen, Fanqing

    2008-01-01

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from preinvasive to invasive phenotype as it may occur “spontaneously” in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted basement membrane cultures. These cells remained noninvasive;...

  5. Studies of cell biomechanics with surface micro-/nano-technology

    International Nuclear Information System (INIS)

    We report the recent progress in our studies of cell biology using micro-/nano-technology. Cells have a size of several to tens of microns, which makes them easily manipulated by micro-/nano-technology. The shape of the cell influences the alignment of the actin cytoskeleton, which bears the main forces of the cell, maintains the shape,and mediates a series of biochemical reactions. We invented a stretching device and studied the real-time actin filament dynamics under stretch. We found that one stretch cycle shortened the actin filaments and promoted their reassemble process. Cell migration is a complex mechanical process. We found that cell geometry determines the cell polarity and migration direction. We fabricated three-dimensional surfaces to mimic the topography in vivo, and further built a cell culture model by integrating the three-dimensional surface, microfluidics, cell patterning,and coculturing of multiple cell types. We also investigated the neuronal guidance by surface patterning. (authors)

  6. Schelling model of cell segregation based only on local information

    Science.gov (United States)

    Nielsen, Alexander Valentin; Gade, Annika Lund; Juul, Jeppe; Strandkvist, Charlotte

    2015-11-01

    While biological studies suggest that motility of cells is involved in cell segregation, few computational models have investigated this mechanism. We apply a simple Schelling model, modified to reflect biological conditions, demonstrating how differences in cell motility arising exclusively from differences in the composition of the local environment can be sufficient to drive segregation. The work presented here demonstrates that the segregation behavior observed in the original Schelling model is robust to a relaxation of the requirement for global information and that the Schelling model may yield insight in the context of biological systems. In the model, the time course of cell segregation follows a power law in accord with experimental observations and previous work.

  7. Pluripotent stem cells in disease modelling and drug discovery.

    Science.gov (United States)

    Avior, Yishai; Sagi, Ido; Benvenisty, Nissim

    2016-03-01

    Experimental modelling of human disorders enables the definition of the cellular and molecular mechanisms underlying diseases and the development of therapies for treating them. The availability of human pluripotent stem cells (PSCs), which are capable of self-renewal and have the potential to differentiate into virtually any cell type, can now help to overcome the limitations of animal models for certain disorders. The ability to model human diseases using cultured PSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases. Several strategies are used to generate such disease models using either embryonic stem cells (ES cells) or patient-specific induced PSCs (iPSCs), creating new possibilities for the establishment of models and their use in drug screening. PMID:26818440

  8. Pluripotent Stem Cells Models for Huntington's Disease: Prospects and Challenges

    Institute of Scientific and Technical Information of China (English)

    Richard L. Carter; Anthony W.S. Chan

    2012-01-01

    Pluripotent cellular models have shown great promise in the study of a number of neurological disorders.Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types,providing a system for researchers to monitor disease progression during neurogenesis,along with serving as a platform for drug discovery.A number of stem cell derived models have been employed to establish in vitro research models of Huntington's disease that can be used to investigate cellular pathology and screen for drug and cell-based therapies.Although some progress has been made,there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved,In this article we review current stem cell models that have been reported,as well as discuss the issues that impair these studies.We also highlight the prospective application of Huntington's disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.

  9. (1) H-NMR relaxometric studies of interaction between apoptosis specific MRI paramagnetic contrast agents and micellar models of apoptotic cells.

    Science.gov (United States)

    Van Koninckxloo, Aurore; Henoumont, Céline; Laurent, Sophie; Muller, Robert N; Vander Elst, Luce

    2016-07-01

    (1) H-NMR was previously used to analyze the interaction between peptides (E3 and R826) selected by phage display to target apoptotic cells and phospholipidic models of these cells. In order to avoid the use of apoptotic cells and to obtain a fast evaluation of the efficiency of the potential MRI contrast agents obtained by grafting these peptides and their scramble analogs on a paramagnetic gadolinium complex, their proton relaxometric behavior was investigated in the presence of micelles mimicking healthy and apoptotic cells. Their preferential interaction with 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine micelles mimicking apoptotic cells as compared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine micelles modeling healthy cells was shown by nuclear magnetic relaxation dispersion profiles and the enhancement of the transverse proton relaxation rates at 60 MHz. The association constant values confirm the stronger interaction of the selected conjugated peptides (Ka Gd-PMN-E3(gadolinium 2,2',2'',2'''-[((4-carboxy)pyridine-2,6-diyl)bis(methylenenitrilo)]-tetrakis acetate) grafted with E3 peptide): 2.43 10(4)  m(-1) ; Ka Gd-DTPA-R826(gadolinium ((1-p-isothiocyanatobenzyl)-diethylenetriaminepentaacetate) grafted with R826 peptide): 2.91 10(4)  m(-1) ) as compared with their conjugated scrambles (Ka Gd-PMN-E3sc(gadolinium 2,2',2'',2'''-[((4-carboxy)pyridine-2,6-diyl)bis(methylenenitrilo)]-tetrakis acetate) grafted with E3 scramble peptide): 0.18 10(4)  m(-1) ; Ka Gd-DTPA-R826sc(gadolinium ((1-p-isothiocyanatobenzyl)-diethylenetriaminepentaacetate) grafted with R826 scramble peptide): 0.32 10(4)  m(-1) ) even if the conjugation of E3 and R826 seems to decrease their interaction. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26647764

  10. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    Institute of Scientific and Technical Information of China (English)

    Guanqun Qiao; Qingquan Li; Gang Peng; Jun Ma; Hongwei Fan; Yingbin Li

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

  11. Comparative study of RBE and cell survival fractions for $^{1}$H, $^{4}$He, $^{12}$C and $^{16}$O beams using Geant4 and Microdosimetric Kinetic model

    CERN Document Server

    Burigo, Lucas; Mishustin, Igor; Bleicher, Marcus

    2014-01-01

    Beams of $^{4}$He and $^{16}$O nuclei are considered for ion-beam cancer therapy as alternative options to protons and $^{12}$C nuclei. Spread-out Bragg peak (SOBP) distributions of physical dose and relative biological effectiveness for 10% survival are calculated by means of our Geant4-based Monte Carlo model for Heavy Ion Therapy (MCHIT) and the modified microdosimetric kinetic model. The depth distributions of cell survival fractions are calculated for $^{1}$H, $^{4}$He, $^{12}$C and $^{16}$O for tissues with normal (HSG cells), low and high radiosensitivity. In each case the cell survival fractions were compared separately for the target volume, behind and in front of it. In the case of normal radiosensitivity $^{4}$He and $^{12}$C better spare tissues in the entrance channel compared to protons and $^{16}$O. The cell survival fractions calculated, respectively, for the entrance channel and target volume are similar for $^{4}$He and $^{12}$C. When it is important to spare healthy tissues located after th...

  12. An electrostatic model for biological cell division

    CERN Document Server

    Faraggi, Eshel

    2010-01-01

    Probably the most fundamental processes for biological systems is their ability to create themselves through the use of cell division and cell differentiation. In this work a simple physical model is proposed for biological cell division. The model consists of a positive ionic gradient across the cell membrane, and concentration of charge at the nodes of the spindle and on the chromosomes. A simple calculation, based on Coulomb's Law, shows that under such circumstances a chromosome will tend to break up to its constituent chromatids and that the chromatids will be separated by a distance that is an order of thirty percent of the distance between the spindle nodes. Further repulsion between the nodes will tend to stretch the cell and eventually break the cell membrane between the separated chromatids, leading to cell division. The importance of this work is in continuing the understanding of the electromagnetic basis of cell division and providing it with an analytical model. A central implication of this and...

  13. The development of an OxyHb animal model in mice and the study on OxyHb-induced apoptosis of mouse brain cells in vivo

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective On the basis of developing a new animal model for oxyhemoglobin(OxyHb)injection into subarachnoid space in mice,this research was to explore the temporal dependence and spatial distribution of OxyHb-induced apoptosis in the mouse brain cells in vivo and the mechanism of neurocyte injury induced by OxyHb.Methods The animal model for OxyHb injection into subarachnoid space in mice was developed.Mice were divided randomly into the experimental group(n=40)and the control group(n=35).The control group ...

  14. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-08-01

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

  15. Studies on DANESS Code Modeling

    International Nuclear Information System (INIS)

    The DANESS code modeling study has been performed. DANESS code is widely used in a dynamic fuel cycle analysis. Korea Atomic Energy Research Institute (KAERI) has used the DANESS code for the Korean national nuclear fuel cycle scenario analysis. In this report, the important models such as Energy-demand scenario model, New Reactor Capacity Decision Model, Reactor and Fuel Cycle Facility History Model, and Fuel Cycle Model are investigated. And, some models in the interface module are refined and inserted for Korean nuclear fuel cycle model. Some application studies have also been performed for GNEP cases and for US fast reactor scenarios with various conversion ratios

  16. CAD MOSFET MODEL FOR EPROM CELLS

    OpenAIRE

    Ballay, N.; Baylac, B.

    1988-01-01

    A CAD model of NOS transistor suitable for circuit simulation of an EPROM cell during writing cycle is proposed. This model is as close as possible of physics to allow the designer to evaluate different schemes and changes in the process variables. It is reliable in the breakdown mode too and takes into account the gate current induced by channel hot electrons.

  17. Cardiac Electromechanical Models: From Cell to Organ

    Directory of Open Access Journals (Sweden)

    Natalia A Trayanova

    2011-08-01

    Full Text Available The heart is a multiphysics and multiscale system that has driven the development of the most sophisticated mathematical models at the frontiers of computation physiology and medicine. This review focuses on electromechanical (EM models of the heart from the molecular level of myofilaments to anatomical models of the organ. Because of the coupling in terms of function and emergent behaviors at each level of biological hierarchy, separation of behaviors at a given scale is difficult. Here, a separation is drawn at the cell level so that the first half addresses subcellular/single cell models and the second half addresses organ models. At the subcelluar level, myofilament models represent actin-myosin interaction and Ca-based activation. Myofilament models and their refinements represent an overview of the development in the field. The discussion of specific models emphasizes the roles of cooperative mechanisms and sarcomere length dependence of contraction force, considered the cellular basis of the Frank-Starling law. A model of electrophysiology and Ca handling can be coupled to a myofilament model to produce an EM cell model, and representative examples are summarized to provide an overview of the progression of field. The second half of the review covers organ-level models that require solution of the electrical component as a reaction-diffusion system and the mechanical component, in which active tension generated by the myocytes produces deformation of the organ as described by the equations of continuum mechanics. As outlined in the review, different organ-level models have chosen to use different ionic and myofilament models depending on the specific application; this choice has been largely dictated by compromises between model complexity and computational tractability. The review also addresses application areas of EM models such as cardiac resynchronization therapy and the role of mechano-electric coupling in arrhythmias and

  18. Mechanistic Evaluation for Mixed-field Agglutination in the K562 Cell Study Model with Exon 3 Deletion of A1 Gene.

    Science.gov (United States)

    Chen, Ding-Ping; Tseng, Ching-Ping; Lin, Chi-Jui; Wang, Wei-Ting; Sun, Chien-Feng

    2015-01-01

    In the case of blood type B3 with typical mixed-field agglutination of RBCs in the presence of anti-B or anti-AB antibody, a number of genetic alternations have been reported. It is well known that the IVS3+5G→A mutation in the B gene destroys the consensus of the splice donor site leading to exon 3 skipping during mRNA splicing. The lack of exon 3 likely causes a short stem region, producing an unstable B3 protein, and is concomitant with a decrease in B3 protein expression. Whether the phenomenon also appears in the type A blood group is of question. In this study, we evaluate whether exon 3 deletion in the blood type A gene also results in mixed-field phenotype. Site-directed mutagenesis was used to generate cDNA encoding A1 gene with exon 3 deletion. The cDNA was stably expressed in K562 cells. The expression of A antigen was compared with expression in parental K562 cells that did not express A antigen and in the stable K562 cell line expressing A(1) cDNA by flow cytometry analyses. The expression of A antigen in A1 stable cells and parental K562 cells was set as 100% and 0%, respectively. The mean relative percentage of A antigen expression for the cells of A1 with exon 3 deletion was 59.9% of A1 stable cells. Consistent with the observations of B3, which is B gene with exon 3 deletion, mixed field agglutination was observed for the cells expressing A1 with exon 3 deletion. Exon 3 deletion results in mixed field phenotype in both type A and B RBCs. However, the degree of antigen expression change for exon 3 deletion in A gene was less severe when compared with the deletion occurred in B gene. PMID:26663798

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

    Science.gov (United States)

    Jena, Siddhartha G

    2016-03-01

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

  20. A transient model to simulate HTPEM fuel cell impedance spectra

    DEFF Research Database (Denmark)

    Vang, Jakob Rabjerg; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2012-01-01

    laboratory. A simultaneous fit to both curves is not achieved. In order to investigate the effects of the fitting parameters on the simulation results, a parameter variation study is carried out. It is concluded that some of the fitting parameters assume values which are not realistic. In order to remedy......This paper presents a spatially resolved transient fuel cell model applied to the simulation of high temperature PEM fuel cell impedance spectra. The model is developed using a 2D finite volume method approach. The model is resolved along the channel and across the membrane. The model considers...

  1. Studying the effect of material parameters on cell performance of tubular-shaped PEM fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Al-Baghdadi, Maher A.R. Sadiq [Department of Mechanical Engineering, International Technological University, 115 Dollis Hill Lane, London NW2 6HS (United Kingdom)

    2008-11-15

    A full three-dimensional, non-isothermal computational fluid dynamics model of a tubular-shaped proton exchange membrane (PEM) fuel cell has been developed. This comprehensive model accounts for the major transport phenomena in a PEM fuel cell: convective and diffusive heat and mass transfer, electrode kinetics, transport and phase change mechanism of water, and potential fields. The model is shown to be able to understand the many interacting, complex electrochemical, and transport phenomena that cannot be studied experimentally. In addition to the new feature of tubular-shaped geometry of PEM fuel cell, this model is used to study the effects of several material parameters on fuel cell performance. Detailed analyses of the temperature distribution inside the tubular cell under various material properties have been conducted and examined. The analysis helped identifying critical parameters and shed insight into the physical mechanisms leading to a fuel cell performance and durability under various material conditions. (author)

  2. Studying the effect of material parameters on cell performance of tubular-shaped PEM fuel cell

    International Nuclear Information System (INIS)

    A full three-dimensional, non-isothermal computational fluid dynamics model of a tubular-shaped proton exchange membrane (PEM) fuel cell has been developed. This comprehensive model accounts for the major transport phenomena in a PEM fuel cell: convective and diffusive heat and mass transfer, electrode kinetics, transport and phase change mechanism of water, and potential fields. The model is shown to be able to understand the many interacting, complex electrochemical, and transport phenomena that cannot be studied experimentally. In addition to the new feature of tubular-shaped geometry of PEM fuel cell, this model is used to study the effects of several material parameters on fuel cell performance. Detailed analyses of the temperature distribution inside the tubular cell under various material properties have been conducted and examined. The analysis helped identifying critical parameters and shed insight into the physical mechanisms leading to a fuel cell performance and durability under various material conditions

  3. Radiobiological modelling with MarCell software

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, J.S.; Jones, T.D.

    1996-10-01

    Jones introduced a bone marrow radiation cell kinetics model with great potential for application in the fields of health physics, radiation research, and medicine. However, until recently, only the model developers have been able to apply it because of the complex array of biological and physical assignments needed for evaluation of a particular radiation exposure protocol. The purpose of this article is to illustrate the use of MarCell (MARrow CELL Kinetics) software for MS-DOS, a user-friendly computer implementation of that mathematical model that allows almost anyone with an elementary knowledge of radiation physics and/or medical procedures to apply the model. A hands-on demonstration of the software will be given by guiding the user through evaluation of a medical total body irradiation protocol and a nuclear fallout scenario. A brief overview of the software is given in the Appendix.

  4. Radiobiological modelling with MarCell software

    International Nuclear Information System (INIS)

    Jones introduced a bone marrow radiation cell kinetics model with great potential for application in the fields of health physics, radiation research, and medicine. However, until recently, only the model developers have been able to apply it because of the complex array of biological and physical assignments needed for evaluation of a particular radiation exposure protocol. The purpose of this article is to illustrate the use of MarCell (MARrow CELL Kinetics) software for MS-DOS, a user-friendly computer implementation of that mathematical model that allows almost anyone with an elementary knowledge of radiation physics and/or medical procedures to apply the model. A hands-on demonstration of the software will be given by guiding the user through evaluation of a medical total body irradiation protocol and a nuclear fallout scenario. A brief overview of the software is given in the Appendix

  5. Seed coat removal improves Fe bioavailability in cooked lentils: studies using an in vitro digestion/Caco-2 cell culture model

    Science.gov (United States)

    This study examined the range of Fe concentration and relative Fe bioavailability of 24 varieties of cooked lentils, as well as the impact of seed coat removal on lentil Fe nutritional quality. Relative Fe bioavailability was assessed by the in vitro/Caco-2 cell culture method. While Fe concentrat...

  6. Establishment and Molecular Cytogenetic Characterization of a Cell Culture Model of Head and Neck Squamous Cell Carcinoma (HNSCC)

    OpenAIRE

    Horst Zitzelsberger; Axel Walch; Johannes Weber; Herbert Braselmann; Reinhard Huber; Ludwig Hieber; Quirin Schaeffner; Bauer, Verena L.

    2010-01-01

    Cytogenetic analysis of head and neck squamous cell carcinoma (HNSCC) established several biomarkers that have been correlated to clinical parameters during the past years. Adequate cell culture model systems are required for functional studies investigating those potential prognostic markers in HNSCC. We have used a cell line, CAL 33, for the establishment of a cell culture model in order to perform functional analyses of interesting candidate genes and proteins. The cell line was cytogeneti...

  7. PLACE CELL FORMATION BY GRID CELL CONVERGENCE IN THE DENDRITES OF A CA1 MODEL NEURON

    Directory of Open Access Journals (Sweden)

    Evangelia Pollali

    2014-04-01

    Full Text Available Place cells are pyramidal neurons in CA1 and CA3 regions of hippocampus which fire selectively when the animal is located in a particular place in space. CA1 place cells receive synaptic input from CA3 via the Schaffer collateral fibers to their proximal apical and basal dendrites and from the third layer of medial entorhinal cortex to their apical tuft dendrites. Both of these input pathways encode spatial information. Grid cells, which form the entorhinal input to CA1 cells, have a spatial firing field with multiple peaks which displays a regularly spaced, triangular grid pattern that covers the entire space of a given environment. Both grid and place cells are phase-modulated by theta rhythm and this modulation may be important for their spatial properties. Studying the formation of place cells is an important step in understanding how representation of the external environment is coded in neural networks that constitute spatial maps. It is not currently known how place fields emerge in CA1 neurons. An influential model of place cell formation predicts the convergence of various grid field inputs which combine linearly to create the place field output of CA1 cells. In this study, we constructed a model of CA1 place cell formation through the convergence of grid field inputs to the distal dendrites of our model neuron. We created a model of grid cell activity which represents the firing of grid cells modulated be the theta rhythm. We varied the number of different grid fields used as synaptic inputs to stimulate the distal dendrites of a biophysically constrained, detailed compartmental CA1 pyramidal cell model. In addition, inhibition was placed in both the distal and proximal dendrites. These inhibitory pathways are known to be active in different phases of the theta rhythm. We used this model to study the properties of CA1 place cell formation and to assess the output of the CA1 model cell during place cell activity. Additionally, we

  8. Modelling Morphogenesis: From Single Cells to Crawling Slugs

    NARCIS (Netherlands)

    Savill, N.J.; Hogeweg, P.

    2002-01-01

    We present a three-dimensional hybrid cellular automata (CA)/partial differential equation (PDE) model that allows for the study of morphogenesis in simple cellular systems. We apply the model to the cellular slime mold Dictyostelium discoideum "from single cells to crawling slug". Using simple loca

  9. Radiobiological modeling with MarCell software

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, J.S.; Jones, T.D. [Oak Ridge National Lab., TN (United States). Health Sciences Research Div.

    1999-01-01

    A nonlinear system of differential equations that models the bone marrow cellular kinetics associated with radiation injury, molecular repair, and compensatory cell proliferation has been extensively documented. Recently, that model has been implemented as MarCell, a user-friendly MS-DOS computer program that allows users with little knowledge of the original model to evaluate complex radiation exposure scenarios. The software allows modeling with the following radiations: tritium beta, 100 kVp X, 250 kVp X, 22 MV X, {sup 60}Co, {sup 137}Cs, 2 MeV electrons, triga neutrons, D-T neutrons, and 3 blends of mixed-field fission radiations. The possible cell lineages are stem, stroma, and leukemia/lymphoma, and the available species include mouse, rat, dog, sheep, swine, burro, and man. An attractive mathematical feature is that any protracted protocol can be expressed as an equivalent prompt dose for either the source used or for a reference, such as 250 kVp X rays or {sup 60}Co. Output from MarCell includes: risk of 30-day mortality; risk of cancer and leukemia based either on cytopenia or compensatory cell proliferation; cell survival plots as a function of time or dose; and 4-week recovery kinetics following treatment. In this article, the program`s applicability and ease of use are demonstrated by evaluating a medical total body irradiation protocol and a nuclear fallout scenario.

  10. A primary study on the phagocytic activity of Kupffer cells with superparamagnetic iron oxide particles enhanced MR imaging in a rat nonalcoholic steatohepatitis model

    International Nuclear Information System (INIS)

    Objective: To investigate the feasibility of using superparamgnetic iron oxide (SPIO) as MRI contrast agent to assess rat nonalcoholic steatohepatitis Kupffer cells (KC) function. Methods: Twenty male SD rats were randomly divided into A and B groups, group A (n=10) was the experimental group fed high fat diet, group B (n=10) was the control group fed normal diet. After 8 weeks, plain MR and SPIO enhanced MR were performed in all the rats. Blood lipids were measured, and HE and Perl's blue staining in all livers specimen was done. The related results of the staining were analyzed with t test. Results: Group A TC and TG levels [(6.58 ± 1.25) and (1.53 ± 0.23) mmol/L respectively] were significantly higher than group B[(1.64 ± 0.22) and (0.55 ± 0.14) mmol/L respectively] (t=11.716 and 11.588, P1WI, ad statistically significant differences (t=-18.451 and -16.240, P2WI, T2WI and T1WI (t=10.745, 19.800, 39.168 and 92.785, P<0.01). Typical histological hepatic lesions of NASH were observed in group A, Perl's staining-positive particles in group A (2.33 ± 0.50) were fewer than in group B (4) (t=-10.000, P<0.01). Conclusion: The high-fat diet induced model of SD rats was close to the human NASH and was easy to establish. Clinical application of SPIO enhanced MR successfullly assessed the phagocytic activity of KC in the study, and it suggested that the pathogenesis of NASH was related to the decreased phagocytic activity of KC. (authors)

  11. Systems Level Modeling of the Cell Cycle Using Budding Yeast

    Directory of Open Access Journals (Sweden)

    D.R. Kim

    2007-01-01

    Full Text Available Proteins involved in the regulation of the cell cycle are highly conserved across all eukaryotes, and so a relatively simple eukaryote such as yeast can provide insight into a variety of cell cycle perturbations including those that occur in human cancer. To date, the budding yeast Saccharomyces cerevisiae has provided the largest amount of experimental and modeling data on the progression of the cell cycle, making it a logical choice for in-depth studies of this process. Moreover, the advent of methods for collection of high-throughput genome, transcriptome, and proteome data has provided a means to collect and precisely quantify simultaneous cell cycle gene transcript and protein levels, permitting modeling of the cell cycle on the systems level. With the appropriate mathematical framework and suffi cient and accurate data on cell cycle components, it should be possible to create a model of the cell cycle that not only effectively describes its operation, but can also predict responses to perturbations such as variation in protein levels and responses to external stimuli including targeted inhibition by drugs. In this review, we summarize existing data on the yeast cell cycle, proteomics technologies for quantifying cell cycle proteins, and the mathematical frameworks that can integrate this data into representative and effective models. Systems level modeling of the cell cycle will require the integration of high-quality data with the appropriate mathematical framework, which can currently be attained through the combination of dynamic modeling based on proteomics data and using yeast as a model organism.

  12. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    International Nuclear Information System (INIS)

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10B (45–74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  13. Thermal-fluid and electrochemical modeling and performance study of a planar solid oxide electrolysis cell : analysis on SOEC resistances, size, and inlet flow conditions.

    Energy Technology Data Exchange (ETDEWEB)

    Yildiz, B.; Smith, J.; Sofu, T.; Nuclear Engineering Division

    2008-06-25

    Argonne National Laboratory and Idaho National Laboratory researchers are analyzing the electrochemical and thermal-fluid behavior of solid oxide electrolysis cells (SOECs) for high temperature steam electrolysis using computational fluid dynamics (CFD) techniques. The major challenges facing commercialization of steam electrolysis technology are related to efficiency, cost, and durability of the SOECs. The goal of this effort is to guide the design and optimization of performance for high temperature electrolysis (HTE) systems. An SOEC module developed by FLUENT Inc. as part of their general CFD code was used for the SOEC analysis by INL. ANL has developed an independent SOEC model that combines the governing electrochemical mechanisms based on first principals to the heat transfer and fluid dynamics in the operation of SOECs. The ANL model was embedded into the commercial STAR-CD CFD software, and is being used for the analysis of SOECs by ANL. The FY06 analysis performed by ANL and reported here covered the influence of electrochemical properties, SOEC component resistances and their contributing factors, SOEC size and inlet flow conditions, and SOEC flow configurations on the efficiency and expected durability of these systems. Some of the important findings from the ANL analysis are: (1) Increasing the inlet mass flux while going to larger cells can be a compromise to overcome increasing thermal and current density gradients while increasing the cell size. This approach could be beneficial for the economics of the SOECs; (2) The presence of excess hydrogen at the SOEC inlet to avoid Ni degradation can result in a sizeable decrease in the process efficiency; (3) A parallel-flow geometry for SOEC operation (if such a thing be achieved without sealing problems) yields smaller temperature gradients and current density gradients across the cell, which is favorable for the durability of the cells; (4) Contact resistances can significantly influence the total cell

  14. Derived vascular endothelial cells induced by mucoepidermoid carcinoma cells: 3-dimensional collagen matrix model*

    OpenAIRE

    Yang, Sen; Guo, Li-Juan; Gao, Qing-hong; Xuan, Ming; Tan, Ke; Zhang, Qiang; Wen, Yu-ming; Wang, Chang-mei; Tang, Xiu-fa; Wang, Xiao-yi

    2010-01-01

    Mucoepidermoid carcinoma undergoes uniquely vigorous angiogenic and neovascularization processes, possibly due to proliferation of vascular endothelial cells (ECs) induced by mucoepidermoid carcinoma cells (MCCs) in their three-dimensional (3D) microenvironment. To date, no studies have dealt with tumor cells and vascular ECs from the same origin of mucoepidermoid carcinoma using the in vitro 3D microenvironment model. In this context, the current research aims to observe neovascularization w...

  15. Dye- and quantum dot-sensitized solar cells based on nanostructured wide-bandgap semiconductors via an integrated experimental and modeling study

    Science.gov (United States)

    Xin, Xukai

    Dye-sensitized solar cells (DSSCs) and quantum dot-sensitized solar cells (QDSSCs) are two promising alternative, cost-effective concepts for solar-to-electric energy conversion that have been offered to challenge conventional Si solar cells over the past decade. The configuration of a DSSC or a QDSSC consists of sintered TiO2 nanoparticle films, ruthenium-based dyes or quantum dots (QDs) (i.e., sensitizers), and electrolytes. Upon the absorption of photons, the dyes or QDs generate excitons (i.e., electron-hole pairs). Subsequently, the electrons inject into the TiO2 photoanode to generate photocurrent; scavenged by a redox couple, holes transport to the cathode. The overall power conversion efficiency (PCE) of a DSSC or QDSSC is dictated by the light harvest efficiency, quantum yield for charge injection, and charge collection efficiency at the electrodes. The goal of our research is to understand the fundamental physics and performance of DSSCs and QDSSCs with improved PCE at the low cost based on rational engineering of TiO2 nanostructures, sensitizers, and electrodes through an integrated experimental and modeling study. In this presentation, I will discuss three aspects that I have accomplished over the last several years. (1) Effects of surface treatment and structural modification of photoanode on the performance of DSSCs. First, our research indicates that the surface treatment with both TiCl4 and oxygen plasma yields the most efficient dye-sensitized TiO2-nanoparticle solar cells. A maximum PCE is achieved with a 21 microm thick TiO2 film; the PCE further increases to 8.35% after TiCl4 and O 2 plasma treatments, compared to the untreated TiO2 ( PCE = 3.86%). Second, we used a layer of TiO2 nanoparticle film coated on the FTO glass, and a bilayer of TiO2nanoparticle/freestanding TiO2 nanotube film deposited on the FTO glass as photoanodes. The J˜V parameter analysis acquired by equivalent circuit model simulation reveals that nanotubular structures are

  16. Optical scattering modeling of etched ZnO:Al superstrates and device simulation studies of a-Si:H solar cells with different texture morphologies.

    Science.gov (United States)

    Yan, Xia; Li, Weimin; Aberle, Armin G; Venkataraj, Selvaraj

    2016-08-20

    Transparent conductive oxide (TCO) materials have been widely used as the front electrodes of thin-film amorphous silicon (a-Si:H) solar cells. To improve the performance of solar cells, textured front TCO is required as the optical layer which effectively scatters the incoming light and thus enhances the photon absorption within the device. One promising TCO material is aluminum-doped zinc oxide (AZO), which is most commonly prepared by magnetron sputtering. After deposition, sputtered AZO films are typically wet-chemically etched using diluted hydrochloric (HCl) or hydrofluoric (HF) acid to obtain rough surface morphologies. In this paper, we report the effects of a textured AZO front electrode on the performance of a-Si:H solar cells based on optical scattering modeling and electrical device simulations, involving four different AZO surface morphologies. The simulated light scattering behaviors indicate that a better textured surface not only scatters more light, but also allows more light get transmitted into the absorber (∼90% of visible light), due to greatly reduced front reflection by the rough surface. Device simulation results show that the two-step AZO texturing process should give improved a-Si:H solar cell performance, with an enhanced short-circuit current density of 16.5  mA/cm2, which leads to a high photovoltaic (PV) efficiency of 9.9%. PMID:27556994

  17. Numerical Model of the DARHT Accelerating Cell

    CERN Document Server

    Hughes, Thomas P; Genoni, Thomas C; Kang, Mike; Prichard, Benjamin A

    2005-01-01

    The DARHT-2 facility at Los Alamos National Laboratory accelerates a 2 microsecond electron beam using a series of inductive accelerating cells. The cell inductance is provided by large Metglas cores, which are driven by a pulse-forming network. The original cell design was susceptible to electrical breakdown near the outer radius of the cores. We developed a numerical model for the magnetic properties of Metglas over the range of dB/dt (magnetization rate) relevant to DARHT. The model was implemented in a radially-resolved circuit code, and in the LSP* electromagnetic code. LSP simulations showed that the field stress distribution across the outer radius of the cores was highly nonuniform. This was subsequently confirmed in experiments at LBNL. The calculated temporal evolution of the electric field stress inside the cores approximately matches experimental measurements. The cells have been redesigned to greatly reduce the field stresses along the outer radius.

  18. A statistical model for red blood cell survival.

    Science.gov (United States)

    Korell, Julia; Coulter, Carolyn V; Duffull, Stephen B

    2011-01-01

    A statistical model for the survival time of red blood cells (RBCs) with a continuous distribution of cell lifespans is presented. The underlying distribution of RBC lifespans is derived from a probability density function with a bathtub-shaped hazard curve, and accounts for death of RBCs due to senescence (age-dependent increasing hazard rate) and random destruction (constant hazard), as well as for death due to initial or delayed failures and neocytolysis (equivalent to early red cell mortality). The model yields survival times similar to those of previously published studies of RBC survival and is easily amenable to inclusion of drug effects and haemolytic disorders. PMID:20950630

  19. Modeling bacterial chemotaxis inside a cell

    OpenAIRE

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

    2014-01-01

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

  20. Large animal models for stem cell therapy

    OpenAIRE

    Harding, John; Roberts, R. Michael; Mirochnitchenko, Oleg

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for nov...

  1. Transient Studies of a Sodium Sulfur Cell

    Science.gov (United States)

    Caprio, Sarah

    Modern grids will include input from fossil-fueled power generation facilities as well as renewable energy sources, and these are expected to work together actively. One major problem with this integrated power production is that most renewable energy sources are intermittent and variable, and thus introduce a very challenging situation with regard to grid stability and reliability. Also, fossil-fueled power generation facilities have load cycles based on expected usage. A non-reliable power source cannot feasibly be used to supply the grid with proper amounts of energy needed in peak times. A solution to this dilemma is power storage. The sodium-sulfur battery has high potential for electrical storage at the grid level due to its high energy density, low cost of the reactants, and high open-circuit voltage. However, the use of sodium-sulfur batteries at the grid level requires high current density operation that can cause cell deterioration, leading to lower sulfur utilization and lower energy efficiency. In addition, it can result in undesired thermal runaway leading to potentially hazardous situations. A rigorous, dynamic model of a sodium-sulfur battery can be used to study these phenomena, design the battery for optimal transient performance, and develop mitigation strategies. Most literature on sodium-sulfur batteries is concerned the dynamics of the sulfur electrode (a sodium-polysulfide melt). There is limited data in the open literature for dynamics of an entire cell. With this motivation, a first-principles dynamic model of a sodium-sulfur cell (with beta"-alumina electrolyte) has been developed. The state of discharge (SOD) of a sodium-sulfur cell significantly affects the heat generation rate, rates of electrochemical reactions, and internal resistance. To capture these phenomena correctly, a fully coupled thermal-electrochemical model has been developed. The thermal model considers heat generation due to Ohmic loss, Peltier heat, and heat due to the

  2. Computational Modeling of Cell Survival Using VHDL

    Directory of Open Access Journals (Sweden)

    Shruti Jain1,

    2010-01-01

    Full Text Available The model for cell survival has been implemented using VeryHigh Speed Integrated Circuit Hardware DescriptionLanguage (VHDL (Xilinx Tool taking three input signals:Tumor necrosis factor-α (TNF, Epidermal growth factor(EGF and Insulin. Cell survival has been regulated by theinteraction of five proteins viz P13K, TNFR1, EGFR, IRS andIKK in a network. In the absence of any one, in protein networkleads to cell death. For the EGF input signal the proteins likeMEK, ERK, AkT, Rac & JNK have been important forregulation of cell survival. Similarly for TNF and Insulin inputsignal proteins like NFκB, AkT, XIAP, JNK, MAP3K & MK2and MEK, ERK, AkT, Rac, mTOR & JNK respectively havebeen important for regulation of cell survival.

  3. Optical models for silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, T.; Sopori, B. [National Renewable Energy Lab., Golden, CO (United States)

    1995-08-01

    Light trapping is an important design feature for high-efficiency silicon solar cells. Because light trapping can considerably enhance optical absorption, a thinner substrate can be used which, in turn, can lower the bulk carrier recombination and concommitantly increase open-circuit voltage, and fill factor of the cell. The basic concepts of light trapping are similar to that of excitation of an optical waveguide, where a prism or a grating structure increases the phase velocity of the incoming optical wave such that waves propagated within the waveguide are totally reflected at the interfaces. Unfortunately, these concepts break down because the entire solar cell is covered with such a structure, making it necessary to develop new analytical approaches to deal with incomplete light trapping in solar cells. This paper describes two models that analyze light trapping in thick and thin solar cells.

  4. The Influence of Copper (Cu) Deficiency in a Cardiomyocyte Cell Model (HL-1 Cell) of Ischemia/Reperfusion Injury

    Science.gov (United States)

    Mitochondria are important mediators of cell death and this study examines whether mitochondrial dysfunction caused by Cu deprivation promotes cell death in a cell culture model for ischemia/reperfusion injury in cardiomyocytes. HL-1 cells (kindly donated by Dr. William C. Claycomb, LSU Health Scien...

  5. Viral cross-class serpin inhibits vascular inflammation and T lymphocyte fratricide; a study in rodent models in vivo and human cell lines in vitro.

    Directory of Open Access Journals (Sweden)

    Kasinath Viswanathan

    Full Text Available Poxviruses express highly active inhibitors, including serine proteinase inhibitors (serpins, designed to target host immune defense pathways. Recent work has demonstrated clinical efficacy for a secreted, myxomaviral serpin, Serp-1, which targets the thrombotic and thrombolytic proteases, suggesting that other viral serpins may have therapeutic application. Serp-2 and CrmA are intracellular cross-class poxviral serpins, with entirely distinct functions from the Serp-1 protein. Serp-2 and CrmA block the serine protease granzyme B (GzmB and cysteine proteases, caspases 1 and 8, in apoptotic pathways, but have not been examined for extracellular anti-inflammatory activity. We examined the ability of these cross-class serpins to inhibit plaque growth after arterial damage or transplant and to reduce leukocyte apoptosis. We observed that purified Serp-2, but not CrmA, given as a systemic infusion after angioplasty, transplant, or cuff-compression injury markedly reduced plaque growth in mouse and rat models in vivo. Plaque growth was inhibited both locally at sites of surgical trauma, angioplasty or transplant, and systemically at non-injured sites in ApoE-deficient hyperlipidemic mice. With analysis in vitro of human cells in culture, Serp-2 selectively inhibited T cell caspase activity and blocked cytotoxic T cell (CTL mediated killing of T lymphocytes (termed fratricide. Conversely, both Serp-2 and CrmA inhibited monocyte apoptosis. Serp-2 inhibitory activity was significantly compromised either in vitro with GzmB antibody or in vivo in ApoE/GzmB double knockout mice. Conclusions The viral cross-class serpin, Serp-2, that targets both apoptotic and inflammatory pathways, reduces vascular inflammation in a GzmB-dependent fashion in vivo, and inhibits human T cell apoptosis in vitro. These findings indicate that therapies targeting Granzyme B and/or T cell apoptosis may be used to inhibit T lymphocyte apoptosis and inflammation in response to

  6. Modelling ion flux in red cells

    International Nuclear Information System (INIS)

    The volume of a circulating red blood cell is a primary function of its water content; this being determined by the cellular amounts of ions such as K+ and Na+. Improper function of transport pathways of these can lead to reduced cell deformability, as occurs in Sickle-cell Anaemia and other disease states. Work in our laboratory has focussed on the kinetics of the calcium-activated potassium (Gardos) channel in the human red cell, and the role this transporter plays in regulation of cell volume. Whole cell 39K, 87Rb, 31P NMR spectroscopy was employed to monitor changes in cellular ion and water content. 19F NMR enabled prediction of the available free calcium using 5,5'-difluoro-l,2-bis(o-aminophenoxy)-ethane-N,N,N'N'-tetraacetic acid (5-F-BAPTA) as a calcium 'probe'. Concurrently a model of red cell ion flux has been written in Mathematica. This model numerically solves a system of time-dependent differential equations with rate constants and other parameters based on experimental evidence

  7. Studying neurodegenerative diseases in culture models

    Directory of Open Access Journals (Sweden)

    Johannes C.M. Schlachetzki

    2013-01-01

    Full Text Available Neurodegenerative diseases are pathological conditions that have an insidious onset and chronic progression. Different models have been established to study these diseases in order to understand their underlying mechanisms and to investigate new therapeutic strategies. Although various in vivo models are currently in use, in vitro models might provide important insights about the pathogenesis of these disorders and represent an interesting approach for the screening of potential pharmacological agents. In the present review, we discuss various in vitro and ex vivo models of neurodegenerative disorders in mammalian cells and tissues.

  8. Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

    Directory of Open Access Journals (Sweden)

    Martin Hoffmann

    Full Text Available Therapeutic application of mesenchymal stem cells (MSC requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The 'tool box' of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.

  9. Modeling cell-in-cell structure into its biological significance

    OpenAIRE

    He, M-f; Wang, S.; Y Wang; Wang, X-n

    2013-01-01

    Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of ‘entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintainin...

  10. System Studies of Fuel Cell Power Plants

    OpenAIRE

    Kivisaari, Timo

    2001-01-01

    This thesis concerns system studies of power plants wheredifferent types of fuel cells accomplish most of the energyconversion. Ever since William Grove observed the fuel cell effect inthe late 1830s fuel cells have been the subject or more or lessintense research and development. Especially in the USA theseactivities intensified during the second part of the 1950s,resulting in the development of the fuel cells used in theApollo-program. Swedish fuel cell activities started in themid-1960s, w...

  11. Study of the interface behaviour of SiC/Si/sub 3/N/sub 4/ composites using a 3-D unit cell model

    International Nuclear Information System (INIS)

    A 3-D unit cell model has been developed to investigate the interface failure behavior of SiC/sub f//Si/sub 3/N/sub 4/ composites under tensile loading at room and elevated temperatures. The model idealizes the composite as a regular rectangular array of fibers embedded in matrix, and it introduces 3-D contact elements between the fiber and the matrix to simulate the interface conditions. Slippage between 0 and 90 degree layers are also considered by introducing another set of contact elements at the layer separation planes. Two interface conditions, namely, infinitely strong and weakly bonded are considered to establish the correlation with the experimental data. To simulate the weak interface, the fiber and matrix are assumed to side over one another with shear stress through Coulomb mechanism. Same assumption has also been adopted for the layer separation planes. A finite element program utilizing these concepts has been developed. Stress strain behavior and the local stress distributions at various temperatures within the unit cell are presented. The investigation has also been conducted with the consideration of residual stress that are invariably developed in composite materials during the curing process because of the thermal expansion mismatch of the fibers and the matrix. (author) 16 figs.; 10 refs

  12. Study of apoptotic deletion mediated by Bifidobacterium longum with construction of recombinant strains for Serpin encoding gene and phenotypes comparison in a pig cell model

    OpenAIRE

    Nissen, Lorenzo

    2008-01-01

    The first part of the research project of the Co-Advisorship Ph.D Thesis was aimed to select the best Bifidobacterium longum strains suitable to set the basis of our study. We were looking for strains with the abilities to colonize the intestinal mucosa and with good adhesion capacities, so that we can test these strains to investigate their ability to induce apoptosis in “damaged” intestinal cells. Adhesion and apoptosis are the two process that we want to study to better unde...

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

    International Nuclear Information System (INIS)

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

  14. A Novel Model System to Study the Role of Catecholamines in Cardiac Lineage Commitment of Embryonic Stem Cells and Functional Response to Proarrhythmic Drugs

    OpenAIRE

    Lehmann, Martin

    2014-01-01

    Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of the blastocyst. These cells possess the ability to differentiate into all cell types of the three germ-layers and to proliferate indefinitely. In defined conditions ES cells are committed to the mesodermal lineage and differentiate, amongst other cell types, into cardiomyocytes (CMs). The processes underlying mesodermal and subsequent cardiac differentiation are yet only partially understood. Catecholamine rel...

  15. Global Dynamics of a Virus Dynamical Model with Cell-to-Cell Transmission and Cure Rate

    Directory of Open Access Journals (Sweden)

    Tongqian Zhang

    2015-01-01

    Full Text Available The cure effect of a virus model with both cell-to-cell transmission and cell-to-virus transmission is studied. By the method of next generation matrix, the basic reproduction number is obtained. The locally asymptotic stability of the virus-free equilibrium and the endemic equilibrium is considered by investigating the characteristic equation of the model. The globally asymptotic stability of the virus-free equilibrium is proved by constructing suitable Lyapunov function, and the sufficient condition for the globally asymptotic stability of the endemic equilibrium is obtained by constructing suitable Lyapunov function and using LaSalle invariance principal.

  16. Biophysical models of transcription in cells

    Science.gov (United States)

    Choubey, Sandeep

    Cells constantly face environmental challenges and deal with them by changing their gene expression patterns. They make decisions regarding which genes to express and which genes not to express based on intra-cellular and environmental cues. These decisions are often made by regulating the process of transcription. While the identities of the different molecules that take part in regulating transcription have been determined for a number of different genes, their dynamics inside the cell are still poorly understood. One key feature of these regulatory dynamics is that the numbers of the bio-molecules involved is typically small, resulting in large temporal fluctuations in transcriptional outputs (mRNA and protein). In this thesis I show that measurements of the cell-to-cell variability of the distribution of transcribing RNA polymerases along a gene provide a previously unexplored method for deciphering the mechanism of its transcription in vivo. First, I propose a simple kinetic model of transcription initiation and elongation from which I calculate transcribing RNA polymerase copy-number fluctuations. I test my theory against published data obtained for yeast genes and propose a novel mechanism of transcription. Rather than transcription being initiated through a single rate-limiting step, as was previously proposed, my single-cell analysis reveals the presence of at least two rate limiting steps. Second, I compute the distribution of inter-polymerase distance distribution along a gene and propose a method for analyzing inter-polymerase distance distributions acquired in experiments. By applying this method to images of polymerases transcribing ribosomal genes in E.coli I show that one model of regulation of these genes is consistent with inter-polymerase distance data while a number of other models are not. The analytical framework described in this thesis can be used to extract quantitative information about the dynamics of transcription from single-cell

  17. Macroscopic Modeling of Transport Phenomena in Direct Methanol Fuel Cells

    DEFF Research Database (Denmark)

    Olesen, Anders Christian

    An increasing need for energy efficiency and high energy density has sparked a growing interest in direct methanol fuel cells for portable power applications. This type of fuel cell directly generates electricity from a fuel mixture consisting of methanol and water. Although this technology...... surpasses batteries in important areas, fundamental research is still required to improve durability and performance. Particularly the transport of methanol and water within the cell structure is difficult to study in-situ. A demand therefore exist for the fundamental development of mathematical models for...... studying their transport. In this PhD dissertation the macroscopic transport phenomena governing direct methanol fuel cell operation are analyzed, discussed and modeled using the two-fluid approach in the computational fluid dynamics framework of CFX 14. The overall objective of this work is to extend the...

  18. Dictyostelium discoideum, a lower eukaryote model for the study of DNA repair: Implications for the role of DNA-damaging chemicals in the evolution of repair proficient cells

    Science.gov (United States)

    Deering, R. A.

    1994-10-01

    The evolution of the ability of living cells to cope with stress is crucial for the maintenance of their genetic integrity. Yet low levels of mutation must remain to allow adaptation to environmental changes. The cellular slime mold D. discoideum is a good system for studying molecular aspects of the repair of lethal and mutagenic damage to DNA by radiation and chemicals. The wild-type strains of this soil microorganism are extremely resistant to DNA damaging agents. In nature the amoeboid cells in their replicative stage feed on soil bacteria and are exposed to numerous DNA-damaging chemicals produced by various soil microorganisms. It is probable that the evolution of repair systems in this organism and perhaps in others is a consequence of the necessity to cope with chemical damage which also confers resistance to radiation.

  19. Advanced impedance modeling of solid oxide electrochemical cells

    DEFF Research Database (Denmark)

    Graves, Christopher R.; Hjelm, Johan

    2014-01-01

    Impedance spectroscopy is a powerful technique for detailed study of the electrochemical and transport processes that take place in fuel cells and electrolysis cells, including solid oxide cells (SOCs). Meaningful analysis of impedance measurements is nontrivial, however, because a large number of...... modeling parameters are fit to the many processes which often overlap in the same frequency ranges. Also, commonly used equivalent circuit (EC) models only provide zero-dimensional (0-D) approximations of the processes of the two electrodes, electrolyte and gas transport. Employing improved analytical...... electrode and 2-D gas transport models which have fewer unknown parameters for the same number of processes, (ii) use of a new model fitting algorithm, “multi-fitting”, in which multiple impedance spectra are fit simultaneously with parameters linked based on the variation of measurement conditions, (iii...

  20. Model quality and safety studies

    DEFF Research Database (Denmark)

    Petersen, K.E.

    1997-01-01

    The paper describes the EC initiative on model quality assessment and emphasizes some of the problems encountered in the selection of data from field tests used in the evaluation process. Further, it discusses the impact of model uncertainties in safety studies of industrial plants. The model...... by the EC Environment Research Programme focusing on assessment of the quality of experimental data and models for dense gas dispersion created within the EC funded research programmes. Technical models are used in a number of areas of industrial hazards assessment. It is becoming more and more...... importance of ensuring that model development is of a standard that is commensurate with the importance of model use. The aim of MEG is to improve the culture in which models are developed and used and so ensure that technical models used in all aspects of major hazard evaluation are up to date with...

  1. Modeling of Silicon Heterojunction Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Luppina, P.; Lugli, P.; Goodnick, S.

    2015-06-14

    Here we present modeling results on crystalline Si/amorphous Si (a-Si) heterojunction solar cells using Sentaurus including various models for defect states in the a-Si barriers, as well as explicit models for the ITO emitter contact. We investigate the impact of the band offsets and barrier heights of the a-Si/c-Si interface, particularly in terms of the open circuit voltage. It is also shown that the solar cell performance is sensitively dependent on the quality of the a-Si in terms of defect states and their distribution, particularly on the emitter side. Finally, we have investigate the role of tunneling and thermionic emission across the heterointerface in terms of transport from the Si to the ITO contact layer

  2. Computational modeling of the enzymatic activities of biomolecules at different scales: from quantum mechanical reaction studies to systemic understanding of cell behavior

    OpenAIRE

    Barbieri,, R.

    2012-01-01

    The aim of the thesis is the development of computational models of the enzymatic activity of biomolecules at different scales. Parallel investigations have been carried out at a quantum level to study the reactivity of an enzyme from an electronic point of view, and at a systemic level using simulation techniques to determine the role of enzymes in the network of cellular reactions. Starting from the lowest complexity level, the thesis begins with two computational studies with the aims ...

  3. Isolated muscle cells as a physiological model.

    Science.gov (United States)

    Lieberman, M; Hauschka, S D; Hall, Z W; Eisenberg, B R; Horn, R; Walsh, J V; Tsien, R W; Jones, A W; Walker, J L; Poenie, M

    1987-09-01

    Summary of a symposium presented by the American Physiological Society (Cell and General Physiology Section and Muscle Group) at the 70th Annual Meeting of the Federation of American Societies for Experimental Biology, St. Louis, Missouri, April 15, 1986, chaired by M. Lieberman and F. Fay. This symposium reflects a growing interest in seeking new technologies to study the basic physiological and biophysical properties of cardiac, smooth, and skeletal muscle cells. Recognizing that technical and analytical problems associated with multicellular preparations limit the physiological significance of many experiments, investigators have increasingly focused on efforts to isolate single, functional embryonic, and adult muscle cells. Progress in obtaining physiologically relevant preparations has been both rapid and significant even though problems regarding cell purification and viability are not fully resolved. The symposium draws attention to a broad, though incomplete, range of studies using isolated or cultured muscle cells. Based on the following reports, investigators should be convinced that a variety of experiments can be designed with preparations of isolated cells and those in tissue culture to resolve questions about fundamental physiological properties of muscle cells. PMID:2443014

  4. MCF-10A-NeoST: A New Cell System for Studying Cell-ECM and Cell-Cell Interactions in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zantek, Nicole Dodge; Walker-Daniels, Jennifer; Stewart, Jane; Hansen, Rhonda K.; Robinson, Daniel; Miao, Hui; Wang, Bingcheng; Kung, Hsing-Jien; Bissell, Mina J.; Kinch, Michael S.

    2001-08-22

    There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers. We report here the isolation and initial characterization of a spontaneously arising variant of MCF-10A cells, NeoST, which provides a new model to study cell adhesion and signal transduction in breast cancer. NeoST cells recapitulate important biological and biochemical features of metastatic breast cancer, including anchorage-independent growth, invasiveness in threedimensional reconstituted membranes, loss of E-cadherin expression, and increased tyrosine kinase activity. A comprehensive analysis of tyrosine kinase expression revealed overexpression or functional activation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells. MCF-10A and these new derivatives provide a genetically matched model to study defects in cell adhesion and signaling that are relevant to cellular behaviors that often typify aggressive breast cancer cells.

  5. Repair-misrepair model of cell survival

    International Nuclear Information System (INIS)

    During the last three years a new model, the repair-misrepair model (RMR) has been proposed, to interpret radiobiological experiments with heavy ions. In using the RMR model it became apparent that some of its features are suitable for handling the effects produced by a variety of environmental agents in addition to ionizing radiation. Two separate sequences of events are assumed to take place in an irradiated cell. The first sequence begins with an initial energy transfer consisting of ionizations and excitations, culminating via fast secondary physical and chemical processes in established macromolecular lesions in essential cell structures. The second sequence contains the responses of the cell to the lesions and consists of the processes of recognition and molecular repair. In normal cells there exists one repair process or at most a few enzymatic repair processes for each essential macromolecular lesion. The enzymatic repair processes may last for hours and minutes, and can be separated in time from the initial physicochemical and later genetic phases

  6. The charophycean green algae as model systems to study plant cell walls and other evolutionary adaptations that gave rise to land plants

    DEFF Research Database (Denmark)

    Sørensen, Iben; Rose, Jocelyn K.C.; Doyle, Jeff J.;

    2012-01-01

    of structural polymers (i. e., cell wall polysaccharides and associated molecules) that must have been in place for land colonization. However, it has been suggested that the success of the earliest land plants was partly based on the frequency of gene duplication, and possibly whole genome...... help reveal when and how the molecular pathways required for synthesis of key structural polymers in land plants arose. © 2012 Landes Bioscience.......The Charophycean green algae (CGA) occupy a key phylogenetic position as the evolutionary grade that includes the sister group of the land plants (embryophytes), and so provide potentially valuable experimental systems to study the development and evolution of traits that were necessary for...

  7. Use of human pluripotent stem cells to study and treatretinopathies

    Institute of Scientific and Technical Information of China (English)

    Karim Ben M’Barek; Florian Regent; Christelle Monville

    2015-01-01

    Human cell types affected by retinal diseases (such asage-related macular degeneration or retinitis pimentosa)are limited in cell number and of reduced accessibility. As aconsequence, their isolation for in vitro studies of diseasemechanisms or for drug screening efforts is fastidious.Human pluripotent stem cells (hPSCs), either of embryonicorigin or through reprogramming of adult somatic cells,represent a new promising way to generate models ofhuman retinopathies, explore the physiopathologicalmechanisms and develop novel therapeutic strategies.Disease-specific human embryonic stem cells were thefirst source of material to be used to study certain diseasestates. The recent demonstration that human somaticcells, such as fibroblasts or blood cells, can be geneticallyconverted to induce pluripotent stem cells together withthe continuous improvement of methods to differentiatethese cells into disease-affected cellular subtypes opensnew perspectives to model and understand a largenumber of human pathologies, including retinopathies.This review focuses on the added value of hPSCs for thedisease modeling of human retinopathies and the study oftheir molecular pathological mechanisms. We also discussthe recent use of these cells for establishing the validationstudies for therapeutic intervention and for the screeningof large compound libraries to identify candidate drugs.

  8. Model for glucagon secretion by pancreatic α-cells.

    Directory of Open Access Journals (Sweden)

    Virginia González-Vélez

    Full Text Available Glucagon hormone is synthesized and released by pancreatic α-cells, one of the islet-cell types. This hormone, along with insulin, maintains blood glucose levels within the physiological range. Glucose stimulates glucagon release at low concentrations (hypoglycemia. However, the mechanisms involved in this secretion are still not completely clear. Here, using experimental calcium time series obtained in mouse pancreatic islets at low and high glucose conditions, we propose a glucagon secretion model for α-cells. Our model takes into account that the resupply of releasable granules is not only controlled by cytoplasmic Ca2+, as in other neuroendocrine and endocrine cells, but also by the level of extracellular glucose. We found that, although calcium oscillations are highly variable, the average secretion rates predicted by the model fall into the range of values reported in the literature, for both stimulated and non-stimulated conditions. For low glucose levels, the model predicts that there would be a well-controlled number of releasable granules refilled slowly from a large reserve pool, probably to ensure a secretion rate that could last for several minutes. Studying the α-cell response to the addition of insulin at low glucose, we observe that the presence of insulin reduces glucagon release by decreasing the islet Ca2+ level. This observation is in line with previous work reporting that Ca2+ dynamics, mainly frequency, is altered by insulin. Thus, the present results emphasize the main role played by Ca2+ and glucose in the control of glucagon secretion by α-cells. Our modeling approach also shows that calcium oscillations potentiate glucagon secretion as compared to constant levels of this cellular messenger. Altogether, the model sheds new light on the subcellular mechanisms involved in α-cell exocytosis, and provides a quantitative predictive tool for studying glucagon secretion modulators in physiological and pathological

  9. Bystander responses in cells models; targets, dosimetry and mechanisms

    International Nuclear Information System (INIS)

    The use of microbeam approaches has been a major advance in probing the relevance of bystander responses in cell and tissue models. Our own studies at the Gray Cancer Institute have used both a charged particle microbeam, producing protons and helium ions and a soft X-ray microprobe, delivering focused carbon-K, aluminium-K and titanium-K soft X-rays. Using these techniques we have been able to build up a comprehensive picture of the underlying differences between bystander responses and direct effects in cell and tissue-like models. What is now clear is that bystander dose-response relationships, the underlying mechanisms of action and the targets involved are not the same as those observed for direct irradiation of DNA in the nucleus. Our recent studies have shown bystander responses induced in human or hamster cells even when radiation is deposited away from the nucleus in cytoplasmic targets either after charged particle or soft X-ray exposure. Importantly, the level of bystander effect, measured as cell killing was similar to that observed when the same amount of energy was deposited but targeted to the nucleus. In other studies, we have shown that underlying determination of the level of response is the energy deposited in a single cell rather than the number of cells hit. Also the overall response at low doses may be dominated by bystander signaling. These observations have significance for our understanding of radiation risk at low doses including those of environmental exposures and the applicability of the Linear Non Threshold model. The realization that cell to cell signaling is important for radiation response may also open up new therapeutic opportunities to either improve tumor cell kill or protect normal tissues if the pathways underpinning bystander signaling can be elucidated and controlled

  10. PEM Fuel Cells from Single Cell to Stack - Fundamental, Modeling, Analysis, and Applications

    OpenAIRE

    Maher A.R. Sadiq Al-Baghdadi

    2015-01-01

    Part I: Fundamentals Chapter 1: Introduction. Chapter 2: PEM fuel cell thermodynamics, electrochemistry, and performance. Chapter 3: PEM fuel cell components. Chapter 4: PEM fuel cell failure modes. Part II: Modeling and Simulation Chapter 5: PEM fuel cell models based on semi-empirical simulation. Chapter 6: PEM fuel cell models based on computational fluid dynamics (CFD). Part III: Analysis Chapter 7: PEM fuel cell analysis. Chapter 8: PEM fuel cell stack desig...

  11. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

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

    Directory of Open Access Journals (Sweden)

    Victoria Doldán-Martelli

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

  13. PEM fuel cell systems performance optimisation using the mathematical modeling

    International Nuclear Information System (INIS)

    PEM fuel cell systems and technologies have emerged as viable energy conversion devices for terrestrial applications (stationary and mobile). They offer huge economical and environmental potentials in the next generation power systems, but they are still more expensive than most conventional power conversion devices. Therefore, there is a need to optimize these technologies from the performance and costs point of view. Mathematical modeling proved to be the most important tool for PEM fuel cell optimization, providing the best solution for design, operating condition, experimentation and exploitation. This paper proposes a study for fluid flow channels optimization in order to improve the performance of PEM fuel cell systems. Thus, we run simulations using 3 types of geometries for the flowing channels: serpentine, parallel and spiral channel in order to find the optimum flowing geometry. Concluding, we can consider the modeling like an important alternative for fuel cell optimization and for exploitation/experimentation costs reduction. (authors)

  14. Mechanical Model of Geometric Cell and Topological Algorithm for Cell Dynamics from Single-Cell to Formation of Monolayered Tissues with Pattern

    KAUST Repository

    Kachalo, Sëma

    2015-05-14

    Geometric and mechanical properties of individual cells and interactions among neighboring cells are the basis of formation of tissue patterns. Understanding the complex interplay of cells is essential for gaining insight into embryogenesis, tissue development, and other emerging behavior. Here we describe a cell model and an efficient geometric algorithm for studying the dynamic process of tissue formation in 2D (e.g. epithelial tissues). Our approach improves upon previous methods by incorporating properties of individual cells as well as detailed description of the dynamic growth process, with all topological changes accounted for. Cell size, shape, and division plane orientation are modeled realistically. In addition, cell birth, cell growth, cell shrinkage, cell death, cell division, cell collision, and cell rearrangements are now fully accounted for. Different models of cell-cell interactions, such as lateral inhibition during the process of growth, can be studied in detail. Cellular pattern formation for monolayered tissues from arbitrary initial conditions, including that of a single cell, can also be studied in detail. Computational efficiency is achieved through the employment of a special data structure that ensures access to neighboring cells in constant time, without additional space requirement. We have successfully generated tissues consisting of more than 20,000 cells starting from 2 cells within 1 hour. We show that our model can be used to study embryogenesis, tissue fusion, and cell apoptosis. We give detailed study of the classical developmental process of bristle formation on the epidermis of D. melanogaster and the fundamental problem of homeostatic size control in epithelial tissues. Simulation results reveal significant roles of solubility of secreted factors in both the bristle formation and the homeostatic control of tissue size. Our method can be used to study broad problems in monolayered tissue formation. Our software is publicly

  15. Methodologies in the study of cell-cell fusion.

    Science.gov (United States)

    Cohen, F S; Melikyan, G B

    1998-10-01

    The process of membrane fusion has been profitably studied by fusing cells that express fusion proteins on their surfaces to the membranes of target cells. Primary methods for monitoring the occurrence of fusion between cells are measurement of formation of heterokaryons, measurement of activation of reporter genes, measurement of transfer of lipidic and aqueous fluorescent dyes, and electrophysiological recording of fusion pores. Fluorescence and electrical methods have been well developed for fusion of a nucleated cell expressing viral fusion proteins to red blood cell targets. These techniques are now being extended to the study of fusion between two nucleated cells. Microscopic observation of spread of fluorescent dyes from one cell to another is a sensitive and convenient means of detecting fusion on the level of single events. In such studies, both the membrane and the aqueous continuities that occur as a result of fusion can be measured in the same experiment. By following spread of aqueous dyes of different sizes from one cell to another, the growth of a fusion pore can also be followed. By labeling cells with fluorescent probes, a state of hemifusion can be identified if probes in outer membrane leaflets transfer but probes in inner leaflets or aqueous spaces do not. Electrical measurements-both capacitance and double-whole-cell voltage-clamp techniques-are the most sensitive methods yet developed for detecting the formation of pores and for quantifying their growth. These powerful single-event methodologies should be directly applicable to further advances in expressing nonviral fusion proteins on cell surfaces. PMID:9790869

  16. Bifurcation structure of a model of bursting pancreatic cells

    DEFF Research Database (Denmark)

    Mosekilde, Erik; Lading, B.; Yanchuk, S.; Maistrenko, Y.

    One- and two-dimensional bifurcation studies of a prototypic model of bursting oscillations in pancreatic P-cells reveal a squid-formed area of chaotic dynamics in the parameter plane, with period-doubling bifurcations on one side of the arms and saddle-node bifurcations on the other. The...

  17. Saltstone SDU6 Modeling Study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Si Y. [Savannah River Site (SRS), Aiken, SC (United States); Hyun, Sinjae [Mercer University, Macon, GA (United States)

    2013-01-10

    A new disposal unit, designated as Saltstone Disposal Unit 6 (SDU6), is being designed for support of site accelerated closure goals and salt waste projections identified in the new Liquid Waste System Plan. The unit is a cylindrical disposal cell of 375 ft in diameter and 43 ft in height, and it has a minimum 30 million gallons of capacity. SRNL was requested to evaluate the impact of an increased grout placement height on the flow patterns radially spread on the floor and to determine whether grout quality is impacted by the height. The primary goals of the work are to develop the baseline Computational Fluid Dynamics (CFD) model and to perform the evaluations for the flow patterns of grout material in SDU6 as a function of elevation of grout discharge port and grout rheology. Two transient grout models have been developed by taking a three-dimensional multiphase CFD approach to estimate the domain size of the grout materials radially spread on the facility floor and to perform the sensitivity analysis with respect to the baseline design and operating conditions such as elevation height of the discharge port and fresh grout properties. For the CFD modeling calculations, air-grout Volume of Fluid (VOF) method combined with Bingham plastic and time-dependent grout models were used for examining the impact of fluid spread performance for the initial baseline configurations and to evaluate the impact of grout pouring height on grout quality. The grout quality was estimated in terms of the air volume fraction for the grout layer formed on the SDU6 floor, resulting in the change of grout density. The study results should be considered as preliminary scoping analyses since benchmarking analysis is not included in this task scope. Transient analyses with the Bingham plastic model were performed with the FLUENTTM code on the high performance parallel computing platform in SRNL. The analysis coupled with a transient grout aging model was performed by using ANSYS-CFX code

  18. Two-Dimensional Modeling of Thermoelectric Cells

    OpenAIRE

    Oliveira, Klaudio S. M.; Cardoso, Rodrigo P.; Hermes, Christian J. L.

    2014-01-01

    The present paper is aimed at putting forward a two-dimensional model for thermoelectric cells. The energy conservation equation was formulated in order to account for the Fourier, the Thomson and the Joule effects on the temperature distribution. The electric field was also solved to come out with the current and voltage distributions. The governing equations were discretized by means of the finite-volume method, whereas the TDMA algorithm was adopted for solving the sets of linear equations...

  19. A General Mechanistic Model of Solid Oxide Fuel Cells

    Institute of Scientific and Technical Information of China (English)

    SHI Yixiang; CAI Ningsheng

    2006-01-01

    A comprehensive model considering all forms of polarization was developed. The model considers the intricate interdependency among the electrode microstructure, the transport phenomena, and the electrochemical processes. The active three-phase boundary surface was expressed as a function of electrode microstructure parameters (porosity, coordination number, contact angle, etc.). The exchange current densities used in the simulation were obtained by fitting a general formulation to the polarization curves proposed as a function of cell temperature and oxygen partial pressure. A validation study shows good agreement with published experimental data. Distributions of overpotentials, gas component partial pressures, and electronic/ionic current densities have been calculated. The effects of a porous electrode structure and of various operation conditions on cell performance were also predicted. The mechanistic model proposed can be used to interpret experimental observations and optimize cell performance by incorporating reliable experimental data.

  20. Studies of bulk heterojunction solar cells

    Science.gov (United States)

    Cossel, Raquel; McIntyre, Max; Tzolov, Marian

    We are studying bulk heterojunction solar cells that were fabricated using a mixture of PCPDTBT and PCBM­C60. The impedance data of the cells in dark responded like a simple RC circuit. The value of the dielectric constant derived from these results is consistent with the values reported in the literature for these materials. We are showing that the parallel resistance in the equivalent circuit of linear lump elements can be interpreted using the DC current­voltage measurements. The impedance spectra under light illumination indicated the existence of additional polarization. This extra feature can be described by a model that includes a series RC circuit in parallel with the equivalent circuit for a device in dark. The physical interpretation of the additional polarization is based on photo­generated charges getting trapped in wells, which have a characteristic relaxation time corresponding to the observed break frequency in the impedance spectra. We have studied the influence of the anode and cathode interface on this phenomena, either by using different interface materials, or by depositing the metal electrode while the substate is heated.

  1. Endostar combined with cryoablation for subcutaneous xenografted tumor model of lung adenocarcinoma cell line A549 in BALB/c nude mice: an experimental study

    International Nuclear Information System (INIS)

    Objective: To investigate the inhibitory effect of Endostar combined with cryoablation on Lung adenocarcinoma cell line A549 in BALB/c nude mice, and to discuss its interaction mechanisms. Methods: The lung adenocarcinoma A549 model in BALB/c nude mice were established. When the largest diameter of tumor reached 1.0 cm, a total of 24 mice were randomly and equally divided into 4 groups: control group, Endostar group, cryoablation group and cryoablation plus Endostar group. The largest diameter and the vertical diameter of the tumors were measured at different points of time after treatment. At the 21st day, the mice were sacrificed and the tumors were removed and the rate of tumor cell apoptosis, the microvessel density (MVD) and the expression level of vascular endothelial growth factor (VEGF) were determined by using immunohistochemistry method. The results were statistically analyzed. Results: The tumor growth velocity of the control group, Endostar group, cryoablation group and cryoablation plus Endostar group was (2.36.68±51.23)%, (220.02±30.61)%, (159.46±29.33)% and (103.34±25.50)%, respectively (P<0.01). The rate of apoptosis of the four groups was (21.67±2.34)%, (22.17±1.47)%, (38.33±1.37)% and (49.17±1.72)%, respectively (P<0.01). The MVD and the expression levels of VEGF of the cryoablation plus Endostar group were significantly lower than those of the other three groups (P<0.01). Statistical analysis revealed that a positive correlation existed between the express of VEGF and MVD. Conclusion: Endostar can obviously enhance the therapeutic efficacy of cryoablation on lung adenocarcinoma A549 in BALB/c nude mice. The underlying mechanisms may be the Endostar-inhibited angiogenesis through down-regulating the expression of VEGF, and the cooperative effect of Endostar and cryoablation on the promotion of tumor cell apoptosis. (authors)

  2. Rabbit Models for Studying Human Infectious Diseases.

    Science.gov (United States)

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-12-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia-lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  3. A study of mental models

    Directory of Open Access Journals (Sweden)

    A. Tarciso Borges

    1997-09-01

    Full Text Available The concept of mental models is being used in several areas of knowledge in order to study the representations users have about physical systems and events, as well as the content of such representations. However, it cannot be considered a unitary concept. This paper discusses the assumptions envolved in different areas of knowledge and describes a study of the mental model of magnetism held by students and professionals such as electricians physics teachers, and engineers. The identified model stress two aspects: what is the origin of permanent magnets and what is the mechanism of the magnetic interaction.

  4. Multiway modeling and analysis in stem cell systems biology

    Directory of Open Access Journals (Sweden)

    Vandenberg Scott L

    2008-07-01

    collagen I substrate accelerated the osteogenic differentiation induced by a static collagen I substrate. Conclusion Our results suggest gene- and protein-level models whereby stem cells undergo transdifferentiation to osteoblasts, and lay the foundation for mechanistic, hypothesis-driven studies. Our analysis methods are applicable to a wide range of stem cell differentiation models.

  5. Model quality and safety studies

    DEFF Research Database (Denmark)

    Petersen, K.E.

    The paper describes the EC initiative on model quality assessment and emphasizes some of the problems encountered in the selection of data from field tests used in the evaluation process. Further, it discusses the impact of model uncertainties in safety studies of industrial plants. The model...... evaluation group (MEG) is a European initiative on evaluation of technical models used within the major industrial hazard area and is supported by the EC DGXII, Directorate-General for Science, Research and Development. Closely related to MEG is REDIPHEM, which is the acronym of a research project supported...... by the EC Environment Research Programme focusing on assessment of the quality of experimental data and models for dense gas dispersion created within the EC funded research programmes. Technical models are used in a number of areas of industrial hazards assessment. It is becoming more and more...

  6. Results from functional and cellular studies using an ovine model to assess response to mesenchymal stem cell therapy after induction of myocardial infarction

    International Nuclear Information System (INIS)

    Full text: Background: Assessing functional and cellular consequences following myocardial infarction (MI) using large animals has advantages of similarity in size, shape and coronary supply to human heart. Aim: To confirm presence of MI and detect recovery of perfusion and function following implantation of ovine bone-marrow derived mesenchymal stem cells (MSC) using intra-myocardial (1M) and intra-coronary (IC) methods. Methods: Eighteen ewes (wt: 45-50kg, LV-EDV: 80-90mL) included, with 10 completing protocol (3=control, 4=IM, 3=IC). MlBI MPI SPECT/CT performed at baseline, 5-7 days post induction of Ml and 6 weeks post cellular therapy with male MSCs. At completion, sheep sacrificed and heart slices reviewed microscopically to confirm Ml, assess neovascularisation and correlate with MPI findings. MPI studies reconstructed using OSEM CT-based AC and analysed using QPS/QGS software. Calculation of Recovery Difference (RD%), Recovery Ratio (RR) and relative change to baseline determined for each study and per segment per study. Results: M I confirmed in 10 of 12 studies (I showed no perfusion abnormality, another pre-existing defect), confirmed anatomically by identification of fibrous scar tissue with lymphoid aggregates, histiocytes and calcium deposits. Reduction in perfusion was 14% to 48%. No improvement in perfusion seen in control (RR=0.8, RD=-16.9) and IC (RR=0.9, RD=-7.1) studies. Significant reperfusion seen on 1M studies, with RR=1.5, RD=1.1 and perfusion recovery 8%, around periphery of infarct zone. Conclusions: Presence of acute Ml identified on MlBl MPI SPECT/CT correlates with anatomical findings. Improvement in perfusion and function at infarct zone seen using 1M method of MSC implantation, correlating with significant neovascularisation identified microscopically.

  7. Proteomic assessment of a cell model of spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Lee Kelvin H

    2011-03-01

    Full Text Available Abstract Background Deletion or mutation(s of the survival motor neuron 1 (SMN1 gene causes spinal muscular atrophy (SMA, a neuromuscular disease characterized by spinal motor neuron death and muscle paralysis. Complete loss of the SMN protein is embryonically lethal, yet reduced levels of this protein result in selective death of motor neurons. Why motor neurons are specifically targeted by SMN deficiency remains to be determined. In this study, embryonic stem (ES cells derived from a severe SMA mouse model were differentiated into motor neurons in vitro by addition of retinoic acid and sonic hedgehog agonist. Proteomic and western blot analyses were used to probe protein expression alterations in this cell-culture model of SMA that could be relevant to the disease. Results When ES cells were primed with Noggin/fibroblast growth factors (bFGF and FGF-8 in a more robust neural differentiation medium for 2 days before differentiation induction, the efficiency of in vitro motor neuron differentiation was improved from ~25% to ~50%. The differentiated ES cells expressed a pan-neuronal marker (neurofilament and motor neuron markers (Hb9, Islet-1, and ChAT. Even though SMN-deficient ES cells had marked reduced levels of SMN (~20% of that in control ES cells, the morphology and differentiation efficiency for these cells are comparable to those for control samples. However, proteomics in conjunction with western blot analyses revealed 6 down-regulated and 14 up-regulated proteins with most of them involved in energy metabolism, cell stress-response, protein degradation, and cytoskeleton stability. Some of these activated cellular pathways showed specificity for either undifferentiated or differentiated cells. Increased p21 protein expression indicated that SMA ES cells were responding to cellular stress. Up-regulation of p21 was confirmed in spinal cord tissues from the same SMA mouse model from which the ES cells were derived. Conclusion SMN

  8. The "occlusis" model of cell fate restriction.

    Science.gov (United States)

    Lahn, Bruce T

    2011-01-01

    A simple model, termed "occlusis", is presented here to account for both cell fate restriction during somatic development and reestablishment of pluripotency during reproduction. The model makes three assertions: (1) A gene's transcriptional potential can assume one of two states: the "competent" state, wherein the gene is responsive to, and can be activated by, trans-acting factors in the cellular milieu, and the "occluded" state, wherein the gene is blocked by cis-acting, chromatin-based mechanisms from responding to trans-acting factors such that it remains silent irrespective of whether transcriptional activators are present in the milieu. (2) As differentiation proceeds in somatic lineages, lineage-inappropriate genes shift progressively and irreversibly from competent to occluded state, thereby leading to the restriction of cell fate. (3) During reproduction, global deocclusion takes place in the germline and/or early zygotic cells to reset the genome to the competent state in order to facilitate a new round of organismal development. PMID:20954221

  9. Methods for the study of mast cells in cancer.

    Science.gov (United States)

    Blatner, Nichole R; Tsai, FuNien; Khazaie, Khashayarsha

    2015-01-01

    Tumor growth requires interactions of tumor cells with a receptive and inductive microenvironment. Two major populations of tumor-infiltrating cells are considered to be essential for producing such a microenvironment: (1) proinflammatory cells that nurture the tumor with growth factors and facilitate invasion and metastasis by secreting proteases and (2) immune suppressive leukocytes including T-regulatory cells (Treg) that hinder tumor-specific CD8 T-cell responses, which otherwise could potentially reject the tumor. Among the proinflammatory cells, accumulation of mast cells (MCs) in human tumors is frequently recorded and was recently linked with poor prognosis. Causative links between mast cell infiltration and tumor progression can be deduced from animal studies. There is an interesting link between mast cells and Treg. The adoptive transfer of Treg from healthy syngeneic mice to mice susceptible to colon cancer suppresses focal mastocytosis and hinders tumor progression. Furthermore, T-cell-deficient mice susceptible to colon cancer show enhanced focal mastocytosis and tumor invasion. Here, we describe methods to assess MCs in mouse models of cancer and to investigate how MCs affect tumor epithelium. Additionally, we will detail methods used to investigate how T cells influence MCs and how MCs influence T cells. PMID:25388267

  10. Cell survival studies using ultrasoft x rays

    International Nuclear Information System (INIS)

    Cell survival was studied for V79 hamster, 10T1/2 mouse, and human skin fibroblast cell lines, using carbon K (0.28 keV), copper K (8.0 keV), and 250 kVp x rays. Because of the rapid attenuation of the carbon x rays, cellular dimensions at the time of exposure were measured using optical and electron microscopy, and frequency distributions of mean dose absorbed by the cell nucleus were obtained. The results indicate that the differences in cell killing between ultra-soft and hard x rays may depend on the nuclear thickness of the cells. Studies of the effects of hypoxia on V79 and 10T1/2 cells using carbon K, aluminum K (1.5 keV), and copper K x rays show decreasing OER values with decreasing x-ray energy and no difference between the two cell lines. Age response studies with V79 cells show similar cell-cycle variation of survival for carbon K and aluminum K x rays as for hard x rays

  11. Sickle cell vaso-occlusion in an animal model

    International Nuclear Information System (INIS)

    Sickle cell disease is clinically characterized with vaso-occlusive painful crisis which is pleomorphic in terms of frequency of occurrence. The intracellular polymerization of deoxygenated hemoglobin S increases the internal viscosity of the sickle cells exponentially, concurrent with binding of hemoglobin S to the membrane and discocyte-drepanocyte transformation. As a result, the red cells in sickle cell disease are heterogenous with cells of varying density and mean corpuscular hemoglobin concentration which alter the rheological features of the blood in the microcirculation. The cellular, physiological, biochemical and rheological factors that contribute to the vaso-occlusive events are not completely understood. Nonetheless, recent clinical studies have demonstrated that a certain fraction of the dense cells disappear during sickle cell painful crisis. In an attempt to elucidate some of the cellular and rheological factors involved in the initiation of vaso-occlusion, the authors have employed intravital videomicroscopy and radionuclide imaging of indium-III labeled sickle cells to determine the dynamics and sites of vaso-occlusion using the rat exchanged-transfused with sickle (HbSS) erythrocytes as a model

  12. Oxygen sensing in neuroendocrine cells and other cell types: pheochromocytoma (PC12) cells as an experimental model.

    Science.gov (United States)

    Spicer, Zachary; Millhorn, David E

    2003-01-01

    A steady supply of oxygen is an absolute requirement for mammalian cells to maintain normal cellular functions. To answer the challenge that oxygen deprivation represents, mammals have evolved specialized cell types that can sense changes in oxygen tension and alter gene expression to enhance oxygen delivery to hypoxic areas. These oxygensensing cells are rare and difficult to study in vivo. As a result, pheochromocytoma (PC12) cells have become a vital in vitro model system for deciphering the molecular events that confer the hypoxia-resistant and oxygen-sensing phenotypes. Research over the last few years has revealed that the hypoxia response in PC12 cells involves the interactions of several signal transduction pathways (Ca2+/calmodulin-dependent kinases, Akt, SAPKs, and MAPKs) and transcription factors (HIFs, CREB, and c-fos/junB). This review summarizes the current understanding of the role these signal transduction pathways and transcription factors play in determining the hypoxic response. PMID:14739486

  13. Human Induced Pluripotent Stem Cell Models of Inherited Cardiovascular Diseases.

    Science.gov (United States)

    Jiang, Wenjian; Lan, Feng; Zhang, Hongjia

    2014-10-16

    Cardiovascular cells derived from patient specific induced Pluripotent Stem Cell (iPSC) harbor gene mutations associated with the pathogenesis of inherited cardiac diseases and congenital heart diseases (CHD). Numerous reports have demonstrated the utilization of human induced Pluripotent Stem Cell (hiPSC) to model cardiac diseases as a means of investigating their underlying mechanisms. So far, they have been shown to investigate the molecular mechanisms of many cardiac disorders, such as long-QT syndrome (LQT), catecholaminergic polymorphic ventricular tachycardia (CPVT), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), LEOPARD syndrome (LS), arrhythmogenic cardiomyopathy (ACM), Friedreich ataxia (FRDA), Barth syndrome (BTHS), hypoplastic left heart syndrome (HLHS), Marfan syndrome (MFS) and other CHD. This article summarizes the growing body of research related to modeling various cardiac diseases using hiPSCs. Moreover, by reviewing the methods used in previous studies, we propose multiple novel applications of hiPSCs to investigate comprehensive cardiovascular disorders and facilitate drug discovery. PMID:25322695

  14. New Modeling Approaches to Investigate Cell Signaling in Radiation Response

    Science.gov (United States)

    Plante, Ianik; Cucinotta, Francis A.; Ponomarev, Artem L.

    2011-01-01

    Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine

  15. Advanced methods of solid oxide fuel cell modeling

    CERN Document Server

    Milewski, Jaroslaw; Santarelli, Massimo; Leone, Pierluigi

    2011-01-01

    Fuel cells are widely regarded as the future of the power and transportation industries. Intensive research in this area now requires new methods of fuel cell operation modeling and cell design. Typical mathematical models are based on the physical process description of fuel cells and require a detailed knowledge of the microscopic properties that govern both chemical and electrochemical reactions. ""Advanced Methods of Solid Oxide Fuel Cell Modeling"" proposes the alternative methodology of generalized artificial neural networks (ANN) solid oxide fuel cell (SOFC) modeling. ""Advanced Methods

  16. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    Science.gov (United States)

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  17. Time-variant clustering model for understanding cell fate decisions.

    Science.gov (United States)

    Huang, Wei; Cao, Xiaoyi; Biase, Fernando H; Yu, Pengfei; Zhong, Sheng

    2014-11-01

    Both spatial characteristics and temporal features are often the subjects of concern in physical, social, and biological studies. This work tackles the clustering problems for time course data in which the cluster number and clustering structure change with respect to time, dubbed time-variant clustering. We developed a hierarchical model that simultaneously clusters the objects at every time point and describes the relationships of the clusters between time points. The hidden layer of this model is a generalized form of branching processes. A reversible-jump Markov Chain Monte Carlo method was implemented for model inference, and a feature selection procedure was developed. We applied this method to explore an open question in preimplantation embryonic development. Our analyses using single-cell gene expression data suggested that the earliest cell fate decision could start at the 4-cell stage in mice, earlier than the commonly thought 8- to 16-cell stage. These results together with independent experimental data from single-cell RNA-seq provided support against a prevailing hypothesis in mammalian development. PMID:25339442

  18. PEM fuel cell modeling using differential evolution

    International Nuclear Information System (INIS)

    This paper develops a differential-evolution-based solution for the problem of proton exchange membrane fuel cell stack modeling. The problem is analytically intractable and computationally hard. The present paper produces results that outperform state-of-the-art approaches on three performance metrics: solution quality corresponding to a given cost, cost of finding a solution of a given quality, and frequency of producing an optimal or near-optimal solution. -- Highlights: ► Provides a new solution approach to the PEMFC modeling problem which is an optimization problem of great practical importance. ► The present method provides solutions that are better than those produced by the best-known approaches in the literature. ► The present method outperforms the state-of-the-art approach on three performance metrics.

  19. Learning about Cancer by Studying Stem Cells

    Science.gov (United States)

    ... View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem Cells By Sharon ... culture. Credit: Anne Weston, London Research Institute, CRUK (image available under a Creative Commons Attribution, Non-Commercial, ...

  20. Immunohistochemical study of perivascular epithelioid cell neoplasms

    Institute of Scientific and Technical Information of China (English)

    夏秋媛

    2013-01-01

    Objective To study the clinicopathologic features,immunophenotype and genetic changes of perivascular epithelioid cell neoplasms (PEComa) .Methods A total of 25 cases of PEComa located in various anatomic sites were selected for immunohistochemical staining (SP or

  1. Study of solar cells based on upgraded metallurgical grade silicon

    Science.gov (United States)

    Schlosser, V.; Kuchar, F.; Seeger, K.

    A study is presented on the applicability of diffused solar cells when cast upgraded metallurgical grade silicon (UMG-Si) is used. Cells have been prepared from differently processed UMG-Si and for comparison from high purity FZ-Si. The material was characterized by the minority carrier diffusion length, which was obtained from spectral response measurements. A two-diode equivalent circuit model was used in order to evaluate pn-junction characteristics under illumination and in the dark.

  2. Hierarchical Nanopatterns for Cell Adhesion Studies

    OpenAIRE

    Schwieder, Marco

    2008-01-01

    Hierarchical nanopatterned interfaces are an intriguing tool to study clustering processes of proteins like for example integrins that mediate cell adhesion. The aim of this work is the development of innovative methods for the fabrication of hierarchical micro-nanopatterned surfaces and the use of such systems as platforms to study cell adhesion. In the first part of this work different approaches are presented which are suitable for preparing micro-nanopatterned interfaces at a large scale ...

  3. Mucosal-associated invariant T cells from induced pluripotent stem cells: A novel approach for modeling human diseases

    Science.gov (United States)

    Sugimoto, Chie; Fujita, Hiroyoshi; Wakao, Hiroshi

    2016-01-01

    Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases. These models help elucidate the mechanisms underlying the disease and in the development of novel therapies. However, if mice are deficient in certain cells and/or effectors associated with human diseases, how can their functions be investigated in this species? Mucosal-associated invariant T (MAIT) cells, a novel innate-like T cell family member, are a good example. MAIT cells are abundant in humans but scarce in laboratory mice. MAIT cells harbor an invariant T cell receptor and recognize nonpeptidic antigens vitamin B2 metabolites from bacteria and yeasts. Recent studies have shown that MAIT cells play a pivotal role in human diseases such as bacterial infections and autoimmune and inflammatory diseases. MAIT cells possess granulysin, a human-specific effector molecule, but granulysin and its homologue are absent in mice. Furthermore, MAIT cells show poor proliferation in vitro. To overcome these problems and further our knowledge of MAIT cells, we have established a method to expand MAIT cells via induced pluripotent stem cells (iPSCs). In this review, we describe recent advances in the field of MAIT cell research and our approach for human disease modeling with iPSC-derived MAIT cells. PMID:27114747

  4. Jordan cells of periodic loop models

    CERN Document Server

    Morin-Duchesne, Alexi

    2013-01-01

    Jordan cells in transfer matrices of finite lattice models are a signature of the logarithmic character of the conformal field theories that appear in their thermodynamical limit. The transfer matrix of periodic loop models, $T_N$, is an element of the periodic Temperley-Lieb algebra $\\eptl(\\beta, \\alpha)$, where $N$ is the number of sites on a section of the cylinder, and $\\beta=-q-q^{-1} = 2 \\cos \\lambda$ and $\\alpha$ the weights of contractible and non-contractible loops. The thermodynamic limit of $T_N$ is believed to describe a conformal field theory of central charge $c=1-6\\lambda^2/(\\pi(\\lambda-\\pi))$. The abstract element $T_N$ acts naturally on (a sum of) spaces $\\tilde V_N^d$, similar to those upon which the standard modules of the (classical) Temperley-Lieb algebra act. These spaces known as {\\em sectors} are labeled by the numbers of defects $d$ and depend on a {\\em twist parameter} $v$ that keeps track of the winding of defects around the cylinder. Criteria are given for non-trivial Jordan cells ...

  5. Modeling Neurological Disorders by Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Tanut Kunkanjanawan

    2011-01-01

    Full Text Available Studies of human brain development are critical as research on neurological disorders have been progressively advanced. However, understanding the process of neurogenesis through analysis of the early embryo is complicated and limited by a number of factors, including the complexity of the embryos, availability, and ethical constrains. The emerging of human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs has shed light of a new approach to study both early development and disease pathology. The cells behave as precursors of all embryonic lineages; thus, they allow tracing the history from the root to individual branches of the cell lineage tree. Systems for neural differentiation of hESCs and iPSCs have provided an experimental model that can be used to augment in vitro studies of in vivo brain development. Interestingly, iPSCs derived from patients, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. This paper summarizes the recent reports of the development of iPSCs from patients who suffer from neurological diseases and evaluates the feasibility of iPSCs as a disease model. The benefits and obstacles of iPSC technology are highlighted in order to raising the cautions of misinterpretation prior to further clinical translations.

  6. Modeling Degradation in Solid Oxide Electrolysis Cells

    Energy Technology Data Exchange (ETDEWEB)

    Manohar S. Sohal; Anil V. Virkar; Sergey N. Rashkeev; Michael V. Glazoff

    2010-09-01

    Idaho National Laboratory has an ongoing project to generate hydrogen from steam using solid oxide electrolysis cells (SOECs). To accomplish this, technical and degradation issues associated with the SOECs will need to be addressed. This report covers various approaches being pursued to model degradation issues in SOECs. An electrochemical model for degradation of SOECs is presented. The model is based on concepts in local thermodynamic equilibrium in systems otherwise in global thermodynamic no equilibrium. It is shown that electronic conduction through the electrolyte, however small, must be taken into account for determining local oxygen chemical potential, , within the electrolyte. The within the electrolyte may lie out of bounds in relation to values at the electrodes in the electrolyzer mode. Under certain conditions, high pressures can develop in the electrolyte just near the oxygen electrode/electrolyte interface, leading to oxygen electrode delamination. These predictions are in accordance with the reported literature on the subject. Development of high pressures may be avoided by introducing some electronic conduction in the electrolyte. By combining equilibrium thermodynamics, no equilibrium (diffusion) modeling, and first-principles, atomic scale calculations were performed to understand the degradation mechanisms and provide practical recommendations on how to inhibit and/or completely mitigate them.

  7. Urban Studies: A Learning Model.

    Science.gov (United States)

    Cooper, Terry L.; Sundeen, Richard

    1979-01-01

    The urban studies learning model described in this article was found to increase students' self-esteem, imbue a more flexible and open perspective, contribute to the capacity for self-direction, produce increases on the feeling reactivity, spontaneity, and acceptance of aggression scales, and expand interpersonal competence. (Author/WI)

  8. A Physics-based Analytical Model for Perovskite Solar Cells

    OpenAIRE

    Sun, Xingshu; Asadpour, Reza; Nie, Wanyi; Mohite, Aditya D.; Alam, Muhammad A.

    2015-01-01

    Perovskites are promising next-generation absorber materials for low-cost and high-efficiency solar cells. Although perovskite cells are configured similar to the classical solar cells, their operation is unique and requires development of a new physical model for characterization, optimization of the cells, and prediction of the panel performance. In this paper, we develop such a physics-based analytical model to describe the operation of different types of perovskite solar cells, explicitly...

  9. Modelling familial dysautonomia in human induced pluripotent stem cells

    OpenAIRE

    Lee, Gabsang; Studer, Lorenz

    2011-01-01

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

  10. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, H M; Rassing, M R; Nielsen, Hanne Mørck

    2000-01-01

    The objective of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium. For this purpose, the permeability of water, mannitol and testosterone across the TR146 cell culture model was compared to the permeability across human, monkey and...... determined. The mannitol and testosterone permeability across the TR146 cell culture model could be related to the permeability across porcine and human buccal mucosa. The permeability of the beta-adrenoceptor antagonists across the TR146 cell culture model varied between 2.2 x 10(-6) cm/s (atenolol) and 165...... increased the permeability only for the hydrophilic atenolol, which may help explain the mechanism for GC-induced enhancement. The present results indicate that the TR146 cell culture model can be used as an in vitro model for permeability studies and mechanistic studies of human buccal drug delivery of...

  11. Pluripotent stem cells: An in vitro model for nanotoxicity assessments.

    Science.gov (United States)

    Handral, Harish K; Tong, Huei Jinn; Islam, Intekhab; Sriram, Gopu; Rosa, Vinicus; Cao, Tong

    2016-10-01

    The advent of technology has led to an established range of engineered nanoparticles that are used in diverse applications, such as cell-cell interactions, cell-material interactions, medical therapies and the target modulation of cellular processes. The exponential increase in the utilization of nanomaterials and the growing number of associated criticisms has highlighted the potential risks of nanomaterials to human health and the ecosystem. The existing in vivo and in vitro platforms show limitations, with fluctuations being observed in the results of toxicity assessments. Pluripotent stem cells (PSCs) are viable source of cells that are capable of developing into specialized cells of the human body. PSCs can be efficiently used to screen new biomaterials/drugs and are potential candidates for studying impairments of biophysical morphology at both the cellular and tissue levels during interactions with nanomaterials and for diagnosing toxicity. Three-dimensional in vitro models obtained using PSC-derived cells would provide a realistic, patient-specific platform for toxicity assessments and in drug screening applications. The current review focuses on PSCs as an alternative in vitro platform for assessing the hazardous effects of nanomaterials on health systems and highlights the importance of PSC-derived in vitro platforms. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27241574

  12. Mouse models for cancer stem cell research

    OpenAIRE

    Cheng, Le; Ramesh, Anirudh V.; Flesken-Nikitin, Andrea; Choi, Jinhyang; Nikitin, Alexander Yu.

    2009-01-01

    Cancer stem cell concept assumes that cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor initiating cells, which are able to reproduce themselves and produce phenotypically heterogeneous cells with lesser tumorigenic potential. Cancer stem cells represent an appealing target for development of more selective and efficient therapies. However, direct testing of the cancer stem cell concept and assessment of its therapeutic implications in human...

  13. Stem cell transplantation in mouse models for Huntington's disease

    OpenAIRE

    Johann, Verena

    2005-01-01

    Cell replacement therapies for neurodegenerative diseases using stem cells require above all a good survival of the graft and therefore an understanding of the possible influence of the surrounding degenerating tissue on the grafted cells. In this thesis, I report on the experiments of stem cell transplantation in mouse models for Huntington´s disease. The most common rodent model for HD is the QA-lesion model, where quinolinic acid is injected unilaterally into the striatum of adult rats. We...

  14. Physical Modeling of the Enzymatic Glucose-Fuelled Fuel Cells

    OpenAIRE

    Vladimir (Zeev) Rubin; Lea Mor

    2013-01-01

    An enzymatic glucose biofuel cell uses glucose as fuel and enzymes as biocatalyst, to transform biochemical energy into electrical energy. An analytical modelling of an enzymatic biofuel cell should be used, while developing fuel cell, to estimate its various enzymatic parameters, to obtain the highest voltage feasibly. The analytical model was developed, and the open circuit voltage (OCV) calculated by the model for various parameters of the fuel cell is in agreement with the experimental re...

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

    Directory of Open Access Journals (Sweden)

    Ajioka Itsuki

    2007-09-01

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

  16. A mouse 3T6 fibroblast cell culture model for the study of normal and protein-engineered collagen synthesis and deposition into the extracellular matrix.

    Science.gov (United States)

    Lamandé, S R; Bateman, J F

    1993-07-01

    Mouse 3T6 fibroblasts deposited an organized collagenous extracellular matrix during long-term culture in the presence of ascorbic acid. The matrix produced by the cells had a similar distribution of collagen types as the mouse dermal matrix, comprising predominantly type I with smaller amounts of types III and V collagens. By day 8 of culture more than 70% of the collagen in the 3T6 matrix was involved in covalent crosslinkages and required pepsin digestion for extraction. Incorporation of NaB3H4 into reducible crosslinks and aldehydes directly demonstrated the involvement of the alpha 1 (I)CB6 and alpha 2(I)CB3.5 in crosslinks. The pattern of reducible crosslinks in the in vitro 3T6 matrix was similar to that in mouse skin suggesting a comparable fibril organization. Processing of procollagen to collagen occurred efficiently throughout the culture period and the rate of collagen production was unaltered during 15 days of culture, indicating that the development of a collagenous matrix does not directly play a role in procollagen processing or biosynthetic regulation. The existence of a preformed matrix did however, increase the efficiency with which newly synthesised collagen was incorporated into the pericellular matrix. At day 0, when there was no measurable matrix present, 29% of the collagen synthesised was deposited, while by day 15, 88% of the collagen was laid down in the matrix. The development of this 3T6 culture system, where collagen is efficiently incorporated into an organized extracellular matrix, will facilitate detailed studies on matrix organization and regulation and provide a system in which protein-engineered mutant collagens can be expressed to determine their effects on the production of a functional extracellular matrix. PMID:8412990

  17. Comparative study of the effects of PEGylated interferon-α2a versus 5-fluorouracil on cancer stem cells in a rat model of hepatocellular carcinoma.

    Science.gov (United States)

    Motawi, Tarek Kamal; El-Boghdady, Noha Ahmed; El-Sayed, Abeer Mostafa; Helmy, Hebatullah Samy

    2016-02-01

    Cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) possess tumor-initiating, metastatic, and drug resistance properties. This study was conducted to evaluate the effects of PEGylated interferon-α2a (PEG-IFN-α2a) and 5-fluorouracil (5-FU) on the expression of CSC markers and on specific pathways that contribute to the propagation of CSCs in HCC. HCC was initiated in rats using a single intraperitoneal dose of diethylnitrosamine (DENA) (200 mg/kg) and promoted by weekly subcutaneous injections of carbon tetrachloride (CCl4) for 6 weeks. After the appearance of dysplastic nodules, the animals received PEG-IFN-α2a or 5-FU for 8 weeks. CSC markers (OV6, CD90) and molecules related to transforming growth factor β (TGF-β) and other signaling pathways were assessed in hepatic tissues. The PEG-IFN-α2a treatment effectively suppressed the hepatic expression of OV6 and CD90, ameliorated the diminished hepatic expression of TGF-β receptor II (TGF-βRII) and β2-spectrin (β2SP), and significantly reduced the elevated hepatic expression of TGF-β1, interleukin6 (IL6), signal transducer and activator of transcription3 (STAT3), and vascular endothelial growth factor (VEGF). In contrast, the 5-FU treatment failed to reduce the overexpression of CSC markers and barely affected the disrupted TGF-β signaling. Furthermore, it had no effect on angiogenesis or nitrosative stress. PEG-IFN-α2a, but not 5-FU, could reduce the propagation of CSCs during the progression of HCC by upregulating the disrupted TGF-β signaling, suppressing the IL6/STAT3 pathway and reducing angiogenesis. PMID:26304505

  18. Biomechanics of epithelial cell islands analyzed by modeling and experimentation

    CERN Document Server

    Coburn, Luke; Noppe, Adrian; Caldwell, Benjamin J; Moussa, Elliott; Yap, Chloe; Priya, Rashmi; Lobaskin, Vladimir; Roberts, Anthony P; Yap, Alpha S; Neufeld, Zoltan; Gomez, Guillermo A

    2016-01-01

    We generated a new computational approach to analyze the biomechanics of epithelial cell islands that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of protrusions (and traction forces) that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions (and monolayer stress) is not homogeneous across the island. Instead it is higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Moreover, our approach has the minimal elements necessary to reproduce mechanical crosstalk between both cell-cell and cell substrate adhesion systems. We found that an i...

  19. Numerical model of dog mast cell tumor treated by electrochemotherapy.

    Science.gov (United States)

    Suzuki, Daniela O H; Anselmo, Jânio; de Oliveira, Krishna D; Freytag, Jennifer O; Rangel, Marcelo M M; Marques, Jefferson L B; Ramos, Airton

    2015-02-01

    Electrochemotherapy is a combination of high electric field and anticancer drugs. The treatment basis is electroporation or electropermeabilization of the cell membrane. Electroporation is a threshold phenomenon and, for efficient treatment, an adequate local distribution of electric field within the treated tissue is important. When this local electric field is not enough, there is a regrown tumor cell; however, if it is stronger than necessary, permanent damage to the tissue occurs. In the treatment of dogs, electrochemotherapy is not yet an established treatment for mast cell tumor in veterinary medicine, although there are studies showing evidence of its effectiveness. In this study, we examined electrochemotherapy of dog mast cell tumor with numerical simulation of local electric field distribution. The experimental result was used to validate the numerical models. The effect of tumor position and tissue thickness (tumor in different parts of dog body) was investigated using plate electrodes. Our results demonstrated that the electrochemotherapy is efficient and flexible, and even when the tumor extends into the subcutis, the treatment with plate electrode eliminated the tumor cells. This result suggests that electrochemotherapy is a suitable method to treat mast cell tumors in dog. PMID:25041415

  20. Computer modeling results on all-Si cascade solar cells

    Science.gov (United States)

    Sparks, P. D.; Allen, F. G.; Daud, T.

    1984-01-01

    The properties of a cascade solar cell made entirely of silicon are investigated numerically with the goal of developing an optimal silicon solar cell grown by molecular-beam epitaxy. The cascade cell is modeled as two standard back-surface field cells with abrupt junctions connected by a tunnel junction. A cascade cell would have approximately twice the open-circuit voltage of a single cell. If the minority carriers generated in the front cell can be reflected before reaching the tunnel junction, then the cascade cell will show an increase in efficiency over a single cell by a percentage point.

  1. Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

    International Nuclear Information System (INIS)

    We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

  2. Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Bok-Nam; Lee, Kwanjae; An, Young-Sil [School of Medicine, Ajou University, Department of Nuclear Medicine and Molecular Imaging, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon (Korea, Republic of); Kim, Jang-Hee; Park, So Hyun [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of)

    2015-05-01

    We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

  3. Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues

  4. Establishment and Molecular Cytogenetic Characterization of a Cell Culture Model of Head and Neck Squamous Cell Carcinoma (HNSCC

    Directory of Open Access Journals (Sweden)

    Horst Zitzelsberger

    2010-11-01

    Full Text Available Cytogenetic analysis of head and neck squamous cell carcinoma (HNSCC established several biomarkers that have been correlated to clinical parameters during the past years. Adequate cell culture model systems are required for functional studies investigating those potential prognostic markers in HNSCC. We have used a cell line, CAL 33, for the establishment of a cell culture model in order to perform functional analyses of interesting candidate genes and proteins. The cell line was cytogenetically characterized using array CGH, spectral karyotyping (SKY and fluorescence in situ hybridization (FISH. As a starting point for the investigation of genetic markers predicting radiosensitivity in tumor cells, irradiation experiments were carried out and radiation responses of CAL 33 have been determined. Radiosensitivity of CAL 33 cells was intermediate when compared to published data on tumor cell lines.

  5. Crawling and turning in a minimal reaction-diffusion cell motility model: coupling cell shape and biochemistry

    CERN Document Server

    Camley, Brian A; Li, Bo; Levine, Herbert; Rappel, Wouter-Jan

    2016-01-01

    We study a minimal model of a crawling eukaryotic cell with a chemical polarity controlled by a reaction-diffusion mechanism describing Rho GTPase dynamics. The size, shape, and speed of the cell emerge from the combination of the chemical polarity, which controls the locations where actin polymerization occurs, and the physical properties of the cell, including its membrane tension. We find in our model both highly persistent trajectories, in which the cell crawls in a straight line, and turning trajectories, where the cell transitions from crawling in a line to crawling in a circle. We discuss the controlling variables for this turning instability, and argue that turning arises from a coupling between the reaction-diffusion mechanism and the shape of the cell. This emphasizes the surprising features that can arise from simple links between cell mechanics and biochemistry. Our results suggest that similar instabilities may be present in a broad class of biochemical descriptions of cell polarity.

  6. 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

  7. System-level modeling and simulation of the cell culture microfluidic biochip ProCell

    DEFF Research Database (Denmark)

    Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan;

    2010-01-01

    -defined micro-channels using valves and pumps. We present an approach to the system-level modeling and simulation of a cell culture microfluidic biochip called ProCell, Programmable Cell Culture Chip. ProCell contains a cell culture chamber, which is envisioned to run 256 simultaneous experiments (viewed as a...

  8. Homogenization of a viscoelastic model for plant cell wall biomechanics

    OpenAIRE

    Ptashnyk, Mariya; Seguin, Brian

    2015-01-01

    The microscopic structure of a plant cell wall is given by cellulose microfibrils embedded in a cell wall matrix. In this paper we consider a microscopic model for interactions between viscoelastic deformations of a plant cell wall and chemical processes in the cell wall matrix. We consider elastic deformations of the cell wall microfibrils and viscoelastic Kelvin--Voigt type deformations of the cell wall matrix. Using homogenization techniques (two-scale convergence and periodic unfolding me...

  9. Dynamic battery cell model and state of charge estimation

    Science.gov (United States)

    Wijewardana, S.; Vepa, R.; Shaheed, M. H.

    2016-03-01

    Mathematical modelling and the dynamic simulation of battery storage systems can be challenging and demanding due to the nonlinear nature of the battery chemistry. This paper introduces a new dynamic battery model, with application to state of charge estimation, considering all possible aspects of environmental conditions and variables. The aim of this paper is to present a suitable convenient, generic dynamic representation of rechargeable battery dynamics that can be used to model any Lithium-ion rechargeable battery. The proposed representation is used to develop a dynamic model considering the thermal balance of heat generation mechanism of the battery cell and the ambient temperature effect including other variables such as storage effects, cyclic charging, battery internal resistance, state of charge etc. The results of the simulations have been used to study the characteristics of a Lithium-ion battery and the proposed battery model is shown to produce responses within 98% of known experimental measurements.

  10. Studies on regulation of the cell cycle in fission yeast.

    Directory of Open Access Journals (Sweden)

    Miroslava Požgajová

    2015-05-01

    Full Text Available All living organisms including plants and animals are composed of millions of cells. These cells perform different functions for the organism although they possess the same chromosomes and carry the same genetic information. Thus, to be able to understand multicellular organism we need to understand the life cycle of individual cells from which the organism comprises. The cell cycle is the life cycle of a single cell in the plant or animal body. It involves series of events in which components of the cell doubles and afterwards equally segregate into daughter cells. Such process ensures growth of the organism, and specialized reductional cell division which leads to production of gamets, assures sexual reproduction. Cell cycle is divided in the G1, S, G2 and M phase. Two gap-phases (G1 and G2 separate S phase (or synthesis and M phase which stays either for mitosis or meiosis. Essential for normal life progression and reproduction is correct chromosome segregation during mitosis and meiosis. Defects in the division program lead to aneuploidy, which in turn leads to birth defects, miscarriages or cancer. Even thou, researchers invented much about the regulation of the cell cycle, there is still long way to understand the complexity of the regulatory machineries that ensure proper segregation of chromosomes. In this paper we would like to describe techniques and materials we use for our studies on chromosome segregation in the model organism Schizosaccharomyces pombe.

  11. Single cell growth and gene expression dynamics in model organisms

    OpenAIRE

    Cookson, Natalie Anne

    2009-01-01

    The developing discipline of synthetic biology attempts to recreate in artificial systems the emergent properties found in natural biology. Progress in this field requires a thorough understanding of the basic cellular functions that underly complex biological networks. Here, we present several studies that use existing and novel methods to probe the dynamic behavior of the model organisms Saccharomyces cerevisiae and Escherichia coli at the single cell level. First, we develop a microfluidic...

  12. Kuala Kemaman hydraulic model study

    International Nuclear Information System (INIS)

    There The problems facing the area of Kuala Kemaman are siltation and erosion at shoreline. The objectives of study are to assess the best alignment of the groyne alignment, to ascertain the most stable shoreline regime and to investigate structural measures to overcome the erosion. The scope of study are data collection, wave analysis, hydrodynamic simulation and sediment transport simulation. Numerical models MIKE 21 are used - MIKE 21 NSW, for wind-wave model, which describes the growth, decay and transformation of wind-generated waves and swell in nearshore areas. The study takes into account effects of refraction and shoaling due to varying depth, energy dissipation due to bottom friction and wave breaking, MIKE 21 HD - modelling system for 2D free-surface flow which to stimulate the hydraulics phenomena in estuaries, coastal areas and seas. Predicted tidal elevation and waves (radiation stresses) are considered into study while wind is not considered. MIKE 21 ST - the system that calculates the rates of non-cohesive (sand) sediment transport for both pure content and combined waves and current situation

  13. Proceedings of the NETL Workshop on Fuel Cell Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Randall S. Gemmen; J. R. Selman

    2000-04-18

    This workshop was the first U.S. DOE sponsored meeting devoted to fuel cell modeling. The workshop was attended by over 45 people from industry, universities, and the government. The goals of the meeting were to assess the status of fuel cell modeling, and determine how new developments in fuel cell modeling can improve cell design, stack design, and power system design. The primary focus was on cell and stack modeling. Following a review of DOE/NETL fuel cell related programs and activities, Professor Robert Selman (Illinois Institute of Technology) kicked off the technical portion of the workshop by presenting an overview of fuel cell phenomena and the status of fuel cell modeling. This overview provided the necessary background for establishing a common framework for discussing fuel cell modeling. A distinction was made between micro modeling, electrode modeling, cell modeling, stack modeling, and system modeling. It was proposed that all modeling levels be supported for further development. In addition, due to significant advances being made outside the U.S., it was proposed that dialog/exchange with other international researchers be established. Following the Overview Session, eight leading researchers in modeling gave individual presentations. These presentations provided additional information on the status and present direction of model developments. All these presentations can be found in Attachment A. Before the workshop, a survey was sent out requesting comments from the attendees. Results from this survey can be found in Attachment B. This survey was then used as initial talking points at the individual breakout sessions on the afternoon of the workshop. Breakouts were organized by microfundamental modeling, cell modeling, stack modeling, and systems modeling.

  14. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Directory of Open Access Journals (Sweden)

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  15. Modelling solar cells with thermal phenomena taken into account

    International Nuclear Information System (INIS)

    The paper is devoted to modelling properties of solar cells. The authors' electrothermal model of such cells is described. This model takes into account the influence of temperature on its characteristics. Some results of calculations and measurements of selected solar cells are presented and discussed. The good agreement between the results of calculations and measurements was obtained, which proves the correctness of the elaborated model.

  16. Perspectives for computational modeling of cell replacement for neurological disorders

    Directory of Open Access Journals (Sweden)

    James B Aimone

    2013-11-01

    Full Text Available Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

  17. Three-dimensional numerical model of cell morphology during migration in multi-signaling substrates.

    Directory of Open Access Journals (Sweden)

    Seyed Jamaleddin Mousavi

    Full Text Available Cell Migration associated with cell shape changes are of central importance in many biological processes ranging from morphogenesis to metastatic cancer cells. Cell movement is a result of cyclic changes of cell morphology due to effective forces on cell body, leading to periodic fluctuations of the cell length and cell membrane area. It is well-known that the cell can be guided by different effective stimuli such as mechanotaxis, thermotaxis, chemotaxis and/or electrotaxis. Regulation of intracellular mechanics and cell's physical interaction with its substrate rely on control of cell shape during cell migration. In this notion, it is essential to understand how each natural or external stimulus may affect the cell behavior. Therefore, a three-dimensional (3D computational model is here developed to analyze a free mode of cell shape changes during migration in a multi-signaling micro-environment. This model is based on previous models that are presented by the same authors to study cell migration with a constant spherical cell shape in a multi-signaling substrates and mechanotaxis effect on cell morphology. Using the finite element discrete methodology, the cell is represented by a group of finite elements. The cell motion is modeled by equilibrium of effective forces on cell body such as traction, protrusion, electrostatic and drag forces, where the cell traction force is a function of the cell internal deformations. To study cell behavior in the presence of different stimuli, the model has been employed in different numerical cases. Our findings, which are qualitatively consistent with well-known related experimental observations, indicate that adding a new stimulus to the cell substrate pushes the cell to migrate more directionally in more elongated form towards the more effective stimuli. For instance, the presence of thermotaxis, chemotaxis and electrotaxis can further move the cell centroid towards the corresponding stimulus, respectively

  18. Validation of noise models for single-cell transcriptomics

    NARCIS (Netherlands)

    Grün, Dominic; Kester, Lennart; van Oudenaarden, Alexander

    2014-01-01

    Single-cell transcriptomics has recently emerged as a powerful technology to explore gene expression heterogeneity among single cells. Here we identify two major sources of technical variability: sampling noise and global cell-to-cell variation in sequencing efficiency. We propose noise models to co

  19. VALIDATION STUDY OF PATH LOSS MODELS ON WIMAX AT 2.6 GHZ FREQUENCY BAND IN SUBURBAN ENVIRONMENT FOR CELL SIZE PLANNING

    OpenAIRE

    Pratibha Maina; Gopal Chandra Manna; Namrata Sahayam

    2014-01-01

    The radio wave propagation in form of path loss model plays very significant role in planning of anywireless communication network. Measurement of signal strength of OFDM driven WiMAX technology at 2.6 GHz band is taken in Suburban Town of India. The results are analyzed and compared with Empirical path loss models such as Hata-Okumura, Modified Hata and COST-231Hata. COST-231 model shows highest path loss for suburban environment. These analyzed results establish that COST-231 model is suita...

  20. LOW-DOSE STUDIES WITH FOCUSED X-RAYS IN CELL AND TISSUE MODELS: MECHANISMS OF BYSTANDER AND GENOMIC INSTABILITY RESPONSES

    Science.gov (United States)

    For low-LET radiations, the concept of DNA damage leading to mutation and cell death has been widely accepted, particularly at high doses (>1 Gy). However, this view has been brought into question with accumulating evidence that a number of transmitted effects play significant r...

  1. USE OF THE SPONTANEOUS TSC2 KNOCKOUT (EKER) RAT MODEL OF HEREDITARY RENAL CELL CARCINOMA FOR THE STUDY OF RENAL CARCINOGENS

    Science.gov (United States)

    The kidney is a frequent site for chemically induced cancers in rodents and among the ten most frequent sites for cancer in human patients. Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. He...

  2. In situ FTIR studies on mammalian cells

    OpenAIRE

    Wolkers, Willem F.; Oldenhof, Harriëtte

    2010-01-01

    In this work, we describe the application of FTIR spectroscopy to study lipids and proteins, in cellular systems during heating and cooling. Various spectral analysis methods are described to simultaneously study membrane phase behavior and heat-induced protein denaturation in cells. Membrane phase behavior was studied by following the temperature dependence of the CH2 stretching vibration bands. Protein denaturation was studied using the amide-I and -III bands. Both amide-I and amide-III ban...

  3. Three-Dimensional Numerical Model of Cell Morphology during Migration in Multi-Signaling Substrates

    Science.gov (United States)

    Mousavi, Seyed Jamaleddin; Hamdy Doweidar, Mohamed

    2015-01-01

    Cell Migration associated with cell shape changes are of central importance in many biological processes ranging from morphogenesis to metastatic cancer cells. Cell movement is a result of cyclic changes of cell morphology due to effective forces on cell body, leading to periodic fluctuations of the cell length and cell membrane area. It is well-known that the cell can be guided by different effective stimuli such as mechanotaxis, thermotaxis, chemotaxis and/or electrotaxis. Regulation of intracellular mechanics and cell’s physical interaction with its substrate rely on control of cell shape during cell migration. In this notion, it is essential to understand how each natural or external stimulus may affect the cell behavior. Therefore, a three-dimensional (3D) computational model is here developed to analyze a free mode of cell shape changes during migration in a multi-signaling micro-environment. This model is based on previous models that are presented by the same authors to study cell migration with a constant spherical cell shape in a multi-signaling substrates and mechanotaxis effect on cell morphology. Using the finite element discrete methodology, the cell is represented by a group of finite elements. The cell motion is modeled by equilibrium of effective forces on cell body such as traction, protrusion, electrostatic and drag forces, where the cell traction force is a function of the cell internal deformations. To study cell behavior in the presence of different stimuli, the model has been employed in different numerical cases. Our findings, which are qualitatively consistent with well-known related experimental observations, indicate that adding a new stimulus to the cell substrate pushes the cell to migrate more directionally in more elongated form towards the more effective stimuli. For instance, the presence of thermotaxis, chemotaxis and electrotaxis can further move the cell centroid towards the corresponding stimulus, respectively, diminishing the

  4. Cell sources for in vitro human liver cell culture models.

    Science.gov (United States)

    Zeilinger, Katrin; Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

    2016-09-01

    In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. PMID:27385595

  5. Investigational Study of Mesenchymal Stem Cells on Lung Cancer Cell Proliferation and Invasion

    Directory of Open Access Journals (Sweden)

    Mei LI

    2015-11-01

    Full Text Available Background and objective Mesenchymal stem cells (MSC are adult stem cells derived from mesoderm. Evidence has shown that MSC could migrate towards tumor tissue and differentiate into tumor associated fibroblast in tumor microenvironment, which influences tumor growth and metastasis. However, the reports of MSC in non-small cell lung cancer (NSCLC are few and controversial. The aim of this study is to explore the chemotaxis of MSC towards NSCLC and to test the effects of MSC on the proliferation and invasion ability of NSCLC. Methods Transwell assay was used to test MSC and NSCLC migration and invasion, and Thymidine incorporation assay was adopted to measure NSCLC cells proliferation. The expression of interleukin-6 (IL-6, insulinlike growth factor (IGF-1, vascular endothelial growth factor (VEGF and dickkopf-related protein 1 (DKK1 of MSCs were determined by real time PCR. A549 lung cancer xenograft animal tumor model was set up to evaluate the MSC effect in vivo. Results Lung cancer cells could attract MSC tropism. MSC conditioned medium favored lung cancer cell proliferation and lung cancer cells stimulated the expression of IL-6, IGF-1, VEGF and DKK1 on MSCs. In vivo animal study showed that the tumor with MSC injection grew much faster compared to control group. Conclusion MSCs could migrate towards NSCLC cells and favor tumor growth. In turn, NSCLC cells could stimulate the overexpression of cytokines on MSCs which are essential for the tumor growth.

  6. Effect of fraxetin on antioxidant defense and stress proteins in human neuroblastoma cell model of rotenone neurotoxicity. Comparative study with myricetin and N-acetylcysteine

    International Nuclear Information System (INIS)

    Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. Recently, it has been shown that fraxetin (coumarin) and myricetin (flavonoid) have significant neuroprotective effects against apoptosis induced by rotenone, increase the total glutathione levels in vitro, and inhibit lipid peroxidation. Thus, these considerations prompted us to investigate the way in which fraxetin and myricetin affect the endogenous antioxidant defense system, such as Mn and CuZn superoxide dismutase (MnSOD, CuZnSOD), catalase, glutathione reductase (GR), and glutathione peroxidase (GPx) on rotenone neurotoxicity in neuroblastoma cells. N-acetylcysteine (NAC), a potent antioxidant, was employed as a comparative agent. Also, the expression and protein levels of HSP70 by Northern and Western blot analysis were assayed in SH-SY5Y cells. After incubation for 16 h, rotenone significantly increased the expression and activity of MnSOD, GPx, and catalase. When cells were preincubated with fraxetin, there was a decrease in the protein levels and activity of both MnSOD and catalase, in comparison with the rotenone treatment. The myricetin effect was less pronounced. Activity and expression of GPx were increased by rotenone and pre-treatment with fraxetin did not modify significantly these levels. The significant enhancement in HSP70 expression at mRNA and protein levels induced by fraxetin was observed by pre-treatment of cells 0.5 h before rotenone insult. These data suggest that major features of rotenone-induced neurotoxicity are partially mediated by free radical formation and oxidative stress, and that fraxetin partially protects against rotenone toxicity affecting the main protection system of the cells against oxidative injury

  7. Computer support for physiological cell modelling using an ontology on cell physiology.

    Science.gov (United States)

    Takao, Shimayoshi; Kazuhiro, Komurasaki; Akira, Amano; Takeshi, Iwashita; Masanori, Kanazawa; Tetsuya, Matsuda

    2006-01-01

    The development of electrophysiological whole cell models to support the understanding of biological mechanisms is increasing rapidly. Due to the complexity of biological systems, comprehensive cell models, which are composed of many imported sub-models of functional elements, can get quite complicated as well, making computer modification difficult. Here, we propose a computer support to enhance structural changes of cell models, employing the markup languages CellML and our original PMSML (physiological model structure markup language), in addition to a new ontology for cell physiological modelling. In particular, a method to make references from CellML files to the ontology and a method to assist manipulation of model structures using markup languages together with the ontology are reported. Using these methods three software utilities, including a graphical model editor, are implemented. Experimental results proved that these methods are effective for the modification of electrophysiological models. PMID:17946607

  8. Extinction Models for Cancer Stem Cell Therapy

    OpenAIRE

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet ,; Lange, Kenneth

    2009-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tool...

  9. Particle-based model to simulate the micromechanics of biological cells

    Science.gov (United States)

    van Liedekerke, P.; Tijskens, E.; Ramon, H.; Ghysels, P.; Samaey, G.; Roose, D.

    2010-06-01

    This paper is concerned with addressing how biological cells react to mechanical impulse. We propose a particle based model to numerically study the mechanical response of these cells with subcellular detail. The model focuses on a plant cell in which two important features are present: (1) the cell’s interior liquidlike phase inducing hydrodynamic phenomena, and (2) the cell wall, a viscoelastic solid membrane that encloses the protoplast. In this particle modeling framework, the cell fluid is modeled by a standard smoothed particle hydrodynamics (SPH) technique. For the viscoelastic solid phase (cell wall), a discrete element method (DEM) is proposed. The cell wall hydraulic conductivity (permeability) is built in through a constitutive relation in the SPH formulation. Simulations show that the SPH-DEM model is in reasonable agreement with compression experiments on an in vitro cell and with analytical models for the basic dynamical modes of a spherical liquid filled shell. We have performed simulations to explore more complex situations such as relaxation and impact, thereby considering two cell types: a stiff plant type and a soft animal-like type. Their particular behavior (force transmission) as a function of protoplasm and cell wall viscosity is discussed. We also show that the mechanics during and after cell failure can be modeled adequately. This methodology has large flexibility and opens possibilities to quantify problems dealing with the response of biological cells to mechanical impulses, e.g., impact, and the prediction of damage on a (sub)cellular scale.

  10. Reliable in vitro studies require appropriate ovarian cancer cell lines.

    Science.gov (United States)

    Jacob, Francis; Nixdorf, Sheri; Hacker, Neville F; Heinzelmann-Schwarz, Viola A

    2014-01-01

    Ovarian cancer is the fifth most common cause of cancer death in women and the leading cause of death from gynaecological malignancies. Of the 75% women diagnosed with locally advanced or disseminated disease, only 30% will survive five years following treatment. This poor prognosis is due to the following reasons: limited understanding of the tumor origin, unclear initiating events and early developmental stages of ovarian cancer, lack of reliable ovarian cancer-specific biomarkers, and drug resistance in advanced cases. In the past, in vitro studies using cell line models have been an invaluable tool for basic, discovery-driven cancer research. However, numerous issues including misidentification and cross-contamination of cell lines have hindered research efforts. In this study we examined all ovarian cancer cell lines available from cell banks. Hereby, we identified inconsistencies in the reporting, difficulties in the identification of cell origin or clinical data of the donor patients, restricted ethnic and histological type representation, and a lack of tubal and peritoneal cancer cell lines. We recommend that all cell lines should be distributed via official cell banks only with strict guidelines regarding the minimal available information required to improve the quality of ovarian cancer research in future. PMID:24936210

  11. A transient fuel cell model to simulate HTPEM fuel cell impedance spectra

    DEFF Research Database (Denmark)

    Vang, Jakob Rabjerg; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2011-01-01

    This paper presents a spatially resolved transient fuel cell model applied to the simulation of high temperature PEM fuel cell impedance spectra. The model is developed using a 2D finite volume method approach. The model is resolved along the channel and across the membrane. The model considers...

  12. Modelling of proton exchange membrane fuel cell performance based on semi-empirical equations

    Energy Technology Data Exchange (ETDEWEB)

    Al-Baghdadi, Maher A.R. Sadiq [Babylon Univ., Dept. of Mechanical Engineering, Babylon (Iraq)

    2005-08-01

    Using semi-empirical equations for modeling a proton exchange membrane fuel cell is proposed for providing a tool for the design and analysis of fuel cell total systems. The focus of this study is to derive an empirical model including process variations to estimate the performance of fuel cell without extensive calculations. The model take into account not only the current density but also the process variations, such as the gas pressure, temperature, humidity, and utilization to cover operating processes, which are important factors in determining the real performance of fuel cell. The modelling results are compared well with known experimental results. The comparison shows good agreements between the modeling results and the experimental data. The model can be used to investigate the influence of process variables for design optimization of fuel cells, stacks, and complete fuel cell power system. (Author)

  13. Theoretical models for near forward light scattering by a Plasmodium falciparum infected red blood cell

    Science.gov (United States)

    Sharma, S. K.

    2012-12-01

    A number of experimental elastic light scattering studies have been performed in the past few years with the aim of developing automated in vivo tools for differentiating a healthy red blood cell from a Plasmodium falciparum infected cell. This paper examines some theoretical aspects of the problem. An attempt has been made to simulate the scattering patterns of healthy as well as infected individual red blood cells. Two models, namely, a homogeneous sphere model and a coated sphere model have been considered. The scattering patterns predicted by these models are examined. A possible method for discriminating infected red blood cells from healthy ones has been suggested.

  14. Therapeutic study of proton beam in vascular disease animal models

    International Nuclear Information System (INIS)

    Proton beam radiation therapy is difficult to apply to animal model. When the cells with DNA damage in the irradiated zebrafish were stained with acridine orange, green fluorescent cell death spots were increased in trunk regions compared to non-irradiated control embryos. From this study, we found that proton radiation therapy can inhibit the blood vessel growth, which is probably induced in vivo in zebrafish embryos, and vascular endothelial cell proliferation.

  15. Phase-field model for collective cell migration

    Science.gov (United States)

    Najem, Sara; Grant, Martin

    2016-05-01

    We construct a phase-field model for collective cell migration based on a Ginzburg-Landau free-energy formulation. We model adhesion, surface tension, repulsion, coattraction, and polarization, enabling us to follow the cells' morphologies and the effect of their membranes fluctuations on collective motion. We were able to measure the tissue surface tension as a function of the individual cell cortical tension and adhesion and identify a density threshold for cell-sheet formation.

  16. A new level set model for cell image segmentation

    Institute of Scientific and Technical Information of China (English)

    Ma Jing-Feng; Hou Kai; Bao Shang-Lian; Chen Chun

    2011-01-01

    In this paper we first determine three phases of cell images: background, cytoplasm and nucleolus according to the general physical characteristics of cell images, and then develop a variational model, based on these characteristics, to segment nucleolus and cytoplasm from their relatively complicated backgrounds. In the meantime, the preprocessing obtained information of cell images using the OTSU algorithm is used to initialize the level set function in the model, which can speed up the segmentation and present satisfactory results in cell image processing.

  17. Cell survival studies for moving targets

    International Nuclear Information System (INIS)

    More than 330 patients with static tumors have been treated at GSI with a scanned C-12 beam. For targets that are subject to respiratory motion, treatment is not yet possible because target motion and scanning motion interfere. GSI is developing a motion compensation system to compensate target motion by adaptation of each individual Bragg peak position. Within this project, the GSI treatment planning software TRiP was extended to calculate physical dose distributions in the presence of motion. These motion extensions were experimentally validated. Recently we included the calculation of cell survival for moving targets. To validate the software, a program of experimental studies with biological samples has been started. In a first set of experiments, living cell cultures were placed on a periodically moving table and irradiated with and without motion compensation. Results are compared to reference cell cultures that were static during standard irradiations. Furthermore, measured cell survival distributions are compared to calculated distributions for all irradiation schemes

  18. Data mining in the study of nuclear fuel cells

    International Nuclear Information System (INIS)

    In this paper is presented a study of data mining application in the analysis of fuel cells and their performance within a nuclear boiling water reactor. A decision tree was used to fulfill questions of the type If (condition) and Then (conclusion) to classify if the fuel cells will have good performance. The performance is measured by compliance or not of the cold shutdown margin, the rate of linear heat generation and the average heat generation in a plane of the reactor. It is assumed that the fuel cells are simulated in the reactor under a fuel reload and rod control patterns pre designed. 18125 fuel cells were simulated according to a steady-state calculation. The decision tree works on a target variable which is one of the three mentioned before. To analyze this objective, the decision tree works with a set of attribute variables. In this case, the attributes are characteristics of the cell as number of gadolinium rods, rods number with certain uranium enrichment mixed with a concentration of gadolinium, etc. The found model was able to predict the execution or not of the shutdown margin with a precision of around 95%. However, the other two variables showed lower percentages due to few learning cases of the model in which these variables were or were not achieved. Even with this inconvenience, the model is quite reliable and can be used in way coupled in optimization systems of fuel cells. (Author)

  19. Current-Voltage Modeling of the Enzymatic Glucose Fuel Cells

    OpenAIRE

    Vladimir Zeev Rubin

    2015-01-01

    Enzymatic fuel cells produce electrical power by oxidation of renewable energy sources. An enzymatic glucose biofuel cell uses glucose as fuel and enzymes as biocatalyst, to convert biochemical energy into electrical energy. The applications which need low electrical voltages and low currents have much of the interest in developing enzymatic fuel cells. An analytical modelling of an enzymatic fuel cell should be used, while developing fuel cell, to estimate its various parameters, to attain t...

  20. Accelerated discovery via a whole-cell model.

    Science.gov (United States)

    Sanghvi, Jayodita C; Regot, Sergi; Carrasco, Silvia; Karr, Jonathan R; Gutschow, Miriam V; Bolival, Benjamin; Covert, Markus W

    2013-12-01

    To test the promise of whole-cell modeling to facilitate scientific inquiry, we compared growth rates simulated in a whole-cell model with experimental measurements for all viable single-gene disruption Mycoplasma genitalium strains. Discrepancies between simulations and experiments led to predictions about kinetic parameters of specific enzymes that we subsequently validated. These findings represent, to our knowledge, the first application of whole-cell modeling to accelerate biological discovery. PMID:24185838

  1. A numerical semiconductor model applicable to organic solar cells

    OpenAIRE

    Minnaert, Ben; Burgelman, Marc; Heereman, Frédéric

    2007-01-01

    Excitons are marginally important in classical semiconductor device physics, and their treatment is not included in standard solar cell modelling. However, in organic semiconductors and solar cells, the role of excitons is essential, as the primary effect of light absorption is exciton generation, and free electrons and holes are created by exciton dissociation. First steps to include excitons in solar cell modelling were presented by Green and Zhang. We extended their model (2006), includin...

  2. Scaffold and stem cell based modeling of brain disease

    OpenAIRE

    Karpiak, Jerome V.

    2016-01-01

    Cellular models of brain disease involve genetic modulation, geometric patterning, neurophysiologic monitoring and analyses of both primary and immortalized cell lines. Additionally, recent neurological disease models often necessitate in vitro directed differentiation and maturation of human stem cell lines. To advance human stem cell based neural disease models within this evolving field, adaptive approaches of progressive complexity are essential. First, I invented an adaptable 3D laminar ...

  3. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    the Cu/ZnO nanoparticles is highly relevant to industrial methanol synthesis for which the direct interaction of Cu and ZnO nanocrystals synergistically boost the catalytic activity. The dynamical behavior of the nanoparticles under reducing and oxidizing environments were studied by means of ex situ...... observed by XPS as the nanoparticles are reduced. The Cu/ZnO nanoparticles are tested on a  µ-reactor platform and prove to be active towards methanol synthesis, making it an excellent model system for further investigations into activity depended morphology changes....

  4. A Hierarchical Multiscale Model for Microfluidic Fuel Cells with Porous Electrodes

    International Nuclear Information System (INIS)

    In this paper a hierarchical multiscale model for microfluidic fuel cells with porous electrodes is developed for the first time. An example of the hierarchical multiscale model for all-vanadium microfluidic fuel cells is presented in this study, in which the diffusion coefficient is used as a bridge between the microscale, mesoscale, and macroscale models. Three-level theories are used to describe the microfluidic fuel cells systems. The development of the model in different time and length scales is emphasized. Results from each scale model are compared with the corresponding experimental and other reasonable data in the literature. We demonstrate that the multiscale model is able to predict the characteristics of microfluidic fuel cells more accurately than before. The hierarchical multiscale model can be a potential tool for developing, designing, and optimizing microfluidic fuel cells

  5. Towards the development of a 3D full cell and external busbars thermo-electric model

    International Nuclear Information System (INIS)

    Taking advantage of the increasing power of computers, it is now practical to consider building a 3D full cell and external busbars thermo-electric model. In the present study, a 3D full cell quarter thermo-electric model and a 3D cathode half plus liquid zone and busbars thermo-electric model have been developed and solved using a PIll 800 MHz computer. Developing a 3D full cell and external busbars thermo-electric model will constitute a step further towards the development of a fully 'multi-physic' unified aluminium reduction cell model. Already, a full cell thermo-electric model will be able to interact with a MHD model by providing it with accurate liquid zone current density and potshell temperature data and by receiving from it local liquid/ledge interface heat transfer coefficients. (author)

  6. Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling

    Directory of Open Access Journals (Sweden)

    Takuya Matsumoto

    2016-03-01

    Full Text Available Modeling of neurological diseases using induced pluripotent stem cells (iPSCs derived from the somatic cells of patients has provided a means of elucidating pathogenic mechanisms and performing drug screening. T cells are an ideal source of patient-specific iPSCs because they can be easily obtained from samples. Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that restricts their differentiation potential. The classical method of differentiation via embryoid body formation was not suitable for T cell-derived iPSCs (TiPSCs. We developed a neurosphere-based robust differentiation protocol, which enabled TiPSCs to differentiate into functional neurons, despite differences in global gene expression between TiPSCs and adult human dermal fibroblast-derived iPSCs. Furthermore, neurons derived from TiPSCs generated from a juvenile patient with Parkinson's disease exhibited several Parkinson's disease phenotypes. Therefore, we conclude that TiPSCs are a useful tool for modeling neurological diseases.

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

    International Nuclear Information System (INIS)

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

  8. NURE uranium deposit model studies

    International Nuclear Information System (INIS)

    The National Uranium Resource Evaluation (NURE) Program has sponsored uranium deposit model studies by Bendix Field Engineering Corporation (Bendix), the US Geological Survey (USGS), and numerous subcontractors. This paper deals only with models from the following six reports prepared by Samuel S. Adams and Associates: GJBX-1(81) - Geology and Recognition Criteria for Roll-Type Uranium Deposits in Continental Sandstones; GJBX-2(81) - Geology and Recognition Criteria for Uraniferous Humate Deposits, Grants Uranium Region, New Mexico; GJBX-3(81) - Geology and Recognition Criteria for Uranium Deposits of the Quartz-Pebble Conglomerate Type; GJBX-4(81) - Geology and Recognition Criteria for Sandstone Uranium Deposits in Mixed Fluvial-Shallow Marine Sedimentary Sequences, South Texas; GJBX-5(81) - Geology and Recognition Criteria for Veinlike Uranium Deposits of the Lower to Middle Proterozoic Unconformity and Strata-Related Types; GJBX-6(81) - Geology and Recognition Criteria for Sandstone Uranium Deposits of the Salt Wash Type, Colorado Plateau Province. A unique feature of these models is the development of recognition criteria in a systematic fashion, with a method for quantifying the various items. The recognition-criteria networks are used in this paper to illustrate the various types of deposits

  9. Animal model of naturally occurring bladder cancer: Characterization of four new canine transitional cell carcinoma cell lines

    OpenAIRE

    Rathore, Kusum; Cekanova, Maria

    2014-01-01

    Background Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer. Methods Four K9TCC cell lines were established from naturally-occurring...

  10. Epithelial cells isolated from chicken jejunum: an experimental model for the study of the functional properties of amino acid transport system b(0,+).

    Science.gov (United States)

    Angelo, S; Rojas, A M; Ramírez, H; Devés, R

    2002-07-01

    The transport of lysine has been investigated in epithelial cells isolated from chicken jejunum. The kinetics of lysine transport and the pattern of interaction with zwitterionic amino acids were consistent with system b(0,+) activity, the broad-spectrum and Na(+)-independent amino acid transporter. The half-saturation constant for lysine entry (K(m)+/-S.E.) was 0.029+/-0.002 mM and the flux was not affected significantly by Na(+) replacement with choline. Lysine influx was inhibited by L-leucine both in Na(+) and choline medium with inhibition constants (K(i)+/-S.E.) 0.068+/-0.006 mM (in Na(+)) and 0.065+/-0.009 mM (in choline). Other inhibitory amino acids (K(i)+/-S.E.) were (mM): L-tyrosine (0.073+/-0.018), L-methionine (0.15+/-0.015), L-cystine (0.42+/-0.04), L-cysteine (1.1+/-0.07), L-isoleucine (1.1+/-0.09), L-glutamine (1.8+/-0.16) and L-valine (2.5+/-0.13). Lysine exit was trans-accelerated (approx. 20 fold) by 2 mM L-lysine and L-leucine. The flux was resistant to pretreatment of the cells with p-chloromercuriphenylsulfonate (0.2 mM), which is an inhibitor of system y(+)L, the broad-spectrum and cation-modulated transporter. PMID:12044773

  11. Modeling the Chagas’ disease after stem cell transplantation

    Science.gov (United States)

    Galvão, Viviane; Miranda, José Garcia Vivas

    2009-04-01

    A recent model for Chagas’ disease after stem cell transplantation is extended for a three-dimensional multi-agent-based model. The computational model includes six different types of autonomous agents: inflammatory cell, fibrosis, cardiomyocyte, proinflammatory cytokine tumor necrosis factor- α, Trypanosoma cruzi, and bone marrow stem cell. Only fibrosis is fixed and the other types of agents can move randomly through the empty spaces using the three-dimensional Moore neighborhood. Bone marrow stem cells can promote apoptosis in inflammatory cells, fibrosis regression and can differentiate in cardiomyocyte. T. cruzi can increase the number of inflammatory cells. Inflammatory cells and tumor necrosis factor- α can increase the quantity of fibrosis. Our results were compared with experimental data giving a fairly fit and they suggest that the inflammatory cells are important for the development of fibrosis.

  12. Coupling primary and stem cell-derived cardiomyocytes in an in vitro model of cardiac cell therapy.

    Science.gov (United States)

    Aratyn-Schaus, Yvonne; Pasqualini, Francesco S; Yuan, Hongyan; McCain, Megan L; Ye, George J C; Sheehy, Sean P; Campbell, Patrick H; Parker, Kevin Kit

    2016-02-15

    The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell-derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell-cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell-cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes. PMID:26858266

  13. A stochastic spatiotemporal model of a response-regulator network in the Caulobacter crescentus cell cycle

    Science.gov (United States)

    Li, Fei; Subramanian, Kartik; Chen, Minghan; Tyson, John J.; Cao, Yang

    2016-06-01

    The asymmetric cell division cycle in Caulobacter crescentus is controlled by an elaborate molecular mechanism governing the production, activation and spatial localization of a host of interacting proteins. In previous work, we proposed a deterministic mathematical model for the spatiotemporal dynamics of six major regulatory proteins. In this paper, we study a stochastic version of the model, which takes into account molecular fluctuations of these regulatory proteins in space and time during early stages of the cell cycle of wild-type Caulobacter cells. We test the stochastic model with regard to experimental observations of increased variability of cycle time in cells depleted of the divJ gene product. The deterministic model predicts that overexpression of the divK gene blocks cell cycle progression in the stalked stage; however, stochastic simulations suggest that a small fraction of the mutants cells do complete the cell cycle normally.

  14. Macro Level Modeling of a Tubular Solid Oxide Fuel Cell

    Directory of Open Access Journals (Sweden)

    Farshid Zabihian

    2010-11-01

    Full Text Available This paper presents a macro-level model of a solid oxide fuel cell (SOFC stack implemented in Aspen Plus® for the simulation of SOFC system. The model is 0-dimensional and accepts hydrocarbon fuels such as reformed natural gas, with user inputs of current density, fuel and air composition, flow rates, temperature, pressure, and fuel utilization factor. The model outputs the composition of the exhaust, work produced, heat available for the fuel reformer, and electrochemical properties of SOFC for model validation. It was developed considering the activation, concentration, and ohmic losses to be the main over-potentials within the SOFC, and mathematical expressions for these were chosen based on available studies in the literature. The model also considered the water shift reaction of CO and the methane reforming reaction. The model results were validated using experimental data from Siemens Westinghouse. The results showed that the model could capture the operating pressure and temperature dependency of the SOFC performance successfully in an operating range of 1–15 atm for pressure and 900 °C–1,000 °C for temperature. Furthermore, a sensitivity analysis was performed to identify the model constants and input parameters that impacted the over-potentials.

  15. Proteomics Study of Cotton Fiber Cells

    Institute of Scientific and Technical Information of China (English)

    LIU Jin-yuan

    2008-01-01

    @@ A comparative proteomic analysis was applied to explore the mechanism of fiber cell development in cotton.Initially,an efficient protein preparation method was established for proteomic analysis of developing cotton fibers by two-dimensional gel electrophoresis,and a microwave enhanced ink staining technique also was created for fast and sensitive protein quantification in proteomic studies.

  16. Cell Formation Techniques – A Study

    Directory of Open Access Journals (Sweden)

    Pawan Kumar Arora,

    2011-02-01

    Full Text Available Cellular manufacturing system has been proved a vital approach for batch and job shop production systems. Group technology has been an essential tool for developing a cellular manufacturing system. Thepaper aims to discuss various cell formation techniques and highlights the significant research work done in past over the years and attempts to points out the gap in research of past studies.

  17. A Comprehensive Fluid Dynamic-Diffusion Model of Blood Microcirculation with Focus on Sickle Cell Disease

    Science.gov (United States)

    Le Floch, Francois; Harris, Wesley L.

    2009-11-01

    A novel methodology has been developed to address sickle cell disease, based on highly descriptive mathematical models for blood flow in the capillaries. Our investigations focus on the coupling between oxygen delivery and red blood cell dynamics, which is crucial to understanding sickle cell crises and is unique to this blood disease. The main part of our work is an extensive study of blood dynamics through simulations of red cells deforming within the capillary vessels, and relies on the use of a large mathematical system of equations describing oxygen transfer, blood plasma dynamics and red cell membrane mechanics. This model is expected to lead to the development of new research strategies for sickle cell disease. Our simulation model could be used not only to assess current researched remedies, but also to spur innovative research initiatives, based on our study of the physical properties coupled in sickle cell disease.

  18. Culture models of human mammary epithelial cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Yaswen, Paul

    2000-11-10

    Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

  19. Modeling of proton exchange membrane fuel cell with variable distance gas flow in anode and cathode

    International Nuclear Information System (INIS)

    A number of fundamental studies have been directed towards increasing our understanding of PEM fuel cell and their performance. Mathematical modeling is one of the way and very essential component in the development of this fuel cell. Model validation is presented, the validated model is then used to investigate the behavior of mole fraction of gases, current density, and the performances of stack using polarization curve depending on distance gases flow in channel. The model incorporates a complete cell with both the membrane electrode assembly (MEA) and the serpentine gas distributor channel. Finally, the parametric studies in single stack design are illustrated

  20. Probabilistic Voxel-Fe model for single cell motility in 3D

    Science.gov (United States)

    Borau, Carlos; Polacheck, William J; Kamm, Roger D; García-Aznar, José Manuel

    2015-01-01

    Background Cells respond to a variety of external stimuli regulated by the environment conditions. Mechanical, chemical and biological factors are of great interest and have been deeply studied. Furthermore, mathematical and computational models have been rapidly growing over the past few years, permitting researches to run complex scenarios saving time and resources. Usually these models focus on specific features of cell migration, making them only suitable to study restricted phenomena. Methods Here we present a versatile finite element (FE) cell-scale 3D migration model based on probabilities depending in turn on ECM mechanical properties, chemical, fluid and boundary conditions. Results With this approach we are able to capture important outcomes of cell migration such as: velocities, trajectories, cell shape and aspect ratio, cell stress or ECM displacements. Conclusions The modular form of the model will allow us to constantly update and redefine it as advancements are made in clarifying how cellular events take place. PMID:26290806

  1. 蛇床子素在Caco-2细胞模型中的转运机制研究%Study on Transport Mechanisms of Osthol in Caco-2 Cell Model

    Institute of Scientific and Technical Information of China (English)

    苑振亭; 王可; 高培平; 赵中华; 胡明

    2011-01-01

    OBJECTIVE To study the transport mechanisms of osthol by using Caco-2 cell model. METHODS The effect of concentration, PEG600, verapamil (P-gp inhibitor)and temperature on transport of osthol in Caco-2 cell model was studied. RESULTS Osthol amount transported in the apical( AP)to basolateral( BL)in Caco-2 cell cell model was increased with loading concentration and temperature. PEG600 enhanced the rate of osthol transport. The PAP and PBL of osthol in Caco-2 model were not affected by verapamil. CONCLUSION The PAP of osthol in Caco-2 model was above 10 × 10 -6 and osthol was absorbed easily by Caco-2 cell Further, there were no significant differences in the ratios of PBL to PAP at three concentrations. Activation energy was quite moderate at 17. 31 kJ·mol-1. The ratio of PBL to PAP of osthol transport were not affected by verapamil, suggesting that the absorption is via passive diffusion.%目的 研究蛇床子素在Caco-2细胞模型中的转运机制.方法 通过研究蛇床子素在Caco-2细胞模型中的转运,考察蛇床子素浓度、PEC600、P-gp抑制剂维拉帕米(verapamil)及温度对蛇床子素转运的影响.结果 随着蛇床子素溶液浓度和温度的升高,蛇床子素在Caco-2细胞中AP-BL的转运量增加;PEG600对蛇床子素在Caco-2细胞中的AP-BL的转运量有显著增加;P-gp抑制剂维拉帕米对蛇床子素在Caco-2细胞中转运的表观通透系数PAP和PBL无显著影响.结论 蛇床子素表现通透系数PAP大于10×10-5cm·s-1,较易被Caco-2细胞吸收,但由于3个浓度蛇床子素溶液的PAP和PBL比值无明显变化、P-gp抑制剂对PAP和PBL无明显影响及转运的活化能较低(17.31 kJ·mol-1),因此,蛇床子素在Caco-2细胞模型中的转运机制主要是被动转运.

  2. A Mathematical Model of Baculovirus Infection on Insect Cells at Low Multiplicity of Infection

    Institute of Scientific and Technical Information of China (English)

    You-Hong ZHANG; Josée C. MERCHUK

    2004-01-01

    The expression efficiency of the insect cells-baculovirus system used for insecticidal virus production and the expression of medically useful foreign genes is closely related with the dynamics of infection. The present studies develop a model of the dynamic process of insect cell infection with baculovirus at low multiplicity of infection (MOI), which is based on the multi-infection cycles of insect cell infection at low MOI. A mathematical model for the amount of viruses released from primary infected cells and the amount of free viruses before secondary infected cells release viruses has been developed. Comparison of the simulation results with the experimental data confirms qualitatively that this model is highly reasonable before secondary infected cells release viruses. This model is considered as a base for further modeling the entire complicated infection process.

  3. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction

    International Nuclear Information System (INIS)

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  4. Modeling optimizes PEM fuel cell durability using three-dimensional multi-phase computational fluid dynamics model

    Energy Technology Data Exchange (ETDEWEB)

    Al-Baghdadi, Maher A.R. Sadiq [Fuel Cell Research Center, International Energy and Environment Foundation, Al-Najaf, P.O.Box 39 (Iraq)

    2010-07-01

    Damage mechanisms in a proton exchange membrane (PEM) fuel cell are accelerated by mechanical stresses arising during fuel cell assembly (bolt assembling), and the stresses arise during fuel cell running, because it consists of the materials with different thermal expansion and swelling coefficients. Therefore, in order to acquire a complete understanding of the damage mechanisms in the membrane and gas diffusion layers, mechanical response under steady-state hygro-thermal stresses should be studied under real cell operating conditions and in real cell geometry (three-dimensional). In this work, full three-dimensional, non-isothermal computational fluid dynamics model of a PEM fuel cell has been developed to simulate the hygro and thermal stresses in PEM fuel cell, which are occurring during the cell operation due to the changes of temperature and relative humidity. A unique feature of the present model is to incorporate the effect of hygro and thermal stresses into actual three-dimensional fuel cell model. The mechanical behaviour of the membrane, catalyst layers, and gas diffusion layers during the operation of a unit cell has been studied and investigated. The model is shown to be able to understand the many interacting, complex electrochemical, transport phenomena, and stresses distribution that have limited experimental data. The results show that the non-uniform distribution of stresses, caused by the temperature gradient in the cell, induces localized bending stresses, which can contribute to delaminating between the membrane and the gas diffusion layers. These results may explain the occurrence of cracks and pinholes in the membrane during regular cell operation. This model is used to study the effect of operating, design, and material parameters on fuel cell hygro-thermal stresses in polymer membrane, catalyst layers, and gas diffusion layers. Detailed analyses of the fuel cell durability under various operating conditions have been conducted and examined

  5. Modeling optimizes PEM fuel cell durability using three-dimensional multi-phase computational fluid dynamics model

    Directory of Open Access Journals (Sweden)

    Maher A.R. Sadiq Al-Baghdadi

    2010-05-01

    Full Text Available Damage mechanisms in a proton exchange membrane (PEM fuel cell are accelerated by mechanical stresses arising during fuel cell assembly (bolt assembling, and the stresses arise during fuel cell running, because it consists of the materials with different thermal expansion and swelling coefficients. Therefore, in order to acquire a complete understanding of the damage mechanisms in the membrane and gas diffusion layers, mechanical response under steady-state hygro-thermal stresses should be studied under real cell operating conditions and in real cell geometry (three-dimensional. In this work, full three-dimensional, non-isothermal computational fluid dynamics model of a PEM fuel cell has been developed to simulate the hygro and thermal stresses in PEM fuel cell, which are occurring during the cell operation due to the changes of temperature and relative humidity. A unique feature of the present model is to incorporate the effect of hygro and thermal stresses into actual three-dimensional fuel cell model. The mechanical behaviour of the membrane, catalyst layers, and gas diffusion layers during the operation of a unit cell has been studied and investigated. The model is shown to be able to understand the many interacting, complex electrochemical, transport phenomena, and stresses distribution that have limited experimental data. The results show that the non-uniform distribution of stresses, caused by the temperature gradient in the cell, induces localized bending stresses, which can contribute to delaminating between the membrane and the gas diffusion layers. These results may explain the occurrence of cracks and pinholes in the membrane during regular cell operation. This model is used to study the effect of operating, design, and material parameters on fuel cell hygro-thermal stresses in polymer membrane, catalyst layers, and gas diffusion layers. Detailed analyses of the fuel cell durability under various operating conditions have been

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

    OpenAIRE

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

    2013-01-01

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

  7. Derivation of feline vaccine-associated fibrosarcoma cell line and its growth on chick embryo chorioallantoic membrane – a new in vivo model for veterinary oncological studies

    OpenAIRE

    Zabielska, K.; Lechowski, R.; M. Król; Pawłowski, K. M.; Motyl, T.; Dolka, I.; Żbikowski, A.

    2012-01-01

    Feline vaccine associated fibrosarcomas are the second most common skin tumor in cats. Methods of treatment are: surgery, chemotherapy and radiotherapy. Nevertheless, the usage of cytostatics in feline vaccine associated sarcoma therapy is limited due to their adverse side effects, high toxicity and low biodistribution after i.v. injection. Therefore, much research on new therapeutic drugs is being conducted. In human medicine, the chick embryo chorioallantoic membrane (CAM) model is used as ...

  8. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Directory of Open Access Journals (Sweden)

    Qiu Z

    2013-07-01

    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  9. Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells.

    Directory of Open Access Journals (Sweden)

    Heather E Wheeler

    Full Text Available There are no effective agents to prevent or treat chemotherapy-induced peripheral neuropathy (CIPN, the most common non-hematologic toxicity of chemotherapy. Therefore, we sought to evaluate the utility of human neuron-like cells derived from induced pluripotent stem cells (iPSCs as a means to study CIPN. We used high content imaging measurements of neurite outgrowth phenotypes to compare the changes that occur to iPSC-derived neuronal cells among drugs and among individuals in response to several classes of chemotherapeutics. Upon treatment of these neuronal cells with the neurotoxic drug paclitaxel, vincristine or cisplatin, we identified significant differences in five morphological phenotypes among drugs, including total outgrowth, mean/median/maximum process length, and mean outgrowth intensity (P < 0.05. The differences in damage among drugs reflect differences in their mechanisms of action and clinical CIPN manifestations. We show the potential of the model for gene perturbation studies by demonstrating decreased expression of TUBB2A results in significantly increased sensitivity of neurons to paclitaxel (0.23 ± 0.06 decrease in total neurite outgrowth, P = 0.011. The variance in several neurite outgrowth and apoptotic phenotypes upon treatment with one of the neurotoxic drugs is significantly greater between than within neurons derived from four different individuals (P < 0.05, demonstrating the potential of iPSC-derived neurons as a genetically diverse model for CIPN. The human neuron model will allow both for mechanistic studies of specific genes and genetic variants discovered in clinical studies and for screening of new drugs to prevent or treat CIPN.

  10. Cellular cardiac electrophysiology modeling with Chaste and CellML

    OpenAIRE

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

    2014-01-01

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

  11. A Computational Model of Deformable Cell Rolling in Shear Flow

    Science.gov (United States)

    Eggleton, Charles; Jadhav, Sameer

    2005-03-01

    Selectin-mediated rolling of polymorphonuclear leukocytes (PMNs) on activated endothelium is critical to their recruitment to sites of inflammation. The cell rolling velocity is influenced by bond interactions on the molecular scale that oppose hydrodynamic forces at the mesoscale. Recent studies have shown that PMN rolling velocity on selectin-coated surfaces in shear flow is significantly slower compared to that of microspheres bearing a similar density of selectin ligands. To investigate whether cell deformability is responsible for these differences, we developed a 3-D computational model which simulates rolling of a deformable cell on a selectin-coated surface under shear flow with a stochastic description of receptor-ligand bond interaction. We observed that rolling velocity increases with increasing membrane stiffness and this effect is larger at high shear rates. The average bond lifetime, number of receptor-ligand bonds and the cell-substrate contact area decreased with increasing membrane stiffness. This study shows that cellular properties along with the kinetics of selectin-ligand interactions affect leukocyte rolling on selectin-coated surfaces.

  12. Prediction and control of number of cells in microdroplets by stochastic modeling

    OpenAIRE

    Ceyhan, Elvan; Xu, Feng; Gürkan, Umut Atakan; Emre, Almet Emrehan; Turalı, Emine Sümeyra; El Assal, Rami; Açıkgenc, Ali; Wu, Chung-an Max; Demirci, Utkan

    2012-01-01

    Manipulation and encapsulation of cells in microdroplets has found many applications in various fields such as clinical diagnostics, pharmaceutical research, and regenerative medicine. The control over the number of cells in individual droplets is important especially for microfluidic and bioprinting applications. There is a growing need for modeling approaches that enable control over a number of cells within individual droplets. In this study, we developed statistical models based on negati...

  13. Pulse radiolysis studies of model membranes

    International Nuclear Information System (INIS)

    In this thesis the influence of the structure of membranes on the processes in cell membranes were examined. Different models of the membranes were evaluated. Pulse radiolysis was used as the technique to examine the membranes. (R.B.)

  14. Mesenchymal stem cells in the treatment of inflammatoryand autoimmune diseases in experimental animal models

    Institute of Scientific and Technical Information of China (English)

    Matthew W Klinker; Cheng-Hong Wei

    2015-01-01

    Multipotent mesenchymal stromal cells [also known asmesenchymal stem cells (MSCs)] are currently beingstudied as a cell-based treatment for inflammatorydisorders. Experimental animal models of humanimmune-mediated diseases have been instrumental inestablishing their immunosuppressive properties. Inthis review, we summarize recent studies examiningthe effectiveness of MSCs as immunotherapy in severalwidely-studied animal models, including type 1 diabetes,experimental autoimmune arthritis, experimentalautoimmune encephalomyelitis, inflammatory boweldisease, graft-vs -host disease, and systemic lupuserythematosus. In addition, we discuss mechanismsidentified by which MSCs mediate immune suppressionin specific disease models, and potential sources offunctional variability of MSCs between studies.

  15. Multiscale Modeling and Simulation of Organic Solar Cells

    CERN Document Server

    de Falco, Carlo; Sacco, Riccardo; Verri, Maurizio

    2012-01-01

    In this article, we continue our mathematical study of organic solar cells (OSCs) and propose a two-scale (micro- and macro-scale) model of heterojunction OSCs with interface geometries characterized by an arbitrarily complex morphology. The microscale model consists of a system of partial and ordinary differential equations in an heterogeneous domain, that provides a full description of excitation/transport phenomena occurring in the bulk regions and dissociation/recombination processes occurring in a thin material slab across the interface. The macroscale model is obtained by a micro-to-macro scale transition that consists of averaging the mass balance equations in the normal direction across the interface thickness, giving rise to nonlinear transmission conditions that are parametrized by the interfacial width. These conditions account in a lumped manner for the volumetric dissociation/recombination phenomena occurring in the thin slab and depend locally on the electric field magnitude and orientation. Usi...

  16. Experimental and modelling studies of infiltration

    International Nuclear Information System (INIS)

    This presentation describes a study of infiltration in the unsaturated soil with the objective of estimating the recharge to a phreatic aquifer. The study area is at the border of the city of Milan (Northern Italy), which draws water for both domestic and industrial purposes from ground water resources located beneath the urban area. The rate of water pumping from the aquifer system has been varying during the XX century, depending upon the number of inhabitants and the development of industrial activities. This caused variations with time of the depth of the water table below the ground surface and in turn some emergencies: the two most prominent episodes correspond to the middle '70s, when the water table in the city centre was about 30 m below the undisturbed natural conditions, and to the last decade, when the water table has raised at a rate of approximately 1 m/year and caused infiltrations in deep constructions (garages and building foundations, the underground railways, etc.). We have developed four ground water flow models at different scales, which share some characteristics: they are based on quasi-3D approximation (horizontal flow in the aquifers and vertical flow in the aquitards), conservative finite-differences schemes for regular grid with square cells in the horizontal plane and are implemented with proprietary computer codes. Among the problems that were studied for the development of these models, I recall some numerical problems, related to the behaviour of the phreatic aquifer under conditions of strong exploitation. Model calibration and validation for ModMil has been performed with a two-stage process, i.e., using some of the available data for model calibration and the remaining data for model validation. The application of geophysical exploration techniques, in particular seismic and geo-electrical prospecting, has been very useful to complete the data and information on the hydro-geological structure obtained from stratigraphic logs

  17. Advanced Cell Development and Degradation Studies

    Energy Technology Data Exchange (ETDEWEB)

    J. E. O' Brien; C. M. Stoots; J. S. Herring; R. C. O' Brien; K. G. Condie; M. Sohal; G. K. Housley; J. J. Hartvigsen; D. Larsen; G. Tao; B. Yildiz; V. Sharma; P. Singh; N. Petigny; T. L. Cable

    2010-09-01

    The Idaho National Laboratory (INL) has been researching the application of solid-oxide electrolysis cells for large-scale hydrogen production from steam over a temperature range of 800 to 900ºC. From 2003 – 2009, this work was sponsored by the DOE Nuclear Hydrogen Initiative (NHI). Starting in 2010, the HTE research program has been sponsored by the Next Generation Nuclear Plant (NGNP) program. HTSE research priorities in FY10 are centered on understanding and reducing cell and stack performance degradation to an acceptable level to advance the technology readiness level of HTSE and to justify further large-scale demonstration activities. This report provides a summary of our FY10 experimental program, which has been focused on advanced cell and stack development and degradation studies. Advanced cell and stack development activities are under way at five technology partners: MSRI, Versa Power, Ceramatec, NASA Glenn, and St. Gobain. Performance evaluation of the advanced technology cells and stacks has been performed by the technology partners, by MIT and the University of Connecticut and at the INL HTE Laboratory. Summaries of these development activities and test results are presented.

  18. Modeling and analysis of CuGaS2 thin-film solar cell

    Science.gov (United States)

    Singh, Pravesh; Gautam, Ruchita; Verma, Ajay Singh; Kumari, Sarita

    2016-05-01

    The authors have performed, the modeling of thin film CuGaS2 based solar cell with ZnTe buffer layer. The efficiency of the cell, short circuit current density and fill factor are calculated. In addition the effect of thickness of absorption layer over performance parameters of the cell is studied and it is found that maximum efficiency of the cell is achieved for 2000 nm thick absorption layer.

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

    Science.gov (United States)

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

    2008-10-01

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

  20. Experimental models to study cholangiocyte biology

    Institute of Scientific and Technical Information of China (English)

    Pamela S. Tietz; Xian-Ming Chen; Ai-Yu Gong; Robert C. Huebert; Anatoliy Masyuk; Tatyana Masyuk; Patrick L. Splinter; Nicholas F. LaRusso

    2002-01-01

    Cholangiocytes-the epithelial cells which line the bileducts-are increasingly recognized as importanttransporting epithelia actively involved in the absorptionand secretion of water, ions, and solutes. Thisrecognition is due in part to the recent development ofnew experimental models. New biologic concepts haveemerged including the identification and topography ofreceptors and flux proteins on the apical and/orbasolateral membrane which are involved in the molecularmechanisms of ductal bile secretion. Individually isolatedand/or perfused bile duct units from livers of rats andmice serve as new, physiologically relevant in vitromodels to study cholangiocyte transport. Biliary treedimensions and novel insights into anatomic remodeling ofproliferating bile ducts have emerged from three-dimensional reconstruction using CT scanning andsophisticated software. Moreover, new pathologicconcepts have arisen regarding the interaction ofcholangiocytes with pathogens such as Cryptosporidiumparvum. These concepts and associated methodologiesmay provide the framework to develop new therapies for the cholangiopathies, a group of important hepatobiliarydiseases in which cholangiocytes are the target cell.Tietz PS, Chen XM, Gong AY, Huebert RC, Masyuk A, MasyukT, Splinter PL, LaRusso NF. Experimental models to studycoholangiocyte biology.

  1. On direct hydrogen fuel cell vehicles : modelling and demonstration

    OpenAIRE

    Haraldsson, Kristina

    2005-01-01

    In this thesis, direct hydrogen Proton Exchange Membrane (PEM) fuel cell systems in vehicles are investigated through modelling, field tests and public acceptance surveys. A computer model of a 50 kW PEM fuel cell system was developed. The fuel cell system efficiency is approximately 50% between 10 and 45% of the rated power. The fuel cell auxiliary system, e.g. compressor and pumps, was shown to clearly affect the overall fuel cell system electrical efficiency. Two hydrogen on-board storage ...

  2. Suofu Qin’s work on studies of cell survival signaling in cancer and epithelial cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Reactive oxygen species (ROS) encompass a variety of diverse chemical species including superoxide anions, hydrogen peroxide, hydroxyl radicals and peroxynitrite, which are mainly produced via mitochondrial oxidative metabolism, enzymatic reactions, and light-initiated lipid peroxidation. Over-production of ROS and/or decrease in the antioxidant capacity cause cells to undergo oxi- dative stress that damages cellular macromolecules such as proteins, lipids, and DNA. Oxidative stress is associated with ageing and the development of agerelated diseases such as cancer and age-related macular degeneration. ROS activate signaling pathways that promote cell survival or lead to cell death, depending on the source and site of ROS production, the specific ROS generated, the concentration and kinetics of ROS generation, and the cell types being challenged. However, how the nature and compartmentalization of ROS contribute to the pathogenesis of individual diseases is poorly understood. Consequently, it is crucial to gain a comprehensive understanding of the molecular bases of cell oxidative stress signaling, which will then provide novel therapeutic opportunities to interfere with disease progression via targeting specific signaling pathways.Currently, Dr. Qin’s work is focused on inflammatory and oxidative stress responses using the retinal pigment epithelial (RPE) cells as a model. The study of RPE cell inflammatory and oxidative stress responses has successfully led to a better understanding of RPE cell biology and identification of potential therapeutic targets.

  3. Examination of in vitro epithelial cell lines as models for Francisella tularensis non-phagocytic infections.

    Science.gov (United States)

    Lo, Karen Yi-Shyuan; Chua, Michael Dominic; Abdulla, Salima; Law, H T; Guttman, Julian Andrew

    2013-05-01

    Francisella tularensis (F. tularensis), the causative agent of tularemia, has long been known to invade and occupy non-phagocytic epithelial cells. Many epithelial cell infection models have been developed to study this process; however, due to the lack of consensus on infection methods and precise experimental procedures to evaluate invasion and replication, selection of appropriate models to use based on the literature is challenging. To evaluate in vitro non-phagocytic cell infection models, we chose 8 epithelial cultured cell lines from published models to infect with F. tularensis subspecies novicida (F. novicida) and compared the results to a recently developed model that used the mouse hepatocyte BNL CL.2 cell line. We utilized classical gentamicin-based invasion assays to determine total intracellular bacterial loads and employed microscopic examination with staining techniques that distinguished between intracellular and extracellular bacteria to provide an accurate assessment of the proportion of invaded host cells and the degree of bacterial replication. We found that COS-7 cells exhibited the greatest invasion rates; CMT-93 cells contained the largest intracellular bacterial loads; ad HEK-293s were capable of invasion and replication rates at high levels, but required shorter infection incubation times. Although COS-7, CMT-93 and HEK-293 cell lines may be suited to study certain aspects of invasion or replication, we found that BNL CL.2 cells appeared the most appropriate to study the overall pathogenesis of F. novicida when examined in toto. PMID:23523968

  4. Modeling and simulation of a reformate supplied PEM fuel cell stack, application to fault detection

    OpenAIRE

    Najafi, Masoud; Dipenta, Damiano; Bencherif, Karim; Sorine, Michel

    2007-01-01

    A method to reduce the model of a nonlinear dynamic fuel cell stack, which is suitable for control and fault detection studies, is presented. In order to model the fuel cell stack, we have assumed that the fuel cells are arranged in a stack, electrically in series, with thermal and electrical contacts. Since in practical applications a stack may be composed of several (at least fifty) fuel cells, such model will be a large set of differential equations which may be difficult to simulate espec...

  5. ADVANCES IN THE MODEL OF CYLINDRICAL ALKALINE CELLS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The advancement of a systematic investigation on the modeling of cylindrical alkaline cells is presented.Initial analysis utilizes thermodynamic and kinetic information to predict alkaline cell performance under low discharge rates.Subsequent modling has taken into consideration detailed information on the chemistry of electrode reactions,mass tranport of dissolved species,physical and chemical properties of the electrolyte and solid phases,and internal geonetry of cell systems.The model is capable of predicting alkaline cell performance under a variety of dicharge conditions.The model also provides information regarding internal cell changes during discharge.The model is the basis of a rational approach for the optimal design of cells.

  6. CML Mouse Model Generated from Leukemia Stem Cells.

    Science.gov (United States)

    Hu, Yiguo

    2016-01-01

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

  7. Modeling Of Proton Exchange Membrane Fuel Cell Systems

    DEFF Research Database (Denmark)

    Nielsen, Mads Pagh

    The objective of this doctoral thesis was to develop reliable steady-state and transient component models suitable to asses-, develop- and optimize proton exchange membrane (PEM) fuel cell systems. Several components in PEM fuel cell systems were characterized and modeled. The developed component...

  8. Device and materials modeling in PEM fuel cells

    CERN Document Server

    Promislow, Keith

    2009-01-01

    Device and Materials Modeling in PEM Fuel Cells is a specialized text that compiles the mathematical details and results of both device and materials modeling in a single volume. Proton exchange membrane (PEM) fuel cells will likely have an impact on our way of life similar to the integrated circuit. The potential applications range from the micron scale to large scale industrial production. Successful integration of PEM fuel cells into the mass market will require new materials and a deeper understanding of the balance required to maintain various operational states. This book contains articles from scientists who contribute to fuel cell models from both the materials and device perspectives. Topics such as catalyst layer performance and operation, reactor dynamics, macroscopic transport, and analytical models are covered under device modeling. Materials modeling include subjects relating to the membrane and the catalyst such as proton conduction, atomistic structural modeling, quantum molecular dynamics, an...

  9. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease...... these diseases, but will lead to even more findings in the future as gene and cell culture technology continues to develop....

  10. Model of mammalian cell reproductive death. Pt. 2

    International Nuclear Information System (INIS)

    A general equation for mammalian cell survival has been derived in the previous paper. This paper presents the results of comparison of theoretical evaluations with survival data available from the literature, including different cell lines, variations. In linear energy transfer, dose rate and dose fractionation and the effects of ultrasoft X-rays and superheavy ions. Merits and demerits of the model are considered in comparison with other models of radiation-induced killing of mammalian cells published in the literature. (orig.)

  11. An innovative method of modeling direct methanol fuel cells

    OpenAIRE

    Anna Trendewicz; Jaroslaw Milewski

    2012-01-01

    In this paper a computer model of a direct methanol fuel cell (DMFC) developed with the use of HYSYS software was presented. Chemical reactions of methanol oxidation and oxygen reduction were executed in HYSYS software which eliminated the need of creating a complex electrochemical model of these reactions. Obtained resutls were used for determining maximum cell voltage and limiting current density of the investigated fuel cell. An equivalent electrical circuit ...

  12. An assessment of the effects of cell size on AGNPS modeling of watershed runoff

    Science.gov (United States)

    Wu, S.-S.; Usery, E.L.; Finn, M.P.; Bosch, D.D.

    2008-01-01

    This study investigates the changes in simulated watershed runoff from the Agricultural NonPoint Source (AGNPS) pollution model as a function of model input cell size resolution for eight different cell sizes (30 m, 60 m, 120 m, 210 m, 240 m, 480 m, 960 m, and 1920 m) for the Little River Watershed (Georgia, USA). Overland cell runoff (area-weighted cell runoff), total runoff volume, clustering statistics, and hot spot patterns were examined for the different cell sizes and trends identified. Total runoff volumes decreased with increasing cell size. Using data sets of 210-m cell size or smaller in conjunction with a representative watershed boundary allows one to model the runoff volumes within 0.2 percent accuracy. The runoff clustering statistics decrease with increasing cell size; a cell size of 960 m or smaller is necessary to indicate significant high-runoff clustering. Runoff hot spot areas have a decreasing trend with increasing cell size; a cell size of 240 m or smaller is required to detect important hot spots. Conclusions regarding cell size effects on runoff estimation cannot be applied to local watershed areas due to the inconsistent changes of runoff volume with cell size; but, optimal cells sizes for clustering and hot spot analyses are applicable to local watershed areas due to the consistent trends.

  13. Microstructured polymeric substrates applied to human stem cells studies

    OpenAIRE

    Grespan, Eleonora

    2015-01-01

    Stem cells are undifferentiated cells that have the capability to differentiate into specialized cells and to subdivide indefinitely to produce more stem cells. Studies on human stem cells represent a powerful method to analyze biological and physiological processes specific of human cells, as well as for tissue engineering, regenerative medicine and cell therapies. When these studies are performed in vitro it is important to take in account that cellular processes such as adhesion, migration...

  14. Micronutrient Sprinkles Add More Bioavailable Iron to some Kenyan Complementary Foods: Studies Using an In Vitro Digestion/Caco-2 Cell Culture Model

    Science.gov (United States)

    Iron deficiency anemia is arguably the most important public health problem in developing countries. Home-fortification of complementary foods using micronutrient Sprinkles has been shown to reduce iron deficiency anemia in many resource poor settings. In this study, the benefit of using the micronu...

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

    OpenAIRE

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

    1999-01-01

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

  16. Solid Polymer Fuel Cells. Electrode and membrane performance studies

    Energy Technology Data Exchange (ETDEWEB)

    Moeller-Holst, S.

    1996-12-31

    This doctoral thesis studies aspects of fuel cell preparation and performance. The emphasis is placed on preparation and analysis of low platinum-loading solid polymer fuel cell (SPEC) electrodes. A test station was built and used to test cells within a wide range of real operating conditions, 40-150{sup o}C and 1-10 bar. Preparation and assembling equipment for single SPFCs was designed and built, and a new technique of spraying the catalyst layer directly onto the membrane was successfully demonstrated. Low Pt-loading electrodes (0.1 mg Pt/cm{sup 2}) prepared by the new technique exhibited high degree of catalyst utilization. The performance of single cells holding these electrodes is comparable to state-of-the-art SPFCs. Potential losses in single cell performance are ascribed to irreversibilities by analysing the efficiency of the Solid Oxide Fuel Cell by means of the second law of thermodynamics. The water management in membranes is discussed for a model system and the results are relevant to fuel cell preparation and performance. The new spray deposition technique should be commercially interesting as it involves few steps as well as techniques that are adequate for larger scale production. 115 refs., 43 figs., 18 tabs.

  17. Studying the Nucleated Mammalian Cell Membrane by Single Molecule Approaches

    Science.gov (United States)

    Wang, Feng; Wu, Jiazhen; Gao, Jing; Liu, Shuheng; Jiang, Junguang; Jiang, Shibo; Wang, Hongda

    2014-01-01

    The cell membrane plays a key role in compartmentalization, nutrient transportation and signal transduction, while the pattern of protein distribution at both cytoplasmic and ectoplasmic sides of the cell membrane remains elusive. Using a combination of single-molecule techniques, including atomic force microscopy (AFM), single molecule force spectroscopy (SMFS) and stochastic optical reconstruction microscopy (STORM), to study the structure of nucleated cell membranes, we found that (1) proteins at the ectoplasmic side of the cell membrane form a dense protein layer (4 nm) on top of a lipid bilayer; (2) proteins aggregate to form islands evenly dispersed at the cytoplasmic side of the cell membrane with a height of about 10–12 nm; (3) cholesterol-enriched domains exist within the cell membrane; (4) carbohydrates stay in microdomains at the ectoplasmic side; and (5) exposed amino groups are asymmetrically distributed on both sides. Based on these observations, we proposed a Protein Layer-Lipid-Protein Island (PLLPI) model, to provide a better understanding of cell membrane structure, membrane trafficking and viral fusion mechanisms. PMID:24806512

  18. Modelling of tandem cell temperature coefficients

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, D.J. [National Renewable Energy Lab., Golden, CO (United States)

    1996-05-01

    This paper discusses the temperature dependence of the basic solar-cell operating parameters for a GaInP/GaAs series-connected two-terminal tandem cell. The effects of series resistance and of different incident solar spectra are also discussed.

  19. Giant Glial Cell: New Insight Through Mechanism-Based Modeling

    DEFF Research Database (Denmark)

    Postnov, D. E.; Ryazanova, L. S.; Brazhe, Nadezda;

    2008-01-01

    The paper describes a detailed mechanism-based model of a tripartite synapse consisting of P- and R-neurons together with a giant glial cell in the ganglia of the medical leech (Hirudo medicinalis), which is a useful object for experimental studies in situ. We describe the two main pathways of the...... establishing the positive feedback in glutamate release that is critical for the self-sustained activity of the postsynaptic neuron. This mechanism differs from the mechanisms of the astrocyte-neuron signaling previously reported....

  20. Modelling spatio-temporal interactions within the cell

    Indian Academy of Sciences (India)

    Padmini Rangamani; Ravi Iyengar

    2007-01-01

    Biological phenomena at the cellular level can be represented by various types of mathematical formulations. Such representations allow us to carry out numerical simulations that provide mechanistic insights into complex behaviours of biological systems and also generate hypotheses that can be experimentally tested. Currently, we are particularly interested in spatio-temporal representations of dynamic cellular phenomena and how such models can be used to understand biological specificity in functional responses. This review describes the capability and limitations of the approaches used to study spatio-temporal dynamics of cell signalling components.