Functional dynamics of cell surface membrane proteins.

Science.gov (United States)

Nishida, Noritaka; Osawa, Masanori; Takeuchi, Koh; Imai, Shunsuke; Stampoulis, Pavlos; Kofuku, Yutaka; Ueda, Takumi; Shimada, Ichio

2014-04-01

Cell surface receptors are integral membrane proteins that receive external stimuli, and transmit signals across plasma membranes. In the conventional view of receptor activation, ligand binding to the extracellular side of the receptor induces conformational changes, which convert the structure of the receptor into an active conformation. However, recent NMR studies of cell surface membrane proteins have revealed that their structures are more dynamic than previously envisioned, and they fluctuate between multiple conformations in an equilibrium on various timescales. In addition, NMR analyses, along with biochemical and cell biological experiments indicated that such dynamical properties are critical for the proper functions of the receptors. In this review, we will describe several NMR studies that revealed direct linkage between the structural dynamics and the functions of the cell surface membrane proteins, such as G-protein coupled receptors (GPCRs), ion channels, membrane transporters, and cell adhesion molecules. Copyright © 2013 Elsevier Inc. All rights reserved.

3D Protein Dynamics in the Cell Nucleus.

Science.gov (United States)

Singh, Anand P; Galland, Rémi; Finch-Edmondson, Megan L; Grenci, Gianluca; Sibarita, Jean-Baptiste; Studer, Vincent; Viasnoff, Virgile; Saunders, Timothy E

2017-01-10

The three-dimensional (3D) architecture of the cell nucleus plays an important role in protein dynamics and in regulating gene expression. However, protein dynamics within the 3D nucleus are poorly understood. Here, we present, to our knowledge, a novel combination of 1) single-objective based light-sheet microscopy, 2) photoconvertible proteins, and 3) fluorescence correlation microscopy, to quantitatively measure 3D protein dynamics in the nucleus. We are able to acquire >3400 autocorrelation functions at multiple spatial positions within a nucleus, without significant photobleaching, allowing us to make reliable estimates of diffusion dynamics. Using this tool, we demonstrate spatial heterogeneity in Polymerase II dynamics in live U2OS cells. Further, we provide detailed measurements of human-Yes-associated protein diffusion dynamics in a human gastric cancer epithelial cell line. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Protein dynamics in individual human cells: experiment and theory.

Directory of Open Access Journals (Sweden)

Ariel Aharon Cohen

Full Text Available A current challenge in biology is to understand the dynamics of protein circuits in living human cells. Can one define and test equations for the dynamics and variability of a protein over time? Here, we address this experimentally and theoretically, by means of accurate time-resolved measurements of endogenously tagged proteins in individual human cells. As a model system, we choose three stable proteins displaying cell-cycle-dependant dynamics. We find that protein accumulation with time per cell is quadratic for proteins with long mRNA life times and approximately linear for a protein with short mRNA lifetime. Both behaviors correspond to a classical model of transcription and translation. A stochastic model, in which genes slowly switch between ON and OFF states, captures measured cell-cell variability. The data suggests, in accordance with the model, that switching to the gene ON state is exponentially distributed and that the cell-cell distribution of protein levels can be approximated by a Gamma distribution throughout the cell cycle. These results suggest that relatively simple models may describe protein dynamics in individual human cells.

Microbial Cell Dynamics Lab (MCDL)

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Federal Laboratory Consortium — The Microbial Cell Dynamics Laboratory at PNNL enables scientists to study the molecular details of microbes under relevant environmental conditions. The MCDL seeks...

Dynamic characterization of human breast cancer cells using a piezoresistive microcantilever.

Science.gov (United States)

Shim, Sangjo; Kim, Man Geun; Jo, Kyoungwoo; Kang, Yong Seok; Lee, Boreum; Yang, Sung; Shin, Sang-Mo; Lee, Jong-Hyun

2010-10-01

In this paper, frequency response (dynamic compression and recovery) is suggested as a new physical marker to differentiate between breast cancer cells (MCF7) and normal cells (MCF10A). A single cell is placed on the laminated piezoelectric actuator and a piezoresistive microcantilever is placed on the upper surface of the cell at a specified preload displacement (or an equivalent force). The piezoelectric actuator excites the single cell in a sinusoidal fashion and its dynamic deformation is then evaluated from the displacement converted by measuring the voltage output through a piezoresistor in the microcantilever. The microcantilever has a flat contact surface with no sharp tip, making it possible to measure the overall properties of the cell rather than the local properties. These results indicate that the MCF7 cells are more deformable in quasi-static conditions compared with MCF10A cells, consistent with known characteristics. Under conditions of high frequency of over 50 Hz at a 1 μm preload displacement, 1 Hz at a 2 μm preload displacement, and all frequency ranges tested at a 3 μm preload displacement, MCF7 cells showed smaller deformation than MCF10A cells. MCF7 cells have higher absorption than MCF10A cells such that MCF7 cells appear to have higher deformability according to increasing frequency. Moreover, larger preload and higher frequencies are shown to enhance the differences in cell deformability between the MCF7 cells and MCF10A cells, which can be used as a physical marker for differentiating between MCF10A cells and MCF7 cells, even for high-speed screening devices.

Cellular adhesome screen identifies critical modulators of focal adhesion dynamics, cellular traction forces and cell migration behaviour

Science.gov (United States)

Fokkelman, Michiel; Balcıoğlu, Hayri E.; Klip, Janna E.; Yan, Kuan; Verbeek, Fons J.; Danen, Erik H. J.; van de Water, Bob

2016-01-01

Cancer cells migrate from the primary tumour into surrounding tissue in order to form metastasis. Cell migration is a highly complex process, which requires continuous remodelling and re-organization of the cytoskeleton and cell-matrix adhesions. Here, we aimed to identify genes controlling aspects of tumour cell migration, including the dynamic organization of cell-matrix adhesions and cellular traction forces. In a siRNA screen targeting most cell adhesion-related genes we identified 200+ genes that regulate size and/or dynamics of cell-matrix adhesions in MCF7 breast cancer cells. In a subsequent secondary screen, the 64 most effective genes were evaluated for growth factor-induced cell migration and validated by tertiary RNAi pool deconvolution experiments. Four validated hits showed significantly enlarged adhesions accompanied by reduced cell migration upon siRNA-mediated knockdown. Furthermore, loss of PPP1R12B, HIPK3 or RAC2 caused cells to exert higher traction forces, as determined by traction force microscopy with elastomeric micropillar post arrays, and led to considerably reduced force turnover. Altogether, we identified genes that co-regulate cell-matrix adhesion dynamics and traction force turnover, thereby modulating overall motility behaviour. PMID:27531518

Cell fate determination dynamics in bacteria

Science.gov (United States)

Kuchina, Anna; Espinar, Lorena; Cagatay, Tolga; Garcia-Ojalvo, Jordi; Suel, Gurol

2010-03-01

The fitness of an organism depends on many processes that serve the purpose to adapt to changing environment in a robust and coordinated fashion. One example of such process is cellular fate determination. In the presence of a variety of alternative responses each cell adopting a particular fate represents a ``choice'' that must be tightly regulated to ensure the best survival strategy for the population taking into account the broad range of possible environmental challenges. We investigated this problem in the model organism B.Subtilis which under stress conditions differentiates terminally into highly resistant spores or initiates an alternative transient state of competence. The dynamics underlying cell fate choice remains largely unknown. We utilize quantitative fluorescent microscopy to track the activities of genes involved in these responses on a single-cell level. We explored the importance of temporal interactions between competing cell fates by re- engineering the differentiation programs. I will discuss how the precise dynamics of cellular ``decision-making'' governed by the corresponding biological circuits may enable cells to adjust to diverse environments and determine survival.

Magneto-responsive liquid crystalline elastomer nanocomposites as potential candidates for dynamic cell culture substrates

Energy Technology Data Exchange (ETDEWEB)

Herrera-Posada, Stephany; Mora-Navarro, Camilo; Ortiz-Bermudez, Patricia; Torres-Lugo, Madeline [Department of Chemical Engineering, Call Box 9000, University of Puerto Rico, Mayagüez PR 00681 (Puerto Rico); McElhinny, Kyle M.; Evans, Paul G. [Department of Materials Science and Engineering, 1509 University Avenue, University of Wisconsin-Madison, WI 53706 (United States); Calcagno, Barbara O. [Department of General Engineering, Call Box 9000, University of Puerto Rico, Mayagüez PR 00681 (Puerto Rico); Acevedo, Aldo, E-mail: aldo.acevedo@upr.edu [Department of Chemical Engineering, Call Box 9000, University of Puerto Rico, Mayagüez PR 00681 (Puerto Rico)

2016-08-01

Recently, liquid crystalline elastomers (LCEs) have been proposed as active substrates for cell culture due to their potential to attach and orient cells, and impose dynamic mechanical signals through the application of external stimuli. In this report, the preparation of anisotropic and oriented nematic magnetic-sensitized LCEs with iron oxide nanoparticles, and the evaluation of the effect of particle addition at low concentrations on the resultant structural, thermal, thermo-mechanical, and mechanical properties is presented. Phase transformations produced by heating in alternating magnetic fields were investigated in LCEs in contact with air, water, and a common liquid cell culture medium was also evaluated. The inclusion of nanoparticles into the elastomers displaced the nematic-to-isotropic phase transition, without affecting the nematic structure as evidenced by similar values of the order parameter, while reducing the maximum thermomechanical deformations. Remote and reversible deformations of the magnetic LCEs were achieved through the application of alternating magnetic fields, which induces the nematic–isotropic phase transition through nanoparticle heat generation. Formulation parameters can be modified to allow for remote actuation at values closer to the human physiological temperature range and within the range of deformations that can affect the cellular behavior of fibroblasts. Finally, a collagen surface treatment was performed to improve compatibility with NIH-3T3 fibroblast cultures, which enabled the attachment and proliferation of fibroblasts on substrates with and without magnetic particles under quiescent conditions. The LCEs developed in this work, which are able to deform and experience stress changes by remote contact-less magnetic stimulation, may allow for further studies on the effect of substrate morphology changes and dynamic mechanical properties during in vitro cell culture. - Highlights: • Magnetic LCE nanocomposites were

Magneto-responsive liquid crystalline elastomer nanocomposites as potential candidates for dynamic cell culture substrates

International Nuclear Information System (INIS)

Herrera-Posada, Stephany; Mora-Navarro, Camilo; Ortiz-Bermudez, Patricia; Torres-Lugo, Madeline; McElhinny, Kyle M.; Evans, Paul G.; Calcagno, Barbara O.; Acevedo, Aldo

2016-01-01

Recently, liquid crystalline elastomers (LCEs) have been proposed as active substrates for cell culture due to their potential to attach and orient cells, and impose dynamic mechanical signals through the application of external stimuli. In this report, the preparation of anisotropic and oriented nematic magnetic-sensitized LCEs with iron oxide nanoparticles, and the evaluation of the effect of particle addition at low concentrations on the resultant structural, thermal, thermo-mechanical, and mechanical properties is presented. Phase transformations produced by heating in alternating magnetic fields were investigated in LCEs in contact with air, water, and a common liquid cell culture medium was also evaluated. The inclusion of nanoparticles into the elastomers displaced the nematic-to-isotropic phase transition, without affecting the nematic structure as evidenced by similar values of the order parameter, while reducing the maximum thermomechanical deformations. Remote and reversible deformations of the magnetic LCEs were achieved through the application of alternating magnetic fields, which induces the nematic–isotropic phase transition through nanoparticle heat generation. Formulation parameters can be modified to allow for remote actuation at values closer to the human physiological temperature range and within the range of deformations that can affect the cellular behavior of fibroblasts. Finally, a collagen surface treatment was performed to improve compatibility with NIH-3T3 fibroblast cultures, which enabled the attachment and proliferation of fibroblasts on substrates with and without magnetic particles under quiescent conditions. The LCEs developed in this work, which are able to deform and experience stress changes by remote contact-less magnetic stimulation, may allow for further studies on the effect of substrate morphology changes and dynamic mechanical properties during in vitro cell culture. - Highlights: • Magnetic LCE nanocomposites were

Functioning islet cell tumor of the pancreas. Localization with dynamic spiral CT

International Nuclear Information System (INIS)

Chung, M.J.; Choi, B.I.; Han, J.K.; Chung, J.W.; Han, M.C.; Bae, S.H.

1997-01-01

Purpose: The purpose of this study was to evaluate the usefulness of dynamic spiral CT, including multidimensional reformation, in the detection and localization of islet cell tumors of the pancreas. Material and Methods: Seven patients with histopathologically proven functioning islet cell tumors of the pancreas were studied with 2-phase contrast-enhanced spiral CT. Scanning of the arterial phase and late phase was started 30 s and 180 s, respectively, after injection of 100 ml of contrast medium at a rate of 3 ml/s. Results: Axial images in the arterial phase depicted the lesions in 5 patients, but in the late phase in only one patient. Multiplanar reformatted images of the arterial phase depicted the lesions in all 7 patients. Maximal intensity projection images demonstrated all lesions with information of their relationship to the vascular structure. Conclusion: Dynamic spiral CT with scanning during the arterial phase and retrospective multidimensional reformation is useful for preoperative detection and localization of small islet cell tumors of the pancreas. (orig.)

Dynamical Adaptation in Terrorist Cells/Networks

DEFF Research Database (Denmark)

Hussain, Dil Muhammad Akbar; Ahmed, Zaki

2010-01-01

Typical terrorist cells/networks have dynamical structure as they evolve or adapt to changes which may occur due to capturing or killing of a member of the cell/network. Analytical measures in graph theory like degree centrality, betweenness and closeness centralities are very common and have long...

Nonequilibrium population dynamics of phenotype conversion of cancer cells.

Directory of Open Access Journals (Sweden)

Joseph Xu Zhou

Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

Collective Dynamics of Intracellular Water in Living Cells

International Nuclear Information System (INIS)

Orecchini, A; Sebastiani, F; Paciaroni, A; Petrillo, C; Sacchetti, F; Jasnin, M; Francesco, A De; Zaccai, G; Moulin, M; Haertlein, M

2012-01-01

Water dynamics plays a fundamental role for the fulfillment of biological functions in living organisms. Decades of hydrated protein powder studies have revealed the peculiar dynamical properties of hydration water with respect to pure water, due to close coupling interactions with the macromolecule. In such a framework, we have studied coherent collective dynamics in protein and DNA hydration water. State-of-the-art neutron instrumentation has allowed us to observe the propagation of coherent density fluctuations within the hydration shell of the biomolecules. The corresponding dispersion curves resulted to be only slightly affected by the coupling with the macromolecules. Nevertheless, the effects of the interaction appeared as a marked increase of the mode damping factors, which suggested a destructuring of the water hydrogen-bond network. Such results were interpreted as the signature of a 'glassy' dynamical character of macromolecule hydration water, in agreement with indications from measurements of the density of vibrational states. Extending the investigations to living organisms at physiological conditions, we present here an in-vivo study of collective dynamics of intracellular water in Escherichia coli cells. The cells and water were fully deuterated to minimise the incoherent neutron scattering background. The water dynamics observed in the living cells is discussed in terms of the dynamics of pure bulk water and that of hydration water measured in powder samples.

Biomimetic and enzyme-responsive dynamic hydrogels for studying cell-matrix interactions in pancreatic ductal adenocarcinoma.

Science.gov (United States)

Liu, Hung-Yi; Korc, Murray; Lin, Chien-Chi

2018-04-01

The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT). Copyright © 2018 Elsevier Ltd. All rights

A computational approach for inferring the cell wall properties that govern guard cell dynamics.

Science.gov (United States)

Woolfenden, Hugh C; Bourdais, Gildas; Kopischke, Michaela; Miedes, Eva; Molina, Antonio; Robatzek, Silke; Morris, Richard J

2017-10-01

Guard cells dynamically adjust their shape in order to regulate photosynthetic gas exchange, respiration rates and defend against pathogen entry. Cell shape changes are determined by the interplay of cell wall material properties and turgor pressure. To investigate this relationship between turgor pressure, cell wall properties and cell shape, we focused on kidney-shaped stomata and developed a biomechanical model of a guard cell pair. Treating the cell wall as a composite of the pectin-rich cell wall matrix embedded with cellulose microfibrils, we show that strong, circumferentially oriented fibres are critical for opening. We find that the opening dynamics are dictated by the mechanical stress response of the cell wall matrix, and as the turgor rises, the pectinaceous matrix stiffens. We validate these predictions with stomatal opening experiments in selected Arabidopsis cell wall mutants. Thus, using a computational framework that combines a 3D biomechanical model with parameter optimization, we demonstrate how to exploit subtle shape changes to infer cell wall material properties. Our findings reveal that proper stomatal dynamics are built on two key properties of the cell wall, namely anisotropy in the form of hoop reinforcement and strain stiffening. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd and Society for Experimental Biology.

Intestinal Stem Cell Dynamics: A Story of Mice and Humans.

Science.gov (United States)

Hodder, Michael C; Flanagan, Dustin J; Sansom, Owen J

2018-06-01

Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations. Copyright © 2018 Elsevier Inc. All rights reserved.

Dynamic evaluation of job search assistance

NARCIS (Netherlands)

Kastoryano, S.; van der Klaauw, B.

2011-01-01

This paper evaluates a job search assistance program for unemployment insurance recipients. The assignment to the program is dynamic. We provide a discussion on dynamic treatment effects and identification conditions. In the empirical analyses we use administrative data from a unique institutional

Cell mass and cell cycle dynamics of an asynchronous budding yeast population

DEFF Research Database (Denmark)

Lencastre Fernandes, Rita; Carlquist, Magnus; Lundin, Luisa

2013-01-01

of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate...

Cell dynamic morphology classification using deep convolutional neural networks.

Science.gov (United States)

Li, Heng; Pang, Fengqian; Shi, Yonggang; Liu, Zhiwen

2018-05-15

Cell morphology is often used as a proxy measurement of cell status to understand cell physiology. Hence, interpretation of cell dynamic morphology is a meaningful task in biomedical research. Inspired by the recent success of deep learning, we here explore the application of convolutional neural networks (CNNs) to cell dynamic morphology classification. An innovative strategy for the implementation of CNNs is introduced in this study. Mouse lymphocytes were collected to observe the dynamic morphology, and two datasets were thus set up to investigate the performances of CNNs. Considering the installation of deep learning, the classification problem was simplified from video data to image data, and was then solved by CNNs in a self-taught manner with the generated image data. CNNs were separately performed in three installation scenarios and compared with existing methods. Experimental results demonstrated the potential of CNNs in cell dynamic morphology classification, and validated the effectiveness of the proposed strategy. CNNs were successfully applied to the classification problem, and outperformed the existing methods in the classification accuracy. For the installation of CNNs, transfer learning was proved to be a promising scheme. © 2018 International Society for Advancement of Cytometry. © 2018 International Society for Advancement of Cytometry.

Quantitative analysis of impact measurements using dynamic load cells

Directory of Open Access Journals (Sweden)

Brent J. Maranzano

2016-03-01

Full Text Available A mathematical model is used to estimate material properties from a short duration transient impact force measured by dropping spheres onto rectangular coupons fixed to a dynamic load cell. The contact stress between the dynamic load cell surface and the projectile are modeled using Hertzian contact mechanics. Due to the short impact time relative to the load cell dynamics, an additional Kelvin–Voigt element is included in the model to account for the finite response time of the piezoelectric crystal. Calculations with and without the Kelvin–Voigt element are compared to experimental data collected from combinations of polymeric spheres and polymeric and metallic surfaces. The results illustrate that the inclusion of the Kelvin–Voigt element qualitatively captures the post impact resonance and non-linear behavior of the load cell signal and quantitatively improves the estimation of the Young's elastic modulus and Poisson's ratio. Mathematically, the additional KV element couples one additional differential equation to the Hertzian spring-dashpot equation. The model can be numerically integrated in seconds using standard numerical techniques allowing for its use as a rapid technique for the estimation of material properties. Keywords: Young's modulus, Poisson's ratio, Dynamic load cell

Cell-substrate impedance fluctuations of single amoeboid cells encode cell-shape and adhesion dynamics.

Science.gov (United States)

Leonhardt, Helmar; Gerhardt, Matthias; Höppner, Nadine; Krüger, Kirsten; Tarantola, Marco; Beta, Carsten

2016-01-01

We show systematic electrical impedance measurements of single motile cells on microelectrodes. Wild-type cells and mutant strains were studied that differ in their cell-substrate adhesion strength. We recorded the projected cell area by time-lapse microscopy and observed irregular oscillations of the cell shape. These oscillations were correlated with long-term variations in the impedance signal. Superposed to these long-term trends, we observed fluctuations in the impedance signal. Their magnitude clearly correlated with the adhesion strength, suggesting that strongly adherent cells display more dynamic cell-substrate interactions.

Cell-substrate impedance fluctuations of single amoeboid cells encode cell-shape and adhesion dynamics

Science.gov (United States)

Leonhardt, Helmar; Gerhardt, Matthias; Höppner, Nadine; Krüger, Kirsten; Tarantola, Marco; Beta, Carsten

2016-01-01

We show systematic electrical impedance measurements of single motile cells on microelectrodes. Wild-type cells and mutant strains were studied that differ in their cell-substrate adhesion strength. We recorded the projected cell area by time-lapse microscopy and observed irregular oscillations of the cell shape. These oscillations were correlated with long-term variations in the impedance signal. Superposed to these long-term trends, we observed fluctuations in the impedance signal. Their magnitude clearly correlated with the adhesion strength, suggesting that strongly adherent cells display more dynamic cell-substrate interactions.

Non-small cell lung cancer: evaluation of the relationship between fibrosis and washout feature at dynamic contrast enhanced CT

International Nuclear Information System (INIS)

Ye Xiaodan; Yuan Zheng; Ye Jianding; Li Huimin; Zhu Yuzhao; Zhang Shunmin; Liu Shiyuan; Xiao Xiangsheng

2010-01-01

Objective: To correlate dynamic parameters at contrast enhanced CT and interstitial fibrosis grade of' non-small cell lung cancer (NSCLC). Methods: Twenty-nine patients with NSCLC were evaluated by multi-slice CT. Images were obtained before and at 20, 30, 45, 60, 75, 90, 120, 180, 300, 540, 720, 900 and 1200 s after the injection of contrast media, which was administered at a rate of 4 ml/s for a total of 420 mg I/kg body weight. Washout parameters were calculated. Lung cancer specimens were stained with hematoxylin-eosin stain and collagen and elastic double stain. Spearman test was made to analyze correlation between dynamic parameters and interstitial fibrosis grade of tumor. Results: Twenty- nine NSCLC demonstrated washout at 20 min 12.1 (0.32-58.0) HU, washout ratio at 20 minutes 15.3% (0.3%-39.2%), slope of washout at 20 minutes 0.0152%/s (0.0007%/s-0.0561%/s). Interstitial fibrosis of 29 lesions was graded as grade Ⅰ (10), grade Ⅱ (14) and grade Ⅲ (5). There were significant correlation between washout at 20 min (r=-0.402, P<0.05), washout ratio at 20 min (r= -0.372, P<0.05), slope of washout ratio (r=-0.459, P<0.05) and interstitial fibrosis grade in tumors. Conclusion: NSCLC washout features at dynamic multi-detector CT correlates with interstitial fibrosis in the tumor. (authors)

Dynamics of the cell-cycle network under genome-rewiring perturbations

International Nuclear Information System (INIS)

Katzir, Yair; Elhanati, Yuval; Braun, Erez; Averbukh, Inna

2013-01-01

The cell-cycle progression is regulated by a specific network enabling its ordered dynamics. Recent experiments supported by computational models have shown that a core of genes ensures this robust cycle dynamics. However, much less is known about the direct interaction of the cell-cycle regulators with genes outside of the cell-cycle network, in particular those of the metabolic system. Following our recent experimental work, we present here a model focusing on the dynamics of the cell-cycle core network under rewiring perturbations. Rewiring is achieved by placing an essential metabolic gene exclusively under the regulation of a cell-cycle's promoter, forcing the cell-cycle network to function under a multitasking challenging condition; operating in parallel the cell-cycle progression and a metabolic essential gene. Our model relies on simple rate equations that capture the dynamics of the relevant protein–DNA and protein–protein interactions, while making a clear distinction between these two different types of processes. In particular, we treat the cell-cycle transcription factors as limited ‘resources’ and focus on the redistribution of resources in the network during its dynamics. This elucidates the sensitivity of its various nodes to rewiring interactions. The basic model produces the correct cycle dynamics for a wide range of parameters. The simplicity of the model enables us to study the interface between the cell-cycle regulation and other cellular processes. Rewiring a promoter of the network to regulate a foreign gene, forces a multitasking regulatory load. The higher the load on the promoter, the longer is the cell-cycle period. Moreover, in agreement with our experimental results, the model shows that different nodes of the network exhibit variable susceptibilities to the rewiring perturbations. Our model suggests that the topology of the cell-cycle core network ensures its plasticity and flexible interface with other cellular processes

An Efficient Dynamic Trust Evaluation Model for Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Zhengwang Ye

2017-01-01

Full Text Available Trust evaluation is an effective method to detect malicious nodes and ensure security in wireless sensor networks (WSNs. In this paper, an efficient dynamic trust evaluation model (DTEM for WSNs is proposed, which implements accurate, efficient, and dynamic trust evaluation by dynamically adjusting the weights of direct trust and indirect trust and the parameters of the update mechanism. To achieve accurate trust evaluation, the direct trust is calculated considering multitrust including communication trust, data trust, and energy trust with the punishment factor and regulating function. The indirect trust is evaluated conditionally by the trusted recommendations from a third party. Moreover, the integrated trust is measured by assigning dynamic weights for direct trust and indirect trust and combining them. Finally, we propose an update mechanism by a sliding window based on induced ordered weighted averaging operator to enhance flexibility. We can dynamically adapt the parameters and the interactive history windows number according to the actual needs of the network to realize dynamic update of direct trust value. Simulation results indicate that the proposed dynamic trust model is an efficient dynamic and attack-resistant trust evaluation model. Compared with existing approaches, the proposed dynamic trust model performs better in defending multiple malicious attacks.

Distributed solar radiation fast dynamic measurement for PV cells

Science.gov (United States)

Wan, Xuefen; Yang, Yi; Cui, Jian; Du, Xingjing; Zheng, Tao; Sardar, Muhammad Sohail

2017-10-01

To study the operating characteristics about PV cells, attention must be given to the dynamic behavior of the solar radiation. The dynamic behaviors of annual, monthly, daily and hourly averages of solar radiation have been studied in detail. But faster dynamic behaviors of solar radiation need more researches. The solar radiation random fluctuations in minute-long or second-long range, which lead to alternating radiation and cool down/warm up PV cell frequently, decrease conversion efficiency. Fast dynamic processes of solar radiation are mainly relevant to stochastic moving of clouds. Even in clear sky condition, the solar irradiations show a certain degree of fast variation. To evaluate operating characteristics of PV cells under fast dynamic irradiation, a solar radiation measuring array (SRMA) based on large active area photodiode, LoRa spread spectrum communication and nanoWatt MCU is proposed. This cross photodiodes structure tracks fast stochastic moving of clouds. To compensate response time of pyranometer and reduce system cost, the terminal nodes with low-cost fast-responded large active area photodiode are placed besides positions of tested PV cells. A central node, consists with pyranometer, large active area photodiode, wind detector and host computer, is placed in the center of the central topologies coordinate to scale temporal envelope of solar irradiation and get calibration information between pyranometer and large active area photodiodes. In our SRMA system, the terminal nodes are designed based on Microchip's nanoWatt XLP PIC16F1947. FDS-100 is adopted for large active area photodiode in terminal nodes and host computer. The output current and voltage of each PV cell are monitored by I/V measurement. AS62-T27/SX1278 LoRa communication modules are used for communicating between terminal nodes and host computer. Because the LoRa LPWAN (Low Power Wide Area Network) specification provides seamless interoperability among Smart Things without the

Human T Cell Memory: A Dynamic View

Directory of Open Access Journals (Sweden)

Derek C. Macallan

2017-02-01

Full Text Available Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy.

Vacuolar and cytoskeletal dynamics during elicitor-induced programmed cell death in tobacco BY-2 cells.

Science.gov (United States)

Higaki, Takumi; Kadota, Yasuhiro; Goh, Tatsuaki; Hayashi, Teruyuki; Kutsuna, Natsumaro; Sano, Toshio; Hasezawa, Seiichiro; Kuchitsu, Kazuyuki

2008-09-01

Responses of plant cells to environmental stresses often involve morphological changes, differentiation and redistribution of various organelles and cytoskeletal network. Tobacco BY-2 cells provide excellent model system for in vivo imaging of these intracellular events. Treatment of the cell cycle-synchronized BY-2 cells with a proteinaceous oomycete elicitor, cryptogein, induces highly synchronous programmed cell death (PCD) and provide a model system to characterize vacuolar and cytoskeletal dynamics during the PCD. Sequential observation revealed dynamic reorganization of the vacuole and actin microfilaments during the execution of the PCD. We further characterized the effects cryptogein on mitotic microtubule organization in cell cycle-synchronized cells. Cryptogein treatment at S phase inhibited formation of the preprophase band, a cortical microtubule band that predicts the cell division site. Cortical microtubules kept their random orientation till their disruption that gradually occurred during the execution of the PCD twelve hours after the cryptogein treatment. Possible molecular mechanisms and physiological roles of the dynamic behavior of the organelles and cytoskeletal network in the pathogenic signal-induced PCD are discussed.

High-frequency microrheology reveals cytoskeleton dynamics in living cells

Science.gov (United States)

Rigato, Annafrancesca; Miyagi, Atsushi; Scheuring, Simon; Rico, Felix

2017-08-01

Living cells are viscoelastic materials, dominated by an elastic response on timescales longer than a millisecond. On shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce. Here, we develop high-frequency microrheology experiments to probe the viscoelastic response of living cells from 1 Hz to 100 kHz. We report the viscoelasticity of different cell types under cytoskeletal drug treatments. On previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequencies, providing a unique mechanical fingerprint. Microrheology over a wide dynamic range--up to the frequency characterizing the molecular components--provides a mechanistic understanding of cell mechanics.

Phosphorylation site dynamics of early T-cell receptor signaling

DEFF Research Database (Denmark)

Chylek, Lily A; Akimov, Vyacheslav; Dengjel, Jörn

2014-01-01

In adaptive immune responses, T-cell receptor (TCR) signaling impacts multiple cellular processes and results in T-cell differentiation, proliferation, and cytokine production. Although individual protein-protein interactions and phosphorylation events have been studied extensively, we lack...... that diverse dynamic patterns emerge within seconds. We detected phosphorylation dynamics as early as 5 s and observed widespread regulation of key TCR signaling proteins by 30 s. Development of a computational model pointed to the presence of novel regulatory mechanisms controlling phosphorylation of sites...... a systems-level understanding of how these components cooperate to control signaling dynamics, especially during the crucial first seconds of stimulation. Here, we used quantitative proteomics to characterize reshaping of the T-cell phosphoproteome in response to TCR/CD28 co-stimulation, and found...

Fractal dynamics in self-evaluation reveal self-concept clarity.

Science.gov (United States)

Wong, Alexander E; Vallacher, Robin R; Nowak, Andrzej

2014-10-01

The structural account of self-esteem and self-evaluation maintains that they are distinct constructs. Trait self-esteem is stable and is expressed over macro timescales, whereas state self-evaluation is unstable and experienced on micro timescales. We compared predictions based on the structural account with those derived from a dynamical systems perspective on the self, which maintains that self-esteem and self-evaluation are hierarchically related and share basic dynamic properties. Participants recorded a 3-minute narrative about themselves, then used the mouse paradigm (Vallacher, Nowak, Froehlich, & Rockloff, 2002) to track the momentary self-evaluation in their narrative. Multiple methods converged to reveal fractal patterns in the resultant temporal patterns, indicative of nested timescales that link micro and macro selfevaluation and thus supportive of the dynamical account. The fractal dynamics were associated with participants' self-concept clarity, suggesting that the hierarchical relation between macro self-evaluation (self-esteem) and momentary self-evaluation is predicted by the coherence of self-concept organization.

Picosecond orientational dynamics of water in living cells.

Science.gov (United States)

Tros, Martijn; Zheng, Linli; Hunger, Johannes; Bonn, Mischa; Bonn, Daniel; Smits, Gertien J; Woutersen, Sander

2017-10-12

Cells are extremely crowded, and a central question in biology is how this affects the intracellular water. Here, we use ultrafast vibrational spectroscopy and dielectric-relaxation spectroscopy to observe the random orientational motion of water molecules inside living cells of three prototypical organisms: Escherichia coli, Saccharomyces cerevisiae (yeast), and spores of Bacillus subtilis. In all three organisms, most of the intracellular water exhibits the same random orientational motion as neat water (characteristic time constants ~9 and ~2 ps for the first-order and second-order orientational correlation functions), whereas a smaller fraction exhibits slower orientational dynamics. The fraction of slow intracellular water varies between organisms, ranging from ~20% in E. coli to ~45% in B. subtilis spores. Comparison with the water dynamics observed in solutions mimicking the chemical composition of (parts of) the cytosol shows that the slow water is bound mostly to proteins, and to a lesser extent to other biomolecules and ions.The cytoplasm's crowdedness leads one to expect that cell water is different from bulk water. By measuring the rotational motion of water molecules in living cells, Tros et al. find that apart from a small fraction of water solvating biomolecules, cell water has the same dynamics as bulk water.

Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells

DEFF Research Database (Denmark)

Stiehler, Maik; Bünger, Cody; Baatrup, Anette

2009-01-01

Ex vivo engineering of autologous bone tissue as an alternative to bone grafting is a major clinical need. In the present study, we evaluated the effect of 3-D dynamic spinner flask culture on the proliferation, distribution, and differentiation of human mesenchymal stem cells (MSCs). Immortalized...... human MSCs were cultured on porous 75:25 PLGA scaffolds for up to 3 weeks. Dynamically cultured cell/scaffold constructs demonstrated a 20% increase in DNA content (21 days), enhanced ALP specific activity (7 days and 21 days), a more than tenfold higher Ca2+ content (21 days), and significantly...

Uses And Characteristics Of Dynamic Tradeoff Evaluation

Science.gov (United States)

Schwuttke, Ursula M.

1995-01-01

Report discusses basic concepts, some applications, and performance characteristics of dynamic tradeoff evaluation (DTE). Basic concepts of DTE also described in "Dynamic Restructuring of Problems in Artificial Intelligence" (NPO-18488). DTE is method of enhancing real-time performance of artificial-intelligence system such as might be used to monitor data from multiple sensors in factory, aircraft, spacecraft, or other complex system of equipment. Report presents evaluation of DTE as applied to spacecraft-monitoring problems.

Fuel Cell Electric Bus Evaluations | Hydrogen and Fuel Cells | NREL

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Bus Evaluations Fuel Cell Electric Bus Evaluations NREL's technology validation team evaluates fuel cell electric buses (FCEBs) to provide comprehensive, unbiased evaluation results of fuel cell bus early transportation applications for fuel cell technology. Buses operate in congested areas where

Relation Between the Cell Volume and the Cell Cycle Dynamics in Mammalian cell

International Nuclear Information System (INIS)

Magno, A.C.G.; Oliveira, I.L.; Hauck, J.V.S.

2016-01-01

The main goal of this work is to add and analyze an equation that represents the volume in a dynamical model of the mammalian cell cycle proposed by Gérard and Goldbeter (2011) [1]. The cell division occurs when the cyclinB/Cdkl complex is totally degraded (Tyson and Novak, 2011)[2] and it reaches a minimum value. At this point, the cell is divided into two newborn daughter cells and each one will contain the half of the cytoplasmic content of the mother cell. The equations of our base model are only valid if the cell volume, where the reactions occur, is constant. Whether the cell volume is not constant, that is, the rate of change of its volume with respect to time is explicitly taken into account in the mathematical model, then the equations of the original model are no longer valid. Therefore, every equations were modified from the mass conservation principle for considering a volume that changes with time. Through this approach, the cell volume affects all model variables. Two different dynamic simulation methods were accomplished: deterministic and stochastic. In the stochastic simulation, the volume affects every model's parameters which have molar unit, whereas in the deterministic one, it is incorporated into the differential equations. In deterministic simulation, the biochemical species may be in concentration units, while in stochastic simulation such species must be converted to number of molecules which are directly proportional to the cell volume. In an effort to understand the influence of the new equation a stability analysis was performed. This elucidates how the growth factor impacts the stability of the model's limit cycles. In conclusion, a more precise model, in comparison to the base model, was created for the cell cycle as it now takes into consideration the cell volume variation (paper)

Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft.

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Ukon, Naoyuki; Zhao, Songji; Yu, Wenwen; Shimizu, Yoichi; Nishijima, Ken-Ichi; Kubo, Naoki; Kitagawa, Yoshimasa; Tamaki, Nagara; Higashikawa, Kei; Yasui, Hironobu; Kuge, Yuji

2016-12-01

Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl- 3 H(N)]-3'-fluoro-3'-deoxythythymidine ([ 3 H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[ 18 F]fluoro-3'-deoxythymidine ([ 18 F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [ 18 F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [ 18 F]FLT. The dynamic pattern of [ 18 F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [ 18 F]FLT phosphorylation (k 3 ) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [ 18 F]FLT forward transport (K 1 ) to reverse transport (k 2 ), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic

A dynamical model for plant cell wall architecture formation.

NARCIS (Netherlands)

Mulder, B.M.; Emons, A.M.C.

2001-01-01

We discuss a dynamical mathematical model to explain cell wall architecture in plant cells. The highly regular textures observed in cell walls reflect the spatial organisation of the cellulose microfibrils (CMFs), the most important structural component of cell walls. Based on a geometrical theory

Direct Adaptive Aircraft Control Using Dynamic Cell Structure Neural Networks

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Jorgensen, Charles C.

1997-01-01

A Dynamic Cell Structure (DCS) Neural Network was developed which learns topology representing networks (TRNS) of F-15 aircraft aerodynamic stability and control derivatives. The network is integrated into a direct adaptive tracking controller. The combination produces a robust adaptive architecture capable of handling multiple accident and off- nominal flight scenarios. This paper describes the DCS network and modifications to the parameter estimation procedure. The work represents one step towards an integrated real-time reconfiguration control architecture for rapid prototyping of new aircraft designs. Performance was evaluated using three off-line benchmarks and on-line nonlinear Virtual Reality simulation. Flight control was evaluated under scenarios including differential stabilator lock, soft sensor failure, control and stability derivative variations, and air turbulence.

Live cell imaging of actin dynamics in dexamethasone-treated porcine trabecular meshwork cells.

Science.gov (United States)

Fujimoto, Tomokazu; Inoue, Toshihiro; Inoue-Mochita, Miyuki; Tanihara, Hidenobu

2016-04-01

The regulation of the actin cytoskeleton in trabecular meshwork (TM) cells is important for controlling outflow of the aqueous humor. In some reports, dexamethasone (DEX) increased the aqueous humor outflow resistance and induced unusual actin structures, such as cross-linked actin networks (CLAN), in TM cells. However, the functions and dynamics of CLAN in TM cells are not completely known, partly because actin stress fibers have been observed only in fixed cells. We conducted live-cell imaging of the actin dynamics in TM cells with or without DEX treatment. An actin-green fluorescent protein (GFP) fusion construct with a modified insect virus was transfected into porcine TM cells. Time-lapse imaging of live TM cells treated with 25 μM Y-27632 and 100 nM DEX was performed using an inverted fluorescence microscope. Fluorescent images were recorded every 15 s for 30 min after Y-27632 treatment or every 30 min for 72 h after DEX treatment. The GFP-actin was expressed in 22.7 ± 10.9% of the transfected TM cells. In live TM cells, many actin stress fibers were observed before the Y-27632 treatment. Y-27632 changed the cell shape and decreased stress fibers in a time-dependent manner. In fixed cells, CLAN-like structures were seen in 26.5 ± 1.7% of the actin-GFP expressed PTM cells treated with DEX for 72 h. In live imaging, there was 28% CLAN-like structure formation at 72 h after DEX treatment, and the lifetime of CLAN-like structures increased after DEX treatment. The DEX-treated cells with CLAN-like structures showed less migration than DEX-treated cells without CLAN-like structures. Furthermore, the control cells (without DEX treatment) with CLAN-like structures also showed less migration than the control cells without CLAN-like structures. These results suggested that CLAN-like structure formation was correlated with cell migration in TM cells. Live cell imaging of the actin cytoskeleton provides valuable information on the actin dynamics in TM

Turbulent Dynamics of Epithelial Cell Cultures

Science.gov (United States)

Blanch-Mercader, C.; Yashunsky, V.; Garcia, S.; Duclos, G.; Giomi, L.; Silberzan, P.

2018-05-01

We investigate the large length and long time scales collective flows and structural rearrangements within in vitro human bronchial epithelial cell (HBEC) cultures. Activity-driven collective flows result in ensembles of vortices randomly positioned in space. By analyzing a large population of vortices, we show that their area follows an exponential law with a constant mean value and their rotational frequency is size independent, both being characteristic features of the chaotic dynamics of active nematic suspensions. Indeed, we find that HBECs self-organize in nematic domains of several cell lengths. Nematic defects are found at the interface between domains with a total number that remains constant due to the dynamical balance of nucleation and annihilation events. The mean velocity fields in the vicinity of defects are well described by a hydrodynamic theory of extensile active nematics.

The dynamic landscape of the cell nucleus.

Science.gov (United States)

Austin, Christopher M; Bellini, Michel

2010-01-01

While the cell nucleus was described for the first time almost two centuries ago, our modern view of the nuclear architecture is primarily based on studies from the last two decades. This surprising late start coincides with the development of new, powerful strategies to probe for the spatial organization of nuclear activities in both fixed and live cells. As a result, three major principles have emerged: first, the nucleus is not just a bag filled with nucleic acids and proteins. Rather, many distinct functional domains, including the chromosomes, resides within the confines of the nuclear envelope. Second, all these nuclear domains are highly dynamic, with molecules exchanging rapidly between them and the surrounding nucleoplasm. Finally, the motion of molecules within the nucleoplasm appears to be mostly driven by random diffusion. Here, the emerging roles of several subnuclear domains are discussed in the context of the dynamic functions of the cell nucleus.

Dynamic characteristics of an automotive fuel cell system for transitory load changes

DEFF Research Database (Denmark)

Rabbani, Raja Abid; Rokni, Masoud

2013-01-01

A dynamic model of Polymer Electrolyte Membrane Fuel Cell (PEMFC) system is developed to investigate the behavior and transient response of a fuel cell system for automotive applications. Fuel cell dynamics are subjected to reactant flows, heat management and water transportation inside the fuel...

High-efficient and high-content cytotoxic recording via dynamic and continuous cell-based impedance biosensor technology.

Science.gov (United States)

Hu, Ning; Fang, Jiaru; Zou, Ling; Wan, Hao; Pan, Yuxiang; Su, Kaiqi; Zhang, Xi; Wang, Ping

2016-10-01

Cell-based bioassays were effective method to assess the compound toxicity by cell viability, and the traditional label-based methods missed much information of cell growth due to endpoint detection, while the higher throughputs were demanded to obtain dynamic information. Cell-based biosensor methods can dynamically and continuously monitor with cell viability, however, the dynamic information was often ignored or seldom utilized in the toxin and drug assessment. Here, we reported a high-efficient and high-content cytotoxic recording method via dynamic and continuous cell-based impedance biosensor technology. The dynamic cell viability, inhibition ratio and growth rate were derived from the dynamic response curves from the cell-based impedance biosensor. The results showed that the biosensors has the dose-dependent manners to diarrhetic shellfish toxin, okadiac acid based on the analysis of the dynamic cell viability and cell growth status. Moreover, the throughputs of dynamic cytotoxicity were compared between cell-based biosensor methods and label-based endpoint methods. This cell-based impedance biosensor can provide a flexible, cost and label-efficient platform of cell viability assessment in the shellfish toxin screening fields.

Dynamically constrained pipeline for tracking neural progenitor cells

DEFF Research Database (Denmark)

Vestergaard, Jacob Schack; Dahl, Anders; Holm, Peter

2013-01-01

. A mitosis detector constructed from empirical observations of cells in a pre-mitotic state interacts with the graph formulation to dynamically allow for cell mitosis when appropriate. Track consistency is ensured by introducing pragmatic constraints and the notion of blob states. We validate the proposed...

Dynamical analysis of uterine cell electrical activity model.

Science.gov (United States)

Rihana, S; Santos, J; Mondie, S; Marque, C

2006-01-01

The uterus is a physiological system consisting of a large number of interacting smooth muscle cells. The uterine excitability changes remarkably with time, generally quiescent during pregnancy, the uterus exhibits forceful synchronized contractions at term leading to fetus expulsion. These changes characterize thus a dynamical system susceptible of being studied through formal mathematical tools. Multiple physiological factors are involved in the regulation process of this complex system. Our aim is to relate the physiological factors to the uterine cell dynamic behaviors. Taking into account a previous work presented, in which the electrical activity of a uterine cell is described by a set of ordinary differential equations, we analyze the impact of physiological parameters on the response of the model, and identify the main subsystems generating the complex uterine electrical activity, with respect to physiological data.

Dynamic modeling of gas turbines in integrated gasification fuel cell systems

Science.gov (United States)

Maclay, James Davenport

2009-12-01

Solid oxide fuel cell-gas turbine (SOFC-GT) hybrid systems for use in integrated gasification fuel cell (IGFC) systems operating on coal will stretch existing fossil fuel reserves, generate power with less environmental impact, while having a cost of electricity advantage over most competing technologies. However, the dynamic performance of a SOFC-GT in IGFC applications has not been previously studied in detail. Of particular importance is how the turbo-machinery will be designed, controlled and operated in such applications; this is the focus of the current work. Perturbation and dynamic response analyses using numerical SimulinkRTM models indicate that compressor surge is the predominant concern for safe dynamic turbo-machinery operation while shaft over-speed and excessive turbine inlet temperatures are secondary concerns. Fuel cell temperature gradients and anode-cathode differential pressures were found to be the greatest concerns for safe dynamic fuel cell operation. Two control strategies were compared, that of constant gas turbine shaft speed and constant fuel cell temperature, utilizing a variable speed gas turbine. Neither control strategy could eliminate all vulnerabilities during dynamic operation. Constant fuel cell temperature control ensures safe fuel cell operation, while constant speed control does not. However, compressor surge is more likely with constant fuel cell temperature control than with constant speed control. Design strategies that provide greater surge margin while utilizing constant fuel cell temperature control include increasing turbine design mass flow and decreasing turbine design inlet pressure, increasing compressor design pressure ratio and decreasing compressor design mass flow, decreasing plenum volume, decreasing shaft moment of inertia, decreasing fuel cell pressure drop, maintaining constant compressor inlet air temperature. However, these strategies in some cases incur an efficiency penalty. A broad comparison of cycles

Red blood cell dynamics: from cell deformation to ATP release.

Science.gov (United States)

Wan, Jiandi; Forsyth, Alison M; Stone, Howard A

2011-10-01

The mechanisms of red blood cell (RBC) deformation under both static and dynamic, i.e., flow, conditions have been studied extensively since the mid 1960s. Deformation-induced biochemical reactions and possible signaling in RBCs, however, were proposed only fifteen years ago. Therefore, the fundamental relationship between RBC deformation and cellular signaling dynamics i.e., mechanotransduction, remains incompletely understood. Quantitative understanding of the mechanotransductive pathways in RBCs requires integrative studies of physical models of RBC deformation and cellular biochemical reactions. In this article we review the physical models of RBC deformation, spanning from continuum membrane mechanics to cellular skeleton dynamics under both static and flow conditions, and elaborate the mechanistic links involved in deformation-induced ATP release. This journal is © The Royal Society of Chemistry 2011

Local Nucleosome Dynamics Facilitate Chromatin Accessibility in Living Mammalian Cells

Directory of Open Access Journals (Sweden)

Saera Hihara

2012-12-01

Full Text Available Genome information, which is three-dimensionally organized within cells as chromatin, is searched and read by various proteins for diverse cell functions. Although how the protein factors find their targets remains unclear, the dynamic and flexible nature of chromatin is likely crucial. Using a combined approach of fluorescence correlation spectroscopy, single-nucleosome imaging, and Monte Carlo computer simulations, we demonstrate local chromatin dynamics in living mammalian cells. We show that similar to interphase chromatin, dense mitotic chromosomes also have considerable chromatin accessibility. For both interphase and mitotic chromatin, we observed local fluctuation of individual nucleosomes (∼50 nm movement/30 ms, which is caused by confined Brownian motion. Inhibition of these local dynamics by crosslinking impaired accessibility in the dense chromatin regions. Our findings show that local nucleosome dynamics drive chromatin accessibility. We propose that this local nucleosome fluctuation is the basis for scanning genome information.

The Dynamic Evaluation of Enterprise's Strategy Based on Rough Set Theory

Institute of Scientific and Technical Information of China (English)

刘恒江; 陈继祥

2003-01-01

This paper presents dynamic evaluation of enterprise's strategy which is suitable for dealing with the complex and dynamic problems of strategic evaluation. Rough Set Theory is a powerful mathematical tool to handle vagueness and uncertainty of dynamic evaluation. By the application of Rough Set Theory, this paper computes the significance and weights of each evaluation criterion and helps to lay evaluation emphasis on the main and effective criteria. From the reduced decision table,evaluators can get decision rules Which direct them to give judgment or suggestion of strategy. The whole evaluation process is decided by data, so the results are certain and reasonable.

Direct and dynamic detection of HIV-1 in living cells.

Directory of Open Access Journals (Sweden)

Jonas Helma

Full Text Available In basic and applied HIV research, reliable detection of viral components is crucial to monitor progression of infection. While it is routine to detect structural viral proteins in vitro for diagnostic purposes, it previously remained impossible to directly and dynamically visualize HIV in living cells without genetic modification of the virus. Here, we describe a novel fluorescent biosensor to dynamically trace HIV-1 morphogenesis in living cells. We generated a camelid single domain antibody that specifically binds the HIV-1 capsid protein (CA at subnanomolar affinity and fused it to fluorescent proteins. The resulting fluorescent chromobody specifically recognizes the CA-harbouring HIV-1 Gag precursor protein in living cells and is applicable in various advanced light microscopy systems. Confocal live cell microscopy and super-resolution microscopy allowed detection and dynamic tracing of individual virion assemblies at the plasma membrane. The analysis of subcellular binding kinetics showed cytoplasmic antigen recognition and incorporation into virion assembly sites. Finally, we demonstrate the use of this new reporter in automated image analysis, providing a robust tool for cell-based HIV research.

Fuel Cell Electric Vehicle Evaluations | Hydrogen and Fuel Cells | NREL

Science.gov (United States)

Electric Vehicle Evaluations Fuel Cell Electric Vehicle Evaluations NREL's technology validation team analyzes hydrogen fuel cell electric vehicles (FCEVs) operating in a real-world setting to include commercial FCEVs for the first time. Current fuel cell electric vehicle evaluations build on the

Bridging the Timescales of Single-Cell and Population Dynamics

Science.gov (United States)

Jafarpour, Farshid; Wright, Charles S.; Gudjonson, Herman; Riebling, Jedidiah; Dawson, Emma; Lo, Klevin; Fiebig, Aretha; Crosson, Sean; Dinner, Aaron R.; Iyer-Biswas, Srividya

2018-04-01

How are granular details of stochastic growth and division of individual cells reflected in smooth deterministic growth of population numbers? We provide an integrated, multiscale perspective of microbial growth dynamics by formulating a data-validated theoretical framework that accounts for observables at both single-cell and population scales. We derive exact analytical complete time-dependent solutions to cell-age distributions and population growth rates as functionals of the underlying interdivision time distributions, for symmetric and asymmetric cell division. These results provide insights into the surprising implications of stochastic single-cell dynamics for population growth. Using our results for asymmetric division, we deduce the time to transition from the reproductively quiescent (swarmer) to the replication-competent (stalked) stage of the Caulobacter crescentus life cycle. Remarkably, population numbers can spontaneously oscillate with time. We elucidate the physics leading to these population oscillations. For C. crescentus cells, we show that a simple measurement of the population growth rate, for a given growth condition, is sufficient to characterize the condition-specific cellular unit of time and, thus, yields the mean (single-cell) growth and division timescales, fluctuations in cell division times, the cell-age distribution, and the quiescence timescale.

Bioreactors to influence stem cell fate: augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems.

Science.gov (United States)

Yeatts, Andrew B; Choquette, Daniel T; Fisher, John P

2013-02-01

Mesenchymal stem cells (MSCs) are a promising cell source for bone and cartilage tissue engineering as they can be easily isolated from the body and differentiated into osteoblasts and chondrocytes. A cell based tissue engineering strategy using MSCs often involves the culture of these cells on three-dimensional scaffolds; however the size of these scaffolds and the cell population they can support can be restricted in traditional static culture. Thus dynamic culture in bioreactor systems provides a promising means to culture and differentiate MSCs in vitro. This review seeks to characterize key MSC differentiation signaling pathways and provides evidence as to how dynamic culture is augmenting these pathways. Following an overview of dynamic culture systems, discussion will be provided on how these systems can effectively modify and maintain important culture parameters including oxygen content and shear stress. Literature is reviewed for both a highlight of key signaling pathways and evidence for regulation of these signaling pathways via dynamic culture systems. The ability to understand how these culture systems are affecting MSC signaling pathways could lead to a shear or oxygen regime to direct stem cell differentiation. In this way the efficacy of in vitro culture and differentiation of MSCs on three-dimensional scaffolds could be greatly increased. Bioreactor systems have the ability to control many key differentiation stimuli including mechanical stress and oxygen content. The further integration of cell signaling investigations within dynamic culture systems will lead to a quicker realization of the promise of tissue engineering and regenerative medicine. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Direct Visualization of DNA Replication Dynamics in Zebrafish Cells.

Science.gov (United States)

Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Tamaru, Yutaka; Ogata, Shin; Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

2015-12-01

Spatiotemporal regulation of DNA replication in the S-phase nucleus has been extensively studied in mammalian cells because it is tightly coupled with the regulation of other nuclear processes such as transcription. However, little is known about the replication dynamics in nonmammalian cells. Here, we analyzed the DNA replication processes of zebrafish (Danio rerio) cells through the direct visualization of replicating DNA in the nucleus and on DNA fiber molecules isolated from the nucleus. We found that zebrafish chromosomal DNA at the nuclear interior was replicated first, followed by replication of DNA at the nuclear periphery, which is reminiscent of the spatiotemporal regulation of mammalian DNA replication. However, the relative duration of interior DNA replication in zebrafish cells was longer compared to mammalian cells, possibly reflecting zebrafish-specific genomic organization. The rate of replication fork progression and ori-to-ori distance measured by the DNA combing technique were ∼ 1.4 kb/min and 100 kb, respectively, which are comparable to those in mammalian cells. To our knowledge, this is a first report that measures replication dynamics in zebrafish cells.

On the origins of the universal dynamics of endogenous granules in mammalian cells.

Science.gov (United States)

Vanapalli, Siva A; Li, Yixuan; Mugele, Frieder; Duits, Michel H G

2009-12-01

Endogenous granules (EGs) that consist of lipid droplets and mitochondria have been commonly used to assess intracellular mechanical properties via multiple particle tracking microrheology (MPTM). Despite their widespread use, the nature of interaction of EGs with the cytoskeletal network and the type of forces driving their dynamics--both of which are crucial for the interpretation of the results from MPTM technique--are yet to be resolved. In this report, we study the dynamics of endogenous granules in mammalian cells using particle tracking methods. We find that the ensemble dynamics of EGs is diffusive in three types of mammalian cells (endothelial cells, smooth muscle cells and fibroblasts), thereby suggesting an apparent universality in their dynamical behavior. Moreover, in a given cell, the amplitude of the mean-squared displacement for EGs is an order of magnitude larger than that of injected particles. This observation along with results from ATP depletion and temperature intervention studies suggests that cytoskeletal active forces drive the dynamics of EGs. To elucidate the dynamical origin of the diffusive-like nonthermal motion, we consider three active force generation mechanisms--molecular motor transport, actomyosin contractility and microtubule polymerization forces. We test these mechanisms using pharmacological interventions. Experimental evidence and model calculations suggest that EGs are intimately linked to microtubules and that microtubule polymerization forces drive their dynamics. Thus, endogenous granules could serve as non-invasive probes for microtubule network dynamics in mammalian cells.

Multispectral fingerprinting for improved in vivo cell dynamics analysis

Directory of Open Access Journals (Sweden)

Cooper Cameron HJ

2010-09-01

Full Text Available Abstract Background Tracing cell dynamics in the embryo becomes tremendously difficult when cell trajectories cross in space and time and tissue density obscure individual cell borders. Here, we used the chick neural crest (NC as a model to test multicolor cell labeling and multispectral confocal imaging strategies to overcome these roadblocks. Results We found that multicolor nuclear cell labeling and multispectral imaging led to improved resolution of in vivo NC cell identification by providing a unique spectral identity for each cell. NC cell spectral identity allowed for more accurate cell tracking and was consistent during short term time-lapse imaging sessions. Computer model simulations predicted significantly better object counting for increasing cell densities in 3-color compared to 1-color nuclear cell labeling. To better resolve cell contacts, we show that a combination of 2-color membrane and 1-color nuclear cell labeling dramatically improved the semi-automated analysis of NC cell interactions, yet preserved the ability to track cell movements. We also found channel versus lambda scanning of multicolor labeled embryos significantly reduced the time and effort of image acquisition and analysis of large 3D volume data sets. Conclusions Our results reveal that multicolor cell labeling and multispectral imaging provide a cellular fingerprint that may uniquely determine a cell's position within the embryo. Together, these methods offer a spectral toolbox to resolve in vivo cell dynamics in unprecedented detail.

Interaction of fast and slow dynamics in endocrine control systems with an application to β-cell dynamics.

Science.gov (United States)

Wang, Yi-Fang; Khan, Michael; van den Berg, Hugo A

2012-01-01

Endocrine dynamics spans a wide range of time scales, from rapid responses to physiological challenges to with slow responses that adapt the system to the demands placed on it. We outline a non-linear averaging procedure to extract the slower dynamics in a way that accounts properly for the non-linear dynamics of the faster time scale and is applicable to a hierarchy of more than two time scales, although we restrict our discussion to two scales for the sake of clarity. The procedure is exact if the slow time scale is infinitely slow (the dimensionless ε-quantity is the period of the fast time scale fluctuation times an upper bound to the slow time scale rate of change). However, even for an imperfect separation of time scales we find that this construction provides an excellent approximation for the slow-time dynamics at considerably reduced computational cost. Besides the computation advantage, the averaged equation provided a qualitative insight into the interaction of the time scales. We demonstrate the procedure and its advantages by applying the theory to the model described by Tolić et al. [I.M. Tolić, E. Mosekilde, J. Sturis, Modeling the insulin-glucose feedback system: the significance of pulsatile insulin secretion, J. Theor. Biol. 207 (2000) 361-375.] for ultradian dynamics of the glucose-insulin homeostasis feedback system, extended to include β-cell dynamics. We find that the dynamics of the β-cell mass are dependent not only on the glycemic load (amount of glucose administered to the system), but also on the way this load is applied (i.e. three meals daily versus constant infusion), effects that are lost in the inappropriate methods used by the earlier authors. Furthermore, we find that the loss of the protection against apoptosis conferred by insulin that occurs at elevated levels of insulin has a functional role in keeping the β-cell mass in check without compromising regulatory function. We also find that replenishment of β-cells from a

Fundamental characteristics and simplified evaluation method of dynamic earth pressure

International Nuclear Information System (INIS)

Nukui, Y.; Inagaki, Y.; Ohmiya, Y.

1989-01-01

In Japan, a method is commonly used in the evaluation of dynamic earth pressure acting on the underground walls of a deeply embedded nuclear reactor building. However, since this method was developed on the basis of the limit state of soil supported by retaining walls, the behavior of dynamic earth pressure acting on the embedded part of a nuclear reactor building may differ from the estimated by this method. This paper examines the fundamental characteristics of dynamic earth pressure through dynamic soil-structure interaction analysis. A simplified method to evaluate dynamic earth pressure for the design of underground walls of a nuclear reactor building is described. The dynamic earth pressure is fluctuating earth pressure during earthquake

Dynamic multiprotein assemblies shape the spatial structure of cell signaling.

Science.gov (United States)

Nussinov, Ruth; Jang, Hyunbum

2014-01-01

Cell signaling underlies critical cellular decisions. Coordination, efficiency as well as fail-safe mechanisms are key elements. How the cell ensures that these hallmarks are at play are important questions. Cell signaling is often viewed as taking place through discrete and cross-talking pathways; oftentimes these are modularized to emphasize distinct functions. While simple, convenient and clear, such models largely neglect the spatial structure of cell signaling; they also convey inter-modular (or inter-protein) spatial separation that may not exist. Here our thesis is that cell signaling is shaped by a network of multiprotein assemblies. While pre-organized, the assemblies and network are loose and dynamic. They contain transiently-associated multiprotein complexes which are often mediated by scaffolding proteins. They are also typically anchored in the membrane, and their continuum may span the cell. IQGAP1 scaffolding protein which binds proteins including Raf, calmodulin, Mek, Erk, actin, and tens more, with actin shaping B-cell (and likely other) membrane-anchored nanoclusters and allosterically polymerizing in dynamic cytoskeleton formation, and Raf anchoring in the membrane along with Ras, provides a striking example. The multivalent network of dynamic proteins and lipids, with specific interactions forming and breaking, can be viewed as endowing gel-like properties. Collectively, this reasons that efficient, productive and reliable cell signaling takes place primarily through transient, preorganized and cooperative protein-protein interactions spanning the cell rather than stochastic, diffusion-controlled processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of diel patterns of relative changes in cell turgor of tomato plants using leaf patch clamp pressure probes

NARCIS (Netherlands)

Lee, K.M.; Driever, S.M.; Heuvelink, E.; Rüger, S.; Zimmermann, U.; Gelder, de A.; Marcelis, L.F.M.

2012-01-01

Relative changes in cell turgor of leaves of well-watered tomato plants were evaluated using the leaf patch clamp pressure probe (LPCP) under dynamic greenhouse climate conditions. Leaf patch clamp pressure changes, a measure for relative changes in cell turgor, were monitored at three different

Dynamic MR imaging of pancreatic cancer

International Nuclear Information System (INIS)

Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo

1994-01-01

Dynamic MRI was performed on 21 patients with pancreatic duct cell carcinoma. Turbo-FLASH or FLASH3D was performed immediately following rapid bolus injection of gadopentetate dimeglumine, and these FLASH images and conventional spin echo images were evaluated about detectability of the lesion. All images were classified into three groups of detectability of the lesion ; good, fair, and poor. On T 1 weighted image, 23% of cases were 'good' and 48% were evaluated as 'fair'. On the other hand, on dynamic MRI, 62% of cases were 'good' and 33% of cases were evaluated as 'fair'. Both T 2 weighted image and enhanced T 1 weighted image were not useful for depiction of the lesion. Direct comparison between T 1 weighted image and dynamic MRI was also done. In 55% of cases, dynamic MRI was superior to T 1 weighted image and in 40% of cases, dynamic MRI was equal to T 1 weighted image. Thus, dynamic MRI was superior to conventional spin echo images for detection of duct cell carcinoma. In 17 patients of duct cell carcinoma who underwent FLASH3D, contrast/noise ratio (CNR) was calculated before and after injection of gadopentetate dimeglumine. The absolute value of CNR became significantly larger by injection of contrast material. In nine resectable pancreatic carcinomas, two cases of INF α and two cases of medullary type were well depicted. It was concluded that dynamic MRI was useful for evaluation of pancreatic carcinoma. (author)

Pea border cell maturation and release involve complex cell wall structural dynamics

DEFF Research Database (Denmark)

Mravec, Jozef; Guo, Xiaoyuan; Hansen, Aleksander Riise

2017-01-01

The adhesion of plant cells is vital for support and protection of the plant body and is maintained by a variety of molecular associations between cell wall components. In some specialized cases though, plant cells are programmed to detach and root cap-derived border cells are examples of this....... Border cells (in some species known as border-like cells) provide an expendable barrier between roots and the environment. Their maturation and release is an important but poorly characterized cell separation event. To gain a deeper insight into the complex cellular dynamics underlying this process, we...... undertook a systematic, detailed analysis of pea (Pisum sativum) root tip cell walls. Our study included immuno-carbohydrate microarray profiling, monosaccharide composition determination, Fourier-transformed infrared microspectroscopy (FT-IR), quantitative RT-PCR of cell wall biosynthetic genes, analysis...

Quantitative analysis of dynamic adhesion properties in human hepatocellular carcinoma cells with fullerenol.

Science.gov (United States)

Liu, Yang; Wang, Zuobin; Wang, Xinyue; Huang, Yanhong

2015-12-01

In this study, the effect of fullerenol (C60(OH)24) on the cellular dynamic biomechanical behaviors of living human hepatocellular carcinoma (SMCC-7721) cancer cells were investigated by atomic force microscope (AFM) nanoindentation. As an important biomarker of cellular information, the cell adhesion is essential to maintain proper functioning as well as links with the pathogenesis and canceration. Nonetheless, it is challenging to properly evaluate the complex adhesion properties as all the biomechanical parameters interfere with each other. To investigate the dynamic adhesion changes, especially in the case of the fullerenol treatment, the detachment force and work, adhesion events, and membrane tether properties were measured and analyzed systematically with the proposed quantitative method. The statistical analyses suggest that, under the same operating parameters of AFM, the dependence of adhesion energy on the tip-cell contact area is weakened after the fullerenol treatment and the probability of adhesion decreases significantly from 30.6% to 4.2%. In addition, the disruption of the cytoskeleton resulted in a 34% decrease of the average membrane tether force and a 21% increase of the average tether length. Benefiting from the quantitative method, this work contributes to revealing the effects of fullerenol on the cellular biomechanical properties of the living SMCC-7721 cells in a precise and rigorous way and additionally is further instructive to interpret the interaction mechanism of other potential nanomedicines with living cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Swimming motility plays a key role in the stochastic dynamics of cell clumping

Science.gov (United States)

Qi, Xianghong; Nellas, Ricky B.; Byrn, Matthew W.; Russell, Matthew H.; Bible, Amber N.; Alexandre, Gladys; Shen, Tongye

2013-04-01

Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell-cell or cell-surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell-cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense.

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

Directory of Open Access Journals (Sweden)

Alexander Lorz

2017-08-01

Full Text Available Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug’s effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large �

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

Science.gov (United States)

Lorz, Alexander; Botesteanu, Dana-Adriana; Levy, Doron

2017-01-01

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug’s effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large “switch-on/switch-off” increase in the average

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

KAUST Repository

Lorz, Alexander; Botesteanu, Dana-Adriana; Levy, Doron

2017-01-01

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug's effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large “switch-on/ switch-off” increase in the average

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

KAUST Repository

Lorz, Alexander

2017-08-30

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug\\'s effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large “switch-on/ switch-off” increase in the average

Fuel cell/back-up battery hybrid energy conversion systems: Dynamic modeling and harmonic considerations

International Nuclear Information System (INIS)

Fathabadi, Hassan

2015-01-01

Highlights: • Novel technique to completely eliminate the harmful harmonics of fuel cell system. • Presenting a novel high accurate detailed electrochemical dynamic model of fuel cells. • Back-up battery system to compensate the slow dynamic response of fuel cell system. • Exact analysis of real electrochemical reactions occurring inside fuel cells. - Abstract: In this study, a novel dynamic model of fuel cells is presented. High accurate static and dynamic responses of the proposed model are experimentally validated by comparing simulated results with real experimental data. The obtained model together with theoretical results shows that a fuel cell or a fuel cell stack has very slow dynamic response, so that, it cannot adapt itself to the fast variations in load demand. It is shown that for adapting well a fuel cell stack to the load demand, the stack should be equipped with a proposed back-up battery system which compensates the slow dynamic response of the stack by providing a bidirectional path to transmit/absorb the extra instant power. It is proved that the conventional switching waveforms used in the converters of the stacks and back-up systems produce an enormous amount of harmful harmonics. Then, a novel technique is proposed to completely eliminate main harmful harmonics. It is worthwhile to note that all the other techniques only reduce the harmful harmonics. Simulated results verify that the back-up battery system together with applying the proposed technique provide a fast dynamic response for the fuel cell/back-up battery system, and also completely eliminate the main harmful harmonics

Static harmonization of dynamically harmonized Fourier transform ion cyclotron resonance cell.

Science.gov (United States)

Zhdanova, Ekaterina; Kostyukevich, Yury; Nikolaev, Eugene

2017-08-01

Static harmonization in the Fourier transform ion cyclotron resonance cell improves the resolving power of the cell and prevents dephasing of the ion cloud in the case of any trajectory of the charged particle, not necessarily axisymmetric cyclotron (as opposed to dynamic harmonization). We reveal that the Fourier transform ion cyclotron resonance cell with dynamic harmonization (paracell) is proved to be statically harmonized. The volume of the statically harmonized potential distribution increases with an increase in the number of trap segments.

The Dynamical Mechanisms of the Cell Cycle Size Checkpoint

International Nuclear Information System (INIS)

Feng Shi-Fu; Yang Ling; Yan Jie; Liu Zeng-Rong

2012-01-01

Cell division must be tightly coupled to cell growth in order to maintain cell size, whereas the mechanisms of how initialization of mitosis is regulated by cell size remain to be elucidated. We develop a mathematical model of the cell cycle, which incorporates cell growth to investigate the dynamical properties of the size checkpoint in embryos of Xenopus laevis. We show that the size checkpoint is naturally raised from a saddle-node bifurcation, and in a mutant case, the cell loses its size control ability due to the loss of this saddle-node point

Comparison between steady-state and dynamic I-V measurements from a single-cell thermionic fuel element

International Nuclear Information System (INIS)

Wernsman, Bernard

1997-01-01

A comparison between steady-state and dynamic I-V measurements from a single-cell thermionic fuel element (TFE) is made. The single-cell TFE used in this study is the prototype for the 40 kW e space nuclear power system that is similar to the 6 kW e TOPAZ-II. The steady-state I-V measurements influence the emitter temperature due to electron cooling. Therefore, to eliminate the steady-state I-V measurement influence on the TFE and provide a better understanding of the behavior of the thermionic energy converter and TFE characteristics, dynamic I-V measurements are made. The dynamic I-V measurements are made at various input power levels, cesium pressures, collector temperatures, and steady-state current levels. From these measurements, it is shown that the dynamic I-V's do not change the TFE characteristics at a given operating point. Also, the evaluation of the collector work function from the dynamic I-V measurements shows that the collector optimization is not due to a minimum in the collector work function but due to an emission optimization. Since the dynamic I-V measurements do not influence the TFE characteristics, it is believed that these measurements can be done at a system level to understand the influence of TFE placement in the reactor as a function of the core thermal distribution

Cell fate reprogramming by control of intracellular network dynamics

Science.gov (United States)

Zanudo, Jorge G. T.; Albert, Reka

Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Although the topic of controlling the dynamics of a system has a long history in control theory, most of this work is not directly applicable to intracellular networks. Here we present a network control method that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our control method takes advantage of certain function-dependent network components and their relation to steady states in order to identify control targets, which are guaranteed to drive any initial state to the target state with 100% effectiveness and need to be applied only transiently for the system to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. This work was supported by NSF Grant PHY 1205840.

More or less-On the influence of labelling strategies to infer cell population dynamics.

Science.gov (United States)

Gabel, Michael; Regoes, Roland R; Graw, Frederik

2017-01-01

The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.

More or less-On the influence of labelling strategies to infer cell population dynamics.

Directory of Open Access Journals (Sweden)

Michael Gabel

Full Text Available The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.

Stem Cell Plasticity and Niche Dynamics in Cancer Progression.

Science.gov (United States)

Picco, Noemi; Gatenby, Robert A; Anderson, Alexander R A

2017-03-01

Cancer stem cells (CSCs) have been hypothesized to initiate and drive tumor growth and recurrence due to their self-renewal ability. If correct, this hypothesis implies that successful therapy must focus primarily on eradication of this CSC fraction. However, recent evidence suggests stemness is niche dependent and may represent one of many phenotypic states that can be accessed by many cancer genotypes when presented with specific environmental cues. A better understanding of the relationship of stemness to niche-related phenotypic plasticity could lead to alternative treatment strategies. Here, we investigate the role of environmental context in the expression of stem-like cell properties through in-silico simulation of ductal carcinoma. We develop a two-dimensional hybrid discrete-continuum cellular automata model to describe the single-cell scale dynamics of multicellular tissue formation. Through a suite of simulations, we investigate interactions between a phenotypically heterogeneous cancer cell population and a dynamic environment. We generate homeostatic ductal structures that consist of a mixture of stem and differentiated cells governed by both intracellular and environmental dynamics. We demonstrate that a wide spectrum of tumor-like histologies can result from these structures by varying microenvironmental parameters. Niche driven phenotypic plasticity offers a simple first-principle explanation for the diverse ductal structures observed in histological sections from breast cancer. Conventional models of carcinogenesis largely focus on mutational events. We demonstrate that variations in the environmental niche can produce intraductal cancers independent of genetic changes in the resident cells. Therapies targeting the microenvironmental niche may offer an alternative cancer prevention strategy.

Dynamic gene expression for metabolic engineering of mammalian cells in culture.

Science.gov (United States)

Le, Huong; Vishwanathan, Nandita; Kantardjieff, Anne; Doo, Inseok; Srienc, Michael; Zheng, Xiaolu; Somia, Nikunj; Hu, Wei-Shou

2013-11-01

Recombinant mammalian cells are the major hosts for the production of protein therapeutics. In addition to high expression of the product gene, a hyper-producer must also harbor superior phenotypic traits related to metabolism, protein secretion, and growth control. Introduction of genes endowing the relevant hyper-productivity traits is a strategy frequently used to enhance the productivity. Most of such cell engineering efforts have been performed using constitutive expression systems. However, cells respond to various environmental cues and cellular events dynamically according to cellular needs. The use of inducible systems allows for time dependent expression, but requires external manipulation. Ideally, a transgene's expression should be synchronous to the host cell's own rhythm, and at levels appropriate for the objective. To that end, we identified genes with different expression dynamics and intensity ranges using pooled transcriptome data. Their promoters may be used to drive the expression of the transgenes following the desired dynamics. We isolated the promoter of the Thioredoxin-interacting protein (Txnip) gene and demonstrated its capability to drive transgene expression in concert with cell growth. We further employed this Chinese hamster promoter to engineer dynamic expression of the mouse GLUT5 fructose transporter in Chinese hamster ovary (CHO) cells, enabling them to utilize sugar according to cellular needs rather than in excess as typically seen in culture. Thus, less lactate was produced, resulting in a better growth rate, prolonged culture duration, and higher product titer. This approach illustrates a novel concept in metabolic engineering which can potentially be used to achieve dynamic control of cellular behaviors for enhanced process characteristics. © 2013 Published by Elsevier Inc.

Feasibility of solid oxide fuel cell dynamic hydrogen coproduction to meet building demand

Science.gov (United States)

Shaffer, Brendan; Brouwer, Jacob

2014-02-01

A dynamic internal reforming-solid oxide fuel cell system model is developed and used to simulate the coproduction of electricity and hydrogen while meeting the measured dynamic load of a typical southern California commercial building. The simulated direct internal reforming-solid oxide fuel cell (DIR-SOFC) system is controlled to become an electrical load following device that well follows the measured building load data (3-s resolution). The feasibility of the DIR-SOFC system to meet the dynamic building demand while co-producing hydrogen is demonstrated. The resulting thermal responses of the system to the electrical load dynamics as well as those dynamics associated with the filling of a hydrogen collection tank are investigated. The DIR-SOFC system model also allows for resolution of the fuel cell species and temperature distributions during these dynamics since thermal gradients are a concern for DIR-SOFC.

Dynamical mechanisms for sensitive response of aperiodic firing cells to external stimulation

International Nuclear Information System (INIS)

Xie Yong; Xu Jianxue; Hu Sanjue; Kang Yanmei; Yang Hongjun; Duan Yubin

2004-01-01

An interesting phenomenon that aperiodic firing neurons have a higher sensitivity to drugs than periodic firing neurons have been reported for the chronically compressed dorsal root ganglion neurons in rats. In this study, the dynamical mechanisms for such a phenomenon are uncovered from the viewpoint of dynamical systems theory. We use the Rose-Hindmarsh neuron model to illustrate our opinions. Periodic orbit theory is introduced to characterize the dynamical behavior of aperiodic firing neurons. It is considered that bifurcations, crises and sensitive dependence of chaotic motions on control parameters can be the underlying mechanisms. And then, a similar analysis is applied to the modified Chay model describing the firing behavior of pancreatic beta cells. The same dynamical mechanisms can be obtained underlying that aperiodic firing cells are more sensitive to external stimulation than periodic firing ones. As a result, we conjecture that sensitive response of aperiodic firing cells to external stimulation is a universal property of excitable cells

Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells.

Science.gov (United States)

Katri, Patricia; Ruan, Shigui

2004-11-01

Stilianakis and Seydel (Bull. Math. Biol., 1999) proposed an ODE model that describes the T-cell dynamics of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). Their model consists of four components: uninfected healthy CD4+ T-cells, latently infected CD4+ T-cells, actively infected CD4+ T-cells, and ATL cells. Mathematical analysis that completely determines the global dynamics of this model has been done by Wang et al. (Math. Biosci., 2002). In this note, we first modify the parameters of the model to distinguish between contact and infectivity rates. Then we introduce a discrete time delay to the model to describe the time between emission of contagious particles by active CD4+ T-cells and infection of pure cells. Using the results in Culshaw and Ruan (Math. Biosci., 2000) in the analysis of time delay with respect to cell-free viral spread of HIV, we study the effect of time delay on the stability of the endemically infected equilibrium. Numerical simulations are presented to illustrate the results.

Mitogen-activated protein kinase (MAPK) dynamics determine cell fate in the yeast mating response.

Science.gov (United States)

Li, Yang; Roberts, Julie; AkhavanAghdam, Zohreh; Hao, Nan

2017-12-15

In the yeast Saccharomyces cerevisiae , the exposure to mating pheromone activates a prototypic mitogen-activated protein kinase (MAPK) cascade and triggers a dose-dependent differentiation response. Whereas a high pheromone dose induces growth arrest and formation of a shmoo-like morphology in yeast cells, lower pheromone doses elicit elongated cell growth. Previous population-level analysis has revealed that the MAPK Fus3 plays an important role in mediating this differentiation switch. To further investigate how Fus3 controls the fate decision process at the single-cell level, we developed a specific translocation-based reporter for monitoring Fus3 activity in individual live cells. Using this reporter, we observed strikingly different dynamic patterns of Fus3 activation in single cells differentiated into distinct fates. Cells committed to growth arrest and shmoo formation exhibited sustained Fus3 activation. In contrast, most cells undergoing elongated growth showed either a delayed gradual increase or pulsatile dynamics of Fus3 activity. Furthermore, we found that chemically perturbing Fus3 dynamics with a specific inhibitor could effectively redirect the mating differentiation, confirming the causative role of Fus3 dynamics in driving cell fate decisions. MAPKs mediate proliferation and differentiation signals in mammals and are therapeutic targets in many cancers. Our results highlight the importance of MAPK dynamics in regulating single-cell responses and open up the possibility that MAPK signaling dynamics could be a pharmacological target in therapeutic interventions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

In vivo microvascular imaging of cutaneous actinic keratosis, Bowen's disease and squamous cell carcinoma using dynamic optical coherence tomography

DEFF Research Database (Denmark)

Themstrup, L; Pellacani, G; Welzel, J

2017-01-01

BACKGROUND: A clear distinction between actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a novel angiographic variant of OCT that allows for non...

Dynamic modeling and experimental investigation of a high temperature PEM fuel cell stack

DEFF Research Database (Denmark)

Nguyen, Gia; Sahlin, Simon Lennart; Andreasen, Søren Juhl

2016-01-01

High temperature polymer fuel cells operating at 100 to 200◦C require simple fuel processing and produce high quality heat that can integrate well with domestic heating systems. Because the transportation of hydrogen is challenging, an alternative option is to reform natural gas on site....... This article presents the development of a dynamic model and the comparison with experimental data from a high temperature proton exchange membrane fuel cell stack operating on hydrogen with carbon monoxide concentrations up to 0.8%, and temperatures from 155 to 175◦C. The dynamic response of the fuel cell...... is investigated with simulated reformate gas. The dynamic response of the fuel cell stack was compared with a step change in current from 0.09 to 0.18 and back to 0.09 A/cm2 . This article shows that the dynamic model calculates the voltage at steady state well. The dynamic response for a change in current shows...

T-cell dynamics in healthy and HIV-infected individuals

NARCIS (Netherlands)

Vrisekoop, N.

2007-01-01

This thesis focuses on T-cell dynamics in healthy and both treated and untreated HIV-infected individuals. Although the progressive decline in CD4+ T-cell numbers is the hallmark of HIV infection, the mechanisms behind this depletion remain controversial. Currently the most prevailing ideas include

Mutation dynamics and fitness effects followed in single cells.

Science.gov (United States)

Robert, Lydia; Ollion, Jean; Robert, Jerome; Song, Xiaohu; Matic, Ivan; Elez, Marina

2018-03-16

Mutations have been investigated for more than a century but remain difficult to observe directly in single cells, which limits the characterization of their dynamics and fitness effects. By combining microfluidics, time-lapse imaging, and a fluorescent tag of the mismatch repair system in Escherichia coli , we visualized the emergence of mutations in single cells, revealing Poissonian dynamics. Concomitantly, we tracked the growth and life span of single cells, accumulating ~20,000 mutations genome-wide over hundreds of generations. This analysis revealed that 1% of mutations were lethal; nonlethal mutations displayed a heavy-tailed distribution of fitness effects and were dominated by quasi-neutral mutations with an average cost of 0.3%. Our approach has enabled the investigation of single-cell individuality in mutation rate, mutation fitness costs, and mutation interactions. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Hardware-in-the-loop vehicle system including dynamic fuel cell model

Energy Technology Data Exchange (ETDEWEB)

Lemes, Z.; Lenhart, T.; Braun, M.; Maencher, H. [MAGNUM Automatisierungstechnik GmbH, Darmstadt (Germany)

2005-07-01

In order to reduce costs and accelerate the development of fuel cells and systems the usage of hardware-in-the-loop (HIL) testing and dynamic modelling opens new possibilities. The dynamic model of a proton exchange membrane fuel cell (PEMFC) together with a vehicle model is used to carry out a comprehensive system investigation, which allows designing and optimising the behaviour of the components and the entire fuel cell system. The set-up of a HIL system enables real time interaction between the selected hardware and the model. (orig.)

Cellular population dynamics control the robustness of the stem cell niche

Directory of Open Access Journals (Sweden)

Adam L. MacLean

2015-11-01

Full Text Available Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain ‘stemness’ through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell–niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell–cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche – and hence of the stem cell pool in the niche – depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.

Assessing the Nano-Dynamics of the Cell Surface

Energy Technology Data Exchange (ETDEWEB)

Bae, Chil Man [Dept. of Physiology and Biophysics, State University of New York, Buffalo (United States); Park, Ik Keun [Mechanical Engineering, Seoul National University of Technology, Seoul (Korea, Republic of); Bulter, Peter J. [Dept. of Bioengineering, The Pennsylvania State University, University Park (United States)

2012-06-15

It is important to know the mechanism of cell membrane fluctuation because it can be readout for the nanomechanical interaction between cytoskeleton and plasma membrane. Traditional techniques, however, have drawbacks such as probe contact with the cell surface, complicate analysis, and limit spatial and temporal resolution. In this study, we developed a new system for non-contact measurement of nano-scale localized-cell surface dynamics using modified-scanning ion-conductance microscopy. With 2 nm resolution, we determined that endothelial cells have local membrane fluctuations of -20 nm, actin depolymerization causes increase in fluctuation amplitude, and ATP depletion abolishes all membrane fluctuations.

Swimming motility plays a key role in the stochastic dynamics of cell clumping

International Nuclear Information System (INIS)

Qi, Xianghong; Nellas, Ricky B; Byrn, Matthew W; Russell, Matthew H; Bible, Amber N; Alexandre, Gladys; Shen, Tongye

2013-01-01

Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell–cell or cell–surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell–cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense. (paper)

MEMS-based dynamic cell-to-cell culture platforms using electrochemical surface modifications

International Nuclear Information System (INIS)

Chang, Jiyoung; Lin, Liwei; Yoon, Sang-Hee; Mofrad, Mohammad R K

2011-01-01

MEMS-based biological platforms with the capability of both spatial placements and time releases of living cells for cell-to-cell culture experiments have been designed and demonstrated utilizing electrochemical surface modification effects. The spatial placement is accomplished by electrochemical surface modification of substrate surfaces to be either adhesive or non-adhesive for living cells. The time control is achieved by the electrical activation of the selective indium tin oxide co-culture electrode to allow the migration of living cells onto the electrode to start the cell-to-cell culture studies. Prototype devices have a three-electrode design with an electrode size of 50 × 50 µm 2 and the separation gaps of 2 µm between them. An electrical voltage of −1.5 V has been used to activate the electrodes independently and sequentially to demonstrate the dynamic cell-to-cell culture experiments of NIH 3T3 fibroblast and Madin Darby canine kidney cells. As such, this MEMS platform could be a basic yet versatile tool to characterize transient cell-to-cell interactions

Arabidopsis Regenerating Protoplast: A Powerful Model System for Combining the Proteomics of Cell Wall Proteins and the Visualization of Cell Wall Dynamics

Science.gov (United States)

Yokoyama, Ryusuke; Kuki, Hiroaki; Kuroha, Takeshi; Nishitani, Kazuhiko

2016-01-01

The development of a range of sub-proteomic approaches to the plant cell wall has identified many of the cell wall proteins. However, it remains difficult to elucidate the precise biological role of each protein and the cell wall dynamics driven by their actions. The plant protoplast provides an excellent means not only for characterizing cell wall proteins, but also for visualizing the dynamics of cell wall regeneration, during which cell wall proteins are secreted. It therefore offers a unique opportunity to investigate the de novo construction process of the cell wall. This review deals with sub-proteomic approaches to the plant cell wall through the use of protoplasts, a methodology that will provide the basis for further exploration of cell wall proteins and cell wall dynamics. PMID:28248244

Temporal dynamics of distinct CA1 cell populations during unconscious state induced by ketamine.

Directory of Open Access Journals (Sweden)

Hui Kuang

2010-12-01

Full Text Available Ketamine is a widely used dissociative anesthetic which can induce some psychotic-like symptoms and memory deficits in some patients during the post-operative period. To understand its effects on neural population dynamics in the brain, we employed large-scale in vivo ensemble recording techniques to monitor the activity patterns of simultaneously recorded hippocampal CA1 pyramidal cells and various interneurons during several conscious and unconscious states such as awake rest, running, slow wave sleep, and ketamine-induced anesthesia. Our analyses reveal that ketamine induces distinct oscillatory dynamics not only in pyramidal cells but also in at least seven different types of CA1 interneurons including putative basket cells, chandelier cells, bistratified cells, and O-LM cells. These emergent unique oscillatory dynamics may very well reflect the intrinsic temporal relationships within the CA1 circuit. It is conceivable that systematic characterization of network dynamics may eventually lead to better understanding of how ketamine induces unconsciousness and consequently alters the conscious mind.

Exploring Neural Cell Dynamics with Digital Holographic Microscopy

KAUST Repository

Marquet, Pierre; Jourdain, Pascal; Boss, Daniel; Depeursinge, Christian D.; Magistretti, Pierre J.

2013-01-01

In this talk, I will present how digital holographic microscopy, as a powerful quantitative phase technique, can non-invasively measure cell dynamics and especially resolve local neuronal network activity through simultaneous multiple site optical recording.

Exploring Neural Cell Dynamics with Digital Holographic Microscopy

KAUST Repository

Marquet, Pierre

2013-04-21

In this talk, I will present how digital holographic microscopy, as a powerful quantitative phase technique, can non-invasively measure cell dynamics and especially resolve local neuronal network activity through simultaneous multiple site optical recording.

Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

Science.gov (United States)

Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

2015-03-01

Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

A Scalable Distribution Network Risk Evaluation Framework via Symbolic Dynamics

Science.gov (United States)

Yuan, Kai; Liu, Jian; Liu, Kaipei; Tan, Tianyuan

2015-01-01

Background Evaluations of electric power distribution network risks must address the problems of incomplete information and changing dynamics. A risk evaluation framework should be adaptable to a specific situation and an evolving understanding of risk. Methods This study investigates the use of symbolic dynamics to abstract raw data. After introducing symbolic dynamics operators, Kolmogorov-Sinai entropy and Kullback-Leibler relative entropy are used to quantitatively evaluate relationships between risk sub-factors and main factors. For layered risk indicators, where the factors are categorized into four main factors – device, structure, load and special operation – a merging algorithm using operators to calculate the risk factors is discussed. Finally, an example from the Sanya Power Company is given to demonstrate the feasibility of the proposed method. Conclusion Distribution networks are exposed and can be affected by many things. The topology and the operating mode of a distribution network are dynamic, so the faults and their consequences are probabilistic. PMID:25789859

Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis.

Directory of Open Access Journals (Sweden)

Mayssa Nassour

Full Text Available Morphogenesis results from the coordination of distinct cell signaling pathways controlling migration, differentiation, apoptosis, and proliferation, along stem/progenitor cell dynamics. To decipher this puzzle, we focused on epithelial-mesenchymal transition (EMT "master genes". EMT has emerged as a unifying concept, involving cell-cell adhesion, migration and apoptotic pathways. EMT also appears to mingle with stemness. However, very little is known on the physiological role and relevance of EMT master-genes. We addressed this question during mammary morphogenesis. Recently, a link between Slug/Snai2 and stemness has been described in mammary epithelial cells, but EMT master genes actual localization, role and targets during mammary gland morphogenesis are not known and we focused on this basic question.Using a Slug-lacZ transgenic model and immunolocalization, we located Slug in a distinct subpopulation covering about 10-20% basal cap and duct cells, mostly cycling cells, coexpressed with basal markers P-cadherin, CK5 and CD49f. During puberty, Slug-deficient mammary epithelium exhibited a delayed development after transplantation, contained less cycling cells, and overexpressed CK8/18, ER, GATA3 and BMI1 genes, linked to luminal lineage. Other EMT master genes were overexpressed, suggesting compensation mechanisms. Gain/loss-of-function in vitro experiments confirmed Slug control of mammary epithelial cell luminal differentiation and proliferation. In addition, they showed that Slug enhances specifically clonal mammosphere emergence and growth, cell motility, and represses apoptosis. Strikingly, Slug-deprived mammary epithelial cells lost their potential to generate secondary clonal mammospheres.We conclude that Slug pathway controls the growth dynamics of a subpopulation of cycling progenitor basal cells during mammary morphogenesis. Overall, our data better define a key mechanism coordinating cell lineage dynamics and morphogenesis, and

Evaluation of Dynamic Methods for Earthwork Assessment

Directory of Open Access Journals (Sweden)

Vlček Jozef

2015-05-01

Full Text Available Rapid development of road construction imposes requests on fast and quality methods for earthwork quality evaluation. Dynamic methods are now adopted in numerous civil engineering sections. Especially evaluation of the earthwork quality can be sped up using dynamic equipment. This paper presents the results of the parallel measurements of chosen devices for determining the level of compaction of soils. Measurements were used to develop the correlations between values obtained from various apparatuses. Correlations show that examined apparatuses are suitable for examination of compaction level of fine-grained soils with consideration of boundary conditions of used equipment. Presented methods are quick and results can be obtained immediately after measurement, and they are thus suitable in cases when construction works have to be performed in a short period of time.

Dynamic heterogeneity and DNA methylation in embryonic stem cells.

KAUST Repository

Singer, Zakary S

2014-07-01

Cell populations can be strikingly heterogeneous, composed of multiple cellular states, each exhibiting stochastic noise in its gene expression. A major challenge is to disentangle these two types of variability and to understand the dynamic processes and mechanisms that control them. Embryonic stem cells (ESCs) provide an ideal model system to address this issue because they exhibit heterogeneous and dynamic expression of functionally important regulatory factors. We analyzed gene expression in individual ESCs using single-molecule RNA-FISH and quantitative time-lapse movies. These data discriminated stochastic switching between two coherent (correlated) gene expression states and burst-like transcriptional noise. We further showed that the "2i" signaling pathway inhibitors modulate both types of variation. Finally, we found that DNA methylation plays a key role in maintaining these metastable states. Together, these results show how ESC gene expression states and dynamics arise from a combination of intrinsic noise, coherent cellular states, and epigenetic regulation.

Image dynamic range test and evaluation of Gaofen-2 dual cameras

Science.gov (United States)

Zhang, Zhenhua; Gan, Fuping; Wei, Dandan

2015-12-01

In order to fully understand the dynamic range of Gaofen-2 satellite data and support the data processing, application and next satellites development, in this article, we evaluated the dynamic range by calculating some statistics such as maximum ,minimum, average and stand deviation of four images obtained at the same time by Gaofen-2 dual cameras in Beijing area; then the maximum ,minimum, average and stand deviation of each longitudinal overlap of PMS1,PMS2 were calculated respectively for the evaluation of each camera's dynamic range consistency; and these four statistics of each latitudinal overlap of PMS1,PMS2 were calculated respectively for the evaluation of the dynamic range consistency between PMS1 and PMS2 at last. The results suggest that there is a wide dynamic range of DN value in the image obtained by PMS1 and PMS2 which contains rich information of ground objects; in general, the consistency of dynamic range between the single camera images is in close agreement, but also a little difference, so do the dual cameras. The consistency of dynamic range between the single camera images is better than the dual cameras'.

Sustainable Deforestation Evaluation Model and System Dynamics Analysis

Science.gov (United States)

Feng, Huirong; Lim, C. W.; Chen, Liqun; Zhou, Xinnian; Zhou, Chengjun; Lin, Yi

2014-01-01

The current study used the improved fuzzy analytic hierarchy process to construct a sustainable deforestation development evaluation system and evaluation model, which has refined a diversified system to evaluate the theory of sustainable deforestation development. Leveraging the visual image of the system dynamics causal and power flow diagram, we illustrated here that sustainable forestry development is a complex system that encompasses the interaction and dynamic development of ecology, economy, and society and has reflected the time dynamic effect of sustainable forestry development from the three combined effects. We compared experimental programs to prove the direct and indirect impacts of the ecological, economic, and social effects of the corresponding deforest techniques and fully reflected the importance of developing scientific and rational ecological harvesting and transportation technologies. Experimental and theoretical results illustrated that light cableway skidding is an ecoskidding method that is beneficial for the sustainable development of resources, the environment, the economy, and society and forecasted the broad potential applications of light cableway skidding in timber production technology. Furthermore, we discussed the sustainable development countermeasures of forest ecosystems from the aspects of causality, interaction, and harmony. PMID:25254225

Sustainable deforestation evaluation model and system dynamics analysis.

Science.gov (United States)

Feng, Huirong; Lim, C W; Chen, Liqun; Zhou, Xinnian; Zhou, Chengjun; Lin, Yi

2014-01-01

The current study used the improved fuzzy analytic hierarchy process to construct a sustainable deforestation development evaluation system and evaluation model, which has refined a diversified system to evaluate the theory of sustainable deforestation development. Leveraging the visual image of the system dynamics causal and power flow diagram, we illustrated here that sustainable forestry development is a complex system that encompasses the interaction and dynamic development of ecology, economy, and society and has reflected the time dynamic effect of sustainable forestry development from the three combined effects. We compared experimental programs to prove the direct and indirect impacts of the ecological, economic, and social effects of the corresponding deforest techniques and fully reflected the importance of developing scientific and rational ecological harvesting and transportation technologies. Experimental and theoretical results illustrated that light cableway skidding is an ecoskidding method that is beneficial for the sustainable development of resources, the environment, the economy, and society and forecasted the broad potential applications of light cableway skidding in timber production technology. Furthermore, we discussed the sustainable development countermeasures of forest ecosystems from the aspects of causality, interaction, and harmony.

Sustainable Deforestation Evaluation Model and System Dynamics Analysis

Directory of Open Access Journals (Sweden)

Huirong Feng

2014-01-01

Full Text Available The current study used the improved fuzzy analytic hierarchy process to construct a sustainable deforestation development evaluation system and evaluation model, which has refined a diversified system to evaluate the theory of sustainable deforestation development. Leveraging the visual image of the system dynamics causal and power flow diagram, we illustrated here that sustainable forestry development is a complex system that encompasses the interaction and dynamic development of ecology, economy, and society and has reflected the time dynamic effect of sustainable forestry development from the three combined effects. We compared experimental programs to prove the direct and indirect impacts of the ecological, economic, and social effects of the corresponding deforest techniques and fully reflected the importance of developing scientific and rational ecological harvesting and transportation technologies. Experimental and theoretical results illustrated that light cableway skidding is an ecoskidding method that is beneficial for the sustainable development of resources, the environment, the economy, and society and forecasted the broad potential applications of light cableway skidding in timber production technology. Furthermore, we discussed the sustainable development countermeasures of forest ecosystems from the aspects of causality, interaction, and harmony.

Evaluating gambles using dynamics

Science.gov (United States)

Peters, O.; Gell-Mann, M.

2016-02-01

Gambles are random variables that model possible changes in wealth. Classic decision theory transforms money into utility through a utility function and defines the value of a gamble as the expectation value of utility changes. Utility functions aim to capture individual psychological characteristics, but their generality limits predictive power. Expectation value maximizers are defined as rational in economics, but expectation values are only meaningful in the presence of ensembles or in systems with ergodic properties, whereas decision-makers have no access to ensembles, and the variables representing wealth in the usual growth models do not have the relevant ergodic properties. Simultaneously addressing the shortcomings of utility and those of expectations, we propose to evaluate gambles by averaging wealth growth over time. No utility function is needed, but a dynamic must be specified to compute time averages. Linear and logarithmic "utility functions" appear as transformations that generate ergodic observables for purely additive and purely multiplicative dynamics, respectively. We highlight inconsistencies throughout the development of decision theory, whose correction clarifies that our perspective is legitimate. These invalidate a commonly cited argument for bounded utility functions.

Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space

Science.gov (United States)

Gmunder, F. K.; Nordau, C. G.; Tschopp, A.; Huber, B.; Cogoli, A.

1988-01-01

The prototype of a miniaturized cell cultivation instrument for animal cell culture experiments aboard Spacelab is presented (Dynamic cell culture system: DCCS). The cell chamber is completely filled and has a working volume of 200 microliters. Medium exchange is achieved with a self-powered osmotic pump (flowrate 1 microliter h-1). The reservoir volume of culture medium is 230 microliters. The system is neither mechanically stirred nor equipped with sensors. Hamster kidney (Hak) cells growing on Cytodex 3 microcarriers were used to test the biological performance of the DCCS. Growth characteristics in the DCCS, as judged by maximal cell density, glucose consumption, lactic acid secretion and pH, were similar to those in cell culture tubes.

cellGPU: Massively parallel simulations of dynamic vertex models

Science.gov (United States)

Sussman, Daniel M.

2017-10-01

Vertex models represent confluent tissue by polygonal or polyhedral tilings of space, with the individual cells interacting via force laws that depend on both the geometry of the cells and the topology of the tessellation. This dependence on the connectivity of the cellular network introduces several complications to performing molecular-dynamics-like simulations of vertex models, and in particular makes parallelizing the simulations difficult. cellGPU addresses this difficulty and lays the foundation for massively parallelized, GPU-based simulations of these models. This article discusses its implementation for a pair of two-dimensional models, and compares the typical performance that can be expected between running cellGPU entirely on the CPU versus its performance when running on a range of commercial and server-grade graphics cards. By implementing the calculation of topological changes and forces on cells in a highly parallelizable fashion, cellGPU enables researchers to simulate time- and length-scales previously inaccessible via existing single-threaded CPU implementations. Program Files doi:http://dx.doi.org/10.17632/6j2cj29t3r.1 Licensing provisions: MIT Programming language: CUDA/C++ Nature of problem: Simulations of off-lattice "vertex models" of cells, in which the interaction forces depend on both the geometry and the topology of the cellular aggregate. Solution method: Highly parallelized GPU-accelerated dynamical simulations in which the force calculations and the topological features can be handled on either the CPU or GPU. Additional comments: The code is hosted at https://gitlab.com/dmsussman/cellGPU, with documentation additionally maintained at http://dmsussman.gitlab.io/cellGPUdocumentation

Evaluating impact of market changes on increasing cell-load variation in dynamic cellular manufacturing systems using a hybrid Tabu search and simulated annealing algorithms

Directory of Open Access Journals (Sweden)

Aidin Delgoshaei

2016-06-01

Full Text Available In this paper, a new method is proposed for scheduling dynamic cellular manufacturing systems (D-CMS in the presence of uncertain product demands. The aim of this method is to control the process of trading off between in-house manufacturing and outsourcing while product demands are uncertain and can be varied from period to period. To solve the proposed problem, a hybrid Tabu Search and Simulated Annealing are developed to overcome hardness of the proposed model and then results are compared with a Branch and Bound and Simulated Annealing algorithms. A Taguchi method (L_27 orthogonal optimization is used to estimate parameters of the proposed method in order to solve experiments derived from literature. An in-depth analysis is conducted on the results in consideration of various factors. For evaluating the system imbalance in dynamic market demands, a new measuring index is developed. Our findings indicate that the uncertain condition of market demands affects the routing of product parts and may induce machine-load variations that yield to cell-load diversity. The results showed that the proposed hybrid method can provide solutions with better quality.

Non-Rigid Contour-Based Registration of Cell Nuclei in 2-D Live Cell Microscopy Images Using a Dynamic Elasticity Model.

Science.gov (United States)

Sorokin, Dmitry V; Peterlik, Igor; Tektonidis, Marco; Rohr, Karl; Matula, Pavel

2018-01-01

The analysis of the pure motion of subnuclear structures without influence of the cell nucleus motion and deformation is essential in live cell imaging. In this paper, we propose a 2-D contour-based image registration approach for compensation of nucleus motion and deformation in fluorescence microscopy time-lapse sequences. The proposed approach extends our previous approach, which uses a static elasticity model to register cell images. Compared with that scheme, the new approach employs a dynamic elasticity model for the forward simulation of nucleus motion and deformation based on the motion of its contours. The contour matching process is embedded as a constraint into the system of equations describing the elastic behavior of the nucleus. This results in better performance in terms of the registration accuracy. Our approach was successfully applied to real live cell microscopy image sequences of different types of cells including image data that was specifically designed and acquired for evaluation of cell image registration methods. An experimental comparison with the existing contour-based registration methods and an intensity-based registration method has been performed. We also studied the dependence of the results on the choice of method parameters.

Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels

Science.gov (United States)

Delorme-Walker, Violaine; Seo, Ji-Yeon; Gohla, Antje; Fowler, Bruce; Bohl, Ben; DerMardirossian, Céline

2015-01-01

Cofilin, a critical player of actin dynamics, is spatially and temporally regulated to control the direction and force of membrane extension required for cell locomotion. In carcinoma cells, although the signaling pathways regulating cofilin activity to control cell direction have been established, the molecular machinery required to generate the force of the protrusion remains unclear. We show that the cofilin phosphatase chronophin (CIN) spatiotemporally regulates cofilin activity at the cell edge to generate persistent membrane extension. We show that CIN translocates to the leading edge in a PI3-kinase–, Rac1-, and cofilin-dependent manner after EGF stimulation to activate cofilin, promotes actin free barbed end formation, accelerates actin turnover, and enhances membrane protrusion. In addition, we establish that CIN is crucial for the balance of protrusion/retraction events during cell migration. Thus, CIN coordinates the leading edge dynamics by controlling active cofilin levels to promote MTLn3 cell protrusion. PMID:26324884

Dynamic changes in transcriptome and cell wall composition underlying brassinosteroid-mediated lignification of switchgrass suspension cells.

Science.gov (United States)

Rao, Xiaolan; Shen, Hui; Pattathil, Sivakumar; Hahn, Michael G; Gelineo-Albersheim, Ivana; Mohnen, Debra; Pu, Yunqiao; Ragauskas, Arthur J; Chen, Xin; Chen, Fang; Dixon, Richard A

2017-01-01

Plant cell walls contribute the majority of plant biomass that can be used to produce transportation fuels. However, the complexity and variability in composition and structure of cell walls, particularly the presence of lignin, negatively impacts their deconstruction for bioenergy. Metabolic and genetic changes associated with secondary wall development in the biofuel crop switchgrass ( Panicum virgatum ) have yet to be reported. Our previous studies have established a cell suspension system for switchgrass, in which cell wall lignification can be induced by application of brassinolide (BL). We have now collected cell wall composition and microarray-based transcriptome profiles for BL-induced and non-induced suspension cultures to provide an overview of the dynamic changes in transcriptional reprogramming during BL-induced cell wall modification. From this analysis, we have identified changes in candidate genes involved in cell wall precursor synthesis, cellulose, hemicellulose, and pectin formation and ester-linkage generation. We have also identified a large number of transcription factors with expression correlated with lignin biosynthesis genes, among which are candidates for control of syringyl (S) lignin accumulation. Together, this work provides an overview of the dynamic compositional changes during brassinosteroid-induced cell wall remodeling, and identifies candidate genes for future plant genetic engineering to overcome cell wall recalcitrance.

Dynamic single-cell NAD(P)H measurement reveals oscillatory metabolism throughout the E. coli cell division cycle.

Science.gov (United States)

Zhang, Zheng; Milias-Argeitis, Andreas; Heinemann, Matthias

2018-02-01

Recent work has shown that metabolism between individual bacterial cells in an otherwise isogenetic population can be different. To investigate such heterogeneity, experimental methods to zoom into the metabolism of individual cells are required. To this end, the autofluoresence of the redox cofactors NADH and NADPH offers great potential for single-cell dynamic NAD(P)H measurements. However, NAD(P)H excitation requires UV light, which can cause cell damage. In this work, we developed a method for time-lapse NAD(P)H imaging in single E. coli cells. Our method combines a setup with reduced background emission, UV-enhanced microscopy equipment and optimized exposure settings, overall generating acceptable NAD(P)H signals from single cells, with minimal negative effect on cell growth. Through different experiments, in which we perturb E. coli's redox metabolism, we demonstrated that the acquired fluorescence signal indeed corresponds to NAD(P)H. Using this new method, for the first time, we report that intracellular NAD(P)H levels oscillate along the bacterial cell division cycle. The developed method for dynamic measurement of NAD(P)H in single bacterial cells will be an important tool to zoom into metabolism of individual cells.

Computational electrochemo-fluid dynamics modeling in a uranium electrowinning cell

International Nuclear Information System (INIS)

Kim, K.R.; Choi, S.Y.; Kim, S.H.; Shim, J.B.; Paek, S.; Kim, I.T.

2014-01-01

A computational electrochemo-fluid dynamics model has been developed to describe the electrowinning behavior in an electrolyte stream through a planar electrode cell system. Electrode reaction of the uranium electrowinning process from a molten-salt electrolyte stream was modeled to illustrate the details of the flow-assisted mass transport of ions to the cathode. This modeling approach makes it possible to represent variations of the convective diffusion limited current density by taking into account the concentration profile at the electrode surface as a function of the flow characteristics and applied current density in a commercially available computational fluid dynamics platform. It was possible to predict the conventional current-voltage relation in addition to details of electrolyte fluid dynamics and electrochemical variables, such as the flow field, species concentrations, potential, and current distributions throughout the galvanostatic electrolysis cell. (author)

Preparation of high bioactivity multilayered bone-marrow mesenchymal stem cell sheets for myocardial infarction using a 3D-dynamic system.

Science.gov (United States)

Wang, Yingwei; Zhang, Jianhua; Qin, Zixi; Fan, Zepei; Lu, Cheng; Chen, Baoxin; Zhao, Jupeng; Li, Xiaojuan; Xiao, Fei; Lin, Xi; Wu, Zheng

2018-05-01

Cell sheet techniques offer a promising future for myocardial infarction (MI) therapy; however, insufficient nutrition supply remains the major limitation in maintaining stem cell bioactivity in vitro. In order to enhance cell sheet mechanical strength and bioactivity, a decellularized porcine pericardium (DPP) scaffold was prepared by the phospholipase A2 method, and aspartic acid was used as a spacer arm to improve the vascular endothelial growth factor crosslink efficiency on the DPP scaffold. Based on this scaffold, multilayered bone marrow mesenchymal stem cell sheets were rapidly constructed, using RAD16-I peptide hydrogel as a temporary 3D scaffold, and cell sheets were cultured in either the 3D-dynamic system (DCcs) or the traditional static condition (SCcs). The multilayered structure, stem cell bioactivity, and ultrastructure of DCcs and SCcs were assessed. The DCcs exhibited lower apoptosis, lower differentiation, and an improved paracrine effect after a 48 h culture in vitro compared to the SCcs. Four groups were set to evaluate the cell sheet effect in rat MI model: sham group, MI control group, DCcs group, and SCcs group. The DCcs group improved cardiac function and decreased the infarcted area compared to the MI control group, while no significant improvements were observed in the SCcs group. Improved cell survival, angiogenesis, and Sca-1 + cell and c-kit + cell amounts were observed in the DCcs group. In conclusion, the DCcs maintained higher stem cell bioactivity by using the 3D-dynamic system to provide sufficient nutrition, and transplanting DCcs significantly improved the cardiac function and angiogenesis. This study provides an efficient method to prepare vascular endothelial growth factor covalent decellularized pericardium scaffold with aspartic acid, and a multilayered bone marrow mesenchymal stem cell (BMSC) sheet is constructed on it using a 3D-dynamic system. The dynamic nutrition supply showed a significant benefit on BMSC bioactivity

Charge transport and recombination dynamics in organic bulk heterojunction solar cells

Energy Technology Data Exchange (ETDEWEB)

Baumann, Andreas

2011-08-02

The charge transport in disordered organic bulk heterojunction (BHJ) solar cells is a crucial process affecting the power conversion efficiency (PCE) of the solar cell. With the need of synthesizing new materials for improving the power conversion efficiency of those cells it is important to study not only the photophysical but also the electrical properties of the new material classes. Thereby, the experimental techniques need to be applicable to operating solar cells. In this work, the conventional methods of transient photoconductivity (also known as ''Time-of-Flight'' (TOF)), as well as the transient charge extraction technique of ''Charge Carrier Extraction by Linearly Increasing Voltage'' (CELIV) are performed on different organic blend compositions. Especially with the latter it is feasible to study the dynamics - i.e. charge transport and charge carrier recombination - in bulk heterojunction (BHJ) solar cells with active layer thicknesses of 100-200 nm. For a well performing organic BHJ solar cells the morphology is the most crucial parameter finding a trade-off between an efficient photogeneration of charge carriers and the transport of the latter to the electrodes. Besides the morphology, the nature of energetic disorder of the active material blend and its influence on the dynamics are discussed extensively in this work. Thereby, the material system of poly(3-hexylthiophene-2,5-diyl) (P3HT) and [6,6]-phenyl-C{sub 61}butyric acid methyl ester (PC{sub 61}BM) serves mainly as a reference material system. New promising donor or acceptor materials and their potential for application in organic photovoltaics are studied in view of charge dynamics and compared with the reference system. With the need for commercialization of organic solar cells the question of the impact of environmental conditions on the PCE of the solar cells raises. In this work, organic BHJ solar cells exposed to synthetic air for finite duration are

Changes in cytoskeletal dynamics and nonlinear rheology with metastatic ability in cancer cell lines

International Nuclear Information System (INIS)

Coughlin, Mark F; Fredberg, Jeffrey J

2013-01-01

Metastatic outcome is impacted by the biophysical state of the primary tumor cell. To determine if changes in cancer cell biophysical properties facilitate metastasis, we quantified cytoskeletal biophysics in well-characterized human skin, bladder, prostate and kidney cell line pairs that differ in metastatic ability. Using magnetic twisting cytometry with optical detection, cytoskeletal dynamics was observed through spontaneous motion of surface bound marker beads and nonlinear rheology was characterized through large amplitude forced oscillations of probe beads. Measurements of cytoskeletal dynamics and nonlinear rheology differed between strongly and weakly metastatic cells. However, no set of biophysical parameters changed systematically with metastatic ability across all cell lines. Compared to their weakly metastatic counterparts, the strongly metastatic kidney cancer cells exhibited both increased cytoskeletal dynamics and stiffness at large deformation which are thought to facilitate the process of vascular invasion. (paper)

Shape and Dynamics of Adhesive Cells: Mechanical Response of Open Systems

Science.gov (United States)

Yang, Yuehua; Jiang, Hongyuan

2017-05-01

Cell adhesion is an essential biological process. However, previous theoretical and experimental studies ignore a key variable, the changes of cellular volume and pressure, during the dynamic adhesion process. Here, we treat cells as open systems and propose a theoretical framework to investigate how the exchange of water and ions with the environment affects the shape and dynamics of cells adhered between two adhesive surfaces. We show that adherent cells can be either stable (convex or concave) or unstable (spontaneous rupture or collapse) depending on the adhesion energy density, the cell size, the separation of two adhesive surfaces, and the stiffness of the flexible surface. Strikingly, we find that the unstable states vanish when cellular volume and pressure are constant. We further show that the detachments of convex and concave cells are very different. The mechanical response of adherent cells is mainly determined by the competition between the loading rate and the regulation of the cellular volume and pressure. Finally, we show that as an open system the detachment of adherent cells is also significantly influenced by the loading history. Thus, our findings reveal a major difference between living cells and nonliving materials.

Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells.

Science.gov (United States)

Knowles, Michelle K; Guenza, Marina G; Capaldi, Roderick A; Marcus, Andrew H

2002-11-12

Subcellular organelle dynamics are strongly influenced by interactions with cytoskeletal filaments and their associated motor proteins, and lead to complex multiexponential relaxations that occur over a wide range of spatial and temporal scales. Here we report spatio-temporal measurements of the fluctuations of the mitochondrial reticulum in osteosarcoma cells by using Fourier imaging correlation spectroscopy, over time and distance scales of 10(-2) to 10(3) s and 0.5-2.5 microm. We show that the method allows a more complete description of mitochondrial dynamics, through the time- and length-scale-dependent collective diffusion coefficient D(k,tau), than available by other means. Addition of either nocodazole to disrupt microtubules or cytochalasin D to disassemble microfilaments simplifies the intermediate scattering function. When both drugs are used, the reticulum morphology of mitochondria is retained even though the cytoskeletal elements have been de-polymerized. The dynamics of the organelle are then primarily diffusive and can be modeled as a collection of friction points interconnected by elastic springs. This study quantitatively characterizes organelle dynamics in terms of collective cytoskeletal interactions in living cells.

Ureaplasma parvum infection alters filamin a dynamics in host cells

Directory of Open Access Journals (Sweden)

Brown Mary B

2011-04-01

Full Text Available Abstract Background Ureaplasmas are among the most common bacteria isolated from the human urogenital tract. Ureaplasmas can produce asymptomatic infections or disease characterized by an exaggerated inflammatory response. Most investigations have focused on elucidating the pathogenic potential of Ureaplasma species, but little attention has been paid to understanding the mechanisms by which these organisms are capable of establishing asymptomatic infection. Methods We employed differential proteome profiling of bladder tissues from rats experimentally infected with U. parvum in order to identify host cell processes perturbed by colonization with the microbe. Tissues were grouped into four categories: sham inoculated controls, animals that spontaneously cleared infection, asymptomatic urinary tract infection (UTI, and complicated UTI. One protein that was perturbed by infection (filamin A was used to further elucidate the mechanism of U. parvum-induced disruption in human benign prostate cells (BPH-1. BPH-1 cells were evaluated by confocal microscopy, immunoblotting and ELISA. Results Bladder tissue from animals actively colonized with U. parvum displayed significant alterations in actin binding proteins (profilin 1, vinculin, α actinin, and filamin A that regulate both actin polymerization and cell cytoskeletal function pertaining to focal adhesion formation and signal transduction (Fisher's exact test, P U. parvum perturbed the regulation of filamin A. Specifically, infected BPH-1 cells exhibited a significant increase in filamin A phosphorylated at serine2152 (P ≤ 0.01, which correlated with impaired proteolysis of the protein and its normal intracellular distribution. Conclusion Filamin A dynamics were perturbed in both models of infection. Phosphorylation of filamin A occurs in response to various cell signaling cascades that regulate cell motility, differentiation, apoptosis and inflammation. Thus, this phenomenon may be a useful

Dynamical principles of cell-cycle arrest: Reversible, irreversible, and mixed strategies

Science.gov (United States)

Pfeuty, Benjamin

2012-08-01

Living cells often alternate between proliferating and nonproliferating states as part of individual or collective strategies to adapt to complex and changing environments. To this aim, they have evolved a biochemical regulatory network enabling them to switch between cell-division cycles (i.e., oscillatory state) and cell-cycle arrests (i.e., steady state) in response to extracellular cues. This can be achieved by means of a variety of bifurcation mechanisms that potentially give rise to qualitatively distinct cell-cycle arrest properties. In this paper, we study the dynamics of a minimal biochemical network model in which a cell-division oscillator and a differentiation switch mutually antagonize. We identify the existence of three biologically plausible bifurcation scenarios organized around a codimension-four swallowtail-homoclinic singularity. As a result, the model exhibits a broad repertoire of cell-cycle arrest properties in terms of reversibility of these arrests, tunability of interdivision time, and ability to track time-varying signals. This dynamic versatility would explain the diversity of cell-cycle arrest strategies developed in different living species and functional contexts.

A dynamic programming–enhanced simulated annealing algorithm for solving bi-objective cell formation problem with duplicate machines

Directory of Open Access Journals (Sweden)

Mohammad Mohammadi

2015-04-01

Full Text Available Cell formation process is one of the first and the most important steps in designing cellular manufacturing systems. It consists of identifying part families according to the similarities in the design, shape, and presses of parts and dedicating machines to each part family based on the operations required by the parts. In this study, a hybrid method based on a combination of simulated annealing algorithm and dynamic programming was developed to solve a bi-objective cell formation problem with duplicate machines. In the proposed hybrid method, each solution was represented as a permutation of parts, which is created by simulated annealing algorithm, and dynamic programming was used to partition this permutation into part families and determine the number of machines in each cell such that the total dissimilarity between the parts and the total machine investment cost are minimized. The performance of the algorithm was evaluated by performing numerical experiments in different sizes. Our computational experiments indicated that the results were very encouraging in terms of computational time and solution quality.

Arabidopsis Regenerating Protoplast: A Powerful Model System for Combining the Proteomics of Cell Wall Proteins and the Visualization of Cell Wall Dynamics

OpenAIRE

Yokoyama, Ryusuke; Kuki, Hiroaki; Kuroha, Takeshi; Nishitani, Kazuhiko

2016-01-01

The development of a range of sub-proteomic approaches to the plant cell wall has identified many of the cell wall proteins. However, it remains difficult to elucidate the precise biological role of each protein and the cell wall dynamics driven by their actions. The plant protoplast provides an excellent means not only for characterizing cell wall proteins, but also for visualizing the dynamics of cell wall regeneration, during which cell wall proteins are secreted. It therefore offers a uni...

A simplified model for dynamics of cell rolling and cell-surface adhesion

International Nuclear Information System (INIS)

Cimrák, Ivan

2015-01-01

We propose a three dimensional model for the adhesion and rolling of biological cells on surfaces. We study cells moving in shear flow above a wall to which they can adhere via specific receptor-ligand bonds based on receptors from selectin as well as integrin family. The computational fluid dynamics are governed by the lattice-Boltzmann method. The movement and the deformation of the cells is described by the immersed boundary method. Both methods are fully coupled by implementing a two-way fluid-structure interaction. The adhesion mechanism is modelled by adhesive bonds including stochastic rules for their creation and rupture. We explore a simplified model with dissociation rate independent of the length of the bonds. We demonstrate that this model is able to resemble the mesoscopic properties, such as velocity of rolling cells

Evaluating dynamic covariance matrix forecasting and portfolio optimization

OpenAIRE

Sendstad, Lars Hegnes; Holten, Dag Martin

2012-01-01

In this thesis we have evaluated the covariance forecasting ability of the simple moving average, the exponential moving average and the dynamic conditional correlation models. Overall we found that a dynamic portfolio can gain significant improvements by implementing a multivariate GARCH forecast. We further divided the global investment universe into sectors and regions in order to investigate the relative portfolio performance of several asset allocation strategies with both variance and c...

Development of an empirical dynamic model for a Nexa PEM fuel cell power module

Energy Technology Data Exchange (ETDEWEB)

Soltani, Mehdi; Mohammad Taghi Bathaee, S. [Power Systems Laboratory, Department of Electrical Engineering, K.N. Toosi University of Technology, 16317-14191 Tehran (Iran)

2010-12-15

The goal of this study is to develop a fuel cell model which is capable of characterizing fuel cell steady-state performance as well as dynamic behavior. In this paper a new dynamic model of a 1.2 kW Polymer Electrolyte Membrane Fuel Cell (PEMFC) is developed and validated through a series of experiments. The experimental results have been obtained from a Nexa trademark PEM fuel cell power module under different load conditions. Based on this model, a simulator software package has been developed using the MATLAB {sup registered} and Simulink {sup registered} software and simulation results have been carried out. The proposed model exhibits good agreement with experiment results in steady-state and dynamic performance. (author)

Dynamic measurements of flowing cells labeled by gold nanoparticles using full-field photothermal interferometric imaging

Science.gov (United States)

Turko, Nir A.; Roitshtain, Darina; Blum, Omry; Kemper, Björn; Shaked, Natan T.

2017-06-01

We present highly dynamic photothermal interferometric phase microscopy for quantitative, selective contrast imaging of live cells during flow. Gold nanoparticles can be biofunctionalized to bind to specific cells, and stimulated for local temperature increase due to plasmon resonance, causing a rapid change of the optical phase. These phase changes can be recorded by interferometric phase microscopy and analyzed to form an image of the binding sites of the nanoparticles in the cells, gaining molecular specificity. Since the nanoparticle excitation frequency might overlap with the sample dynamics frequencies, photothermal phase imaging was performed on stationary or slowly dynamic samples. Furthermore, the computational analysis of the photothermal signals is time consuming. This makes photothermal imaging unsuitable for applications requiring dynamic imaging or real-time analysis, such as analyzing and sorting cells during fast flow. To overcome these drawbacks, we utilized an external interferometric module and developed new algorithms, based on discrete Fourier transform variants, enabling fast analysis of photothermal signals in highly dynamic live cells. Due to the self-interference module, the cells are imaged with and without excitation in video-rate, effectively increasing signal-to-noise ratio. Our approach holds potential for using photothermal cell imaging and depletion in flow cytometry.

Super-resolution microscopy reveals cell wall dynamics and peptidoglycan architecture in ovococcal bacteria.

Science.gov (United States)

Wheeler, Richard; Mesnage, Stéphane; Boneca, Ivo G; Hobbs, Jamie K; Foster, Simon J

2011-12-01

Cell morphology and viability in Eubacteria is dictated by the architecture of peptidoglycan, the major and essential structural component of the cell wall. Although the biochemical composition of peptidoglycan is well understood, how the peptidoglycan architecture can accommodate the dynamics of growth and division while maintaining cell shape remains largely unknown. Here, we elucidate the peptidoglycan architecture and dynamics of bacteria with ovoid cell shape (ovococci), which includes a number of important pathogens, by combining biochemical analyses with atomic force and super-resolution microscopies. Atomic force microscopy analysis showed preferential orientation of the peptidoglycan network parallel to the short axis of the cell, with distinct architectural features associated with septal and peripheral wall synthesis. Super-resolution three-dimensional structured illumination fluorescence microscopy was applied for the first time in bacteria to unravel the dynamics of peptidoglycan assembly in ovococci. The ovococci have a unique peptidoglycan architecture and growth mode not observed in other model organisms. © 2011 Blackwell Publishing Ltd.

Experimental investigation of dynamic performance and transient responses of a kW-class PEM fuel cell stack under various load changes

International Nuclear Information System (INIS)

Tang Yong; Yuan Wei; Pan Minqiang; Li Zongtao; Chen Guoqing; Li Yong

2010-01-01

The dynamic performance is a very important evaluation index of proton exchange membrane (PEM) fuel cells used for real application, which is mostly related with water, heat and gas management. A commercial PEM fuel cell system of Nexa module is employed to experimentally investigate the dynamic behavior and transient response of a PEM fuel cell stack and reveal involved influential factors. Five groups of dynamic tests are conducted and divided into different stage such as start-up, shut-down, step-up load, regular load variation and irregular load variation. It is observed that the external load changes the current output proportionally and reverses stack voltage accordingly. The purge operation benefits performance recovery and enhancement during a constant load and its time strongly depends on the operational current level. Overshoot and undershoot behaviors are observed during transience. But the current undershoot does not appear due to charge double-layer effect. Additionally, magnitudes of the peaks of the voltage overshoot and undershoot vary at different current levels. The operating temperature responds fast to current load but changes slowly showing an arc-like profile without any overshoot and undershoot events. The air flow rate changes directly following the dynamic load demand. But the increased amount of air flow rate during different step-change is not identical, which depends on the requirement of internal reaction and flooding intensity. The results can be utilized for validation of dynamic fuel cell models, and regarded as reference for effective control and management strategies.

Technology Validation: Fuel Cell Bus Evaluations

Energy Technology Data Exchange (ETDEWEB)

Eudy, Leslie [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2018-01-02

This presentation describing the FY 2016 accomplishments for the National Renewable Energy Laboratory's Fuel Cell Bus Evaluations project was presented at the U.S. Department of Energy Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting, June 7, 2016.

Dynamic instability of genomic methylation patterns in pluripotent stem cells

Directory of Open Access Journals (Sweden)

Ooi Steen KT

2010-09-01

Full Text Available Abstract Background Genomic methylation patterns are established during gametogenesis, and perpetuated in somatic cells by faithful maintenance methylation. There have been previous indications that genomic methylation patterns may be less stable in embryonic stem (ES cells than in differentiated somatic cells, but it is not known whether different mechanisms of de novo and maintenance methylation operate in pluripotent stem cells compared with differentiating somatic cells. Results In this paper, we show that ablation of the DNA methyltransferase regulator DNMT3L (DNA methyltransferase 3-like in mouse ES cells renders them essentially incapable of de novo methylation of newly integrated retroviral DNA. We also show that ES cells lacking DNMT3L lose DNA methylation over time in culture, suggesting that DNA methylation in ES cells is the result of dynamic loss and gain of DNA methylation. We found that wild-type female ES cells lose DNA methylation at a much faster rate than do male ES cells; this defect could not be attributed to sex-specific differences in expression of DNMT3L or of any DNA methyltransferase. We also found that human ES and induced pluripotent stem cell lines showed marked but variable loss of methylation that could not be attributed to sex chromosome constitution or time in culture. Conclusions These data indicate that DNA methylation in pluripotent stem cells is much more dynamic and error-prone than is maintenance methylation in differentiated cells. DNA methylation requires DNMT3L in stem cells, but DNMT3L is not expressed in differentiating somatic cells. Error-prone maintenance methylation will introduce unpredictable phenotypic variation into clonal populations of pluripotent stem cells, and this variation is likely to be much more pronounced in cultured female cells. This epigenetic variability has obvious negative implications for the clinical applications of stem cells.

Arabidopsis FH1 Formin Affects Cotyledon Pavement Cell Shape by Modulating Cytoskeleton Dynamics.

Science.gov (United States)

Rosero, Amparo; Oulehlová, Denisa; Stillerová, Lenka; Schiebertová, Petra; Grunt, Michal; Žárský, Viktor; Cvrčková, Fatima

2016-03-01

Plant cell morphogenesis involves concerted rearrangements of microtubules and actin microfilaments. We previously reported that FH1, the main Arabidopsis thaliana housekeeping Class I membrane-anchored formin, contributes to actin dynamics and microtubule stability in rhizodermis cells. Here we examine the effects of mutations affecting FH1 (At3g25500) on cell morphogenesis and above-ground organ development in seedlings, as well as on cytoskeletal organization and dynamics, using a combination of confocal and variable angle epifluorescence microscopy with a pharmacological approach. Homozygous fh1 mutants exhibited cotyledon epinasty and had larger cotyledon pavement cells with more pronounced lobes than the wild type. The pavement cell shape alterations were enhanced by expression of the fluorescent microtubule marker GFP-microtubule-associated protein 4 (MAP4). Mutant cotyledon pavement cells exhibited reduced density and increased stability of microfilament bundles, as well as enhanced dynamics of microtubules. Analogous results were also obtained upon treatments with the formin inhibitor SMIFH2 (small molecule inhibitor of formin homology 2 domains). Pavement cell shape in wild-type (wt) and fh1 plants in some situations exhibited a differential response towards anti-cytoskeletal drugs, especially the microtubule disruptor oryzalin. Our observations indicate that FH1 participates in the control of microtubule dynamics, possibly via its effects on actin, subsequently influencing cell morphogenesis and macroscopic organ development. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Dynamics of cell area and force during spreading.

Science.gov (United States)

Brill-Karniely, Yifat; Nisenholz, Noam; Rajendran, Kavitha; Dang, Quynh; Krishnan, Ramaswamy; Zemel, Assaf

2014-12-16

Experiments on human pulmonary artery endothelial cells are presented to show that cell area and the force exerted on a substrate increase simultaneously, but with different rates during spreading; rapid-force increase systematically occurred several minutes past initial spreading. We examine this theoretically and present three complementary mechanisms that may accompany the development of lamellar stress during spreading and underlie the observed behavior. These include: 1), the dynamics of cytoskeleton assembly at the cell basis; 2), the strengthening of acto-myosin forces in response to the generated lamellar stresses; and 3), the passive strain-stiffening of the cytoskeleton. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A quantitative and dynamic model for plant stem cell regulation.

Directory of Open Access Journals (Sweden)

Florian Geier

Full Text Available Plants maintain pools of totipotent stem cells throughout their entire life. These stem cells are embedded within specialized tissues called meristems, which form the growing points of the organism. The shoot apical meristem of the reference plant Arabidopsis thaliana is subdivided into several distinct domains, which execute diverse biological functions, such as tissue organization, cell-proliferation and differentiation. The number of cells required for growth and organ formation changes over the course of a plants life, while the structure of the meristem remains remarkably constant. Thus, regulatory systems must be in place, which allow for an adaptation of cell proliferation within the shoot apical meristem, while maintaining the organization at the tissue level. To advance our understanding of this dynamic tissue behavior, we measured domain sizes as well as cell division rates of the shoot apical meristem under various environmental conditions, which cause adaptations in meristem size. Based on our results we developed a mathematical model to explain the observed changes by a cell pool size dependent regulation of cell proliferation and differentiation, which is able to correctly predict CLV3 and WUS over-expression phenotypes. While the model shows stem cell homeostasis under constant growth conditions, it predicts a variation in stem cell number under changing conditions. Consistent with our experimental data this behavior is correlated with variations in cell proliferation. Therefore, we investigate different signaling mechanisms, which could stabilize stem cell number despite variations in cell proliferation. Our results shed light onto the dynamic constraints of stem cell pool maintenance in the shoot apical meristem of Arabidopsis in different environmental conditions and developmental states.

Image segmentation and dynamic lineage analysis in single-cell fluorescence microscopy.

Science.gov (United States)

Wang, Quanli; Niemi, Jarad; Tan, Chee-Meng; You, Lingchong; West, Mike

2010-01-01

An increasingly common component of studies in synthetic and systems biology is analysis of dynamics of gene expression at the single-cell level, a context that is heavily dependent on the use of time-lapse movies. Extracting quantitative data on the single-cell temporal dynamics from such movies remains a major challenge. Here, we describe novel methods for automating key steps in the analysis of single-cell, fluorescent images-segmentation and lineage reconstruction-to recognize and track individual cells over time. The automated analysis iteratively combines a set of extended morphological methods for segmentation, and uses a neighborhood-based scoring method for frame-to-frame lineage linking. Our studies with bacteria, budding yeast and human cells, demonstrate the portability and usability of these methods, whether using phase, bright field or fluorescent images. These examples also demonstrate the utility of our integrated approach in facilitating analyses of engineered and natural cellular networks in diverse settings. The automated methods are implemented in freely available, open-source software.

Neoantigen landscape dynamics during human melanoma-T cell interactions

DEFF Research Database (Denmark)

Verdegaal, Els M. E.; De Miranda, Noel F. C. C.; Visser, Marten

2016-01-01

Recognition of neoantigens that are formed as a consequence of DNA damage is likely to form a major driving force behind the clinical activity of cancer immunotherapies such as T-cell checkpoint blockade and adoptive T-cell therapy. Therefore, strategies to selectively enhance T-cell reactivity...... against genetically defined neoantigens are currently under development. In mouse models, T-cell pressure can sculpt the antigenicity of tumours, resulting in the emergence of tumours that lack defined mutant antigens. However, whether the T-cell-recognized neoantigen repertoire in human cancers...... by overall reduced expression of the genes or loss of the mutant alleles. Notably, loss of expression of T-cell-recognized neoantigens was accompanied by development of neoantigen-specific T-cell reactivity in tumour-infiltrating lymphocytes. These data demonstrate the dynamic interactions between cancer...

Chromatin dynamics during cell cycle mediate conversion of DNA damage into chromatid breaks and affect formation of chromosomal aberrations: Biological and clinical significance

International Nuclear Information System (INIS)

Terzoudi, Georgia I.; Hatzi, Vasiliki I.; Donta-Bakoyianni, Catherine; Pantelias, Gabriel E.

2011-01-01

The formation of diverse chromosomal aberrations following irradiation and the variability in radiosensitivity at different cell-cycle stages remain a long standing controversy, probably because most of the studies have focused on elucidating the enzymatic mechanisms involved using simple DNA substrates. Yet, recognition, processing and repair of DNA damage occur within the nucleoprotein complex of chromatin which is dynamic in nature, capable of rapid unfolding, disassembling, assembling and refolding. The present work reviews experimental work designed to investigate the impact of chromatin dynamics and chromosome conformation changes during cell-cycle in the formation of chromosomal aberrations. Using conventional cytogenetics and premature chromosome condensation to visualize interphase chromatin, the data presented support the hypothesis that chromatin dynamic changes during cell-cycle are important determinants in the conversion of sub-microscopic DNA lesions into chromatid breaks. Consequently, the type and yield of radiation-induced chromosomal aberrations at a given cell-cycle-stage depends on the combined effect of DNA repair processes and chromatin dynamics, which is cell-cycle-regulated and subject to up- or down-regulation following radiation exposure or genetic alterations. This new hypothesis is used to explain the variability in radiosensitivity observed at various cell-cycle-stages, among mutant cells and cells of different origin, or among different individuals, and to revisit unresolved issues and unanswered questions. In addition, it is used to better understand hypersensitivity of AT cells and to provide an improved predictive G2-assay for evaluating radiosensitivity at individual level. Finally, experimental data at single cell level obtained using hybrid cells suggest that the proposed hypothesis applies only to the irradiated component of the hybrid.

Mechanosensation Dynamically Coordinates Polar Growth and Cell Wall Assembly to Promote Cell Survival.

Science.gov (United States)

Davì, Valeria; Tanimoto, Hirokazu; Ershov, Dmitry; Haupt, Armin; De Belly, Henry; Le Borgne, Rémi; Couturier, Etienne; Boudaoud, Arezki; Minc, Nicolas

2018-04-23

How growing cells cope with size expansion while ensuring mechanical integrity is not known. In walled cells, such as those of microbes and plants, growth and viability are both supported by a thin and rigid encasing cell wall (CW). We deciphered the dynamic mechanisms controlling wall surface assembly during cell growth, using a sub-resolution microscopy approach to monitor CW thickness in live rod-shaped fission yeast cells. We found that polar cell growth yielded wall thinning and that thickness negatively influenced growth. Thickness at growing tips exhibited a fluctuating behavior with thickening phases followed by thinning phases, indicative of a delayed feedback promoting thickness homeostasis. This feedback was mediated by mechanosensing through the CW integrity pathway, which probes strain in the wall to adjust synthase localization and activity to surface growth. Mutants defective in thickness homeostasis lysed by rupturing the wall, demonstrating its pivotal role for walled cell survival. Copyright © 2018 Elsevier Inc. All rights reserved.

Modeling and dynamics of an autothermal JP5 fuel reformer for marine fuel cell applications

International Nuclear Information System (INIS)

Tsourapas, Vasilis; Sun, Jing; Nickens, Anthony

2008-01-01

In this work, a dynamic model of an integrated autothermal reformer (ATR) and proton exchange membrane fuel cell (PEM FC) system and model-based evaluation of its dynamic characteristics are presented. The ATR reforms JP5 fuel into a hydrogen rich flow. The hydrogen is extracted from the reformate flow by a separator membrane (SEP), then supplied to the PEM FC for power generation. A catalytic burner (CB) and a turbine are also incorporated to recuperate energy from the remaining SEP flow that would otherwise be wasted. A dynamic model of this system, based on the ideal gas law and energy balance principles, is developed and used to explore the effects of the operating setpoint selection of the SEP on the overall system efficiency. The analysis reveals that a trade-off exists between the SEP efficiency and the overall system efficiency. Finally the open loop system simulation results are presented and conclusions are drawn on the SEP operation

Effect of process parameters on the dynamic behavior of polymer electrolyte membrane fuel cells for electric vehicle applications

Directory of Open Access Journals (Sweden)

A.A. Abd El Monem

2014-03-01

Full Text Available This paper presents a dynamic mathematical model for Polymer Electrolyte Membrane “PEM” fuel cell systems to be used for electric vehicle applications. The performance of the fuel cell, depending on the developed model and taking the double layer charging effect into account, is investigated with different process parameters to evaluate their effect on the unit behavior. Thus, it will be easy to develop suitable controllers to regulate the unit operation, which encourages the use of fuel cells especially with electric vehicles applications. The steady-state performance of the fuel cell is verified using a comparison with datasheet data and curves provided by the manufacturer. The results and conclusions introduced in this paper provide a base for further investigation of fuel cells-driven dc motors for electric vehicle.

Study on dynamic team performance evaluation methodology based on team situation awareness model

International Nuclear Information System (INIS)

Kim, Suk Chul

2005-02-01

The purpose of this thesis is to provide a theoretical framework and its evaluation methodology of team dynamic task performance of operating team at nuclear power plant under the dynamic and tactical environment such as radiological accident. This thesis suggested a team dynamic task performance evaluation model so called team crystallization model stemmed from Endsely's situation awareness model being comprised of four elements: state, information, organization, and orientation and its quantification methods using system dynamics approach and a communication process model based on a receding horizon control approach. The team crystallization model is a holistic approach for evaluating the team dynamic task performance in conjunction with team situation awareness considering physical system dynamics and team behavioral dynamics for a tactical and dynamic task at nuclear power plant. This model provides a systematic measure to evaluate time-dependent team effectiveness or performance affected by multi-agents such as plant states, communication quality in terms of transferring situation-specific information and strategies for achieving the team task goal at given time, and organizational factors. To demonstrate the applicability of the proposed model and its quantification method, the case study was carried out using the data obtained from a full-scope power plant simulator for 1,000MWe pressurized water reactors with four on-the-job operating groups and one expert group who knows accident sequences. Simulated results team dynamic task performance with reference key plant parameters behavior and team-specific organizational center of gravity and cue-and-response matrix illustrated good symmetry with observed value. The team crystallization model will be useful and effective tool for evaluating team effectiveness in terms of recruiting new operating team for new plant as cost-benefit manner. Also, this model can be utilized as a systematic analysis tool for

Study on dynamic team performance evaluation methodology based on team situation awareness model

Energy Technology Data Exchange (ETDEWEB)

Kim, Suk Chul

2005-02-15

The purpose of this thesis is to provide a theoretical framework and its evaluation methodology of team dynamic task performance of operating team at nuclear power plant under the dynamic and tactical environment such as radiological accident. This thesis suggested a team dynamic task performance evaluation model so called team crystallization model stemmed from Endsely's situation awareness model being comprised of four elements: state, information, organization, and orientation and its quantification methods using system dynamics approach and a communication process model based on a receding horizon control approach. The team crystallization model is a holistic approach for evaluating the team dynamic task performance in conjunction with team situation awareness considering physical system dynamics and team behavioral dynamics for a tactical and dynamic task at nuclear power plant. This model provides a systematic measure to evaluate time-dependent team effectiveness or performance affected by multi-agents such as plant states, communication quality in terms of transferring situation-specific information and strategies for achieving the team task goal at given time, and organizational factors. To demonstrate the applicability of the proposed model and its quantification method, the case study was carried out using the data obtained from a full-scope power plant simulator for 1,000MWe pressurized water reactors with four on-the-job operating groups and one expert group who knows accident sequences. Simulated results team dynamic task performance with reference key plant parameters behavior and team-specific organizational center of gravity and cue-and-response matrix illustrated good symmetry with observed value. The team crystallization model will be useful and effective tool for evaluating team effectiveness in terms of recruiting new operating team for new plant as cost-benefit manner. Also, this model can be utilized as a systematic analysis tool for

Quantitative Microscopic Analysis of Plasma Membrane Receptor Dynamics in Living Plant Cells.

Science.gov (United States)

Luo, Yu; Russinova, Eugenia

2017-01-01

Plasma membrane-localized receptors are essential for cellular communication and signal transduction. In Arabidopsis thaliana, BRASSINOSTEROID INSENSITIVE1 (BRI1) is one of the receptors that is activated by binding to its ligand, the brassinosteroid (BR) hormone, at the cell surface to regulate diverse plant developmental processes. The availability of BRI1 in the plasma membrane is related to its signaling output and is known to be controlled by the dynamic endomembrane trafficking. Advances in fluorescence labeling and confocal microscopy techniques enabled us to gain a better understanding of plasma membrane receptor dynamics in living cells. Here we describe different quantitative microscopy methods to monitor the relative steady-state levels of the BRI1 protein in the plasma membrane of root epidermal cells and its relative exocytosis and recycling rates. The methods can be applied also to analyze similar dynamics of other plasma membrane-localized receptors.

Endocytosis of collagen by hepatic stellate cells regulates extracellular matrix dynamics.

Science.gov (United States)

Bi, Yan; Mukhopadhyay, Dhriti; Drinane, Mary; Ji, Baoan; Li, Xing; Cao, Sheng; Shah, Vijay H

2014-10-01

Hepatic stellate cells (HSCs) generate matrix, which in turn may also regulate HSCs function during liver fibrosis. We hypothesized that HSCs may endocytose matrix proteins to sense and respond to changes in microenvironment. Primary human HSCs, LX2, or mouse embryonic fibroblasts (MEFs) [wild-type; c-abl(-/-); or Yes, Src, and Fyn knockout mice (YSF(-/-))] were incubated with fluorescent-labeled collagen or gelatin. Fluorescence-activated cell sorting analysis and confocal microscopy were used for measuring cellular internalization of matrix proteins. Targeted PCR array and quantitative real-time PCR were used to evaluate gene expression changes. HSCs and LX2 cells endocytose collagens in a concentration- and time-dependent manner. Endocytosed collagen colocalized with Dextran 10K, a marker of macropinocytosis, and 5-ethylisopropyl amiloride, an inhibitor of macropinocytosis, reduced collagen internalization by 46%. Cytochalasin D and ML7 blocked collagen internalization by 47% and 45%, respectively, indicating that actin and myosin are critical for collagen endocytosis. Wortmannin and AKT inhibitor blocked collagen internalization by 70% and 89%, respectively, indicating that matrix macropinocytosis requires phosphoinositide-3-kinase (PI3K)/AKT signaling. Overexpression of dominant-negative dynamin-2 K44A blocked matrix internalization by 77%, indicating a role for dynamin-2 in matrix macropinocytosis. Whereas c-abl(-/-) MEF showed impaired matrix endocytosis, YSF(-/-) MEF surprisingly showed increased matrix endocytosis. It was also associated with complex gene regulations that related with matrix dynamics, including increased matrix metalloproteinase 9 (MMP-9) mRNA levels and zymographic activity. HSCs endocytose matrix proteins through macropinocytosis that requires a signaling network composed of PI3K/AKT, dynamin-2, and c-abl. Interaction with extracellular matrix regulates matrix dynamics through modulating multiple gene expressions including MMP-9

Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

Directory of Open Access Journals (Sweden)

Matilde Cacciatore

2012-01-01

Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

Live cell CRISPR-imaging in plants reveals dynamic telomere movements

KAUST Repository

Dreissig, Steven

2017-05-16

Elucidating the spatio-temporal organization of the genome inside the nucleus is imperative to understand the regulation of genes and non-coding sequences during development and environmental changes. Emerging techniques of chromatin imaging promise to bridge the long-standing gap between sequencing studies which reveal genomic information and imaging studies that provide spatial and temporal information of defined genomic regions. Here, we demonstrate such an imaging technique based on two orthologues of the bacterial CRISPR-Cas9 system. By fusing eGFP/mRuby2 to the catalytically inactive version of Streptococcus pyogenes and Staphylococcus aureus Cas9, we show robust visualization of telomere repeats in live leaf cells of Nicotiana benthamiana. By tracking the dynamics of telomeres visualized by CRISPR-dCas9, we reveal dynamic telomere movements of up to 2 μm within 30 minutes during interphase. Furthermore, we show that CRISPR-dCas9 can be combined with fluorescence-labelled proteins to visualize DNA-protein interactions in vivo. By simultaneously using two dCas9 orthologues, we pave the way for imaging of multiple genomic loci in live plants cells. CRISPR-imaging bears the potential to significantly improve our understanding of the dynamics of chromosomes in live plant cells.

A hybrid total internal reflection fluorescence and optical tweezers microscope to study cell adhesion and membrane protein dynamics of single living cells

NARCIS (Netherlands)

Snijder-van As, M.I.; Rieger, B.; Joosten, B.; Subramaniam, Vinod; Figdor, Carl; Kanger, Johannes S.

2009-01-01

The dynamics of cell surface membrane proteins plays an important role in cell–cell interactions. The onset of the interaction is typically not precisely controlled by current techniques, making especially difficult the visualization of early-stage dynamics. We have developed a novel method where

Pea Border Cell Maturation and Release Involve Complex Cell Wall Structural Dynamics.

Science.gov (United States)

Mravec, Jozef; Guo, Xiaoyuan; Hansen, Aleksander Riise; Schückel, Julia; Kračun, Stjepan Krešimir; Mikkelsen, Maria Dalgaard; Mouille, Grégory; Johansen, Ida Elisabeth; Ulvskov, Peter; Domozych, David S; Willats, William George Tycho

2017-06-01

The adhesion of plant cells is vital for support and protection of the plant body and is maintained by a variety of molecular associations between cell wall components. In some specialized cases, though, plant cells are programmed to detach, and root cap-derived border cells are examples of this. Border cells (in some species known as border-like cells) provide an expendable barrier between roots and the environment. Their maturation and release is an important but poorly characterized cell separation event. To gain a deeper insight into the complex cellular dynamics underlying this process, we undertook a systematic, detailed analysis of pea ( Pisum sativum ) root tip cell walls. Our study included immunocarbohydrate microarray profiling, monosaccharide composition determination, Fourier-transformed infrared microspectroscopy, quantitative reverse transcription-PCR of cell wall biosynthetic genes, analysis of hydrolytic activities, transmission electron microscopy, and immunolocalization of cell wall components. Using this integrated glycobiology approach, we identified multiple novel modes of cell wall structural and compositional rearrangement during root cap growth and the release of border cells. Our findings provide a new level of detail about border cell maturation and enable us to develop a model of the separation process. We propose that loss of adhesion by the dissolution of homogalacturonan in the middle lamellae is augmented by an active biophysical process of cell curvature driven by the polarized distribution of xyloglucan and extensin epitopes. © 2017 American Society of Plant Biologists. All Rights Reserved.

Using simulated fluorescence cell micrographs for the evaluation of cell image segmentation algorithms.

Science.gov (United States)

Wiesmann, Veit; Bergler, Matthias; Palmisano, Ralf; Prinzen, Martin; Franz, Daniela; Wittenberg, Thomas

2017-03-18

Manual assessment and evaluation of fluorescent micrograph cell experiments is time-consuming and tedious. Automated segmentation pipelines can ensure efficient and reproducible evaluation and analysis with constant high quality for all images of an experiment. Such cell segmentation approaches are usually validated and rated in comparison to manually annotated micrographs. Nevertheless, manual annotations are prone to errors and display inter- and intra-observer variability which influence the validation results of automated cell segmentation pipelines. We present a new approach to simulate fluorescent cell micrographs that provides an objective ground truth for the validation of cell segmentation methods. The cell simulation was evaluated twofold: (1) An expert observer study shows that the proposed approach generates realistic fluorescent cell micrograph simulations. (2) An automated segmentation pipeline on the simulated fluorescent cell micrographs reproduces segmentation performances of that pipeline on real fluorescent cell micrographs. The proposed simulation approach produces realistic fluorescent cell micrographs with corresponding ground truth. The simulated data is suited to evaluate image segmentation pipelines more efficiently and reproducibly than it is possible on manually annotated real micrographs.

Evaluation of mechanical and morphologic features of PLLA membranes as supports for perfusion cells culture systems

Energy Technology Data Exchange (ETDEWEB)

Montesanto, S., E-mail: salvatore.montesanto1985@gmail.com [Department of Civil, Environmental, Aerospace, Materials Engineering (DICAM), University of Palermo, Viale delle Scienze Ed. 8, 90128 Palermo (Italy); Brucato, V. [Department of Civil, Environmental, Aerospace, Materials Engineering (DICAM), University of Palermo, Viale delle Scienze Ed. 8, 90128 Palermo (Italy); La Carrubba, V. [Department of Civil, Environmental, Aerospace, Materials Engineering (DICAM), University of Palermo, Viale delle Scienze Ed. 8, 90128 Palermo (Italy); Euro-Mediterranean Institute of Science and Technology (IEMEST), Via Michele Miraglia, 20, 90128 Palermo (Italy)

2016-12-01

Porous biodegradable PLLA membranes, which can be used as supports for perfusion cell culture systems were designed, developed and characterized. PLLA membranes were prepared via diffusion induced phase separation (DIPS). A glass slab was coated with a binary PLLA–dioxane solution (8 wt.% PLLA) via dip coating, then pool immersed in two subsequent coagulation baths, and finally dried in a humidity-controlled environment. Surface and mechanical properties were evaluated by measuring pore size, porosity via scanning electron microscopy, storage modulus, loss modulus and loss angle by using a dynamic mechanical analysis (DMA). Cell adhesion assays on different membrane surfaces were also performed by using a standard count method. Results provide new insights into the foaming methods for producing polymeric membranes and supply indications on how to optimise the fabrication parameters to design membranes for tissue cultures and regeneration. - Highlights: • Design, development and characterization of porous biodegradable PLLA membranes via DIPS technology. • Easy-to-tune processing parameters in terms of surface and volumetric properties and cell adhesion. • Evaluation of the impact of the interconnection degree on membrane's mechanical properties. • Evaluation of cell adhesion on different membrane surface textures.

Evaluation of mechanical and morphologic features of PLLA membranes as supports for perfusion cells culture systems

International Nuclear Information System (INIS)

Montesanto, S.; Brucato, V.; La Carrubba, V.

2016-01-01

Porous biodegradable PLLA membranes, which can be used as supports for perfusion cell culture systems were designed, developed and characterized. PLLA membranes were prepared via diffusion induced phase separation (DIPS). A glass slab was coated with a binary PLLA–dioxane solution (8 wt.% PLLA) via dip coating, then pool immersed in two subsequent coagulation baths, and finally dried in a humidity-controlled environment. Surface and mechanical properties were evaluated by measuring pore size, porosity via scanning electron microscopy, storage modulus, loss modulus and loss angle by using a dynamic mechanical analysis (DMA). Cell adhesion assays on different membrane surfaces were also performed by using a standard count method. Results provide new insights into the foaming methods for producing polymeric membranes and supply indications on how to optimise the fabrication parameters to design membranes for tissue cultures and regeneration. - Highlights: • Design, development and characterization of porous biodegradable PLLA membranes via DIPS technology. • Easy-to-tune processing parameters in terms of surface and volumetric properties and cell adhesion. • Evaluation of the impact of the interconnection degree on membrane's mechanical properties. • Evaluation of cell adhesion on different membrane surface textures.

Non-Hermitian Operator Modelling of Basic Cancer Cell Dynamics

Science.gov (United States)

Bagarello, Fabio; Gargano, Francesco

2018-04-01

We propose a dynamical system of tumor cells proliferation based on operatorial methods. The approach we propose is quantum-like: we use ladder and number operators to describe healthy and tumor cells birth and death, and the evolution is ruled by a non-hermitian Hamiltonian which includes, in a non reversible way, the basic biological mechanisms we consider for the system. We show that this approach is rather efficient in describing some processes of the cells. We further add some medical treatment, described by adding a suitable term in the Hamiltonian, which controls and limits the growth of tumor cells, and we propose an optimal approach to stop, and reverse, this growth.

Discrete dynamic modeling of T cell survival signaling networks

Science.gov (United States)

Zhang, Ranran

2009-03-01

Biochemistry-based frameworks are often not applicable for the modeling of heterogeneous regulatory systems that are sparsely documented in terms of quantitative information. As an alternative, qualitative models assuming a small set of discrete states are gaining acceptance. This talk will present a discrete dynamic model of the signaling network responsible for the survival and long-term competence of cytotoxic T cells in the blood cancer T-LGL leukemia. We integrated the signaling pathways involved in normal T cell activation and the known deregulations of survival signaling in leukemic T-LGL, and formulated the regulation of each network element as a Boolean (logic) rule. Our model suggests that the persistence of two signals is sufficient to reproduce all known deregulations in leukemic T-LGL. It also indicates the nodes whose inactivity is necessary and sufficient for the reversal of the T-LGL state. We have experimentally validated several model predictions, including: (i) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. (ii) Sphingosine kinase 1 and NFκB are essential for the long-term survival of T cells in T-LGL leukemia. (iii) T box expressed in T cells (T-bet) is constitutively activated in the T-LGL state. The model has identified potential therapeutic targets for T-LGL leukemia and can be used for generating long-term competent CTL necessary for tumor and cancer vaccine development. The success of this model, and of other discrete dynamic models, suggests that the organization of signaling networks has an determining role in their dynamics. Reference: R. Zhang, M. V. Shah, J. Yang, S. B. Nyland, X. Liu, J. K. Yun, R. Albert, T. P. Loughran, Jr., Network Model of Survival Signaling in LGL Leukemia, PNAS 105, 16308-16313 (2008).

A Nonlinear Mixed Effects Approach for Modeling the Cell-To-Cell Variability of Mig1 Dynamics in Yeast.

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Joachim Almquist

Full Text Available The last decade has seen a rapid development of experimental techniques that allow data collection from individual cells. These techniques have enabled the discovery and characterization of variability within a population of genetically identical cells. Nonlinear mixed effects (NLME modeling is an established framework for studying variability between individuals in a population, frequently used in pharmacokinetics and pharmacodynamics, but its potential for studies of cell-to-cell variability in molecular cell biology is yet to be exploited. Here we take advantage of this novel application of NLME modeling to study cell-to-cell variability in the dynamic behavior of the yeast transcription repressor Mig1. In particular, we investigate a recently discovered phenomenon where Mig1 during a short and transient period exits the nucleus when cells experience a shift from high to intermediate levels of extracellular glucose. A phenomenological model based on ordinary differential equations describing the transient dynamics of nuclear Mig1 is introduced, and according to the NLME methodology the parameters of this model are in turn modeled by a multivariate probability distribution. Using time-lapse microscopy data from nearly 200 cells, we estimate this parameter distribution according to the approach of maximizing the population likelihood. Based on the estimated distribution, parameter values for individual cells are furthermore characterized and the resulting Mig1 dynamics are compared to the single cell times-series data. The proposed NLME framework is also compared to the intuitive but limited standard two-stage (STS approach. We demonstrate that the latter may overestimate variabilities by up to almost five fold. Finally, Monte Carlo simulations of the inferred population model are used to predict the distribution of key characteristics of the Mig1 transient response. We find that with decreasing levels of post-shift glucose, the transient

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

Evaluation and optimization of the bandwidth of static converters: application to multi-cell converters; Evaluation et optimisation de la bande passante des convertisseurs statiques

Energy Technology Data Exchange (ETDEWEB)

Aime, M.

2003-11-15

Thanks to the technological progress achieved in the field of power electronics, the use of static converters has spread to new applications. In particular, some applications such as active filtering or the supply of special AC machines require power converters having good dynamic performances. The subject of this thesis is to evaluate systematically the dynamic performances of multi-cell converters, and then to optimize these performances. This document is organized in four chapters. The first one summarizes the main multilevel converter structures, and some control strategies dedicated to these structures. The second chapter presents the evaluation criteria chosen to quantify the dynamic performances of static converters. These criteria are then used to compare the performances obtained with two different PWM strategies. An optimized strategy which results from a trade-off between the two former strategies is then introduced. The third chapter shows a new control strategy of multi-cell voltage source converters. This new strategy enables to control the peak current at a fixed switching frequency. The operation of this controller is explained, and the results obtained by digital simulations are presented and discussed. The fourth chapter deals with the experimental achievement of the peak current control. In particular, the implementation of the control algorithm within a FPGA is demonstrated. Finally, the conclusion of this thesis presents some orientations for further developments, in order to improve the current control strategy and to widen its field of applications. (author)

Dynamic mapping of genes controlling cancer stem cell proliferation

Directory of Open Access Journals (Sweden)

Zhong eWang

2012-05-01

Full Text Available The growing evidence that cancer originates from stem cells holds a great promise to eliminate this disease by designing specific drug therapies for removing cancer stem cells. Translation of this knowledge into predictive tests for the clinic is hampered due to the lack of methods to discriminate cancer stem cells from non-cancer stem cells. Here, we address this issue by describing a conceptual strategy for identifying the genetic origins of cancer stem cells. The strategy incorporates a high-dimensional group of differential equations that characterizes the proliferation, differentiation, and reprogramming of cancer stem cells in a dynamic cellular and molecular system. The deployment of robust mathematical models will help uncover and explain many still unknown aspects of cell behavior, tissue function, and network organization related to the formation and division of cancer stem cells. The statistical method developed allows biologically meaningful hypotheses about the genetic control mechanisms of carcinogenesis and metastasis to be tested in a quantitative manner.

The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy

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Arnauld eSergé

2016-05-01

Full Text Available The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single-molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation and metastasis.

Temporal dynamics and transcriptional control using single-cell gene expression analysis.

Science.gov (United States)

Kouno, Tsukasa; de Hoon, Michiel; Mar, Jessica C; Tomaru, Yasuhiro; Kawano, Mitsuoki; Carninci, Piero; Suzuki, Harukazu; Hayashizaki, Yoshihide; Shin, Jay W

2013-01-01

Changes in environmental conditions lead to expression variation that manifest at the level of gene regulatory networks. Despite a strong understanding of the role noise plays in synthetic biological systems, it remains unclear how propagation of expression heterogeneity in an endogenous regulatory network is distributed and utilized by cells transitioning through a key developmental event. Here we investigate the temporal dynamics of a single-cell transcriptional network of 45 transcription factors in THP-1 human myeloid monocytic leukemia cells undergoing differentiation to macrophages. We systematically measure temporal regulation of expression and variation by profiling 120 single cells at eight distinct time points, and infer highly controlled regulatory modules through which signaling operates with stochastic effects. This reveals dynamic and specific rewiring as a cellular strategy for differentiation. The integration of both positive and negative co-expression networks further identifies the proto-oncogene MYB as a network hinge to modulate both the pro- and anti-differentiation pathways. Compared to averaged cell populations, temporal single-cell expression profiling provides a much more powerful technique to probe for mechanistic insights underlying cellular differentiation. We believe that our approach will form the basis of novel strategies to study the regulation of transcription at a single-cell level.

β-Cell Ca(2+) dynamics and function are compromised in aging.

Science.gov (United States)

Barker, Christopher J; Li, Luosheng; Köhler, Martin; Berggren, Per-Olof

2015-01-01

Defects in pancreatic β-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in β-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca(2+)]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca(2+) via voltage-dependent Ca(2+) channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca(2+) from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca(2+) regulation and loss of β-cell function, including disturbed [Ca(2+)]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca(2+)]i dynamics in mouse β-cells, particularly in the pattern of [Ca(2+)]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca(2+) mobilization from intracellular stores and decreased β-cell Ca(2+) influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in β-cell signal-transduction result in compromised insulin release and in a diabetic phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

The scale-free dynamics of eukaryotic cells.

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Miguel A Aon

Full Text Available Temporal organization of biological processes requires massively parallel processing on a synchronized time-base. We analyzed time-series data obtained from the bioenergetic oscillatory outputs of Saccharomyces cerevisiae and isolated cardiomyocytes utilizing Relative Dispersional (RDA and Power Spectral (PSA analyses. These analyses revealed broad frequency distributions and evidence for long-term memory in the observed dynamics. Moreover RDA and PSA showed that the bioenergetic dynamics in both systems show fractal scaling over at least 3 orders of magnitude, and that this scaling obeys an inverse power law. Therefore we conclude that in S. cerevisiae and cardiomyocytes the dynamics are scale-free in vivo. Applying RDA and PSA to data generated from an in silico model of mitochondrial function indicated that in yeast and cardiomyocytes the underlying mechanisms regulating the scale-free behavior are similar. We validated this finding in vivo using single cells, and attenuating the activity of the mitochondrial inner membrane anion channel with 4-chlorodiazepam to show that the oscillation of NAD(PH and reactive oxygen species (ROS can be abated in these two evolutionarily distant species. Taken together these data strongly support our hypothesis that the generation of ROS, coupled to redox cycling, driven by cytoplasmic and mitochondrial processes, are at the core of the observed rhythmicity and scale-free dynamics. We argue that the operation of scale-free bioenergetic dynamics plays a fundamental role to integrate cellular function, while providing a framework for robust, yet flexible, responses to the environment.

Evaluating Learner Autonomy: A Dynamic Model with Descriptors

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Maria Giovanna Tassinari

2012-03-01

Full Text Available Every autonomous learning process should entail an evaluation of the learner’s competencies for autonomy. The dynamic model of learner autonomy described in this paper is a tool designed in order to support the self-assessment and evaluation of learning competencies and to help both learners and advisors to focus on relevant aspects of the learning process. The dynamic model accounts for cognitive, metacognitive, action-oriented and affective components of learner autonomy and provides descriptors of learners’ attitudes, competencies and behaviors. It is dynamic in order to allow learners to focus on their own needs and goals.The model (http://www.sprachenzentrum.fuberlin.de/v/autonomiemodell/index.html has been validated in several workshops with experts at the Université Nancy 2, France and at the Freie Universität Berlin, Germany and tested by students, advisors and teachers. It is currently used at the Centre for Independent Language Learning at the Freie Universität Berlin for language advising. Learners can freely choose the components they would like to assess themselves in. Their assessment is then discussed in an advising session, where the learner and the advisor can compare their perspectives, focus on single aspects of the leaning process and set goals for further learning. The students’ feedback gathered in my PhD investigation shows that they are able to benefit from this evaluation; their awareness, self-reflection and decision-making in the autonomous learning process improved.

Spatial and dynamic organization of molecular structures in the cell nucleus

NARCIS (Netherlands)

Brouwer, Anne-Kee

2010-01-01

In this thesis we attempt to provide a better understanding of the principles that underlie the spatial dynamic organization of the cell nucleus. Chapter 1 reviews the current status of knowledge about the structural and functional organization of the cell nucleus. In chapter 2, the development of a

Dynamic model of a micro-tubular solid oxide fuel cell stack including an integrated cooling system

Science.gov (United States)

Hering, Martin; Brouwer, Jacob; Winkler, Wolfgang

2017-02-01

A novel dynamic micro-tubular solid oxide fuel cell (MT-SOFC) and stack model including an integrated cooling system is developed using a quasi three-dimensional, spatially resolved, transient thermodynamic, physical and electrochemical model that accounts for the complex geometrical relations between the cells and cooling-tubes. The modeling approach includes a simplified tubular geometry and stack design including an integrated cooling structure, detailed pressure drop and gas property calculations, the electrical and physical constraints of the stack design that determine the current, as well as control strategies for the temperature. Moreover, an advanced heat transfer balance with detailed radiative heat transfer between the cells and the integrated cooling-tubes, convective heat transfer between the gas flows and the surrounding structures and conductive heat transfer between the solid structures inside of the stack, is included. The detailed model can be used as a design basis for the novel MT-SOFC stack assembly including an integrated cooling system, as well as for the development of a dynamic system control strategy. The evaluated best-case design achieves very high electrical efficiency between around 75 and 55% in the entire power density range between 50 and 550 mW /cm2 due to the novel stack design comprising an integrated cooling structure.

The expression of VE-cadherin in breast cancer cells modulates cell dynamics as a function of tumor differentiation and promotes tumor-endothelial cell interactions.

Science.gov (United States)

Rezaei, Maryam; Cao, Jiahui; Friedrich, Katrin; Kemper, Björn; Brendel, Oliver; Grosser, Marianne; Adrian, Manuela; Baretton, Gustavo; Breier, Georg; Schnittler, Hans-Joachim

2018-01-01

The cadherin switch has profound consequences on cancer invasion and metastasis. The endothelial-specific vascular endothelial cadherin (VE-cadherin) has been demonstrated in diverse cancer types including breast cancer and is supposed to modulate tumor progression and metastasis, but underlying mechanisms need to be better understood. First, we evaluated VE-cadherin expression by tissue microarray in 392 cases of breast cancer tumors and found a diverse expression and distribution of VE-cadherin. Experimental expression of fluorescence-tagged VE-cadherin (VE-EGFP) in undifferentiated, fibroblastoid and E-cadherin-negative MDA-231 (MDA-VE-EGFP) as well as in differentiated E-cadherin-positive MCF-7 human breast cancer cell lines (MCF-VE-EGFP), respectively, displayed differentiation-dependent functional differences. VE-EGFP expression reversed the fibroblastoid MDA-231 cells to an epithelial-like phenotype accompanied by increased β-catenin expression, actin and vimentin remodeling, increased cell spreading and barrier function and a reduced migration ability due to formation of VE-cadherin-mediated cell junctions. The effects were largely absent in both MDA-VE-EGFP and in control MCF-EGFP cell lines. However, MCF-7 cells displayed a VE-cadherin-independent planar cell polarity and directed cell migration that both developed in MDA-231 only after VE-EGFP expression. Furthermore, VE-cadherin expression had no effect on tumor cell proliferation in monocultures while co-culturing with endothelial cells enhanced tumor cell proliferation due to integration of the tumor cells into monolayer where they form VE-cadherin-mediated cell contacts with the endothelium. We propose an interactive VE-cadherin-based crosstalk that might activate proliferation-promoting signals. Together, our study shows a VE-cadherin-mediated cell dynamics and an endothelial-dependent proliferation in a differentiation-dependent manner.

A computational framework for cortical microtubule dynamics in realistically shaped plant cells.

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Bandan Chakrabortty

2018-02-01

Full Text Available Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

A computational framework for cortical microtubule dynamics in realistically shaped plant cells

KAUST Repository

Chakrabortty, Bandan; Blilou, Ikram; Scheres, Ben; Mulder, Bela M.

2018-01-01

Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

A computational framework for cortical microtubule dynamics in realistically shaped plant cells

KAUST Repository

Chakrabortty, Bandan

2018-02-02

Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

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

Directory of Open Access Journals (Sweden)

David Fouchet

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

Sox17-Mediated XEN Cell Conversion Identifies Dynamic Networks Controlling Cell-Fate Decisions in Embryo-Derived Stem Cells

Directory of Open Access Journals (Sweden)

Angela C.H. McDonald

2014-10-01

Full Text Available Little is known about the gene regulatory networks (GRNs distinguishing extraembryonic endoderm (ExEn stem (XEN cells from those that maintain the extensively characterized embryonic stem cell (ESC. An intriguing network candidate is Sox17, an essential transcription factor for XEN derivation and self-renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn, generating XEN cells that contribute to ExEn when placed back into early mouse embryos. Transient Sox17 expression is sufficient to drive this fate change during which time cells transit through distinct intermediate states prior to the generation of functional XEN-like cells. To orchestrate this conversion process, Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the regulation of cell-fate changes and reveals GRNs regulating lineage decisions in the mouse embryo.

Stem cell transplantation as a dynamical system: are clinical outcomes deterministic?

Science.gov (United States)

Toor, Amir A; Kobulnicky, Jared D; Salman, Salman; Roberts, Catherine H; Jameson-Lee, Max; Meier, Jeremy; Scalora, Allison; Sheth, Nihar; Koparde, Vishal; Serrano, Myrna; Buck, Gregory A; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Sabo, Roy T; Neale, Michael C

2014-01-01

Outcomes in stem cell transplantation (SCT) are modeled using probability theory. However, the clinical course following SCT appears to demonstrate many characteristics of dynamical systems, especially when outcomes are considered in the context of immune reconstitution. Dynamical systems tend to evolve over time according to mathematically determined rules. Characteristically, the future states of the system are predicated on the states preceding them, and there is sensitivity to initial conditions. In SCT, the interaction between donor T cells and the recipient may be considered as such a system in which, graft source, conditioning, and early immunosuppression profoundly influence immune reconstitution over time. This eventually determines clinical outcomes, either the emergence of tolerance or the development of graft versus host disease. In this paper, parallels between SCT and dynamical systems are explored and a conceptual framework for developing mathematical models to understand disparate transplant outcomes is proposed.

Usefulness of dynamic MR imaging for the evaluation of transcatheter arterial embolization for hepatocellular carcinoma

International Nuclear Information System (INIS)

Kyomasu, Yoshinori; Nakayama, Masafumi; Kawakami, Mutsumi; Mashima, Yasuoki; Ichinose, Akira; Endou, Kazuo; Chiba, Kazuo; Tanno, Munehiko; Yamada, Hideo

1992-01-01

Thirteen patients with hepatocellular carcinoma (HCC) were studied with dynamic MR imaging in addition to conventional T 1 - and T 2 -weighted and enhanced T 1 -weighted images before and after the treatment of HCC by transcatheter arterial embolization (TAE). Dynamic MR imaging was performed using GRASS (gradient recalled acquisition in the steady state) sequences. The imaging was started at 10 seconds after rapid injection of Gd-diethylenetriaminepentaacetic acid (Gd-DTPA) with 6s breath hold. Thereafter about 12 images were obtained during 6s breath-holding with 20 seconds intervals. On T 1 - and T 2 -weighted images, signal intensity at the tumor tended to increase during the early period after TAE and to decrease later. Intensities of the HCC, however, were heterogeneous. Differentiation among embolic area, necrosis, viable cells and recurrent area, was often difficult only by conventional images. Dynamic GRASS images could clearly demonstrate an embolic area as a region without contrast enhancement. While recurrent tumor could be diagnosed as an area with early enhancement at the arterial phase. Development of the collateral circulation and dominancy of tumor feeding vessels after TAE could also be deduced on dynamic MR images together with enhanced T 1 -weighted images. The dynamic MR imaging was concluded to be a potentially useful procedure for the clinical evaluation of HCC after TAE. (author)

Exploring neural cell dynamics with digital holographic microscopy

KAUST Repository

Marquet, Pierre; Depeursinge, Christian D.; Magistretti, Pierre J.

2013-01-01

In this review, we summarize how the new concept of digital optics applied to the field of holographic microscopy has allowed the development of a reliable and flexible digital holographic quantitative phase microscopy (DH-QPM) technique at the nanoscale particularly suitable for cell imaging. Particular emphasis is placed on the original biological ormation provided by the quantitative phase signal. We present the most relevant DH-QPM applications in the field of cell biology, including automated cell counts, recognition, classification, three-dimensional tracking, discrimination between physiological and pathophysiological states, and the study of cell membrane fluctuations at the nanoscale. In the last part, original results show how DH-QPM can address two important issues in the field of neurobiology, namely, multiple-site optical recording of neuronal activity and noninvasive visualization of dendritic spine dynamics resulting from a full digital holographic microscopy tomographic approach. Copyright © 2013 by Annual Reviews.

Exploring neural cell dynamics with digital holographic microscopy

KAUST Repository

Marquet, Pierre

2013-07-11

In this review, we summarize how the new concept of digital optics applied to the field of holographic microscopy has allowed the development of a reliable and flexible digital holographic quantitative phase microscopy (DH-QPM) technique at the nanoscale particularly suitable for cell imaging. Particular emphasis is placed on the original biological ormation provided by the quantitative phase signal. We present the most relevant DH-QPM applications in the field of cell biology, including automated cell counts, recognition, classification, three-dimensional tracking, discrimination between physiological and pathophysiological states, and the study of cell membrane fluctuations at the nanoscale. In the last part, original results show how DH-QPM can address two important issues in the field of neurobiology, namely, multiple-site optical recording of neuronal activity and noninvasive visualization of dendritic spine dynamics resulting from a full digital holographic microscopy tomographic approach. Copyright © 2013 by Annual Reviews.

Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus

Directory of Open Access Journals (Sweden)

Maki Takagishi

2017-07-01

Full Text Available Motile cilia in ependymal cells, which line the cerebral ventricles, exhibit a coordinated beating motion that drives directional cerebrospinal fluid (CSF flow and guides neuroblast migration. At the apical cortex of these multi-ciliated cells, asymmetric localization of planar cell polarity (PCP proteins is required for the planar polarization of microtubule dynamics, which coordinates cilia orientation. Daple is a disheveled-associating protein that controls the non-canonical Wnt signaling pathway and cell motility. Here, we show that Daple-deficient mice present hydrocephalus and their ependymal cilia lack coordinated orientation. Daple regulates microtubule dynamics at the anterior side of ependymal cells, which in turn orients the cilial basal bodies required for the directional cerebrospinal fluid flow. These results demonstrate an important role for Daple in planar polarity in motile cilia and provide a framework for understanding the mechanisms and functions of planar polarization in the ependymal cells.

Solving dynamic multi-objective problems with vector evaluated particle swarm optimisation

CSIR Research Space (South Africa)

Greeff, M

2008-06-01

Full Text Available Many optimisation problems are multi-objective and change dynamically. Many methods use a weighted average approach to the multiple objectives. This paper introduces the usage of the vector evaluated particle swarm optimiser (VEPSO) to solve dynamic...

An antitubulin agent BCFMT inhibits proliferation of cancer cells and induces cell death by inhibiting microtubule dynamics.

Directory of Open Access Journals (Sweden)

Ankit Rai

Full Text Available Using cell based screening assay, we identified a novel anti-tubulin agent (Z-5-((5-(4-bromo-3-chlorophenylfuran-2-ylmethylene-2-thioxothiazolidin-4-one (BCFMT that inhibited proliferation of human cervical carcinoma (HeLa (IC(50, 7.2 ± 1.8 µM, human breast adenocarcinoma (MCF-7 (IC(50, 10.0 ± 0.5 µM, highly metastatic breast adenocarcinoma (MDA-MB-231 (IC(50, 6.0 ± 1 µM, cisplatin-resistant human ovarian carcinoma (A2780-cis (IC(50, 5.8 ± 0.3 µM and multi-drug resistant mouse mammary tumor (EMT6/AR1 (IC(50, 6.5 ± 1 µM cells. Using several complimentary strategies, BCFMT was found to inhibit cancer cell proliferation at G2/M phase of the cell cycle apparently by targeting microtubules. In addition, BCFMT strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory concentration (10 µM, BCFMT reduced the rates of growing and shortening phases of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased the time microtubules spent in the pause (neither growing nor shortening detectably state by 135% and reduced the dynamicity (dimer exchange per unit time of microtubules by 70%. In vitro, BCFMT bound to tubulin with a dissociation constant of 8.3 ± 1.8 µM, inhibited tubulin assembly and suppressed GTPase activity of microtubules. BCFMT competitively inhibited the binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration (K(i of 5.2 ± 1.5 µM suggesting that it binds to tubulin at the vinblastine site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules, perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and Mad2 at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear accumulation of p53 and its downstream p21, which consequently activated apoptosis in these cells. The results suggested that BCFMT inhibits proliferation of several types of cancer cells including drug

Sensitivity evaluation of dynamic speckle activity measurements using clustering methods

International Nuclear Information System (INIS)

Etchepareborda, Pablo; Federico, Alejandro; Kaufmann, Guillermo H.

2010-01-01

We evaluate and compare the use of competitive neural networks, self-organizing maps, the expectation-maximization algorithm, K-means, and fuzzy C-means techniques as partitional clustering methods, when the sensitivity of the activity measurement of dynamic speckle images needs to be improved. The temporal history of the acquired intensity generated by each pixel is analyzed in a wavelet decomposition framework, and it is shown that the mean energy of its corresponding wavelet coefficients provides a suited feature space for clustering purposes. The sensitivity obtained by using the evaluated clustering techniques is also compared with the well-known methods of Konishi-Fujii, weighted generalized differences, and wavelet entropy. The performance of the partitional clustering approach is evaluated using simulated dynamic speckle patterns and also experimental data.

Rapid and dynamic arginylation of the leading edge β-actin is required for cell migration.

Science.gov (United States)

Pavlyk, Iuliia; Leu, Nicolae A; Vedula, Pavan; Kurosaka, Satoshi; Kashina, Anna

2018-04-01

β-actin plays key roles in cell migration. Our previous work demonstrated that β-actin in migratory non-muscle cells is N-terminally arginylated and that this arginylation is required for normal lamellipodia extension. Here, we examined the function of β-actin arginylation in cell migration. We found that arginylated β-actin is concentrated at the leading edge of lamellipodia and that this enrichment is abolished after serum starvation as well as in contact-inhibited cells in confluent cultures, suggesting that arginylated β-actin at the cell leading edge is coupled to active migration. Arginylated actin levels exhibit dynamic changes in response to cell stimuli, lowered after serum starvation and dramatically elevating within minutes after cell stimulation by readdition of serum or lysophosphatidic acid. These dynamic changes require active translation and are not seen in confluent contact-inhibited cell cultures. Microinjection of arginylated actin antibodies into cells severely and specifically inhibits their migration rates. Together, these data strongly suggest that arginylation of β-actin is a tightly regulated dynamic process that occurs at the leading edge of locomoting cells in response to stimuli and is integral to the signaling network that regulates cell migration. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Time series modeling of live-cell shape dynamics for image-based phenotypic profiling.

Science.gov (United States)

Gordonov, Simon; Hwang, Mun Kyung; Wells, Alan; Gertler, Frank B; Lauffenburger, Douglas A; Bathe, Mark

2016-01-01

Live-cell imaging can be used to capture spatio-temporal aspects of cellular responses that are not accessible to fixed-cell imaging. As the use of live-cell imaging continues to increase, new computational procedures are needed to characterize and classify the temporal dynamics of individual cells. For this purpose, here we present the general experimental-computational framework SAPHIRE (Stochastic Annotation of Phenotypic Individual-cell Responses) to characterize phenotypic cellular responses from time series imaging datasets. Hidden Markov modeling is used to infer and annotate morphological state and state-switching properties from image-derived cell shape measurements. Time series modeling is performed on each cell individually, making the approach broadly useful for analyzing asynchronous cell populations. Two-color fluorescent cells simultaneously expressing actin and nuclear reporters enabled us to profile temporal changes in cell shape following pharmacological inhibition of cytoskeleton-regulatory signaling pathways. Results are compared with existing approaches conventionally applied to fixed-cell imaging datasets, and indicate that time series modeling captures heterogeneous dynamic cellular responses that can improve drug classification and offer additional important insight into mechanisms of drug action. The software is available at http://saphire-hcs.org.

High fidelity visualization of cell-to-cell variation and temporal dynamics in nascent extracellular matrix formation.

Science.gov (United States)

McLeod, Claire M; Mauck, Robert L

2016-12-12

Extracellular matrix dynamics are key to tissue morphogenesis, homeostasis, injury, and repair. The spatiotemporal organization of this matrix has profound biological implications, but is challenging to monitor using standard techniques. Here, we address these challenges by using noncanonical amino acid tagging to fluorescently label extracellular matrix synthesized in the presence of bio-orthogonal methionine analogs. This strategy labels matrix proteins with high resolution, without compromising their distribution or mechanical function. We demonstrate that the organization and temporal dynamics of the proteinaceous matrix depend on the biophysical features of the microenvironment, including the biomaterial scaffold and the niche constructed by cells themselves. Pulse labeling experiments reveal that, in immature constructs, nascent matrix is highly fibrous and interdigitates with pre-existing matrix, while in more developed constructs, nascent matrix lacks fibrous organization and is retained in the immediate pericellular space. Inhibition of collagen crosslinking increases matrix synthesis, but compromises matrix organization. Finally, these data demonstrate marked cell-to-cell heterogeneity amongst both chondrocytes and mesenchymal stem cells undergoing chondrogenesis. Collectively, these results introduce fluorescent noncanonical amino acid tagging as a strategy to investigate spatiotemporal matrix organization, and demonstrate its ability to identify differences in phenotype, microenvironment, and matrix assembly at the single cell level.

Dynamics of Receptor-Mediated Nanoparticle Internalization into Endothelial Cells

Science.gov (United States)

Gonzalez-Rodriguez, David; Barakat, Abdul I.

2015-01-01

Nanoparticles offer a promising medical tool for targeted drug delivery, for example to treat inflamed endothelial cells during the development of atherosclerosis. To inform the design of such therapeutic strategies, we develop a computational model of nanoparticle internalization into endothelial cells, where internalization is driven by receptor-ligand binding and limited by the deformation of the cell membrane and cytoplasm. We specifically consider the case of nanoparticles targeted against ICAM-1 receptors, of relevance for treating atherosclerosis. The model computes the kinetics of the internalization process, the dynamics of binding, and the distribution of stresses exerted between the nanoparticle and the cell membrane. The model predicts the existence of an optimal nanoparticle size for fastest internalization, consistent with experimental observations, as well as the role of bond characteristics, local cell mechanical properties, and external forces in the nanoparticle internalization process. PMID:25901833

Static and dynamic light scattering by red blood cells: A numerical study.

Science.gov (United States)

Mauer, Johannes; Peltomäki, Matti; Poblete, Simón; Gompper, Gerhard; Fedosov, Dmitry A

2017-01-01

Light scattering is a well-established experimental technique, which gains more and more popularity in the biological field because it offers the means for non-invasive imaging and detection. However, the interpretation of light-scattering signals remains challenging due to the complexity of most biological systems. Here, we investigate static and dynamic scattering properties of red blood cells (RBCs) using two mesoscopic hydrodynamics simulation methods-multi-particle collision dynamics and dissipative particle dynamics. Light scattering is studied for various membrane shear elasticities, bending rigidities, and RBC shapes (e.g., biconcave and stomatocyte). Simulation results from the two simulation methods show good agreement, and demonstrate that the static light scattering of a diffusing RBC is not very sensitive to the changes in membrane properties and moderate alterations in cell shapes. We also compute dynamic light scattering of a diffusing RBC, from which dynamic properties of RBCs such as diffusion coefficients can be accessed. In contrast to static light scattering, the dynamic measurements can be employed to differentiate between the biconcave and stomatocytic RBC shapes and generally allow the differentiation based on the membrane properties. Our simulation results can be used for better understanding of light scattering by RBCs and the development of new non-invasive methods for blood-flow monitoring.

Distinct migration and contact dynamics of resting and IL-2-activated human natural killer cells

Directory of Open Access Journals (Sweden)

Per Erik Olofsson

2014-03-01

Full Text Available Natural killer (NK cells serve as one of the first lines of defense against viral infections and transformed cells. NK cell cytotoxicity is not dependent on antigen presentation by target cells, but is dependent on integration of activating and inhibitory signals triggered by receptor–ligand interactions formed at a tight intercellular contact between the NK and target cell, i.e. the immune synapse. We have studied the single-cell migration behavior and target-cell contact dynamics of resting and IL-2-activated human peripheral blood NK cells. Small populations of NK cells and target cells were confined in microwells and imaged by fluorescence microscopy for >8 h. Only the IL-2-activated population of NK cells showed efficient cytotoxicity against the human embryonic kidney (HEK 293T target cells. We found that although the average migration speeds were comparable, activated NK cells showed significantly more dynamic migration behavior, with more frequent transitions between periods of low and high motility. Resting NK cells formed fewer and weaker contacts with target cells, which manifested as shorter conjugation times and in many cases a complete lack of post-conjugation attachment to target cells. Activated NK cells were approximately twice as big as the resting cells, displayed a more migratory phenotype, and were more likely to employ motile scanning of the target cell surface during conjugation. Taken together, our experiments quantify, at the single-cell level, how activation by IL-2 leads to altered NK cell cytotoxicity, migration behavior and contact dynamics.

Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

Directory of Open Access Journals (Sweden)

Katja M. Piltti

2015-09-01

Full Text Available The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.

A multiplexed microfluidic system for evaluation of dynamics of immune-tumor interactions.

Science.gov (United States)

Moore, N; Doty, D; Zielstorff, M; Kariv, I; Moy, L Y; Gimbel, A; Chevillet, J R; Lowry, N; Santos, J; Mott, V; Kratchman, L; Lau, T; Addona, G; Chen, H; Borenstein, J T

2018-05-25

Recapitulation of the tumor microenvironment is critical for probing mechanisms involved in cancer, and for evaluating the tumor-killing potential of chemotherapeutic agents, targeted therapies and immunotherapies. Microfluidic devices have emerged as valuable tools for both mechanistic studies and for preclinical evaluation of therapeutic agents, due to their ability to precisely control drug concentrations and gradients of oxygen and other species in a scalable and potentially high throughput manner. Most existing in vitro microfluidic cancer models are comprised of cultured cancer cells embedded in a physiologically relevant matrix, collocated with vascular-like structures. However, the recent emergence of immune checkpoint inhibitors (ICI) as a powerful therapeutic modality against many cancers has created a need for preclinical in vitro models that accommodate interactions between tumors and immune cells, particularly for assessment of unprocessed tumor fragments harvested directly from patient biopsies. Here we report on a microfluidic model, termed EVIDENT (ex vivo immuno-oncology dynamic environment for tumor biopsies), that accommodates up to 12 separate tumor biopsy fragments interacting with flowing tumor-infiltrating lymphocytes (TILs) in a dynamic microenvironment. Flow control is achieved with a single pump in a simple and scalable configuration, and the entire system is constructed using low-sorption materials, addressing two principal concerns with existing microfluidic cancer models. The system sustains tumor fragments for multiple days, and permits real-time, high-resolution imaging of the interaction between autologous TILs and tumor fragments, enabling mapping of TIL-mediated tumor killing and testing of various ICI treatments versus tumor response. Custom image analytic algorithms based on machine learning reported here provide automated and quantitative assessment of experimental results. Initial studies indicate that the system is capable of

Navier-Stokes Predictions of Dynamic Stability Derivatives: Evaluation of Steady-State Methods

National Research Council Canada - National Science Library

DeSpirito, James; Silton, Sidra I; Weinacht, Paul

2008-01-01

The prediction of the dynamic stability derivatives-roll-damping, Magnus, and pitch-damping moments-were evaluated for three spin-stabilized projectiles using steady-state computational fluid dynamic (CFD) calculations...

Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling

Directory of Open Access Journals (Sweden)

Sarah Filippi

2016-06-01

Full Text Available Cellular signaling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell-to-cell variability in cellular signaling systems remain poorly understood. Here, we measure the dynamics of phosphorylated MEK and ERK across cell populations and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modeling framework to show that extrinsic noise, particularly that from upstream MEK, is the dominant factor causing cell-to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. We furthermore show that without extrinsic noise in the core module, variable (including noisy signals would be faithfully reproduced downstream, but the within-module extrinsic variability distorts these signals and leads to a drastic reduction in the mutual information between incoming signal and ERK activity.

The usefulness of dynamic MR imaging for the evaluation of cervical cancer

International Nuclear Information System (INIS)

Yoon, Jeong Hee; Park, Yeong Mi

2004-01-01

We wished to evaluate the diagnostic usefulness of dynamic MRI in assessing tumor visualization and the parametrial invasion of cervical cancer, and we also wished to determine the most adequate enhancing time by comparing the T2-weighted image (T2WI) and enhanced T1-weighted image (Gd-T1WI). Fifty-three women with histopathologically proven cervical cancer underwent a preoperative MRI. Using a 1.5 T magnet, the fast spin echo axial T2WI without fat saturation was taken; after contrast administration, 20, 40, 60, 90, 120 sec-dynamic MRIs were taken using fast SPGR and spin echo axial Gd-T1WI. Tumor conspicuity and parametrial invasion in each pulse sequence and the most adequate enhancing time for the evaluation of the tumor on dynamic MRI were evaluated prospectively by three radiologists working at three separate sessions. The results were then correlated with the histopathologic findings. The conspicuity of tumor on dynamic MRI (99.4%) and T2WI (95.6%) were better than on Gd-T1WI (89.3%). In the assessment of parametrial invasion of the tumor, the diagnostic accuracy of dynamic MRI, Gd-T1WI and T2WI was 79.9%, 78% and 76.1%, respectively; the highest values were for the dynamic MRI, but there was no statistically significant difference among three pulse sequences. The most adequate enhancing time on dynamic MRI was between 90 seconds and 120 seconds. Dynamic MRI is useful for the assessment of tumor visualization of cervical cancer, and the most appropriate scan time on dynamic MRI is between 90 seconds and 120 seconds. For the determination of parametrial invasion, the dynamic MRI revealed a higher diagnostic accuracy than that of T2WI or Gd-T1WI, but the differences were statistically insignificant

Dynamic J-R Characteristics of RCS Pipe Materials for Ulchin Unit 3/4. (Evaluation of Dynamic Strain Aging Effects)

Energy Technology Data Exchange (ETDEWEB)

Hong, Jun Hwa; Lee, Bong Sang; Yoon, Ji Hyun; Oh, Jong Myung; Kim, Jin Won [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1997-09-01

5 materials (45 1T-CT specimens) were tested to evaluate dynamic J-R characteristics of RCS Pipe Materials for Ulchin Unit 3/4 (Evaluation of Dynamic Strain Aging Effects). The tests were performed by DCPD method at 316 deg C and 25 deg C. The loading rates were 1000mm/min and 2000mm/min. The objectives of this project were to obtain the dynamic J-R curves data of ferritic steels for application of LBB to the RCS pipes of Ulchin Unit 3/4. The test results showed that all of the tested dynamic J-R curves of 5 materials were above the lower bound curve of static J-R curve of pipe materials for Ulchin Unit 3/4. 10 refs., 4 tabs., 16 figs. (author)

Screening dynamic evaluation of SRS cooling water line

International Nuclear Information System (INIS)

Bezler, P.; Shteyngart, S.; Breidenbach, G.

1991-01-01

The production reactors at the Savannah River Site (SRS) have been shut down due to perceived safety concerns. A major concern is the seismic integrity of the plant. A comprehensive program is underway to assess the seismic capacity of the existing systems and components and to upgrade them to acceptable levels. The evaluation of the piping systems at the SRS is a major element of this program. Many of the piping systems at the production reactors were designed without performing dynamic analyses. Instead their design complied with good design practice for dead weight supported systems with proper accommodation of thermal expansion effects. In order to gain some insight as to the seismic capacity of piping installed in this fashion, dynamic analyses were performed for some lines. Since the piping was not seismically supported, the evaluations involved various approximations and the results are only used as a screening test of seismic adequacy. In this paper, the screening evaluations performed for the raw water inlet line are described. This line was selected for evaluation since it was considered typical of the smaller diameter piping systems at the plant. It is a dead weight supported system made up of a run of small diameter piping which extends for great distances over many dead weight supports and through wall penetrations. The results of several evaluations for the system using different approximations to represent the support system are described. 2 figs., 4 tabs

An experimental study of the dynamic behavior of a 2 kW proton exchange membrane fuel cell stack under various loading conditions

International Nuclear Information System (INIS)

Jian, Qifei; Zhao, Yang; Wang, Haoting

2015-01-01

The dynamic behavior of the PEM (proton exchange membrane) fuel cell stack has great effect on the safety and effective operation of its applications. In this paper, a self-designed bulb-array is used to simulate the various loading conditions and study the dynamic behavior of a 2 kW PEM fuel cell stack. An evaluation index, including oscillation rate, pressure variation and dynamic resistance factor, is used to analyze the transient response of the PEM fuel cell stack. It is observed that the stack current increases about 8.6%, and the Oscillation rate decreases more rapidly after activation. In the step-up load stage, the oscillation rate and the dynamic resistance decrease more rapidly as the external load increases. Due to the periodic anodic purge process, a periodic voltage fluctuation can be seen. In addition, when the stack works in the open-loop state (working without the external load), the transient response of the stack current is significantly affected by the hydrogen humidity and the charge double-layer. - Highlights: • The working time of open-loop state significantly affects the transient response. • Oscillation rate decreases faster as the external load increases. • Dynamic resistance factor decreases as the external load increases. • The periodic anodic purge process leads to a slight periodic oscillation of voltage

ClC-3 Promotes Osteogenic Differentiation in MC3T3-E1 Cell After Dynamic Compression.

Science.gov (United States)

Wang, Dawei; Wang, Hao; Gao, Feng; Wang, Kun; Dong, Fusheng

2017-06-01

ClC-3 chloride channel has been proved to have a relationship with the expression of osteogenic markers during osteogenesis, persistent static compression can upregulate the expression of ClC-3 and regulate osteodifferentiation in osteoblasts. However, there was no study about the relationship between the expression of ClC-3 and osteodifferentiation after dynamic compression. In this study, we applied dynamic compression on MC3T3-E1 cells to detect the expression of ClC-3, runt-related transcription factor 2 (Runx2), bone morphogenic protein-2 (BMP-2), osteopontin (OPN), nuclear-associated antigen Ki67 (Ki67), and proliferating cell nuclear antigen (PCNA) in biopress system, then we investigated the expression of these genes after dynamic compression with Chlorotoxin (specific ClC-3 chloride channel inhibitor) added. Under transmission electron microscopy, there were more cell surface protrusions, rough surfaced endoplasmic reticulum, mitochondria, Golgi apparatus, abundant glycogen, and lysosomes scattered in the cytoplasm in MC3T3-E1 cells after dynamic compression. The nucleolus was more obvious. We found that ClC-3 was significantly up-regulated after dynamic compression. The compressive force also up-regulated Runx2, BMP-2, and OPN after dynamic compression for 2, 4 and 8 h. The proliferation gene Ki67 and PCNA did not show significantly change after dynamic compression for 8 h. Chlorotoxin did not change the expression of ClC-3 but reduced the expression of Runx2, BMP-2, and OPN after dynamic compression compared with the group without Cltx added. The data from the current study suggested that ClC-3 may promotes osteogenic differentiation in MC3T3-E1 cell after dynamic compression. J. Cell. Biochem. 118: 1606-1613, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Identifying mechanisms for superdiffusive dynamics in cell trajectories

Science.gov (United States)

Passucci, Giuseppe; Brasch, Megan; Henderson, James; Manning, M. Lisa

Self-propelled particle (SPP) models have been used to explore features of active matter such as motility-induced phase separation, jamming, and flocking, and are often used to model biological cells. However, many cells exhibit super-diffusive trajectories, where displacements scale faster than t 1 / 2 in all directions, and these are not captured by traditional SPP models. We extract cell trajectories from image stacks of mouse fibroblast cells moving on 2D substrates and find super-diffusive mean-squared displacements in all directions across varying densities. Two SPP model modifications have been proposed to capture super-diffusive dynamics: Levy walks and heterogeneous motility parameters. In mouse fibroblast cells displacement probability distributions collapse when time is rescaled by a power greater than 1/2, which is consistent with Levy walks. We show that a simple SPP model with heterogeneous rotational noise can also generate a similar collapse. Furthermore, a close examination of statistics extracted directly from cell trajectories is consistent with a heterogeneous mobility SPP model and inconsistent with a Levy walk model. Our work demonstrates that a simple set of analyses can distinguish between mechanisms for anomalous diffusion in active matter.

Dynamic ubiquitin signaling in cell cycle regulation.

Science.gov (United States)

Gilberto, Samuel; Peter, Matthias

2017-08-07

The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. © 2017 Gilberto and Peter.

Dynamic analysis of magnetic nanoparticles crossing cell membrane

Energy Technology Data Exchange (ETDEWEB)

Pedram, Maysam Z. [Department of Mechanical Engineering, Sharif University of Tech., Azadi Ave., Tehran (Iran, Islamic Republic of); Shamloo, Amir, E-mail: shamloo@sharif.edu [Department of Mechanical Engineering, Sharif University of Tech., Azadi Ave., Tehran (Iran, Islamic Republic of); Ghafar-Zadeh, Ebrahim [Biologically-Inspired Sensors and Actuators Laboratory, Department of Electrical Engineering and Computer science, York University, Keel Street, Toronto (Canada); Alasty, Aria, E-mail: aalasti@sharif.edu [Department of Mechanical Engineering, Sharif University of Tech., Azadi Ave., Tehran (Iran, Islamic Republic of)

2017-05-01

Nowadays, nanoparticles (NPs) are used in a variety of biomedical applications including brain disease diagnostics and subsequent treatments. Among the various types of NPs, magnetic nanoparticles (MNPs) have been implemented by many research groups for an array of life science applications. In this paper, we studied MNPs controlled delivery into the endothelial cells using a magnetic field. Dynamics equations of MNPs were defined in the continuous domain using control theory methods and were applied to crossing the cell membrane. This study, dedicated to clinical and biomedical research applications, offers a guideline for the generation of a magnetic field required for the delivery of MNPs.

Tracking the mechanical dynamics of human embryonic stem cell chromatin

Directory of Open Access Journals (Sweden)

Hinde Elizabeth

2012-12-01

Full Text Available Abstract Background A plastic chromatin structure has emerged as fundamental to the self-renewal and pluripotent capacity of embryonic stem (ES cells. Direct measurement of chromatin dynamics in vivo is, however, challenging as high spatiotemporal resolution is required. Here, we present a new tracking-based method which can detect high frequency chromatin movement and quantify the mechanical dynamics of chromatin in live cells. Results We use this method to study how the mechanical properties of chromatin movement in human embryonic stem cells (hESCs are modulated spatiotemporally during differentiation into cardiomyocytes (CM. Notably, we find that pluripotency is associated with a highly discrete, energy-dependent frequency of chromatin movement that we refer to as a ‘breathing’ state. We find that this ‘breathing’ state is strictly dependent on the metabolic state of the cell and is progressively silenced during differentiation. Conclusions We thus propose that the measured chromatin high frequency movements in hESCs may represent a hallmark of pluripotency and serve as a mechanism to maintain the genome in a transcriptionally accessible state. This is a result that could not have been observed without the high spatial and temporal resolution provided by this novel tracking method.

Four dimensional imaging of E. coli nucleoid organization and dynamics in living cells

Science.gov (United States)

Fisher, J. K.; Bourniquel, A.; Witz, G.; Weiner, B.; Prentiss, M.; Kleckner, N.

2013-01-01

Visualization of living E. coli nucleoids, defined by HupA-mCherry, reveals a discrete, dynamic helical ellipsoid. Three basic features emerge. (i) Nucleoid density efficiently coalesces into longitudinal bundles, giving a stiff, low DNA density ellipsoid. (ii) This ellipsoid is radially confined within the cell cylinder. Radial confinement gives helical shape and drives and directs global nucleoid dynamics, including sister segregation. (iii) Longitudinal density waves flux back and forth along the nucleoid, with 5–10% of density shifting within 5s, enhancing internal nucleoid mobility. Furthermore, sisters separate end-to-end in sequential discontinuous pulses, each elongating the nucleoid by 5–15%. Pulses occur at 20min intervals, at defined cell cycle times. This progression is mediated by sequential installation and release of programmed tethers, implying cyclic accumulation and relief of intra-nucleoid mechanical stress. These effects could comprise a chromosome-based cell cycle engine. Overall, the presented results suggest a general conceptual framework for bacterial nucleoid morphogenesis and dynamics. PMID:23623305

Single-cell resolution of intracellular T cell Ca2+ dynamics in response to frequency-based H2O2 stimulation.

Science.gov (United States)

Kniss-James, Ariel S; Rivet, Catherine A; Chingozha, Loice; Lu, Hang; Kemp, Melissa L

2017-03-01

Adaptive immune cells, such as T cells, integrate information from their extracellular environment through complex signaling networks with exquisite sensitivity in order to direct decisions on proliferation, apoptosis, and cytokine production. These signaling networks are reliant on the interplay between finely tuned secondary messengers, such as Ca 2+ and H 2 O 2 . Frequency response analysis, originally developed in control engineering, is a tool used for discerning complex networks. This analytical technique has been shown to be useful for understanding biological systems and facilitates identification of the dominant behaviour of the system. We probed intracellular Ca 2+ dynamics in the frequency domain to investigate the complex relationship between two second messenger signaling molecules, H 2 O 2 and Ca 2+ , during T cell activation with single cell resolution. Single-cell analysis provides a unique platform for interrogating and monitoring cellular processes of interest. We utilized a previously developed microfluidic device to monitor individual T cells through time while applying a dynamic input to reveal a natural frequency of the system at approximately 2.78 mHz stimulation. Although our network was much larger with more unknown connections than previous applications, we are able to derive features from our data, observe forced oscillations associated with specific amplitudes and frequencies of stimuli, and arrive at conclusions about potential transfer function fits as well as the underlying population dynamics.

Seismic evaluation of a hot cell structure

International Nuclear Information System (INIS)

Srinivasan, M.G.; Kot, C.A.

1995-01-01

The evaluation of the structural capacity of and the seismic demand on an existing hot cell structure in a nuclear facility is described. An ANSYS finite-element model of the cell was constructed, treating the walls as plates and the floor and ceiling as a system of discrete beams. A modal analysis showed that the fundamental frequencies of the cell walls lie far above the earthquake frequency range. An equivalent static analysis of the structure was performed. Based on the analysis it was demonstrated that the hot cell structure, would readily withstand the evaluation basis earthquake

Photoexcitation dynamics in organic solar cell donor/acceptor system

Energy Technology Data Exchange (ETDEWEB)

Aarnio, H.

2012-07-01

In this work, photoinduced absorption techniques have been used in a number of ways to clarify the charge generation and recombination processes in two polymers used in organic solar cells, namely APFO3 and P3HT. Emphasis has been on identifying photoexcitations, modeling their dynamics and determining their lifetimes.

Evaluation of dynamic MRCP after secretin stimulation for biliopancreatic diseases

International Nuclear Information System (INIS)

Ohhigashi, Seiji; Nishio, Takeki; Watanabe, Fumihiko; Haradome, Hiroki; Doi, Osamu

2000-01-01

Both pancreaticobiliary maljunction and pancreatogastrostomy after pancreatoduodenectomy were analyzed to assess the utility of dynamic MRCP after secretin stimulation. Dynamic MRCP obtained every 60 seconds for 15 minutes after secretin administration revealed the bile and pancreatic fluid kinetics. Calculating the intensity value from the MR images allowed objective estimation of the bile and pancreatic fluid kinetics. Thus, this study demonstrated that dynamic MRCP after secretin stimulation was significantly useful in evaluating not only the morphologic features in pancreaticobiliary maljunction but also pancreatic exocrine function after resection of the pancreas. (author)

Particle Image Velocimetry and Computational Fluid Dynamics Analysis of Fuel Cell Manifold

DEFF Research Database (Denmark)

Lebæk, Jesper; Blazniak Andreasen, Marcin; Andresen, Henrik Assenholm

2010-01-01

The inlet effect on the manifold flow in a fuel cell stack was investigated by means of numerical methods (computational fluid dynamics) and experimental methods (particle image velocimetry). At a simulated high current density situation the flow field was mapped on a 70 cell simulated cathode...

Dynamics and Synchrony of Pancreatic beta-cells and Islets

DEFF Research Database (Denmark)

Pedersen, Morten Gram

2006-01-01

description of these processes and their interactions would provide important input in the search for a better treatment of the disease. The thesis describes several aspects of mathematical modeling of beta-cells relevant for the understanding of glucose stimulated insulin secretion. It consists...... and the synchronized behavior of many coupled beta-cells as well as to the synchrony of islets. Rather than developing new biophysical models, the thesis investigates existing models, their integration and simplifications, and analyzed the corresponding dynamics, in order to use these models for investigating...

Feedback dynamics and cell function: Why systems biology is called Systems Biology.

Science.gov (United States)

Wolkenhauer, Olaf; Mesarovic, Mihajlo

2005-05-01

A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.

Dynamic energy budget approach to evaluate antibiotic effects on biofilms

Science.gov (United States)

Birnir, Bjorn; Carpio, Ana; Cebrián, Elena; Vidal, Perfecto

2018-01-01

Quantifying the action of antibiotics on biofilms is essential to devise therapies against chronic infections. Biofilms are bacterial communities attached to moist surfaces, sheltered from external aggressions by a polymeric matrix. Coupling a dynamic energy budget based description of cell metabolism to surrounding concentration fields, we are able to approximate survival curves measured for different antibiotics. We reproduce numerically stratified distributions of cell types within the biofilm and introduce ways to incorporate different resistance mechanisms. Qualitative predictions follow that are in agreement with experimental observations, such as higher survival rates of cells close to the substratum when employing antibiotics targeting active cells or enhanced polymer production when antibiotics are administered. The current computational model enables validation and hypothesis testing when developing therapies.

Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets

Science.gov (United States)

2017-01-01

CD4 T cells, including T regulatory cells (Treg cells) and effector T helper cells (Th cells), and recently identified innate lymphoid cells (ILCs) play important roles in host defense and inflammation. Both CD4 T cells and ILCs can be classified into distinct lineages based on their functions and the expression of lineage-specific genes, including those encoding effector cytokines, cell surface markers, and key transcription factors. It was first recognized that each lineage expresses a specific master transcription factor and the expression of these factors is mutually exclusive because of cross-regulation among these factors. However, recent studies indicate that the master regulators are often coexpressed. Furthermore, the expression of master regulators can be dynamic and quantitative. In this review, we will first discuss similarities and differences between the development and functions of CD4 T cell and ILC subsets and then summarize recent literature on quantitative, dynamic, and cell type–specific balance between the master transcription factors in determining heterogeneity and plasticity of these subsets. PMID:28630089

Evaluating the fermionic determinant of dynamical configurations

International Nuclear Information System (INIS)

Hasenfratz, Anna; Alexandru, Andrei

2002-01-01

We propose and study an improved method to calculate the fermionic determinant of dynamical configurations. The evaluation or at least stochastic estimation of the ratios of fermionic determinants is essential for a recently proposed updating method of smeared link dynamical fermions. This update creates a sequence of configurations by changing a subset of the gauge links by a pure gauge heat bath or over-relaxation step. The acceptance of the proposed configuration depends on the ratio of the fermionic determinants on the new and original configurations. We study this ratio as a function of the number of links that are changed in the heat bath update. We find that even when every link of a given direction and parity of a 10 fm 4 configuration is updated, the average of the determinant ratio is still close to one and with the improved stochastic estimator the proposed change is accepted with about 20% probability. This improvement suggests that the new updating technique can be efficient even on large lattices and could provide an updating method for dynamical overlap actions

Evaluating human cancer cell metastasis in zebrafish

International Nuclear Information System (INIS)

Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

2013-01-01

In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

Interrogation of inhibitor of nuclear factor κB α/nuclear factor κB (IκBα/NF-κB) negative feedback loop dynamics: from single cells to live animals in vivo.

Science.gov (United States)

Moss, Britney L; Elhammali, Adnan; Fowlkes, Tiffanie; Gross, Shimon; Vinjamoori, Anant; Contag, Christopher H; Piwnica-Worms, David

2012-09-07

Full understanding of the biological significance of negative feedback processes requires interrogation at multiple scales as follows: in single cells, cell populations, and live animals in vivo. The transcriptionally coupled IκBα/NF-κB negative feedback loop, a pivotal regulatory node of innate immunity and inflammation, represents a model system for multiscalar reporters. Using a κB(5)→IκBα-FLuc bioluminescent reporter, we rigorously evaluated the dynamics of ΙκBα degradation and subsequent NF-κB transcriptional activity in response to diverse modes of TNFα stimulation. Modulating TNFα concentration or pulse duration yielded complex, reproducible, and differential ΙκBα dynamics in both cell populations and live single cells. Tremendous heterogeneity in the transcriptional amplitudes of individual responding cells was observed, which was greater than the heterogeneity in the transcriptional kinetics of responsive cells. Furthermore, administration of various TNFα doses in vivo generated ΙκBα dynamic profiles in the liver resembling those observed in single cells and populations of cells stimulated with TNFα pulses. This suggested that dose modulation of circulating TNFα was perceived by hepatocytes in vivo as pulses of increasing duration. Thus, a robust bioluminescent reporter strategy enabled rigorous quantitation of NF-κB/ΙκBα dynamics in both live single cells and cell populations and furthermore, revealed reproducible behaviors that informed interpretation of in vivo studies.

On the dynamics of StemBells: Microbubble-conjugated stem cells for ultrasound-controlled delivery

Science.gov (United States)

Kokhuis, Tom J. A.; Naaijkens, Benno A.; Juffermans, Lynda J. M.; Kamp, Otto; van der Steen, Antonius F. W.; Versluis, Michel; de Jong, Nico

2017-07-01

The use of stem cells for regenerative tissue repair is promising but hampered by the low number of cells delivered to the site of injury. To increase the delivery, we propose a technique in which stem cells are linked to functionalized microbubbles, creating echogenic complex dubbed StemBells. StemBells are highly susceptible to acoustic radiation force which can be employed after injection to push the StemBells locally to the treatment site. To optimally benefit from the delivery technique, a thorough characterization of the dynamics of StemBells during ultrasound exposure is needed. Using high-speed optical imaging, we study the dynamics of StemBells as a function of the applied frequency from which resonance curves were constructed. A theoretical model, based on a modified Rayleigh-Plesset type equation, captured the experimental resonance characteristics and radial dynamics in detail.

Ultra-soft PDMS-based magnetoactive elastomers as dynamic cell culture substrata.

Directory of Open Access Journals (Sweden)

Matthias Mayer

Full Text Available Mechanical cues such as extracellular matrix stiffness and movement have a major impact on cell differentiation and function. To replicate these biological features in vitro, soft substrata with tunable elasticity and the possibility for controlled surface translocation are desirable. Here we report on the use of ultra-soft (Young's modulus <100 kPa PDMS-based magnetoactive elastomers (MAE as suitable cell culture substrata. Soft non-viscous PDMS (<18 kPa is produced using a modified extended crosslinker. MAEs are generated by embedding magnetic microparticles into a soft PDMS matrix. Both substrata yield an elasticity-dependent (14 vs. 100 kPa modulation of α-smooth muscle actin expression in primary human fibroblasts. To allow for static or dynamic control of MAE material properties, we devise low magnetic field (≈40 mT stimulation systems compatible with cell-culture environments. Magnetic field-instigated stiffening (14 to 200 kPa of soft MAE enhances the spreading of primary human fibroblasts and decreases PAX-7 transcription in human mesenchymal stem cells. Pulsatile MAE movements are generated using oscillating magnetic fields and are well tolerated by adherent human fibroblasts. This MAE system provides spatial and temporal control of substratum material characteristics and permits novel designs when used as dynamic cell culture substrata or cell culture-coated actuator in tissue engineering applications or biomedical devices.

Dynamic culture induces a cell type-dependent response impacting on the thickness of engineered connective tissues.

Science.gov (United States)

Fortier, Guillaume Marceau; Gauvin, Robert; Proulx, Maryse; Vallée, Maud; Fradette, Julie

2013-04-01

Mesenchymal cells are central to connective tissue homeostasis and are widely used for tissue-engineering applications. Dermal fibroblasts and adipose-derived stromal cells (ASCs) allow successful tissue reconstruction by the self-assembly approach of tissue engineering. This method leads to the production of multilayered tissues, devoid of exogenous biomaterials, that can be used as stromal compartments for skin or vesical reconstruction. These tissues are formed by combining cell sheets, generated through cell stimulation with ascorbic acid, which favours the cell-derived production/organization of matrix components. Since media motion can impact on cell behaviour, we investigated the effect of dynamic culture on mesenchymal cells during tissue reconstruction, using the self-assembly method. Tissues produced using ASCs in the presence of a wave-like movement were nearly twice thicker than under standard conditions, while no difference was observed for tissues produced from dermal fibroblasts. The increased matrix deposition was not correlated with an increased proliferation of ASCs, or by higher transcript levels of fibronectin or collagens I and III. A 30% increase of type V collagen mRNA was observed. Interestingly, tissues engineered from dermal fibroblasts featured a four-fold higher level of MMP-1 transcripts under dynamic conditions. Mechanical properties were similar for tissues reconstructed using dynamic or static conditions. Finally, cell sheets produced using ASCs under dynamic conditions could readily be manipulated, resulting in a 2 week reduction of the production time (from 5 to 3 weeks). Our results describe a distinctive property of ASCs' response to media motion, indicating that their culture under dynamic conditions leads to optimized tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.

Expression dynamics of self-renewal factors for spermatogonial stem cells in the mouse testis.

Science.gov (United States)

Sakai, Mizuki; Masaki, Kaito; Aiba, Shota; Tone, Masaaki; Takashima, Seiji

2018-04-16

Glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are bona fide self-renewal factors for spermatogonial stem cells (SSCs). Although GDNF is indispensable for the maintenance of SSCs, the role of FGF2 in the testis remains to be elucidated. To clarify this, the expression dynamics and regulatory mechanisms of Fgf2 and Gdnf in the mouse testes were analyzed. It is well known that Sertoli cells express Gdnf, and its receptor is expressed in a subset of undifferentiated spermatogonia, including SSCs. However, we found that Fgf2 was mainly expressed in the germ cells and its receptors were expressed not only in the cultured spermatogonial cell line, but also in testicular somatic cells. Aging, hypophysectomy, retinoic acid treatment, and testicular injury induced distinct Fgf2 and Gdnf expression dynamics, suggesting a difference in the expression mechanism of Fgf2 and Gdnf in the testis. Such differences might cause a dynamic fluctuation of Gdnf/Fgf2 ratio depending on the intrinsic/extrinsic cues. Considering that FGF2-cultured spermatogonia exhibit more differentiated phenotype than those cultured with GDNF, FGF2 might play a role distinct from that of GDNF in the testis, despite the fact that both factors are self-renewal factor for SSC in vitro.

Pea Border Cell Maturation and Release Involve Complex Cell Wall Structural Dynamics1[OPEN

Science.gov (United States)

2017-01-01

The adhesion of plant cells is vital for support and protection of the plant body and is maintained by a variety of molecular associations between cell wall components. In some specialized cases, though, plant cells are programmed to detach, and root cap-derived border cells are examples of this. Border cells (in some species known as border-like cells) provide an expendable barrier between roots and the environment. Their maturation and release is an important but poorly characterized cell separation event. To gain a deeper insight into the complex cellular dynamics underlying this process, we undertook a systematic, detailed analysis of pea (Pisum sativum) root tip cell walls. Our study included immunocarbohydrate microarray profiling, monosaccharide composition determination, Fourier-transformed infrared microspectroscopy, quantitative reverse transcription-PCR of cell wall biosynthetic genes, analysis of hydrolytic activities, transmission electron microscopy, and immunolocalization of cell wall components. Using this integrated glycobiology approach, we identified multiple novel modes of cell wall structural and compositional rearrangement during root cap growth and the release of border cells. Our findings provide a new level of detail about border cell maturation and enable us to develop a model of the separation process. We propose that loss of adhesion by the dissolution of homogalacturonan in the middle lamellae is augmented by an active biophysical process of cell curvature driven by the polarized distribution of xyloglucan and extensin epitopes. PMID:28400496

Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming.

Science.gov (United States)

Li, Rui; Cauchy, Pierre; Ramamoorthy, Senthilkumar; Boller, Sören; Chavez, Lukas; Grosschedl, Rudolf

2018-01-15

B-cell fate determination requires the action of transcription factors that operate in a regulatory network to activate B-lineage genes and repress lineage-inappropriate genes. However, the dynamics and hierarchy of events in B-cell programming remain obscure. To uncouple the dynamics of transcription factor expression from functional consequences, we generated induction systems in developmentally arrested Ebf1 -/- pre-pro-B cells to allow precise experimental control of EBF1 expression in the genomic context of progenitor cells. Consistent with the described role of EBF1 as a pioneer transcription factor, we show in a time-resolved analysis that EBF1 occupancy coincides with EBF1 expression and precedes the formation of chromatin accessibility. We observed dynamic patterns of EBF1 target gene expression and sequential up-regulation of transcription factors that expand the regulatory network at the pro-B-cell stage. A continuous EBF1 function was found to be required for Cd79a promoter activity and for the maintenance of an accessible chromatin domain that is permissive for binding of other transcription factors. Notably, transient EBF1 occupancy was detected at lineage-inappropriate genes prior to their silencing in pro-B cells. Thus, persistent and transient functions of EBF1 allow for an ordered sequence of epigenetic and transcriptional events in B-cell programming. © 2018 Li et al.; Published by Cold Spring Harbor Laboratory Press.

Evaluation of renal function with dynamic MRI-T2-weighted gradient echo technique

International Nuclear Information System (INIS)

Kato, Katsuya

1995-01-01

To evaluate the usefulness of dynamic MRI of kidneys in healthy volunteers and patients with different 24-hour creatinine clearance (Ccr) levels, a dynamic study that employed the T2 weighted gradient echo technique (FLASH: TR/TE=34/25 msec, flip angle= 20 degrees) with single images during breathhold was performed on 10 healthy volunteers and 35 patients, all examined for the Ccr and suspected of having renal parenchymal disease after a phantom study. T1-weighted and dynamic MR imagings were obtained with a 1.5T imager. I analyzed the time-intensity curve of renal cortex and medulla, and defined a cortex decreased ratio (CDR) and medulla decreased ratio (MDR) in comparison with the Ccr. The cortico-medullary difference ratio (CMDR) of T1WI was also compared with the Ccr. The parameters of the T2 dynamic MRI study (CDR, MDR) better correlated with the Ccr than CMDR. Renal function can be quantitatively evaluated with the T2 dynamic MRI and there is a possibility that we can qualitatively evaluate the renal dysfunction and estimate its cause. (author)

Computational fluid dynamics analysis of an innovative start-up method of high temperature fuel cells using dynamic 3d model

Directory of Open Access Journals (Sweden)

Kupecki Jakub

2017-03-01

Full Text Available The article presents a numerical analysis of an innovative method for starting systems based on high temperature fuel cells. The possibility of preheating the fuel cell stacks from the cold state to the nominal working conditions encounters several limitations related to heat transfer and stability of materials. The lack of rapid and safe start-up methods limits the proliferation of MCFCs and SOFCs. For that reason, an innovative method was developed and verified using the numerical analysis presented in the paper. A dynamic 3D model was developed that enables thermo-fluidic investigations and determination of measures for shortening the preheating time of the high temperature fuel cell stacks. The model was implemented in ANSYS Fluent computational fluid dynamic (CFD software and was used for verification of the proposed start-up method. The SOFC was chosen as a reference fuel cell technology for the study. Results obtained from the study are presented and discussed.

Variable-angle epifluorescence microscopy characterizes protein dynamics in the vicinity of plasma membrane in plant cells.

Science.gov (United States)

Chen, Tong; Ji, Dongchao; Tian, Shiping

2018-03-14

The assembly of protein complexes and compositional lipid patterning act together to endow cells with the plasticity required to maintain compositional heterogeneity with respect to individual proteins. Hence, the applications for imaging protein localization and dynamics require high accuracy, particularly at high spatio-temporal level. We provided experimental data for the applications of Variable-Angle Epifluorescence Microscopy (VAEM) in dissecting protein dynamics in plant cells. The VAEM-based co-localization analysis took penetration depth and incident angle into consideration. Besides direct overlap of dual-color fluorescence signals, the co-localization analysis was carried out quantitatively in combination with the methodology for calculating puncta distance and protein proximity index. Besides, simultaneous VAEM tracking of cytoskeletal dynamics provided more insights into coordinated responses of actin filaments and microtubules. Moreover, lateral motility of membrane proteins was analyzed by calculating diffusion coefficients and kymograph analysis, which represented an alternative method for examining protein motility. The present study presented experimental evidence on illustrating the use of VAEM in tracking and dissecting protein dynamics, dissecting endosomal dynamics, cell structure assembly along with membrane microdomain and protein motility in intact plant cells.

An evaluation of Dynamic TOPMODEL for low flow simulation

Science.gov (United States)

Coxon, G.; Freer, J. E.; Quinn, N.; Woods, R. A.; Wagener, T.; Howden, N. J. K.

2015-12-01

Hydrological models are essential tools for drought risk management, often providing input to water resource system models, aiding our understanding of low flow processes within catchments and providing low flow predictions. However, simulating low flows and droughts is challenging as hydrological systems often demonstrate threshold effects in connectivity, non-linear groundwater contributions and a greater influence of water resource system elements during low flow periods. These dynamic processes are typically not well represented in commonly used hydrological models due to data and model limitations. Furthermore, calibrated or behavioural models may not be effectively evaluated during more extreme drought periods. A better understanding of the processes that occur during low flows and how these are represented within models is thus required if we want to be able to provide robust and reliable predictions of future drought events. In this study, we assess the performance of dynamic TOPMODEL for low flow simulation. Dynamic TOPMODEL was applied to a number of UK catchments in the Thames region using time series of observed rainfall and potential evapotranspiration data that captured multiple historic droughts over a period of several years. The model performance was assessed against the observed discharge time series using a limits of acceptability framework, which included uncertainty in the discharge time series. We evaluate the models against multiple signatures of catchment low-flow behaviour and investigate differences in model performance between catchments, model diagnostics and for different low flow periods. We also considered the impact of surface water and groundwater abstractions and discharges on the observed discharge time series and how this affected the model evaluation. From analysing the model performance, we suggest future improvements to Dynamic TOPMODEL to improve the representation of low flow processes within the model structure.

A Novel Method for Dynamic Multicriteria Decision Making with Hybrid Evaluation Information

OpenAIRE

Shihu Liu; Tauqir Ahmed Moughal

2014-01-01

How to select the most desirable pattern(s) is often a crucial step for decision making problem. By taking uncertainty as well as dynamic of database into consideration, in this paper, we construct a dynamic multicriteria decision making procedure, where the evaluation information of criteria is expressed by real number, intuitionistic fuzzy number, and interval-valued intuitionistic fuzzy number. During the process of algorithm construction, the evaluation information at all time episodes is...

A dynamic simulation tool for the battery-hybrid hydrogen fuel cell vehicle

Energy Technology Data Exchange (ETDEWEB)

Moore, R.M. [Hawaii Natural Energy Institute, University of Hawaii, Manoa (United States); Ramaswamy, S.; Cunningham, J.M. [California Univ., Berkeley, CA (United States); Hauer, K.H. [xcellvision, Major-Hirst-Strasse 11, 38422 Wolfsburg (Germany)

2006-10-15

This paper describes a dynamic fuel cell vehicle simulation tool for the battery-hybrid direct-hydrogen fuel cell vehicle. The emphasis is on simulation of the hybridized hydrogen fuel cell system within an existing fuel cell vehicle simulation tool. The discussion is focused on the simulation of the sub-systems that are unique to the hybridized direct-hydrogen vehicle, and builds on a previous paper that described a simulation tool for the load-following direct-hydrogen vehicle. The configuration of the general fuel cell vehicle simulation tool has been previously presented in detail, and is only briefly reviewed in the introduction to this paper. Strictly speaking, the results provided in this paper only serve as an example that is valid for the specific fuel cell vehicle design configuration analyzed. Different design choices may lead to different results, depending strongly on the parameters used and choices taken during the detailed design process required for this highly non-linear and n-dimensional system. The primary purpose of this paper is not to provide a dynamic simulation tool that is the ''final word'' for the ''optimal'' hybrid fuel cell vehicle design. The primary purpose is to provide an explanation of a simulation method for analyzing the energetic aspects of a hybrid fuel cell vehicle. (Abstract Copyright [2006], Wiley Periodicals, Inc.)

T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

Science.gov (United States)

Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

2016-10-27

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment

Local difference measures between complex networks for dynamical system model evaluation.

Science.gov (United States)

Lange, Stefan; Donges, Jonathan F; Volkholz, Jan; Kurths, Jürgen

2015-01-01

A faithful modeling of real-world dynamical systems necessitates model evaluation. A recent promising methodological approach to this problem has been based on complex networks, which in turn have proven useful for the characterization of dynamical systems. In this context, we introduce three local network difference measures and demonstrate their capabilities in the field of climate modeling, where these measures facilitate a spatially explicit model evaluation.Building on a recent study by Feldhoff et al. [8] we comparatively analyze statistical and dynamical regional climate simulations of the South American monsoon system [corrected]. types of climate networks representing different aspects of rainfall dynamics are constructed from the modeled precipitation space-time series. Specifically, we define simple graphs based on positive as well as negative rank correlations between rainfall anomaly time series at different locations, and such based on spatial synchronizations of extreme rain events. An evaluation against respective networks built from daily satellite data provided by the Tropical Rainfall Measuring Mission 3B42 V7 reveals far greater differences in model performance between network types for a fixed but arbitrary climate model than between climate models for a fixed but arbitrary network type. We identify two sources of uncertainty in this respect. Firstly, climate variability limits fidelity, particularly in the case of the extreme event network; and secondly, larger geographical link lengths render link misplacements more likely, most notably in the case of the anticorrelation network; both contributions are quantified using suitable ensembles of surrogate networks. Our model evaluation approach is applicable to any multidimensional dynamical system and especially our simple graph difference measures are highly versatile as the graphs to be compared may be constructed in whatever way required. Generalizations to directed as well as edge- and node

Automated analysis of invadopodia dynamics in live cells

Directory of Open Access Journals (Sweden)

Matthew E. Berginski

2014-07-01

Full Text Available Multiple cell types form specialized protein complexes that are used by the cell to actively degrade the surrounding extracellular matrix. These structures are called podosomes or invadopodia and collectively referred to as invadosomes. Due to their potential importance in both healthy physiology as well as in pathological conditions such as cancer, the characterization of these structures has been of increasing interest. Following early descriptions of invadopodia, assays were developed which labelled the matrix underneath metastatic cancer cells allowing for the assessment of invadopodia activity in motile cells. However, characterization of invadopodia using these methods has traditionally been done manually with time-consuming and potentially biased quantification methods, limiting the number of experiments and the quantity of data that can be analysed. We have developed a system to automate the segmentation, tracking and quantification of invadopodia in time-lapse fluorescence image sets at both the single invadopodia level and whole cell level. We rigorously tested the ability of the method to detect changes in invadopodia formation and dynamics through the use of well-characterized small molecule inhibitors, with known effects on invadopodia. Our results demonstrate the ability of this analysis method to quantify changes in invadopodia formation from live cell imaging data in a high throughput, automated manner.

Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments.

Directory of Open Access Journals (Sweden)

Peter Ashcroft

2017-10-01

Full Text Available Hematopoietic stem cells in mammals are known to reside mostly in the bone marrow, but also transitively passage in small numbers in the blood. Experimental findings have suggested that they exist in a dynamic equilibrium, continuously migrating between these two compartments. Here we construct an individual-based mathematical model of this process, which is parametrised using existing empirical findings from mice. This approach allows us to quantify the amount of migration between the bone marrow niches and the peripheral blood. We use this model to investigate clonal hematopoiesis, which is a significant risk factor for hematologic cancers. We also analyse the engraftment of donor stem cells into non-conditioned and conditioned hosts, quantifying the impact of different treatment scenarios. The simplicity of the model permits a thorough mathematical analysis, providing deeper insights into the dynamics of both the model and of the real-world system. We predict the time taken for mutant clones to expand within a host, as well as chimerism levels that can be expected following transplantation therapy, and the probability that a preconditioned host is reconstituted by donor cells.

Controlled initiation and quantitative visualization of cell interaction dynamics - a novel hybrid microscopy method -

NARCIS (Netherlands)

Snijder-van As, M.I.

2010-01-01

This thesis describes the development, validation, and application of a hybrid microscopy technique to study cell-substrate and cell-cell interactions in a controlled and quantitative manner. We studied the spatial and temporal dynamics of the selected membrane molecules CD6 and the activated

Evaluations of high-resolution dynamically downscaled ensembles over the contiguous United States Climate Dynamics

Energy Technology Data Exchange (ETDEWEB)

Zobel, Zachary; Wang, Jiali; Wuebbles, Donald J.; Kotamarthi, V. Rao

2018-02-01

This study uses Weather Research and Forecast (WRF) model to evaluate the performance of six dynamical downscaled decadal historical simulations with 12-km resolution for a large domain (7200 x 6180 km) that covers most of North America. The initial and boundary conditions are from three global climate models (GCMs) and one reanalysis data. The GCMs employed in this study are the Geophysical Fluid Dynamics Laboratory Earth System Model with Generalized Ocean Layer Dynamics component, Community Climate System Model, version 4, and the Hadley Centre Global Environment Model, version 2-Earth System. The reanalysis data is from the National Centers for Environmental Prediction-US. Department of Energy Reanalysis II. We analyze the effects of bias correcting, the lateral boundary conditions and the effects of spectral nudging. We evaluate the model performance for seven surface variables and four upper atmospheric variables based on their climatology and extremes for seven subregions across the United States. The results indicate that the simulation’s performance depends on both location and the features/variable being tested. We find that the use of bias correction and/or nudging is beneficial in many situations, but employing these when running the RCM is not always an improvement when compared to the reference data. The use of an ensemble mean and median leads to a better performance in measuring the climatology, while it is significantly biased for the extremes, showing much larger differences than individual GCM driven model simulations from the reference data. This study provides a comprehensive evaluation of these historical model runs in order to make informed decisions when making future projections.

Continuous administration of short-lived isotopes for evaluating dynamic parameters

International Nuclear Information System (INIS)

Selikson, M.

1985-01-01

In this paper it is shown that continuous but varying infusions (specifically, exponential infusions) of a short-lived radionuclide can be used to evaluate a wide range of dynamic parameters. The detector response to exponential infusions is derived. An example of an inert diffusible substrate for evaluating regional flow and a glucose model for evaluating regional metabolic rate are both worked out. The advantages of using exponential infusion methods are discussed

Estimation of Cell Proliferation Dynamics Using CFSE Data

Science.gov (United States)

Banks, H.T.; Sutton, Karyn L.; Thompson, W. Clayton; Bocharov, Gennady; Roose, Dirk; Schenkel, Tim; Meyerhans, Andreas

2010-01-01

Advances in fluorescent labeling of cells as measured by flow cytometry have allowed for quantitative studies of proliferating populations of cells. The investigations (Luzyanina et al. in J. Math. Biol. 54:57–89, 2007; J. Math. Biol., 2009; Theor. Biol. Med. Model. 4:1–26, 2007) contain a mathematical model with fluorescence intensity as a structure variable to describe the evolution in time of proliferating cells labeled by carboxyfluorescein succinimidyl ester (CFSE). Here, this model and several extensions/modifications are discussed. Suggestions for improvements are presented and analyzed with respect to statistical significance for better agreement between model solutions and experimental data. These investigations suggest that the new decay/label loss and time dependent effective proliferation and death rates do indeed provide improved fits of the model to data. Statistical models for the observed variability/noise in the data are discussed with implications for uncertainty quantification. The resulting new cell dynamics model should prove useful in proliferation assay tracking and modeling, with numerous applications in the biomedical sciences. PMID:20195910

Evaluation of a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay (SOT)

Science.gov (United States)

The Embryonic Stem Cell Test (EST) has been used to evaluate the effects of xenobiotics using three endpoints, stem cell differentiation, stem cell viability and 3T3-cell viability. Our research goal is to establish amodel system that would evaluate chemical effects using a singl...

An oscillating dynamic model of collective cells in a monolayer

Science.gov (United States)

Lin, Shao-Zhen; Xue, Shi-Lei; Li, Bo; Feng, Xi-Qiao

2018-03-01

Periodic oscillations of collective cells occur in the morphogenesis and organogenesis of various tissues and organs. In this paper, an oscillating cytodynamic model is presented by integrating the chemomechanical interplay between the RhoA effector signaling pathway and cell deformation. We show that both an isolated cell and a cell aggregate can undergo spontaneous oscillations as a result of Hopf bifurcation, upon which the system evolves into a limit cycle of chemomechanical oscillations. The dynamic characteristics are tailored by the mechanical properties of cells (e.g., elasticity, contractility, and intercellular tension) and the chemical reactions involved in the RhoA effector signaling pathway. External forces are found to modulate the oscillation intensity of collective cells in the monolayer and to polarize their oscillations along the direction of external tension. The proposed cytodynamic model can recapitulate the prominent features of cell oscillations observed in a variety of experiments, including both isolated cells (e.g., spreading mouse embryonic fibroblasts, migrating amoeboid cells, and suspending 3T3 fibroblasts) and multicellular systems (e.g., Drosophila embryogenesis and oogenesis).

Dynamic thermal model of photovoltaic cell illuminated by laser beam

Science.gov (United States)

Liu, Xiaoguang; Hua, Wenshen; Guo, Tong

2015-07-01

Photovoltaic cell is one of the most important components of laser powered unmanned aerial vehicle. Illuminated by high power laser beam, photovoltaic cell temperature increases significantly, which leads to efficiency drop, or even physical damage. To avoid such situation, the temperature of photovoltaic cell must be predicted precisely. A dynamic thermal model of photovoltaic cell is established in this paper, and the relationships between photovoltaic cell temperature and laser power, wind speed, ambient temperature are also analyzed. Simulation result indicates that illuminated by a laser beam, the temperature of photovoltaic cell rises gradually and reach to a constant maximum value. There is an approximately linear rise in photovoltaic cell temperature as the laser flux gets higher. The higher wind speed is, the stronger forced convection is, and then the lower photovoltaic cell temperature is. But the relationship between photovoltaic cell temperature and wind speed is not linear. Photovoltaic cell temperature is proportional to the ambient temperature. For each increase of 1 degree of ambient temperature, there is approximate 1 degree increase in photovoltaic cell temperature. The result will provide fundamentals to take reasonable measures to control photovoltaic cell temperature.

Single-cell and population NF-κB dynamic responses depend on lipopolysaccharide preparation.

Directory of Open Access Journals (Sweden)

Miriam V Gutschow

Full Text Available Lipopolysaccharide (LPS, found in the outer membrane of gram-negative bacteria, elicits a strong response from the transcription factor family Nuclear factor (NF-κB via Toll-like receptor (TLR 4. The cellular response to lipopolysaccharide varies depending on the source and preparation of the ligand, however. Our goal was to compare single-cell NF-κB dynamics across multiple sources and concentrations of LPS.Using live-cell fluorescence microscopy, we determined the NF-κB activation dynamics of hundreds of single cells expressing a p65-dsRed fusion protein. We used computational image analysis to measure the nuclear localization of the fusion protein in the cells over time. The concentration range spanned up to nine orders of magnitude for three E. coli LPS preparations. We find that the LPS preparations induce markedly different responses, even accounting for potency differences. We also find that the ability of soluble TNF receptor to affect NF-κB dynamics varies strikingly across the three preparations.Our work strongly suggests that the cellular response to LPS is highly sensitive to the source and preparation of the ligand. We therefore caution that conclusions drawn from experiments using one preparation may not be applicable to LPS in general.

A model of cell-wall dynamics during sporulation in Bacillus subtilis

Science.gov (United States)

Yap, Li-Wei; Endres, Robert G.

To survive starvation, Bacillus subtilis forms durable spores. After asymmetric cell division, the septum grows around the forespore in a process called engulfment, but the mechanism of force generation is unknown. Here, we derived a novel biophysical model for the dynamics of cell-wall remodeling during engulfment based on a balancing of dissipative, active, and mechanical forces. By plotting phase diagrams, we predict that sporulation is promoted by a line tension from the attachment of the septum to the outer cell wall, as well as by an imbalance in turgor pressures in the mother-cell and forespore compartments. We also predict that significant mother-cell growth hinders engulfment. Hence, relatively simple physical principles may guide this complex biological process.

Modeling universal dynamics of cell spreading on elastic substrates.

Science.gov (United States)

Fan, Houfu; Li, Shaofan

2015-11-01

A three-dimensional (3D) multiscale moving contact line model is combined with a soft matter cell model to study the universal dynamics of cell spreading over elastic substrates. We have studied both the early stage and the late stage cell spreading by taking into account the actin tension effect. In this work, the cell is modeled as an active nematic droplet, and the substrate is modeled as a St. Venant Kirchhoff elastic medium. A complete 3D simulation of cell spreading has been carried out. The simulation results show that the spreading area versus spreading time at different stages obeys specific power laws, which is in good agreement with experimental data and theoretical prediction reported in the literature. Moreover, the simulation results show that the substrate elasticity may affect force dipole distribution inside the cell. The advantage of this approach is that it combines the hydrodynamics of actin retrograde flow with moving contact line model so that it can naturally include actin tension effect resulting from actin polymerization and actomyosin contraction, and thus it might be capable of simulating complex cellular scale phenomenon, such as cell spreading or even crawling.

Biomechanical Analysis and Evaluation Technology Using Human Multi-Body Dynamic Model

Energy Technology Data Exchange (ETDEWEB)

Kim, Yoon Hyuk; Shin, June Ho; Khurelbaatar, Tsolmonbaatar [Kyung Hee University, Yongin (Korea, Republic of)

2011-10-15

This paper presents the biomechanical analysis and evaluation technology of musculoskeletal system by multi-body human dynamic model and 3-D motion capture data. First, medical image based geometric model and material properties of tissue were used to develop the human dynamic model and 3-D motion capture data based motion analysis techniques were develop to quantify the in-vivo joint kinematics, joint moment, joint force, and muscle force. Walking and push-up motion was investigated using the developed model. The present model and technologies would be useful to apply the biomechanical analysis and evaluation of human activities.

The improvement of dynamic universal testing machine for hot cell usages

International Nuclear Information System (INIS)

Ahn, Sang Bok; Lee, Key Soon; Park, Dae Kyu; Hong, Kwon Pyo; Choo, Yong Sun

1998-01-01

Dynamic universal testing machine(UTM) were developed for hot cell usages, which can perform tensile, compression, bending, fracture toughness and fatigue crack growth tests. In this report, technical reviews in the course of developing machine were described. Detailed subjects are as follows; 1. Outline of testing method using dynamic UTM 2. Detailed testing system organizations 3. Technical specification to develop machine 4. Setting up load string 5. Inspection and pre-commissioning tests on machine. (author). 14 figs

Feedback Linearized Aircraft Control Using Dynamic Cell Structure

Science.gov (United States)

Jorgensen, C. C.

1998-01-01

A Dynamic Cell Structure (DCS ) Neural Network was developed which learns a topology representing network (TRN) of F-15 aircraft aerodynamic stability and control derivatives. The network is combined with a feedback linearized tracking controller to produce a robust control architecture capable of handling multiple accident and off-nominal flight scenarios. This paper describes network and its performance for accident scenarios including differential stabilator lock, soft sensor failure, control, stability derivative variation, and turbulence.

Dynamic load balancing algorithm for molecular dynamics based on Voronoi cells domain decompositions

Energy Technology Data Exchange (ETDEWEB)

Fattebert, J.-L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Richards, D.F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Glosli, J.N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2012-12-01

We present a new algorithm for automatic parallel load balancing in classical molecular dynamics. It assumes a spatial domain decomposition of particles into Voronoi cells. It is a gradient method which attempts to minimize a cost function by displacing Voronoi sites associated with each processor/sub-domain along steepest descent directions. Excellent load balance has been obtained for quasi-2D and 3D practical applications, with up to 440·10⁶ particles on 65,536 MPI tasks.

Heterogeneous fates and dynamic rearrangement of regenerative epidermis-derived cells during zebrafish fin regeneration.

Science.gov (United States)

Shibata, Eri; Ando, Kazunori; Murase, Emiko; Kawakami, Atsushi

2018-04-13

The regenerative epidermis (RE) is a specialized tissue that plays an essential role in tissue regeneration. However, the fate of the RE during and after regeneration is unknown. In this study, we performed Cre- loxP -mediated cell fate tracking and revealed the fates of a major population of the RE cells that express fibronectin 1b ( fn1b ) during zebrafish fin regeneration. Our study showed that these RE cells are mainly recruited from the inter-ray epidermis, and that they follow heterogeneous cell fates. Early recruited cells contribute to initial wound healing and soon disappear by apoptosis, while the later recruited cells contribute to the regenerated epidermis. Intriguingly, many of these cells are also expelled from the regenerated tissue by a dynamic caudal movement of the epidermis over time, and in turn the loss of epidermal cells is replenished by a global self-replication of basal and suprabasal cells in fin. De-differentiation of non-basal epidermal cells into the basal epidermal cells did not occur during regeneration. Overall, our study reveals the heterogeneous fates of RE cells and a dynamic rearrangement of the epidermis during and after regeneration. © 2018. Published by The Company of Biologists Ltd.

Evaluation of dynamic testing of as-built civil engineering structures

International Nuclear Information System (INIS)

Srinivasan, M.G.; Kot, C.A.; Hsieh, B.J.

1985-01-01

This paper summarizes an evaluation of dynamic tests performed on large as-built structures. The objectives and methods (excitation and data analysis) of tests are reviewed. The utility and limitations of dynamic testing in light of actual experience is discussed. Though low-level tests in themselves will not be useful for predicting structural response to strong ground motion, they are useful for verifying linear models and for clarifying physical phenomena related to soil-structure interaction

A dynamic course of T cell defects in individuals at risk for mood disorders

NARCIS (Netherlands)

Snijders, G.; Schiweck, C.; Mesman, E.; Grosse, L.; De Wit, H.; Nolen, W. A.; Drexhage, H. A.; Hillegers, M. H. J.

Objectives: T cell abnormalities have been repeatedly reported in adult patients with mood disorders, suggesting a role of these cells in the pathogenesis of these disorders. In the present study, we explored the dynamics of circulating T cell subsets over time in a population at high familial risk

A dynamic course of T cell defects in individuals at risk for mood disorders

NARCIS (Netherlands)

Snijders, G.; Schiweck, C.; Mesman, E.; Grosse, L.; De Wit, H.; Nolen, W. A.; Drexhage, H. A.; Hillegers, M. H. J.

2016-01-01

OBJECTIVES: T cell abnormalities have been repeatedly reported in adult patients with mood disorders, suggesting a role of these cells in the pathogenesis of these disorders. In the present study, we explored the dynamics of circulating T cell subsets over time in a population at high familial risk

Cell cycle evaluation of granulosa cells in the {gamma}-irradiated mouse ovarian follicles

Energy Technology Data Exchange (ETDEWEB)

KIm, Jin Kyu; Lee, Chang Joo; Lee, Young Keun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Song, Kang Won; Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

1999-03-01

This study was carried out to evaluate the biochemical and morphological effects of ionizing radiation on mouse ovarian follicles. Immature mice (ICR, 3 week-old) were irradiated with a dose of LD{sub 80(30)} at KAERI. The ovaries were collected after 6 hours, 12 hours, 1 day, and 2 days post irradiation. With the morphological basis of the histological staining with hematoxylin-eosin, immunohistochemical preparation using in situ 3'-end labeling was evaluated. Flow cytometric evaluation of DNA extracted from the whole ovary was performed. The percentage of A{sub 0} (subpopulation of cells with degraded DNA and with lower DNA fluorescence than G{sub 0}/G{sub 1} cells), apoptotic, cells in the cell cycle was significantly higher in the irradiated group than in the control group. The number of in situ 3'-end labeled follicles increased at 6 hours post irradiation. All the analyses represented that the ionizing radiation-induced follicular atresia was taken place via an apoptotic degeneration. Such a degeneration underwent very fast and acutely. Therefore, it is concluded that the radiation-induced follicular degeneration is, like the spontaneous atresia, mediated by an acute apoptosis of follicular granulosa cells. Flow cytometric evaluation of cell cycles can make the role for quantifying the atretic follicles and understanding the mechanism of the radiation-induced cell death.

Regeneration of Achilles' tendon: the role of dynamic stimulation for enhanced cell proliferation and mechanical properties.

Science.gov (United States)

Lee, Jongman; Guarino, Vincenzo; Gloria, Antonio; Ambrosio, Luigi; Tae, Giyoong; Kim, Young Ha; Jung, Youngmee; Kim, Sang-Heon; Kim, Soo Hyun

2010-01-01

The tissue engineering of tendon was studied using highly elastic poly(L-lactide-co-epsilon-caprolactone) (PLCL) scaffolds and focusing on the effect of dynamic tensile stimulation. Tenocytes from rabbit Achilles tendon were seeded (1.0 x 10(6) cells/scaffold) onto porous PLCL scaffolds and cultured for periods of 2 weeks and 4 weeks. This was performed in a static system and also in a bioreactor equipped with tensile modulation which mimicked the environmental surroundings of tendons with respect to tensile extension. The degradation of the polymeric scaffolds during the culture was relatively slow. However, there was an indication that cells accelerated the degradation of PLCL scaffolds. The scaffold/cell adducts from the static culture exhibited inferior strength (at 2 weeks 350 kPa, 4 weeks 300 kPa) compared to the control without cells (at 2 weeks 460 kPa, 4 weeks 340 kPa), indicating that the cells contributed to the enhanced degradation. On the contrary, the corresponding values of the adducts from the dynamic culture (at 2 weeks 430 kPa, 4 weeks 370 kPa) were similar to, or higher than, those from the control. This could be explained by the increased quantity of cells and neo-tissues in the case of dynamic culture compensating for the loss in tensile strength. Compared with static and dynamic culture conditions, mechanical stimulation played a crucial role in the regeneration of tendon tissue. In the case of the dynamic culture system, cell proliferation was enhanced and secretion of collagen type I was increased, as evidenced by DNA assay and histological and immunofluorescence analysis. Thus, tendon regeneration, indicated by improved mechanical and biological properties, was demonstrated, confirming the effect of mechanical stimulation. It could be concluded that the dynamic tensile stimulation appeared to be an essential factor in tendon/ligament tissue engineering, and that elastic PLCL co-polymers could be very beneficial in this process.

Evolutionary dynamics of adult stem cells: comparison of random and immortal-strand segregation mechanisms.

Science.gov (United States)

Tannenbaum, Emmanuel; Sherley, James L; Shakhnovich, Eugene I

2005-04-01

This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell and (2) "immortal DNA strand" co-segregation, for which the stem cell retains the daughter chromosomes with the oldest parent strands. Immortal strand co-segregation is a mechanism, originally proposed by [Cairns Nature (London) 255, 197 (1975)], by which stem cells preserve the integrity of their genomes. For random segregation, we develop an ordered strand pair formulation of the dynamics, analogous to the ordered strand pair formalism developed for quasispecies dynamics involving semiconservative replication with imperfect lesion repair (in this context, lesion repair is taken to mean repair of postreplication base-pair mismatches). Interestingly, a similar formulation is possible with immortal strand co-segregation, despite the fact that this segregation mechanism is age dependent. From our model we are able to mathematically show that, when lesion repair is imperfect, then immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosome segregation. Furthermore, our model allows us to estimate the optimal lesion repair efficiency for preserving an adult stem cell population for a given period of time. For human stem cells, we obtain that mispaired bases still present after replication and cell division should be left untouched, to avoid potentially fixing a mutation in both DNA strands.

Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters

Science.gov (United States)

Wang, Hai-yi; Su, Zi-hua; Xu, Xiao; Sun, Zhi-peng; Duan, Fei-xue; Song, Yuan-yuan; Li, Lu; Wang, Ying-wei; Ma, Xin; Guo, Ai-tao; Ma, Lin; Ye, Hui-yi

2016-01-01

Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan–rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K trans & Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID:27380733

Dynamic CT in the abdominal organ, 2. Dynamics in the abdominal malignancies

Energy Technology Data Exchange (ETDEWEB)

Fukuda, K [Jikei Univ., Tokyo (Japan). School of Medicine

1980-03-01

The potential role of the abdominal dynamic CT in malignant tumors was evaluated. Among total of 112 cases dynamically studied included were, 22 cases of abdominal malignancies, renal cell carcinoma in 7, hepatocellular carcinoma in 7, metastatic liver tumor in 5, renal pelvic carcinoma in 2, and pancreatic cystadenocarcinoma in one. The results led to the following advantages of the abdominal dynamic CT over conventional CT. (1) The tumor thrombus and the lymphnode involvement could be better demonstrated. (2) The tumor vessels and the tumor stain could be depicted. (3) The extent of the tumor in the parenchyma could be better appreciated. The more invasive catheter angiography would likely to be replaced by the abdominal dynamic CT in the selected case.

Dynamic simulation of a direct carbonate fuel cell power plant

Energy Technology Data Exchange (ETDEWEB)

Ernest, J.B. [Fluor Daniel, Inc., Irvine, CA (United States); Ghezel-Ayagh, H.; Kush, A.K. [Fuel Cell Engineering, Danbury, CT (United States)

1996-12-31

Fuel Cell Engineering Corporation (FCE) is commercializing a 2.85 MW Direct carbonate Fuel Cell (DFC) power plant. The commercialization sequence has already progressed through construction and operation of the first commercial-scale DFC power plant on a U.S. electric utility, the 2 MW Santa Clara Demonstration Project (SCDP), and the completion of the early phases of a Commercial Plant design. A 400 kW fuel cell stack Test Facility is being built at Energy Research Corporation (ERC), FCE`s parent company, which will be capable of testing commercial-sized fuel cell stacks in an integrated plant configuration. Fluor Daniel, Inc. provided engineering, procurement, and construction services for SCDP and has jointly developed the Commercial Plant design with FCE, focusing on the balance-of-plant (BOP) equipment outside of the fuel cell modules. This paper provides a brief orientation to the dynamic simulation of a fuel cell power plant and the benefits offered.

Numerical Investigation on Dynamic Crushing Behavior of Auxetic Honeycombs with Various Cell-Wall Angles

Directory of Open Access Journals (Sweden)

Xin-chun Zhang

2015-02-01

Full Text Available Auxetic honeycombs have proven to be an attractive advantage in actual engineering applications owing to their unique mechanical characteristic and better energy absorption ability. The in-plane dynamic crushing behaviors of the honeycombs with various cell-wall angles are studied by means of explicit dynamic finite element simulation. The influences of the cell-wall angle, the impact velocity, and the edge thickness on the macro/microdeformation behaviors, the plateau stresses, and the specific energy absorption of auxetic honeycombs are discussed in detail. Numerical results show, that except for the impact velocity and the edge thickness, the in-plane dynamic performances of auxetic honeycombs also rely on the cell-wall angle. The “> <”-mode local deformation bands form under low- or moderate-velocity impacting, which results in lateral compression shrinkage and shows negative Poisson's ratio during the crushing. For the given impact velocity, the plateau stress at the proximal end and the energy-absorbed ability can be improved by increasing the negative cell angle, the relative density, the impact velocity, and the matrix material strength. When the microcell parameters are the constant, the plateau stresses are proportional to the square of impact velocity.

Dynamic cell culture system (7-IML-1)

Science.gov (United States)

Cogoli, Augusto

1992-01-01

This experiment is one of the Biorack experiments being flown on the International Microgravity Laboratory 1 (MIL-1) mission as part of an investigation studying cell proliferation and performance in space. One of the objectives of this investigation is to assess the potential benefits of bioprocessing in space with the ultimate goal of developing a bioreactor for continuous cell cultures in space. This experiment will test the operation of an automated culture chamber that was designed for use in a Bioreactor in space. The device to be tested is called the Dynamic Cell Culture System (DCCS). It is a simple device in which media are renewed or chemicals are injected automatically, by means of osmotic pumps. This experiment uses four Type I/O experiment containers. One DCCS unit, which contains a culture chamber with renewal of medium and a second chamber without a medium supply fits in each container. Two DCCS units are maintained under zero gravity conditions during the on-orbit period. The other two units are maintained under 1 gh conditions in a 1 g centrifuge. The schedule for incubator transfer is given.

Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data.

Science.gov (United States)

Kyoda, Koji; Tohsato, Yukako; Ho, Kenneth H L; Onami, Shuichi

2015-04-01

Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

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

KAUST Repository

Kachalo, Së ma; Naveed, Hammad; Cao, Youfang; Zhao, Jieling; Liang, Jie

2015-01-01

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

A Group Creativity Support System for Dynamic Idea Evaluation

DEFF Research Database (Denmark)

Ulrich, Frank

2015-01-01

Idea evaluation is necessary in most modern organizations to identify the level of novelty and usefulness of new ideas. However, current idea evaluation research hinders creativity by primarily supporting convergent thinking (narrowing down ideas to a few tangible solutions), while divergent...... thinking (the development of wildly creative and novel thoughts patterns) is discounted. In this paper, this current view of idea evaluation is challenged through the development of a prototype that supports dynamic idea evaluation. The prototype uses knowledge created during evaluative processes...... to facilitate divergent thinking in a Group Creativity Support System (GCSS) designed from state-of-the-art research. The prototype is interpretively explored through a field experiment in a Danish IS research department. Consequently, the prototype demonstrates the ability to including divergent thinking...

Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.

Science.gov (United States)

Hopke, Alex; Brown, Alistair J P; Hall, Rebecca A; Wheeler, Robert T

2018-04-01

Deadly infections from opportunistic fungi have risen in frequency, largely because of the at-risk immunocompromised population created by advances in modern medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and therapy because it acts as both an environmental barrier and as the major interface with the host immune system. Human fungal pathogens use architectural strategies to mask epitopes from the host and prevent immune surveillance, and recent work elucidates how biotic and abiotic stresses present during infection can either block or enhance masking. The signaling components implicated in regulating fungal immune recognition can teach us how cell wall dynamics are controlled, and represent potential targets for interventions designed to boost or dampen immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

Energy Technology Data Exchange (ETDEWEB)

Blom, Magdalena; Reis, Katarina [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Heldin, Johan [Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala SE-751 22 Uppsala (Sweden); Kreuger, Johan [Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala (Sweden); Aspenström, Pontus, E-mail: pontus.aspenstrom@ki.se [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden)

2017-03-15

RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

International Nuclear Information System (INIS)

Blom, Magdalena; Reis, Katarina; Heldin, Johan; Kreuger, Johan; Aspenström, Pontus

2017-01-01

RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

Science.gov (United States)

Kagawa, Yoshinori; Matsumoto, Shinji; Kamioka, Yuji; Mimori, Koshi; Naito, Yoko; Ishii, Taeko; Okuzaki, Daisuke; Nishida, Naohiro; Maeda, Sakae; Naito, Atsushi; Kikuta, Junichi; Nishikawa, Keizo; Nishimura, Junichi; Haraguchi, Naotsugu; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Ishii, Hideshi; Doki, Yuichiro; Matsuda, Michiyuki; Kikuchi, Akira; Mori, Masaki; Ishii, Masaru

2013-01-01

The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

Directory of Open Access Journals (Sweden)

Yoshinori Kagawa

Full Text Available The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP, was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

Cryopreservation of testicular tissue before long-term testicular cell culture does not alter in vitro cell dynamics

NARCIS (Netherlands)

Baert, Yoni; Braye, Aude; Struijk, Robin B.; van Pelt, Ans M. M.; Goossens, Ellen

2015-01-01

To assess whether testicular cell dynamics are altered during long-term culture after testicular tissue cryopreservation. Experimental basic science study. Reproductive biology laboratory. Testicular tissue with normal spermatogenesis was obtained from six donors. None. Detection and comparison of

The dynamic and steady state behavior of a PEM fuel cell as an electric energy source

Energy Technology Data Exchange (ETDEWEB)

Costa, R.A. [Fundacao Educacional de Barretos (FEB), School of Electrical Engineering, Av. Prof. Roberto Frade Monte, 389 Aeroporto, 14783.226, Barretos, SP (Brazil); Camacho, J.R. [Universidade Federal de Uberlandia, School of Electrical Engineering, Rural Electricity and Alternative Energy Sources Lab., Av. Joao N. de Avila, 2121, 38400.902, Uberlandia, MG (Brazil)

2006-10-27

The main objective of this work is to extract information on the internal behavior of three small polymer electrolyte membrane fuel cells under static and dynamic load conditions. A computational model was developed using Scilab [SCILAB 4, Scilab-a free scientific software package, http://www.scilab.org/, INRIA, France, December, 2005] to simulate the static and dynamic performance [J.M. Correa, A.F. Farret, L.N. Canha, An analysis of the dynamic performance of proton exchange membrane fuel cells using an electrochemical model, in: 27th Annual Conference of IEEE Industrial Electronics Society, 2001, pp. 141-146] of this particular type of fuel cell. This dynamic model is based on electrochemical equations and takes into consideration most of the chemical and physical characteristics of the device in order to generate electric power. The model takes into consideration the operating, design parameters and physical material properties. The results show the internal losses and concentration effects behavior, which are of interest for power engineers and researchers. (author)

The dynamic and steady state behavior of a PEM fuel cell as an electric energy source

Science.gov (United States)

Costa, R. A.; Camacho, J. R.

The main objective of this work is to extract information on the internal behavior of three small polymer electrolyte membrane fuel cells under static and dynamic load conditions. A computational model was developed using Scilab [SCILAB 4, Scilab-a free scientific software package, http://www.scilab.org/, INRIA, France, December, 2005] to simulate the static and dynamic performance [J.M. Correa, A.F. Farret, L.N. Canha, An analysis of the dynamic performance of proton exchange membrane fuel cells using an electrochemical model, in: 27th Annual Conference of IEEE Industrial Electronics Society, 2001, pp. 141-146] of this particular type of fuel cell. This dynamic model is based on electrochemical equations and takes into consideration most of the chemical and physical characteristics of the device in order to generate electric power. The model takes into consideration the operating, design parameters and physical material properties. The results show the internal losses and concentration effects behavior, which are of interest for power engineers and researchers.

The dynamic behavior of chemically "stiffened" red blood cells in microchannel flows.

Science.gov (United States)

Forsyth, Alison M; Wan, Jiandi; Ristenpart, William D; Stone, Howard A

2010-07-01

The rigidity of red blood cells (RBCs) plays an important role in whole blood viscosity and is correlated with several cardiovascular diseases. Two chemical agents that are commonly used to study cell deformation are diamide and glutaraldehyde. Despite diamide's common usage, there are discrepancies in the literature surrounding diamide's effect on the deformation of RBCs in shear and pressure-driven flows; in particular, shear flow experiments have shown that diamide stiffens cells, while pressure-driven flow in capillaries did not give this result. We performed pressure-driven flow experiments with RBCs in a microfluidic constriction and quantified the cell dynamics using high-speed imaging. Diamide, which affects RBCs by cross-linking spectrin skeletal membrane proteins, did not reduce deformation and showed an unchanged effective strain rate when compared to healthy cells. In contrast, glutaraldehyde, which is a non-specific fixative that acts on all components of the cell, did reduce deformation and showed increased instances of tumbling, both of which are characteristic features of stiffened, or rigidified, cells. Because glutaraldehyde increases the effective viscosity of the cytoplasm and lipid membrane while diamide does not, one possible explanation for our results is that viscous effects in the cytoplasm and/or lipid membrane are a dominant factor in dictating dynamic responses of RBCs in pressure-driven flows. Finally, literature on the use of diamide as a stiffening agent is summarized, and provides supporting evidence for our conclusions. Copyright 2010 Elsevier Inc. All rights reserved.

EVALUATION OF DYNAMIC INDICATORS OF SIX-AXLE LOCOMOTIVE

Directory of Open Access Journals (Sweden)

S. V. Myamlin

2015-04-01

Full Text Available Purpose. The paper is devoted to dynamic characteristics evaluation of the locomotive with prospective design and determination the feasibility of its use on the Ukrainian railways. Methodology. The methods of mathematical and computer modeling of the dynamics of railway vehicles, as well as methods for the numerical integration of systems of ordinary nonlinear differential equations were used to solve the problem. Findings. The calculated diagram of a locomotive on three-axle bogies was built to solve the problem, and it is a system of rigid bodies connected by various elements of rheology. The mathematical model of the locomotive movement, allowing studying its spatial vibrations at driving on straight and curved sections of the track with random irregularities in plan and profile was developed with use of this calculated diagram. At compiling the mathematical model took into account both geometric (nonlinearity profile of the wheel roll surface and physical nonlinearity of the system (the work forces of dry friction, nonlinearity characteristics of interaction forces between wheels and rails. The multivariate calculations, which allowed assessing the dynamic qualities of the locomotive at its movement along straight and curved sections of the track, were realized with the use of computer modeling. The smoothness movement indicators of the locomotive in horizontal and vertical planes, frame strength, coefficients of vertical dynamics in the first and second stages of the suspension, the load factor of resistance against the derailment of the wheel from the rail were determined at the period of research. In addition, a comparison of the obtained results with similar characteristics is widely used on the Ukrainian railways in six-axle locomotive TE 116. The influence of speed and technical state of the track on the locomotive traffic safety was determined.Originality. A mathematical model of the spatial movement of a six-axle locomotive with

Evaluating the Dynamic Characteristics of Retrofitted RC Beams

International Nuclear Information System (INIS)

Ghods, Amir S.; Esfahani, Mohamad R.; Moghaddasie, Behrang

2008-01-01

The aim of this experimental study was to investigate the relationship between the damage and changes in dynamic characteristics of reinforced concrete members strengthened with Carbon Fiber Reinforced Polymer (CFRP). Modal analysis is a popular non-destructive method for evaluating health of structural systems. A total of 8 reinforced concrete beams with similar dimensions were made using concrete with two different compressive strengths and reinforcement ratios. Monotonic loading was applied with four-point-bending setup in order to generate different damage levels in the specimens while dynamic testing was conducted to monitor the changes in dynamic characteristics of the specimens. In order to investigate the effect of CFRP on static and dynamic properties of specimens, some of the beams were loaded to half of their ultimate load carrying capacity and then were retrofitted using composite laminates with different configuration. Retrofitted specimens demonstrated elevated load carrying capacity, higher flexural stiffness and lower displacement ductility. By increasing the damage level in specimens, frequencies of the beams were decreased and after strengthening these values were improved significantly. The intensity of the damage level in each specimen affects the shape of its mode as well. Fixed points and curvatures of mode shapes of beams tend to move toward the location of the damage in each case

Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state.

Directory of Open Access Journals (Sweden)

Grace E Fox

Full Text Available Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC, an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine's psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA, and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine.

The cell engineering construction and function evaluation of multi-layer biochip dialyzer.

Science.gov (United States)

Zhu, Wen; Li, Jiwei; Liu, Jianfeng

2013-10-01

We report the fabrication and function evaluation of multi-layer biochip dialyzer. Such device may potentially be applied to the wearable hemodialysis systems. By merging the advantages of microfluidic chip technology with cell engineering, both functions of glomerular filtration and renal tubule physiological activity are integrated in the same device. This device is designed into a laminated structure, in which the chip number of the superimposed layer can be arbitrarily tailored in accordance with the requirements of dialysis capacity. We propose that such structure can overcome the obstacles of large size and detached structure of the traditional hollow fiber dialyzer. To construct this multilayer biochips dialyzer, two types of dialyzer device with two-layered and six-layered chips are assembled, respectively. Cell adhesion and proliferation on three different dialysis membrane materials under static and dynamic conditions are investigated and compared. The filtration capability, re-absorption function and excrete ammonia function of the resulting multi-layer biochip dialyzer are evaluated. The results reveal that the constructed device can perform higher filtration efficiency and also play a role of renal tubule. This methodology may be useful in developing "scaling down" artificial kidneys that can act as wearable or even implantable hemodialysis systems.

Accelerating molecular dynamic simulation on the cell processor and Playstation 3.

Science.gov (United States)

Luttmann, Edgar; Ensign, Daniel L; Vaidyanathan, Vishal; Houston, Mike; Rimon, Noam; Øland, Jeppe; Jayachandran, Guha; Friedrichs, Mark; Pande, Vijay S

2009-01-30

Implementation of molecular dynamics (MD) calculations on novel architectures will vastly increase its power to calculate the physical properties of complex systems. Herein, we detail algorithmic advances developed to accelerate MD simulations on the Cell processor, a commodity processor found in PlayStation 3 (PS3). In particular, we discuss issues regarding memory access versus computation and the types of calculations which are best suited for streaming processors such as the Cell, focusing on implicit solvation models. We conclude with a comparison of improved performance on the PS3's Cell processor over more traditional processors. (c) 2008 Wiley Periodicals, Inc.

Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

Science.gov (United States)

Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

2017-01-01

A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

Lukasiewicz-Topos Models of Neural Networks, Cell Genome and Interactome Nonlinear Dynamic Models

CERN Document Server

Baianu, I C

2004-01-01

A categorical and Lukasiewicz-Topos framework for Lukasiewicz Algebraic Logic models of nonlinear dynamics in complex functional systems such as neural networks, genomes and cell interactomes is proposed. Lukasiewicz Algebraic Logic models of genetic networks and signaling pathways in cells are formulated in terms of nonlinear dynamic systems with n-state components that allow for the generalization of previous logical models of both genetic activities and neural networks. An algebraic formulation of variable 'next-state functions' is extended to a Lukasiewicz Topos with an n-valued Lukasiewicz Algebraic Logic subobject classifier description that represents non-random and nonlinear network activities as well as their transformations in developmental processes and carcinogenesis.

Neutral dynamics and cell renewal of colonic crypts in homeostatic regime

Science.gov (United States)

Fendrik, A. J.; Romanelli, L.; Rotondo, E.

2018-05-01

The self renewal process in colonic crypts is the object of several studies. We present here a new compartment model with the following characteristics: (a) we distinguish different classes of cells: stem cells, six generations of transit amplifying cells and the differentiated cells; (b) in order to take into account the monoclonal character of crypts in homeostatic regimes we include symmetric divisions of the stem cells. We first consider the dynamic differential equations that describe the evolution of the mean values of the populations, but the small observed value of the total number of cells involved plus the huge dispersion of experimental data found in the literature leads us to study the stochastic discrete process. This analysis allows us to study fluctuations, the neutral drift that leads to monoclonality, and the effects of the fixation of mutant clones.

Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells.

Science.gov (United States)

Shipony, Zohar; Mukamel, Zohar; Cohen, Netta Mendelson; Landan, Gilad; Chomsky, Elad; Zeliger, Shlomit Reich; Fried, Yael Chagit; Ainbinder, Elena; Friedman, Nir; Tanay, Amos

2014-09-04

Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type-specific gene expression. Here we develop new methods for quantitative inference of DNA methylation turnover rates, and show that human embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells. In contrast, somatic cells transmit considerable epigenetic information to progenies. Paradoxically, the persistence of the somatic epigenome makes it more vulnerable to noise, since random epimutations can accumulate to massively perturb the epigenomic ground state. The rate of epigenetic perturbation depends on the genomic context, and, in particular, DNA methylation loss is coupled to late DNA replication dynamics. Epigenetic perturbation is not observed in the pluripotent state, because the rapid turnover-based equilibrium continuously reinforces the canonical state. This dynamic epigenetic equilibrium also explains how the epigenome can be reprogrammed quickly and to near perfection after induced pluripotency.

An integrated methodology for the dynamic performance and reliability evaluation of fault-tolerant systems

International Nuclear Information System (INIS)

Dominguez-Garcia, Alejandro D.; Kassakian, John G.; Schindall, Joel E.; Zinchuk, Jeffrey J.

2008-01-01

We propose an integrated methodology for the reliability and dynamic performance analysis of fault-tolerant systems. This methodology uses a behavioral model of the system dynamics, similar to the ones used by control engineers to design the control system, but also incorporates artifacts to model the failure behavior of each component. These artifacts include component failure modes (and associated failure rates) and how those failure modes affect the dynamic behavior of the component. The methodology bases the system evaluation on the analysis of the dynamics of the different configurations the system can reach after component failures occur. For each of the possible system configurations, a performance evaluation of its dynamic behavior is carried out to check whether its properties, e.g., accuracy, overshoot, or settling time, which are called performance metrics, meet system requirements. Markov chains are used to model the stochastic process associated with the different configurations that a system can adopt when failures occur. This methodology not only enables an integrated framework for evaluating dynamic performance and reliability of fault-tolerant systems, but also enables a method for guiding the system design process, and further optimization. To illustrate the methodology, we present a case-study of a lateral-directional flight control system for a fighter aircraft

The Living Cell as a Multi-agent Organisation: A Compositional Organisation Model of Intracellular Dynamics

Science.gov (United States)

Jonker, C. M.; Snoep, J. L.; Treur, J.; Westerhoff, H. V.; Wijngaards, W. C. A.

Within the areas of Computational Organisation Theory and Artificial Intelligence, techniques have been developed to simulate and analyse dynamics within organisations in society. Usually these modelling techniques are applied to factories and to the internal organisation of their process flows, thus obtaining models of complex organisations at various levels of aggregation. The dynamics in living cells are often interpreted in terms of well-organised processes, a bacterium being considered a (micro)factory. This suggests that organisation modelling techniques may also benefit their analysis. Using the example of Escherichia coli it is shown how indeed agent-based organisational modelling techniques can be used to simulate and analyse E.coli's intracellular dynamics. Exploiting the abstraction levels entailed by this perspective, a concise model is obtained that is readily simulated and analysed at the various levels of aggregation, yet shows the cell's essential dynamic patterns.

Programming Cells for Dynamic Assembly of Inorganic Nano-Objects with Spatiotemporal Control.

Science.gov (United States)

Wang, Xinyu; Pu, Jiahua; An, Bolin; Li, Yingfeng; Shang, Yuequn; Ning, Zhijun; Liu, Yi; Ba, Fang; Zhang, Jiaming; Zhong, Chao

2018-04-01

Programming living cells to organize inorganic nano-objects (NOs) in a spatiotemporally precise fashion would advance new techniques for creating ordered ensembles of NOs and new bio-abiotic hybrid materials with emerging functionalities. Bacterial cells often grow in cellular communities called biofilms. Here, a strategy is reported for programming dynamic biofilm formation for the synchronized assembly of discrete NOs or hetero-nanostructures on diverse interfaces in a dynamic, scalable, and hierarchical fashion. By engineering Escherichia coli to sense blue light and respond by producing biofilm curli fibers, biofilm formation is spatially controlled and the patterned NOs' assembly is simultaneously achieved. Diverse and complex fluorescent quantum dot patterns with a minimum patterning resolution of 100 µm are demonstrated. By temporally controlling the sequential addition of NOs into the culture, multilayered heterostructured thin films are fabricated through autonomous layer-by-layer assembly. It is demonstrated that biologically dynamic self-assembly can be used to advance a new repertoire of nanotechnologies and materials with increasing complexity that would be otherwise challenging to produce. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic Model of High Temperature PEM Fuel Cell Stack Temperature

DEFF Research Database (Denmark)

Andreasen, Søren Juhl; Kær, Søren Knudsen

2007-01-01

cathode air cooled 30 cell HTPEM fuel cell stack developed at the Institute of Energy Technology at Aalborg University. This fuel cell stack uses PEMEAS Celtec P-1000 membranes, runs on pure hydrogen in a dead end anode configuration with a purge valve. The cooling of the stack is managed by running......The present work involves the development of a model for predicting the dynamic temperature of a high temperature PEM (HTPEM) fuel cell stack. The model is developed to test different thermal control strategies before implementing them in the actual system. The test system consists of a prototype...... the stack at a high stoichiometric air flow. This is possible because of the PBI fuel cell membranes used, and the very low pressure drop in the stack. The model consists of a discrete thermal model dividing the stack into three parts: inlet, middle and end and predicting the temperatures in these three...

Numerical modelling of closed-cell aluminium foam under dynamic loading

Science.gov (United States)

Hazell, Paul; Kader, M. A.; Islam, M. A.; Escobedo, J. P.; Saadatfar, M.

2015-06-01

Closed-cell aluminium foams are extensively used in aerospace and automobile industries. The understanding of their behaviour under impact loading conditions is extremely important since impact problems are directly related to design of these engineering structures. This research investigates the response of a closed-cell aluminium foam (CYMAT) subjected to dynamic loading using the finite element software ABAQUS/explicit. The aim of this research is to numerically investigate the material and structural properties of closed-cell aluminium foam under impact loading conditions with interest in shock propagation and its effects on cell wall deformation. A μ-CT based 3D foam geometry is developed to simulate the local cell collapse behaviours. A number of numerical techniques are applied for modelling the crush behaviour of aluminium foam to obtain the more accurate results. The simulation results are compared with experimental data. Comparison of the results shows a good correlation between the experimental results and numerical predictions.

Structural dynamics of the cell nucleus

Science.gov (United States)

Wiegert, Simon; Bading, Hilmar

2011-01-01

Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons. PMID:21738832

GPI-anchored protein organization and dynamics at the cell surface.

Science.gov (United States)

Saha, Suvrajit; Anilkumar, Anupama Ambika; Mayor, Satyajit

2016-02-01

The surface of eukaryotic cells is a multi-component fluid bilayer in which glycosylphosphatidylinositol (GPI)-anchored proteins are an abundant constituent. In this review, we discuss the complex nature of the organization and dynamics of GPI-anchored proteins at multiple spatial and temporal scales. Different biophysical techniques have been utilized for understanding this organization, including fluorescence correlation spectroscopy, fluorescence recovery after photobleaching, single particle tracking, and a number of super resolution methods. Major insights into the organization and dynamics have also come from exploring the short-range interactions of GPI-anchored proteins by fluorescence (or Förster) resonance energy transfer microscopy. Based on the nanometer to micron scale organization, at the microsecond to the second time scale dynamics, a picture of the membrane bilayer emerges where the lipid bilayer appears inextricably intertwined with the underlying dynamic cytoskeleton. These observations have prompted a revision of the current models of plasma membrane organization, and suggest an active actin-membrane composite. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Efficiency of dynamic esophagoscintigraphy for evaluation of therapy of patients with esophagus cancer

International Nuclear Information System (INIS)

Shishkina, V.V.; Polyakova, N.I.; Zamyatin, S.S.; Grinevich, S.Yu.; Mikhajlenko, V.E.; Krakhmalev, S.N.

1991-01-01

The evaluation of efficiency was given of dynamic esophagoscintigraphy (ES) for revealing possible postoperative complications before and after conducted treatment in 38 patients with esophagus cancer. Esophageal transit time (ETT) of hard and liquid food and per cent of esophagus clearance (C %) were evaluated when analyzing dynamic ES. Quantitative indices -ETT and C% - are characteristic for esophagus function. Control radionuclide examination is expedient to conduct not early than 1.5-2 mos after operative and other treatment methods

D2D-Enabled Small Cell Network Control Scheme Based on the Dynamic Stackelberg Game

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Sungwook Kim

2017-01-01

Full Text Available For current and future cellular networks, small cell structure with licensed and unlicensed bandwidth, caching content provisioning, and device-to-device (D2D communications is seen as a necessary architecture. Recently, a series of control methods have been developed to address a myriad of challenges in next-generation small cell networks. In this study, we focus on the design of novel D2D-enabled small cell network control scheme by allowing caching and unlicensed D2D communications. Motivated by game theory and learning algorithm, the proposed scheme adaptively selects caching contents and splits the available bandwidth for licensed and unlicensed communications. Under dynamically changing network environments, we capture the dynamics of the network system and design a new dynamic Stackelberg game model. Based on a hierarchical and feedback based control manner, small base stations and users can be leaders or followers dynamically while improving 5G network performance. Simulations and performance analysis verify the efficiency of the proposed scheme, showing that our approach can outperform existing schemes by about 5%~15% in terms of bandwidth utilization, cache hit ratio, and system throughput.

Research and development for evaluation system of solar cell

Energy Technology Data Exchange (ETDEWEB)

1986-08-01

In order to evaluate the performance and capability of solar cell properly and impartially, the evaluation systems for the performance and reliability have been assured. The results are as follows. 1. Development for performance evaluation method; (1) The international comparisons of standard solar cell calibration methods and our method has been assured to be mostly near to the average value. (2) Experimental solar cell has been made and the indoors and outdoors evaluation of solar cell module have become to be possible with same accuracy. (3) As the spectro-radiometer of high performance have been developed, the measurements of the output of the solar cell module have become possible, monitering spectrum of wide range of natural solar beam. (4) With use of several kinds of standard solar cell, measurement errors have been assured. (5) As for nominal operating cell temperature of module, experimental researches have been done indoors and outdoors and the diffeneces have been assured. 2. Development of reliability evaluation method; (1) In outdoor exposure test, the basic data of the accelerating degradation test have been accumulated and it has been assured that the degradation of crystal type is few. (2) By the acceleration degradation test with use of weathermeter, and temperature and humidity cycling test device, the proceses of degradation have been assured. (3) In the processes of enviromental tests and mechanical strength tests, remarkable degradation has not been recognized.(1 tab)

Dynamic focus optical coherence tomography: feasibility for improved basal cell carcinoma investigation

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Nasiri-Avanaki, M. R.; Aber, Ahmed; Hojjatoleslami, S. A.; Sira, Mano; Schofield, John B.; Jones, Carole; Podoleanu, A. Gh.

2012-03-01

Basal cell carcinoma (BCC) is the most common form of skin cancer. To improve the diagnostic accuracy, additional non-invasive methods of making a preliminary diagnosis have been sought. We have implemented an En-Face optical coherence tomography (OCT) for this study in which the dynamic focus was integrated into it. With the dynamic focus scheme, the coherence gate moves synchronously with the peak of confocal gate determined by the confocal interface optics. The transversal resolution is then conserved throughout the depth range and an enhanced signal is returned from all depths. The Basal Cell Carcinoma specimens were obtained from the eyelid a patient. The specimens under went analysis by DF-OCT imaging. We searched for remarkable features that were visualized by OCT and compared these findings with features presented in the histology slices.

Cytogenetic heterogeneity and their serial dynamic changes during acquisition of cytogenetic aberrations in cultured mesenchymal stem cells

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Kim, Jung-Ah [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Im, Kyong Ok; Park, Si Nae; Kwon, Ji Seok [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Seon Young [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Oh, Keunhee; Lee, Dong-Sup [Laboratory of Immunology and Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul (Korea, Republic of); Transplantation Research Institute, Seoul National University College of Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Min Kyung; Kim, Seong Who [Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jang, Mi; Lee, Gene [Lab of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Oh, Yeon-Mok; Lee, Sang Do [Department of Pulmonary and Critical Care Medicine, Asthma Center and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Dong Soon, E-mail: soonlee@snu.ac.kr [Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2015-07-15

Highlights: • We evaluated cytogenetic aberrations of MSC during culture using G-banding and FISH. • We tracked the quantitative changes of each clone among heterogeneity upon passages. • The changes of cytogenetic profile upon passages were similar to cancer stem cell. - Abstract: To minimize the risk of tumorigenesis in mesenchymal stem cells (MSCs), G-banding analysis is widely used to detect chromosomal aberrations in MSCs. However, a critical limitation of G-banding is that it only reflects the status of metaphase cells, which can represent as few as 0.01% of tested cells. During routine cytogenetic testing in MSCs, we often detect chromosomal aberrations in minor cell populations. Therefore, we aimed to investigate whether such a minority of cells can expand over time or if they ultimately disappear during MSC passaging. We passaged MSCs serially while monitoring quantitative changes for each aberrant clone among heterogeneous MSCs. To investigate the cytogenetic status of interphase cells, which represent the main population, we also performed interphase FISH analysis, in combination with G-banding and telomere length determination. In human adipose tissue-derived MSCs, 4 types of chromosomal aberrations were found during culturing, and in umbilical cord MSCs, 2 types of chromosomal aberrations were observed. Sequential dynamic changes among heterogeneous aberrant clones during passaging were similar to the dynamic changes observed in cancer stem cells during disease progression. Throughout all passages, the quantitative G-banding results were inconsistent with those of the interphase FISH analysis. Interphase FISH revealed hidden aberrations in stem cell populations with normal karyotypes by G-banding analysis. We found that telomere length gradually decreased during passaging until the point at which cytogenetic aberrations appeared. The present study demonstrates that rare aberrant clones at earlier passages can become predominant clones during

Cytogenetic heterogeneity and their serial dynamic changes during acquisition of cytogenetic aberrations in cultured mesenchymal stem cells

International Nuclear Information System (INIS)

Kim, Jung-Ah; Im, Kyong Ok; Park, Si Nae; Kwon, Ji Seok; Kim, Seon Young; Oh, Keunhee; Lee, Dong-Sup; Kim, Min Kyung; Kim, Seong Who; Jang, Mi; Lee, Gene; Oh, Yeon-Mok; Lee, Sang Do; Lee, Dong Soon

2015-01-01

Highlights: • We evaluated cytogenetic aberrations of MSC during culture using G-banding and FISH. • We tracked the quantitative changes of each clone among heterogeneity upon passages. • The changes of cytogenetic profile upon passages were similar to cancer stem cell. - Abstract: To minimize the risk of tumorigenesis in mesenchymal stem cells (MSCs), G-banding analysis is widely used to detect chromosomal aberrations in MSCs. However, a critical limitation of G-banding is that it only reflects the status of metaphase cells, which can represent as few as 0.01% of tested cells. During routine cytogenetic testing in MSCs, we often detect chromosomal aberrations in minor cell populations. Therefore, we aimed to investigate whether such a minority of cells can expand over time or if they ultimately disappear during MSC passaging. We passaged MSCs serially while monitoring quantitative changes for each aberrant clone among heterogeneous MSCs. To investigate the cytogenetic status of interphase cells, which represent the main population, we also performed interphase FISH analysis, in combination with G-banding and telomere length determination. In human adipose tissue-derived MSCs, 4 types of chromosomal aberrations were found during culturing, and in umbilical cord MSCs, 2 types of chromosomal aberrations were observed. Sequential dynamic changes among heterogeneous aberrant clones during passaging were similar to the dynamic changes observed in cancer stem cells during disease progression. Throughout all passages, the quantitative G-banding results were inconsistent with those of the interphase FISH analysis. Interphase FISH revealed hidden aberrations in stem cell populations with normal karyotypes by G-banding analysis. We found that telomere length gradually decreased during passaging until the point at which cytogenetic aberrations appeared. The present study demonstrates that rare aberrant clones at earlier passages can become predominant clones during

An agar gel membrane-PDMS hybrid microfluidic device for long term single cell dynamic study.

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Wong, Ieong; Atsumi, Shota; Huang, Wei-Chih; Wu, Tung-Yun; Hanai, Taizo; Lam, Miu-Ling; Tang, Ping; Yang, Jian; Liao, James C; Ho, Chih-Ming

2010-10-21

Significance of single cell measurements stems from the substantial temporal fluctuations and cell-cell variability possessed by individual cells. A major difficulty in monitoring surface non-adherent cells such as bacteria and yeast is that these cells tend to aggregate into clumps during growth, obstructing the tracking or identification of single-cells over long time periods. Here, we developed a microfluidic platform for long term single-cell tracking and cultivation with continuous media refreshing and dynamic chemical perturbation capability. The design highlights a simple device-assembly process between PDMS microchannel and agar membrane through conformal contact, and can be easily adapted by microbiologists for their routine laboratory use. The device confines cell growth in monolayer between an agar membrane and a glass surface. Efficient nutrient diffusion through the membrane and reliable temperature maintenance provide optimal growth condition for the cells, which exhibited fast exponential growth and constant distribution of cell sizes. More than 24 h of single-cell tracking was demonstrated on a transcription-metabolism integrated synthetic biological model, the gene-metabolic oscillator. Single cell morphology study under alcohol toxicity allowed us to discover and characterize cell filamentation exhibited by different E. coli isobutanol tolerant strains. We believe this novel device will bring new capabilities to quantitative microbiology, providing a versatile platform for single cell dynamic studies.

Melanosomal dynamics assessed with a live-cell fluorescent melanosomal marker.

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Jan M Bruder

Full Text Available Melanocytes present in skin and other organs synthesize and store melanin pigment within membrane-delimited organelles called melanosomes. Exposure of human skin to ultraviolet radiation (UV stimulates melanin production in melanosomes, followed by transfer of melanosomes from melanocytes to neighboring keratinocytes. Melanosomal function is critical for protecting skin against UV radiation, but the mechanisms underlying melanosomal movement and transfer are not well understood. Here we report a novel fluorescent melanosomal marker, which we used to measure real-time melanosomal dynamics in live human epidermal melanocytes (HEMs and transfer in melanocyte-keratinocyte co-cultures. A fluorescent fusion protein of Ocular Albinism 1 (OA1 localized to melanosomes in both B16-F1 cells and HEMs, and its expression did not significantly alter melanosomal distribution. Live-cell tracking of OA1-GFP-tagged melanosomes revealed a bimodal kinetic profile, with melanosomes exhibiting combinations of slow and fast movement. We also found that exposure to UV radiation increased the fraction of melanosomes exhibiting fast versus slow movement. In addition, using OA1-GFP in live co-cultures, we monitored melanosomal transfer using time-lapse microscopy. These results highlight OA1-GFP as a specific and effective melanosomal marker for live-cell studies, reveal new aspects of melanosomal dynamics and transfer, and are relevant to understanding the skin's physiological response to UV radiation.

Dynamic laser speckle for non-destructive quality evaluation of bread

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Stoykova, E.; Ivanov, B.; Shopova, M.; Lyubenova, T.; Panchev, I.; Sainov, V.

2010-10-01

Coherent illumination of a diffuse object yields a randomly varying interference pattern, which changes over time at any modification of the object. This phenomenon can be used for detection and visualization of physical or biological activity in various objects (e.g. fruits, seeds, coatings) through statistical description of laser speckle dynamics. The present report aims at non-destructive full-field evaluation of bread by spatial-temporal characterization of laser speckle. The main purpose of the conducted experiments was to prove the ability of the dynamic speckle method to indicate activity within the studied bread samples. In the set-up for acquisition and storage of dynamic speckle patterns an expanded beam from a DPSS laser (532 nm and 100mW) illuminated the sample through a ground glass diffuser. A CCD camera, adjusted to focus the sample, recorded regularly a sequence of images (8 bits and 780 x 582 squared pixels, sized 8.1 × 8.1 μm) at sampling frequency 0.25 Hz. A temporal structure function was calculated to evaluate activity of the bread samples in time using the full images in the sequence. In total, 7 samples of two types of bread were monitored during a chemical and physical process of bread's staling. Segmentation of images into matrixes of isometric fragments was also utilized. The results proved the potential of dynamic speckle as effective means for monitoring the process of bread staling and ability of this approach to differentiate between different types of bread.

Evaluation of Stem Cell Markers, CD44/CD24 in Breast Cancer Cell Lines

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Masoud Hashemi Arabi

2014-05-01

Four breast cancer cell lines, MCF-7 ، T47D ، MDA-MB231 and MDA-MB468 were purchased from National cell Bank of Iran based in Iran Pasture Institute and were cultured in high glucose DMEM supplemented with 10% FCS. Cells were stained with antiCD44-PE and antiCD24-FITC antibodies and Status of CD44 and CD24 as markers of breast cancer stem cells were evaluated using flow cytometer and fluorescent microscopy.Evaluation of CD44 and CD24 as markers of breast cancer stem cells showed that MDA-MB231 with 97±1.2% CD44+/CD24-/low cells is significantly different from the others that they were mainly CD44 and CD24 positive cells(p

Modelling and Simulation of Fuel Cell Dynamics for Electrical Energy Usage of Hercules Airplanes

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Hamid Radmanesh

2014-01-01

Full Text Available Dynamics of proton exchange membrane fuel cells (PEMFC with hydrogen storage system for generating part of Hercules airplanes electrical energy is presented. Feasibility of using fuel cell (FC for this airplane is evaluated by means of simulations. Temperature change and dual layer capacity effect are considered in all simulations. Using a three-level 3-phase inverter, FC’s output voltage is connected to the essential bus of the airplane. Moreover, it is possible to connect FC’s output voltage to airplane DC bus alternatively. PID controller is presented to control flow of hydrogen and oxygen to FC and improve transient and steady state responses of the output voltage to load disturbances. FC’s output voltage is regulated via an ultracapacitor. Simulations are carried out via MATLAB/SIMULINK and results show that the load tracking and output voltage regulation are acceptable. The proposed system utilizes an electrolyser to generate hydrogen and a tank for storage. Therefore, there is no need for batteries. Moreover, the generated oxygen could be used in other applications in airplane.

The cell wall of Arabidopsis thaliana influences actin network dynamics.

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Tolmie, Frances; Poulet, Axel; McKenna, Joseph; Sassmann, Stefan; Graumann, Katja; Deeks, Michael; Runions, John

2017-07-20

In plant cells, molecular connections link the cell wall-plasma membrane-actin cytoskeleton to form a continuum. It is hypothesized that the cell wall provides stable anchor points around which the actin cytoskeleton remodels. Here we use live cell imaging of fluorescently labelled marker proteins to quantify the organization and dynamics of the actin cytoskeleton and to determine the impact of disrupting connections within the continuum. Labelling of the actin cytoskeleton with green fluorescent protein (GFP)-fimbrin actin-binding domain 2 (FABD2) resulted in a network composed of fine filaments and thicker bundles that appeared as a highly dynamic remodelling meshwork. This differed substantially from the GFP-Lifeact-labelled network that appeared much more sparse with thick bundles that underwent 'simple movement', in which the bundles slightly change position, but in such a manner that the structure of the network was not substantially altered during the time of observation. Label-dependent differences in actin network morphology and remodelling necessitated development of two new image analysis techniques. The first of these, 'pairwise image subtraction', was applied to measurement of the more rapidly remodelling actin network labelled with GFP-FABD2, while the second, 'cumulative fluorescence intensity', was used to measure bulk remodelling of the actin cytoskeleton when labelled with GFP-Lifeact. In each case, these analysis techniques show that the actin cytoskeleton has a decreased rate of bulk remodelling when the cell wall-plasma membrane-actin continuum is disrupted either by plasmolysis or with isoxaben, a drug that specifically inhibits cellulose deposition. Changes in the rate of actin remodelling also affect its functionality, as observed by alteration in Golgi body motility. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Applicability of the tissue stem cell turnover concept on the validity of cumulative dose based radiation risk evaluation

International Nuclear Information System (INIS)

Otsuka, Kensuke; Hamada, Nobuyuki; Iwasaki, Toshiyasu; Yoshida, Kazuo

2011-01-01

The radiation protection system adopts the linear no-threshold model to achieve proper radiation protection for considering cancer risks resulting from radiation exposure. This model uses cumulative dose to a tissue for risk evaluation in which cumulative dose is related to the amount of DNA damage and consequential induction of gene mutation. In this concept, gene mutation accumulates in tissue stem cells, the putative target of carcinogenesis, with total dose given to the tissue. Unlike high-dose-rate exposure, epidemiological studies in high radiation background areas, such as Kerala in India, revealed that cancer risks is not elevated by the dose to the inhabitants, suggesting that there exists some mechanisms to eliminate the damage/mutation in the exposed tissue under extremely low-dose-rate exposure situations. In this report, the dynamics of tissue stem cell turnover is evaluated as a possible mechanism under extremely low-dose-rate exposure situations. To this end, we reviewed recent literatures studying tissue stem cell turnover, and found that great advances in stem cell research have made it possible to trace a fate of stem cells in tissues. Furthermore, turnover of tissue stem cells is found to occur after irradiation, due to competition of stem cells within tissues. This raises a possibility that radiation effects may not accumulate in a tissue depending on the dose-rate and duration of exposure period. (author)

Benzopyrene exposure disrupts DNA methylation and growth dynamics in breast cancer cells

International Nuclear Information System (INIS)

Sadikovic, Bekim; Rodenhiser, David I.

2006-01-01

Exposures to environmental carcinogens and unhealthy lifestyle choices increase the incidence of breast cancer. One such compound, benzo(a)pyrene (BaP), leads to covalent DNA modifications and the deregulation of gene expression. To date, these mechanisms of BaP-induced carcinogenesis are poorly understood, particularly in the case of breast cancer. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in four breast cancer cell lines since disruptions in DNA methylation lead to deregulated gene expression and the loss of genomic integrity. We observed robust time- and concentration-dependent loss of proliferation, S phase and G2M accumulation and apoptosis in p53 positive MCF-7 and T47-D cells. We observed minimal responses in p53 negative HCC-1086 and MDA MB 231 cells. Furthermore, BaP increased p53 levels in both p53 positive cell lines, as well as p21 levels in MCF-7 cells, an effect that was prevented by the p53-specific inhibitor pifithrin-α. No changes in global levels of DNA methylation levels induced by BaP were detected by the methyl acceptor assay (MAA) in any cell line, however, methylation profiling by AIMS (amplification of intermethylated sites) analysis showed dynamic, sequence-specific hypo- and hypermethylation events in all cell lines. We also identified BaP-induced hypomethylation events at a number of genomic repeats. Our data confirm the p53-specific disruption of the cell cycle as well as the disruption of DNA methylation as a consequence of BaP treatment, thus reinforcing the link between environmental exposures, DNA methylation and breast cancer

Modeling population dynamics of mitochondria in mammalian cells

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Kornick, Kellianne; Das, Moumita

Mitochondria are organelles located inside eukaryotic cells and are essential for several key cellular processes such as energy (ATP) production, cell signaling, differentiation, and apoptosis. All organisms are believed to have low levels of variation in mitochondrial DNA (mtDNA), and alterations in mtDNA are connected to a range of human health conditions, including epilepsy, heart failure, Parkinsons disease, diabetes, and multiple sclerosis. Therefore, understanding how changes in mtDNA accumulate over time and are correlated to changes in mitochondrial function and cell properties can have a profound impact on our understanding of cell physiology and the origins of some diseases. Motivated by this, we develop and study a mathematical model to determine which cellular parameters have the largest impact on mtDNA population dynamics. The model consists of coupled ODEs to describe subpopulations of healthy and dysfunctional mitochondria subject to mitochondrial fission, fusion, autophagy, and mutation. We study the time evolution and stability of each sub-population under specific selection biases and pressures by tuning specific terms in our model. Our results may provide insights into how sub-populations of mitochondria survive and evolve under different selection pressures. This work was supported by a Grant from the Moore Foundation.

Clinical evaluation of the dynamic observing tonometer.

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Morgan, Andrew J; Hosking, Sarah L; Salmon, John F

2002-08-01

The Dynamic Observing Tonometer (SmartLens, Ophthalmic Development Company AG, Zürich, Switzerland) is a diagnostic contact lens that allows continuous measurement of intraocular pressure, in addition to providing the investigator with a view of the posterior pole and anterior chamber angle. The purpose of this study was to determine the accuracy of this tonometer and the repeatability of the intraocular pressure measurements. The intraocular pressure was measured by Goldmann applanation tonometry in one randomly chosen eye of 40 subjects (median age 66 years, range 21-77 years). The intraocular pressure, pulse amplitude and 10-second continuous tonometric recordings were then taken using the Dynamic Observing Tonometer and a pneumatonometer. Accuracy was determined by calculating the mean bias and 95% limits of agreement of measurements made with the Dynamic Observing Tonometer against measurements made with the Goldmann and pneumatonometer. Repeatability was evaluated by calculating the differences between pairs of repeated measurements against the mean value and by calculating reliability coefficients. Intraocular pressure measurements made with the Dynamic Observing Tonometer had a mean bias of +2.1 mm Hg (95% limits of agreement: -4.0 to +8.2 mm Hg) compared with Goldmann tonometry. There was a reasonable correlation between Goldmann and Dynamic Observing Tonometer intraocular pressure readings (r = 0.78, P Tonometer was found to have a mean bias of +0.4 mm Hg (95% limits of agreement: -1.6 to +2.3 mm Hg) compared with the pneumatonometer (r = 0.78, P Tonometer reading was on average 0.4 mm Hg higher than the second (95% limits of agreement: -3.8 to +4.6 mm Hg) with a coefficient of reliability of 0.91. For pulse amplitude readings, the first reading was on average 0.1 mm Hg lower than the second (95% limits of agreement: -1.4 to +1.2 mm Hg) with a coefficient of reliability of 0.90. Intraocular pressure measurements taken with the Dynamic Observing Tonometer

Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range and Receptive Field Organization of Mouse Retinal Ganglion Cells.

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Ströh, Sebastian; Puller, Christian; Swirski, Sebastian; Hölzel, Maj-Britt; van der Linde, Lea I S; Segelken, Jasmin; Schultz, Konrad; Block, Christoph; Monyer, Hannah; Willecke, Klaus; Weiler, Reto; Greschner, Martin; Janssen-Bienhold, Ulrike; Dedek, Karin

2018-02-21

In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial, and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells. This genetic modification allowed us to investigate the impact of horizontal cells on ganglion cell signaling independent of the actual mode of feedback in the outer retina and without pharmacological manipulation of signal transmission. In control and genetically modified mice (both sexes), we recorded the light responses of transient OFF-α retinal ganglion cells in the intact retina. Excitatory postsynaptic currents (EPSCs) were reduced and the cells were tuned to lower temporal frequencies and higher contrasts, presumably because photoreceptor output was attenuated. Moreover, receptive fields of recorded cells showed a significantly altered surround structure. Our data thus suggest that horizontal cells are responsible for adjusting the dynamic range of retinal ganglion cells and, together with amacrine cells, contribute to the center/surround organization of ganglion cell receptive fields in the mouse. SIGNIFICANCE STATEMENT Horizontal cells represent a major neuronal class in the mammalian retina and provide lateral feedback and feedforward signals to photoreceptors and bipolar cells, respectively. The mode of signal transmission remains controversial and, moreover, the contribution of horizontal cells to visual processing is still elusive. To address the question of how horizontal cells affect retinal output signals, we recorded the light

Quantitative evaluation of skeletal tumors with dynamic 18F-FDG PET

International Nuclear Information System (INIS)

Wu Hua; Heichel, T.O.; Lehner, B.; Bernd, L.; Ewerbeck, V.; Burger, C.

2002-01-01

Objective: To evaluate bone lesions using fluorodeoxyglucose (FIX;) PET and explore if dynamic and quantitative PET data may help to differentiate benign lesions from malignant masses. Methods: A group of forty patients with primary bone lesions were studied. The final diagnosis was confirmed with histopathology. A dynamic acquisition of FDG PET with the duration over 60 min was undertaken in all subjects. From the dynamic PET images the indexes such as average and maximal standardized uptake value ( SUV ), tumor SUV-to-muscle SUV ratios ( T/M ), and SUV at 60 min-to-SUV at 30 min ratio (SUV aver60/30main and SUV max60/30min ) were produced. Patlak graphical analysis were used to obtain influx constant ( K i ) and metabolic rate of FDG (MR-FDG) was thus calculated. Based on the receiver operation characteristic curve the sensitivity and specificity for each parameter in differentiation between malignant and benign lesions was evaluated. Results: The histologic results revealed there were 21 cases with malignant tumors and 19 with benign lesions in this group. The MRFDG and SUV indexes in malignant lesions were significantly higher than those in benign lesions. However, each index showed a considerable overlap between benign and malignant type. Average SUV positively correlated with MR-FDG (r = 0.67). When use of a 1.8 cutoff for average SUV, the sensitivity and specificity for discrimination of malignancy from benignity were 85.0% and 82.4%, respectively. MRFDG showed a similar sensitivity (82.4%) and a better specificity (92.9%). When evaluated with a cutoff from the combination of average SUV (1.8) and SUV aver60/3Omin (1.1), the specificity was improved to 93.3% with a small reduction of sensitivity (81.3%) compared with using SUV exclusively. Conclusions: The results indicate that detectable difference in glucose metabolism exists between malignant and benign skeletal lesions. It may not be feasible to use exclusively the static FDG uptake indexes to achieve a

Alveolar architecture of clear cell renal carcinomas (≤5.0 cm) show high attenuation on dynamic CT scanning

International Nuclear Information System (INIS)

Fujimoto, Hiroyuki; Wakao, Fumihiko; Moriyama, Noriyuki; Tobisu, Kenichi; Kakizoe, Tadao; Sakamoto, Michiie

1999-01-01

To establish the correlation between tumor appearance on CT and tumor histology in renal cell carcinomas. The density and attenuation patterns of 96 renal cell carcinomas, each ≤5 cm in greatest diameter, were studied by non-enhanced CT and early and late after bolus injection of contrast medium using dynamic CT. The density and attenuation patterns and pathological maps of each tumor were individually correlated. High attenuated areas were present in 72 of the 96 tumors on early enhanced dynamic CT scanning. All 72 high attenuated areas were of the clear cell renal cell carcinoma and had alveolar architecture. The remaining 24 tumors that did not demonstrate high attenuated foci on early enhanced scanning included three clear cell, nine granular cell, six papillary, five chromophobe and one collecting duct type. With respect to tumor architecture, all clear cell tumors of alveolar architecture demonstrated high attenuation on early enhanced scanning. Clear cell renal cell carcinomas of alveolar architecture show high attenuation on early enhanced dynamic CT scanning. A larger number of patients are indispensable to obtaining clear results. However, these findings seem to be an important clue to the diagnosis of renal cell carcinomas as having an alveolar structure. (author)

Utility of a Novel Three-Dimensional and Dynamic (3DD Cell Culture System for PK/PD Studies: Evaluation of a Triple Combination Therapy at Overcoming Anti-HER2 Treatment Resistance in Breast Cancer

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Anusha Ande

2018-05-01

Full Text Available Background: Emergence of Human epidermal growth factor receptor 2 (HER2 therapy resistance in HER2-positive (HER2+ breast cancer (BC poses a major clinical challenge. Mechanisms of resistance include the over-activation of the PI3K/mTOR and Src pathways. This work aims to investigate a novel combination therapy that employs paclitaxel (PAC, a mitotic inhibitor, with everolimus (EVE, an mTOR inhibitor, and dasatinib (DAS, an Src kinase inhibitor, as a modality to overcome resistance.Methods: Static (two dimensional, 2D and three-dimensional dynamic (3DD cell culture studies were conducted using JIMT-1 cells, a HER2+ BC cell line refractory to HER2 therapies. Cell viability and caspase-3 expression were examined after JIMT-1 cell exposure to agents as monotherapy or in combination using a 2D setting. A pharmacokinetic/pharmacodynamic (PK/PD combination study with PAC+DAS+EVE was conducted over 3 weeks in a 3DD setting. PAC was administered into the system via a 3 h infusion followed by the addition of a continuous infusion of EVE+DAS 24 h post-PAC dosing. Cell counts and caspase-3 expression were quantified every 2 days. A semi-mechanistic PK/PD model was developed using the 2D data and scaled up to capture the 3DD data. The final model integrated active caspase-3 as a biomarker to bridge between drug exposures and cancer cell dynamics. Model fittings were performed using Monolix software.Results: The triple combination significantly induced caspase-3 activity in the 2D cell culture setting. In the 3DD cell culture setting, sequential dosing of PAC then EVE+DAS showed a 5-fold increase in caspase-3 activity and 8.5-fold decrease in the total cell number compared to the control. The semi-mechanistic PK/PD models fit the data well, capturing the time-course profiles of drug concentrations, caspase-3 expression, and cell counts in the 2D and 3DD settings.Conclusion: A novel, sequential triple combination therapeutic regimen was successfully evaluated

Experimental evaluation of cell liners

International Nuclear Information System (INIS)

Wierman, R.W.; Simmons, L.D.; Muhlestein, L.D.

Cell liners may be used in breeder reactor sodium pipe ways, sodium cells, and lower cavity region to provide a leak-tight cell and to protect the concrete from sodium in the unlikely event of a sodium spill. The objectives of the HEDL liner verification test program are to evaluate the integrity of liner concepts under postulated accident conditions and to develop the experimental data base which will demonstrate that liners will not fail. Two specific tests are reported; a high temperature liner feature test, and a large-scale liner sodium spill test. In both tests no failures of the liners or tendencies toward failure were detected. The discussed liner designs appeared to be conservative, and the liner strength appeared to be more than adequate

Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis

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Shen, Keyue; Luk, Samantha; Elman, Jessica; Murray, Ryan; Mukundan, Shilpaa; Parekkadan, Biju

2016-02-01

Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells

Energy Technology Data Exchange (ETDEWEB)

Mukai, Atsushi [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Kurisaki, Tomohiro [Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Sato, Satoshi B. [Research Center for Low Temperature and Material Sciences, Kyoto University, Yoshida-honmachi, Kyoto 606-8501 (Japan); Kobayashi, Toshihide [Lipid Biology Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351-0198 (Japan); Kondoh, Gen [Laboratory of Animal Experiments for Regeneration, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Hashimoto, Naohiro, E-mail: nao@nils.go.jp [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan)

2009-10-15

Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, {beta}-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.

Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells

International Nuclear Information System (INIS)

Mukai, Atsushi; Kurisaki, Tomohiro; Sato, Satoshi B.; Kobayashi, Toshihide; Kondoh, Gen; Hashimoto, Naohiro

2009-01-01

Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, β-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.

Evolutionary dynamics of adult stem cells: Comparison of random and immortal strand segregation mechanisms

OpenAIRE

Tannenbaum, Emmanuel; Sherley, James L.; Shakhnovich, Eugene I.

2004-01-01

This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) Random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell. (2) ``Immortal DNA strand'' co-segregation, for which the stem cell reta...

Dynamic Modeling, Model-Based Control, and Optimization of Solid Oxide Fuel Cells

Science.gov (United States)

Spivey, Benjamin James

2011-07-01

Solid oxide fuel cells are a promising option for distributed stationary power generation that offers efficiencies ranging from 50% in stand-alone applications to greater than 80% in cogeneration. To advance SOFC technology for widespread market penetration, the SOFC should demonstrate improved cell lifetime and load-following capability. This work seeks to improve lifetime through dynamic analysis of critical lifetime variables and advanced control algorithms that permit load-following while remaining in a safe operating zone based on stress analysis. Control algorithms typically have addressed SOFC lifetime operability objectives using unconstrained, single-input-single-output control algorithms that minimize thermal transients. Existing SOFC controls research has not considered maximum radial thermal gradients or limits on absolute temperatures in the SOFC. In particular, as stress analysis demonstrates, the minimum cell temperature is the primary thermal stress driver in tubular SOFCs. This dissertation presents a dynamic, quasi-two-dimensional model for a high-temperature tubular SOFC combined with ejector and prereformer models. The model captures dynamics of critical thermal stress drivers and is used as the physical plant for closed-loop control simulations. A constrained, MIMO model predictive control algorithm is developed and applied to control the SOFC. Closed-loop control simulation results demonstrate effective load-following, constraint satisfaction for critical lifetime variables, and disturbance rejection. Nonlinear programming is applied to find the optimal SOFC size and steady-state operating conditions to minimize total system costs.

Dynamics of Lgr6+ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis

Directory of Open Access Journals (Sweden)

Anja Füllgrabe

2015-11-01

Full Text Available The dynamics and interactions between stem cell pools in the hair follicle (HF, sebaceous gland (SG, and interfollicular epidermis (IFE of murine skin are still poorly understood. In this study, we used multicolor lineage tracing to mark Lgr6-expressing basal cells in the HF isthmus, SG, and IFE. We show that these Lgr6+ cells constitute long-term self-renewing populations within each compartment in adult skin. Quantitative analysis of clonal dynamics revealed that the Lgr6+ progenitor cells compete neutrally in the IFE, isthmus, and SG, indicating population asymmetry as the underlying mode of tissue renewal. Transcriptional profiling of Lgr6+ and Lgr6− cells did not reveal a distinct Lgr6-associated gene expression signature, raising the question of whether Lgr6 expression requires extrinsic niche signals. Our results elucidate the interrelation and behavior of Lgr6+ populations in the IFE, HF, and SG and suggest population asymmetry as a common mechanism for homeostasis in several epithelial skin compartments.

Dynamics of ballistically injected latex particles in living human endothelial cells

NARCIS (Netherlands)

Li, Y.; Vanapalli Veera, V.S.A.R.; Vanapalli, Srinivas; Duits, Michael H.G.

2009-01-01

We studied the dynamics of ballistically injected latex particles (BIP) inside endothelial cells, using video particle tracking to measure the mean squared displacement (MSD) as a function of lag time. The MSD shows a plateau at short times and a linear behavior at longer times, indicating that the

Numerical evaluation of cracked pipes under dynamic loading

International Nuclear Information System (INIS)

Petit, M.; Jamet, P.

1989-01-01

In order to apply the leak-before-break concept to piping systems, the behavior of cracked pipes under dynamic, and especially seismic, loadings must be studied. A simple finite element model of a cracked pipe has been developed and implemented in the general purpose computer code CASTEM 2000. The model is a generalization of the approach proposed by Paris and Tada (1). Considered loads are bending moment and axial force (representing thermal expansion and internal pressure.) The elastic characteristics of the model are determined using the Zahoor formulae for the geometry-dependent factors. Owing to the material behabior plasticity must be taken into account. To represent the crack growth, the material is defined by two characteristic values: J 1c which is the level of energy corresponding to crack initiation and the tearing modulus, T, which governs the length of propagation of the crack. For dynamic loads, unilateral conditions are imposed to represent crack closure. The model has been used for the design of dynamic tests to be conducted on shaking tables. Test principle is briefly described and numerical results are presented. Finally evaluation of margin, due to plasticity, in comparison with the standard design procedure is made

A Self-adaptive Dynamic Evaluation Model for Diabetes Mellitus, Based on Evolutionary Strategies

Directory of Open Access Journals (Sweden)

An-Jiang Lu

2016-03-01

Full Text Available In order to evaluate diabetes mellitus objectively and accurately, this paper builds a self-adaptive dynamic evaluation model for diabetes mellitus, based on evolutionary strategies. First of all, on the basis of a formalized description of the evolutionary process of diabetes syndromes, using a state transition function, it judges whether a disease is evolutionary, through an excitation parameter. It then, provides evidence for the rebuilding of the evaluation index system. After that, by abstracting and rebuilding the composition of evaluation indexes, it makes use of a heuristic algorithm to determine the composition of the evolved evaluation index set of diabetes mellitus, It then, calculates the weight of each index in the evolved evaluation index set of diabetes mellitus by building a dependency matrix and realizes the self-adaptive dynamic evaluation of diabetes mellitus under an evolutionary environment. Using this evaluation model, it is possible to, quantify all kinds of diagnoses and treatment experiences of diabetes and finally to adopt ideal diagnoses and treatment measures for different patients with diabetics.

Erucin, the major isothiocyanate in arugula (Eruca sativa, inhibits proliferation of MCF7 tumor cells by suppressing microtubule dynamics.

Directory of Open Access Journals (Sweden)

Olga Azarenko

Full Text Available Consumption of cruciferous vegetables is associated with reduced risk of various types of cancer. Isothiocyanates including sulforaphane and erucin are believed to be responsible for this activity. Erucin [1-isothiocyanato-4-(methylthiobutane], which is metabolically and structurally related to sulforaphane, is present in large quantities in arugula (Eruca sativa, Mill., kohlrabi and Chinese cabbage. However, its cancer preventive mechanisms remain poorly understood. We found that erucin inhibits proliferation of MCF7 breast cancer cells (IC50 = 28 µM in parallel with cell cycle arrest at mitosis (IC50 = 13 µM and apoptosis, by a mechanism consistent with impairment of microtubule dynamics. Concentrations of 5-15 µM erucin suppressed the dynamic instability of microtubules during interphase in the cells. Most dynamic instability parameters were inhibited, including the rates and extents of growing and shortening, the switching frequencies between growing and shortening, and the overall dynamicity. Much higher erucin concentrations were required to reduce the microtubule polymer mass. In addition, erucin suppressed dynamic instability of microtubules reassembled from purified tubulin in similar fashion. The effects of erucin on microtubule dynamics, like those of sulforaphane, are similar qualitatively to those of much more powerful clinically-used microtubule-targeting anticancer drugs, including taxanes and the vinca alkaloids. The results suggest that suppression of microtubule dynamics by erucin and the resulting impairment of critically important microtubule-dependent cell functions such as mitosis, cell migration and microtubule-based transport may be important in its cancer preventive activities.

Dynamic MRI evaluation of urethral hypermobility post-radical prostatectomy.

Science.gov (United States)

Suskind, Anne M; DeLancey, John O L; Hussain, Hero K; Montgomery, Jeffrey S; Latini, Jerilyn M; Cameron, Anne P

2014-03-01

One postulated cause of post-prostatectomy incontinence is urethral and bladder neck hypermobility. The objective of this study was to determine the magnitude of anatomical differences of urethral and bladder neck position at rest and with valsalva in continent and incontinent men post-prostatectomy based on dynamic MRI. All subjects underwent a dynamic MRI protocol with valsalva and non-valsalva images and a standard urodynamic evaluation. MRI measurements were taken at rest and with valsalva, including (1) bladder neck to sacrococcygeal inferior pubic point line (SCIPP), (2) urethra to pubis, and (3) bulbar urethra to SCIPP. Data were analyzed in SAS using two-tailed t tests. A total of 21 subjects (13 incontinent and 8 continent) had complete data and were included in the final analysis. The two groups had similar demographic characteristics. On MRI, there were no statistically significant differences in anatomic position of the bladder neck or urethra either at rest or with valsalva. The amount of hypermobility ranged from 0.8 to 2 mm in all measures. There were also no differences in the amount of hypermobility (position at rest minus position at valsalva) between groups. We found no statistically significant differences in bladder neck and urethral position or mobility on dynamic MRI evaluation between continent and incontinent men status post-radical prostatectomy. A more complex mechanism for post-prostatectomy incontinence needs to be modeled in order to better understand the continence mechanism in this select group of men. © 2013 Wiley Periodicals, Inc.

Cellular dynamics of bovine aortic smooth muscle cells measured using MEMS force sensors

Science.gov (United States)

Tsukagoshi, Takuya; Nguyen, Thanh-Vinh; Hirayama Shoji, Kayoko; Takahashi, Hidetoshi; Matsumoto, Kiyoshi; Shimoyama, Isao

2018-04-01

Adhesive cells perceive the mechanical properties of the substrates to which they adhere, adjusting their cellular mechanical forces according to their biological characteristics. This mechanical interaction subsequently affects the growth, locomotion, and differentiation of the cell. However, little is known about the detailed mechanism that underlies this interaction between adherent cells and substrates because dynamically measuring mechanical phenomena is difficult. Here, we utilize microelectromechamical systems force sensors that can measure cellular traction forces with high temporal resolution (~2.5 µs) over long periods (~3 h). We found that the cellular dynamics reflected physical phenomena with time scales from milliseconds to hours, which contradicts the idea that cellular motion is slow. A single focal adhesion (FA) generates an average force of 7 nN, which disappears in ms via the action of trypsin-ethylenediaminetetraacetic acid. The force-changing rate obtained from our measurements suggests that the time required for an FA to decompose was nearly proportional to the force acting on the FA.

Modeling and simulation of the dynamic behavior of portable proton exchange membrane fuel cells

Energy Technology Data Exchange (ETDEWEB)

Ziegler, C.

2005-07-01

In order to analyze the operational behavior, a mathematical model of planar self-breathing fuel cells is developed and validated in Chapter 3 of this thesis. The multicomponent transport of the species is considered as well as the couplings between the transport processes of heat, charge, and mass and the electrochemical reactions. Furthermore, to explain the oxygen mass transport limitation in the porous electrode of the cathode side an agglomerate model for the oxygen reduction reaction is developed. In Chapter 4 the important issue of liquid water generation and transport in PEMFCs is addressed. One of the major tasks when operating this type of fuel cell is avoiding the complete flooding of the PEMFC during operation. A one-dimensional and isothermal model is developed that is based on a coupled system of partial differential equations. The model contains a dynamic and two-phase description of the proton exchange membrane fuel cell. The mass transport in the gas phase and in the liquid phase is considered as well as the phase transition between liquid water and water vapor. The transport of charges and the electrochemical reactions are part of the model. Flooding effects that are caused by liquid water accumulation are described by this model. Moreover, the model contains a time-dependent description of the membrane that accounts for Schroeder's paradox. The model is applied to simulate cyclic voltammograms. Chapter 5 is focused on the dynamic investigation of PEMFC stacks. Understanding the dynamic behavior of fuel cell stacks is important for the operation and control of fuel cell stacks. Using the single cell model of Chapter 3 and the dynamic model of Chapter 4 as basis, a mathematical model of a PEMFC stack is developed. However, due to the complexity of a fuel cell stack, the spatial resolution and dynamic description of the liquid water transport are not accounted for. These restrictions allow for direct comparison between the solution variables of

Dynamics of circulating endothelial cells and endothelial progenitor cells in breast cancer patients receiving cytotoxic chemotherapy

Directory of Open Access Journals (Sweden)

Kuo Yu-Hsuan

2012-12-01

Full Text Available Abstract Background The abundance of circulating endothelial cells (CECs and circulating endothelial progenitor cells (CEPs, which serve as surrogate markers for angiogenesis, may be affected by chemotherapy. We studied their dynamic change during consecutive cycles of chemotherapy. Methods We collected blood samples from 15 breast cancer patients, who received a total of 56 courses of systemic chemotherapy, and measured the CECs, viable CECs (V-CECs, and CEPs by six-color flow cytometry within the seven days prior to chemotherapy, twice a week during the first and second cycles of chemotherapy, and then once a week during the subsequent cycles. Results The CEC, V-CEC, and CEP levels all significantly decreased from day 1 of treatment to the first week of chemotherapy. After one week of chemotherapy, the CEC and V-CEC levels returned to a level similar to day 1. The CEP level remained significantly reduced after the first week of chemotherapy, but gradually rebounded until the next course of chemotherapy. After six cycles of chemotherapy, the total number of CEC and V-CEC cells trended toward a decrease and the CEP cells toward an increase. Clinical factors, including the existence of a tumor, chemotherapy regimens, and the use of granulocyte colony stimulating factor, did not significantly affect these results. Conclusions The CEC and CEP counts change dynamically during each course of chemotherapy and after the chemotherapy cycles, providing background data for any future study planning to use CECs and CEPs as surrogate markers of angiogenesis in antiangiogenesis treatments combined with chemotherapy.

Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations.

Science.gov (United States)

Cosette, Jérémie; Moussy, Alice; Onodi, Fanny; Auffret-Cariou, Adrien; Neildez-Nguyen, Thi My Anh; Paldi, Andras; Stockholm, Daniel

2015-12-09

Cell fate choice during the process of differentiation may obey to deterministic or stochastic rules. In order to discriminate between these two strategies we used time-lapse microscopy of individual murine CD4 + T cells that allows investigating the dynamics of proliferation and fate commitment. We observed highly heterogeneous division and death rates between individual clones resulting in a Pareto-like dominance of a few clones at the end of the experiment. Commitment to the Treg fate was monitored using the expression of a GFP reporter gene under the control of the endogenous Foxp3 promoter. All possible combinations of proliferation and differentiation were observed and resulted in exclusively GFP-, GFP+ or mixed phenotype clones of very different population sizes. We simulated the process of proliferation and differentiation using a simple mathematical model of stochastic decision-making based on the experimentally observed parameters. The simulations show that a stochastic scenario is fully compatible with the observed Pareto-like imbalance in the final population.

A methodology for the quantitative evaluation of NPP fault diagnostic systems' dynamic aspects

International Nuclear Information System (INIS)

Kim, J.H.; Seong, P.H.

2000-01-01

A fault diagnostic system (FDS) is an operator decision support system which is implemented both to increase NPP efficiency as well as to reduce human error and cognitive workload that may cause nuclear power plant (NPP) accidents. Evaluation is an indispensable activity in constructing a reliable FDS. We first define the dynamic aspects of fault diagnostic systems (FDSs) for evaluation in this work. The dynamic aspect is concerned with the way a FDS responds to input. Next, we present a hierarchical structure in the evaluation for the dynamic aspects of FDSs. Dynamic aspects include both what a FDS provides and how a FDS operates. We define the former as content and the latter as behavior. Content and behavior contain two elements and six elements in the lower hierarchies, respectively. Content is a criterion for evaluating the integrity of a FDS, the problem types which a FDS deals with, along with the level of information. Behavior contains robustness, understandability, timeliness, transparency, effectiveness, and communicativeness of FDSs. On the other hand, the static aspects are concerned with the hardware and the software of the system. For quantitative evaluation, the method used to gain and aggregate the priorities of the criteria in this work is the analytic hierarchy process (AHP). The criteria at the lowest level are quantified through simple numerical expressions and questionnaires developed in this work. these well describe the characteristics of the criteria and appropriately use subjective, empirical, and technical methods. Finally, in order to demonstrate the feasibility of our evaluation method, we have performed one case study for the fault diagnosis module of OASYS TM (On-Line Operator Aid SYStem for Nuclear Power Plant), which is an operator support system developed at the Korea Advanced Institute of Science and Technology (KAIST)

Effect of Dynamic Culture and Periodic Compression on Human Mesenchymal Stem Cell Proliferation and Chondrogenesis.

Science.gov (United States)

Guo, Ting; Yu, Li; Lim, Casey G; Goodley, Addison S; Xiao, Xuan; Placone, Jesse K; Ferlin, Kimberly M; Nguyen, Bao-Ngoc B; Hsieh, Adam H; Fisher, John P

2016-07-01

We have recently developed a bioreactor that can apply both shear and compressive forces to engineered tissues in dynamic culture. In our system, alginate hydrogel beads with encapsulated human mesenchymal stem cells (hMSCs) were cultured under different dynamic conditions while subjected to periodic, compressive force. A customized pressure sensor was developed to track the pressure fluctuations when shear forces and compressive forces were applied. Compared to static culture, dynamic culture can maintain a higher cell population throughout the study. With the application of only shear stress, qRT-PCR and immunohistochemistry revealed that hMSCs experienced less chondrogenic differentiation than the static group. The second study showed that chondrogenic differentiation was enhanced by additional mechanical compression. After 14 days, alcian blue staining showed more extracellular matrix formed in the compression group. The upregulation of the positive chondrogenic markers such as Sox 9, aggrecan, and type II collagen were demonstrated by qPCR. Our bioreactor provides a novel approach to apply mechanical forces to engineered cartilage. Results suggest that a combination of dynamic culture with proper mechanical stimulation may promote efficient progenitor cell expansion in vitro, thereby allowing the culture of clinically relevant articular chondrocytes for the treatment of articular cartilage defects.

The dynamics of long-term transgene expression in engrafted neural stem cells.

Science.gov (United States)

Lee, Jean-Pyo; Tsai, David J; In Park, Kook; Harvey, Alan R; Snyder, Evan Y

2009-07-01

To assess the dynamics and confounding variables that influence transgene expression in neural stem cells (NSCs), we generated distinct NSC clones from the same pool of cells, carrying the same reporter gene transcribed from the same promoter, transduced by the same retroviral vector, and transplanted similarly at the same differentiation state, at the same time and location, into the brains of newborn mouse littermates, and monitored in parallel for over a year in vivo (without immunosuppression). Therefore, the sole variables were transgene chromosomal insertion site and copy number. We then adapted and optimized a technique that tests, at the single cell level, persistence of stem cell-mediated transgene expression in vivo based on correlating the presence of the transgene in a given NSC's nucleus (by fluorescence in situ hybridization [FISH]) with the frequency of that transgene's product within the same cell (by combined immunohistochemistry [IHC]). Under the above-stated conditions, insertion site is likely the most contributory variable dictating transgene downregulation in an NSC after 3 months in vivo. We also observed that this obstacle could be effectively and safely counteracted by simple serial infections (as few as three) inserting redundant copies of the transgene into the prospective donor NSC. (The preservation of normal growth control mechanisms and an absence of tumorigenic potential can be readily screened and ensured ex vivo prior to transplantation.) The combined FISH/IHC strategy employed here for monitoring the dynamics of transgene expression at the single cell level in vivo may be used for other types of therapeutic and housekeeping genes in endogenous and exogenous stem cells of many organs and lineages. Copyright 2009 Wiley-Liss, Inc.

Temperature-responsive poly(ε-caprolactone) cell culture platform with dynamically tunable nano-roughness and elasticity for control of myoblast morphology.

Science.gov (United States)

Uto, Koichiro; Ebara, Mitsuhiro; Aoyagi, Takao

2014-01-21

We developed a dynamic cell culture platform with dynamically tunable nano-roughness and elasticity. Temperature-responsive poly(ε-caprolactone) (PCL) films were successfully prepared by crosslinking linear and tetra-branched PCL macromonomers. By optimizing the mixing ratios, the crystal-amorphous transition temperature (Tm) of the crosslinked film was adjusted to the biological relevant temperature (~33 °C). While the crosslinked films are relatively stiff (50 MPa) below the Tm, they suddenly become soft (1 MPa) above the Tm. Correspondingly, roughness of the surface was decreased from 63.4-12.4 nm. It is noted that the surface wettability was independent of temperature. To investigate the role of dynamic surface roughness and elasticity on cell adhesion, cells were seeded on PCL films at 32 °C. Interestingly, spread myoblasts on the film became rounded when temperature was suddenly increased to 37 °C, while significant changes in cell morphology were not observed for fibroblasts. These results indicate that cells can sense dynamic changes in the surrounding environment but the sensitivity depends on cell types.

Potential of dynamically harmonized Fourier transform ion cyclotron resonance cell for high-throughput metabolomics fingerprinting: control of data quality.

Science.gov (United States)

Habchi, Baninia; Alves, Sandra; Jouan-Rimbaud Bouveresse, Delphine; Appenzeller, Brice; Paris, Alain; Rutledge, Douglas N; Rathahao-Paris, Estelle

2018-01-01

Due to the presence of pollutants in the environment and food, the assessment of human exposure is required. This necessitates high-throughput approaches enabling large-scale analysis and, as a consequence, the use of high-performance analytical instruments to obtain highly informative metabolomic profiles. In this study, direct introduction mass spectrometry (DIMS) was performed using a Fourier transform ion cyclotron resonance (FT-ICR) instrument equipped with a dynamically harmonized cell. Data quality was evaluated based on mass resolving power (RP), mass measurement accuracy, and ion intensity drifts from the repeated injections of quality control sample (QC) along the analytical process. The large DIMS data size entails the use of bioinformatic tools for the automatic selection of common ions found in all QC injections and for robustness assessment and correction of eventual technical drifts. RP values greater than 10 6 and mass measurement accuracy of lower than 1 ppm were obtained using broadband mode resulting in the detection of isotopic fine structure. Hence, a very accurate relative isotopic mass defect (RΔm) value was calculated. This reduces significantly the number of elemental composition (EC) candidates and greatly improves compound annotation. A very satisfactory estimate of repeatability of both peak intensity and mass measurement was demonstrated. Although, a non negligible ion intensity drift was observed for negative ion mode data, a normalization procedure was easily applied to correct this phenomenon. This study illustrates the performance and robustness of the dynamically harmonized FT-ICR cell to perform large-scale high-throughput metabolomic analyses in routine conditions. Graphical abstract Analytical performance of FT-ICR instrument equipped with a dynamically harmonized cell.

Evaluation of endometrial carcinoma by multislice dynamic MR imaging with Turbo FLASH

Energy Technology Data Exchange (ETDEWEB)

Asakawa, Mari [Okayama Univ. (Japan). School of Medicine

1995-04-01

The purpose of this study was to investigate the usefulness of multislice dynamic MR imaging with Turbo FLASH in assessing myometrial invasion by endometrial carcinoma. Dynamic MR imaging was performed with bolus injection of Gd-DTPA and with 1.5-T Siemens Magnetom imager using Turbo FLASH. Thirty-six endometrial carcinomas were evaluated with pathologic correlation. Junctional zone showed more rapid contrast enhancement effects than myometrium even after menopause. Contrast to noise ratio between junctional zone and endometrial carcinoma was the highest about fifty seconds after bolus injection. Only at that time could the degree of invasion to junctional zone in post-menopausal women whose junctional zones could not be seen on T{sub 2}-weighted images or contrast-enhanced T{sub 1}-weighted images be evaluated correctly. The accuracy in assessing myometrial invasion with T{sub 2}-weighted images, postcontrast T{sub 1}-weighted images, and dynamic MR imaging was 75%, 81% and 89% respectively. Though there was no statistically significant difference, multislice dynamic imaging with Turbo FLASH technique is considered to be a useful imaging method for the pre-operative assessment of myometrial invasion by endometrial carcinoma. (author).

AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

Science.gov (United States)

Fassina, L; Magenes, G; Inzaghi, A; Palumbo, S; Allavena, G; Miracco, C; Pirtoli, L; Biggiogera, M; Comincini, S

2012-10-11

An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

Method to investigate temporal dynamics of ganglion and other retinal cells in the living human eye

Science.gov (United States)

Kurokawa, Kazuhiro; Liu, Zhuolin; Crowell, James; Zhang, Furu; Miller, Donald T.

2018-02-01

The inner retina is critical for visual processing, but much remains unknown about its neural circuitry and vulnerability to disease. A major bottleneck has been our inability to observe the structure and function of the cells composing these retinal layers in the living human eye. Here, we present a noninvasive method to observe both structural and functional information. Adaptive optics optical coherence tomography (AO-OCT) is used to resolve the inner retinal cells in all three dimensions and novel post processing algorithms are applied to extract structure and physiology down to the cellular level. AO-OCT captured the 3D mosaic of individual ganglion cell somas, retinal nerve fiber bundles of micron caliber, and microglial cells, all in exquisite detail. Time correlation analysis of the AO-OCT videos revealed notable temporal differences between the principal layers of the inner retina. The GC layer was more dynamic than the nerve fiber and inner plexiform layers. At the cellular level, we applied a customized correlation method to individual GCL somas, and found a mean time constant of activity of 0.57 s and spread of +/-0.1 s suggesting a range of physiological dynamics even in the same cell type. Extending our method to slower dynamics (from minutes to one year), time-lapse imaging and temporal speckle contrast revealed appendage and soma motion of resting microglial cells at the retinal surface.

Dynamics of picornavirus RNA replication within infected cells

DEFF Research Database (Denmark)

Belsham, Graham; Normann, Preben

2008-01-01

Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks the initiat......Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks...... the initiation of negative-strand synthesis. We have now examined the dynamics of RNA replication, measured by quantitative RT-PCR, within cells infected with either swine vesicular disease virus (an enterovirus) or foot-and-mouth disease virus as regulated by the presence or absence of guanidine. Following...... the removal of guanidine from the infected cells, RNA replication occurs after a significant lag phase. This restoration of RNA synthesis requires de novo protein synthesis. Viral RNA can be maintained for at least 72 h within cells in the absence of apparent replication but guanidine-resistant virus can...

Topological defects control collective dynamics in neural progenitor cell cultures

Science.gov (United States)

Kawaguchi, Kyogo; Kageyama, Ryoichiro; Sano, Masaki

2017-04-01

Cultured stem cells have become a standard platform not only for regenerative medicine and developmental biology but also for biophysical studies. Yet, the characterization of cultured stem cells at the level of morphology and of the macroscopic patterns resulting from cell-to-cell interactions remains largely qualitative. Here we report on the collective dynamics of cultured murine neural progenitor cells (NPCs), which are multipotent stem cells that give rise to cells in the central nervous system. At low densities, NPCs moved randomly in an amoeba-like fashion. However, NPCs at high density elongated and aligned their shapes with one another, gliding at relatively high velocities. Although the direction of motion of individual cells reversed stochastically along the axes of alignment, the cells were capable of forming an aligned pattern up to length scales similar to that of the migratory stream observed in the adult brain. The two-dimensional order of alignment within the culture showed a liquid-crystalline pattern containing interspersed topological defects with winding numbers of +1/2 and -1/2 (half-integer due to the nematic feature that arises from the head-tail symmetry of cell-to-cell interaction). We identified rapid cell accumulation at +1/2 defects and the formation of three-dimensional mounds. Imaging at the single-cell level around the defects allowed us to quantify the velocity field and the evolving cell density; cells not only concentrate at +1/2 defects, but also escape from -1/2 defects. We propose a generic mechanism for the instability in cell density around the defects that arises from the interplay between the anisotropic friction and the active force field.

Drug-induced cellular death dynamics monitored by a highly sensitive organic electrochemical system.

Science.gov (United States)

Romeo, Agostino; Tarabella, Giuseppe; D'Angelo, Pasquale; Caffarra, Cristina; Cretella, Daniele; Alfieri, Roberta; Petronini, Pier Giorgio; Iannotta, Salvatore

2015-06-15

We propose and demonstrate a sensitive diagnostic device based on an Organic Electrochemical Transistor (OECT) for direct in-vitro monitoring cell death. The system efficiently monitors cell death dynamics, being able to detect signals related to specific death mechanisms, namely necrosis or early/late apoptosis, demonstrating a reproducible correlation between the OECT electrical response and the trends of standard cell death assays. The innovative design of the Twell-OECT system has been modeled to better correlate electrical signals with cell death dynamics. To qualify the device, we used a human lung adenocarcinoma cell line (A549) that was cultivated on the micro-porous membrane of a Transwell (Twell) support, and exposed to the anticancer drug doxorubicin. Time-dependent and dose-dependent dynamics of A549 cells exposed to doxorubicin are evaluated by monitoring cell death upon exposure to a range of doses and times that fully covers the protocols used in cancer treatment. The demonstrated ability to directly monitor cell stress and death dynamics upon drug exposure using simple electronic devices and, possibly, achieving selectivity to different cell dynamics is of great interest for several application fields, including toxicology, pharmacology, and therapeutics. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural polarity and dynamics of male germline stem cells in an insect (milkweed bug Oncopeltus fasciatus).

Science.gov (United States)

Dorn, David C; Dorn, August

2008-01-01

Knowing the structure opens a door for a better understanding of function because there is no function without structure. Male germline stem cells (GSCs) of the milkweed bug (Oncopeltus fasciatus) exhibit a very extraordinary structure and a very special relationship with their niche, the apical cells. This structural relationship is strikingly different from that known in the fruit fly (Drosophila melanogaster) -- the most successful model system, which allowed deep insights into the signaling interactions between GSCs and niche. The complex structural polarity of male GSCs in the milkweed bug combined with their astonishing dynamics suggest that cell morphology and dynamics are causally related with the most important regulatory processes that take place between GSCs and niche and ensure maintenance, proliferation, and differentiation of GSCs in accordance with the temporal need of mature sperm. The intricate structure of the GSCs of the milkweed bug (and probably of some other insects, i.e., moths) is only accessible by electron microscopy. But, studying singular sections through the apical complex (i.e., GSCs and apical cells) is not sufficient to obtain a full picture of the GSCs; especially, the segregation of projection terminals is not tangible. Only serial sections and their overlay can establish whether membrane ingrowths merely constrict projections or whether a projection terminal is completely cut off. To sequence the GSC dynamics, it is necessary to include juvenile stages, when the processes start and the GSCs occur in small numbers. The fine structural analysis of segregating projection terminals suggests that these terminals undergo autophagocytosis. Autophagosomes can be labeled by markers. We demonstrated acid phosphatase and thiamine pyrophosphatase (TPPase). Both together are thought to identify autophagosomes. Using the appropriate substrate of the enzymes and cerium chloride, the precipitation of electron-dense cerium phosphate granules

Dynamic modulation of thymidylate synthase gene expression and fluorouracil sensitivity in human colorectal cancer cells.

Directory of Open Access Journals (Sweden)

Kentaro Wakasa

Full Text Available Biomarkers have revolutionized cancer chemotherapy. However, many biomarker candidates are still in debate. In addition to clinical studies, a priori experimental approaches are needed. Thymidylate synthase (TS expression is a long-standing candidate as a biomarker for 5-fluorouracil (5-FU treatment of cancer patients. Using the Tet-OFF system and a human colorectal cancer cell line, DLD-1, we first constructed an in vitro system in which TS expression is dynamically controllable. Quantitative assays have elucidated that TS expression in the transformant was widely modulated, and that the dynamic range covered 15-fold of the basal level. 5-FU sensitivity of the transformant cells significantly increased in response to downregulated TS expression, although being not examined in the full dynamic range because of the doxycycline toxicity. Intriguingly, our in vitro data suggest that there is a linear relationship between TS expression and the 5-FU sensitivity in cells. Data obtained in a mouse model using transformant xenografts were highly parallel to those obtained in vitro. Thus, our in vitro and in vivo observations suggest that TS expression is a determinant of 5-FU sensitivity in cells, at least in this specific genetic background, and, therefore, support the possibility of TS expression as a biomarker for 5-FU-based cancer chemotherapy.

Dynamics of iterative reader feedback. An analysis of two successive plus-minus evaluation studies

NARCIS (Netherlands)

de Jong, Menno D.T.; Rijnks, Dietha

2006-01-01

A brochure that had been revised on the basis of feedback from readers using the plus-minus evaluation method was evaluated again using the same method. This article compares the results of these two successive evaluation studies to examine the dynamics of evaluating and revising using a

Evaluation of permanent deformation of CRM-reinforced SMA and its correlation with dynamic stiffness and dynamic creep.

Science.gov (United States)

Mashaan, Nuha Salim; Karim, Mohamed Rehan

2013-01-01

Today, rapid economic and industrial growth generates increasing amounts of waste materials such as waste tyre rubber. Attempts to inspire a green technology which is more environmentally friendly that can produce economic value are a major consideration in the utilization of waste materials. The aim of this study is to evaluate the effect of waste tyre rubber (crumb rubber modifier (CRM)), in stone mastic asphalt (SMA 20) performance. The virgin bitumen (80/100) penetration grade was used, modified with crumb rubber at four different modification levels, namely, 6%, 12%, 16%, and 20% by weight of the bitumen. The testing undertaken on the asphalt mix comprises the indirect tensile (dynamic stiffness), dynamic creep, and wheel tracking tests. By the experimentation, the appropriate amount of CRM was found to be 16% by weight of bitumen. The results show that the addition of CRM into the mixture has an obvious significant effect on the performance properties of SMA which could improve the mixture's resistance against permanent deformation. Further, higher correlation coefficient was obtained between the rut depth and permanent strain as compared to resilient modulus; thus dynamic creep test might be a more reliable test in evaluating the rut resistance of asphalt mixture.

Evaluation of Permanent Deformation of CRM-Reinforced SMA and Its Correlation with Dynamic Stiffness and Dynamic Creep

Directory of Open Access Journals (Sweden)

Nuha Salim Mashaan

2013-01-01

Full Text Available Today, rapid economic and industrial growth generates increasing amounts of waste materials such as waste tyre rubber. Attempts to inspire a green technology which is more environmentally friendly that can produce economic value are a major consideration in the utilization of waste materials. The aim of this study is to evaluate the effect of waste tyre rubber (crumb rubber modifier (CRM, in stone mastic asphalt (SMA 20 performance. The virgin bitumen (80/100 penetration grade was used, modified with crumb rubber at four different modification levels, namely, 6%, 12%, 16%, and 20% by weight of the bitumen. The testing undertaken on the asphalt mix comprises the indirect tensile (dynamic stiffness, dynamic creep, and wheel tracking tests. By the experimentation, the appropriate amount of CRM was found to be 16% by weight of bitumen. The results show that the addition of CRM into the mixture has an obvious significant effect on the performance properties of SMA which could improve the mixture's resistance against permanent deformation. Further, higher correlation coefficient was obtained between the rut depth and permanent strain as compared to resilient modulus; thus dynamic creep test might be a more reliable test in evaluating the rut resistance of asphalt mixture.

Nonlinear empirical model of gas humidity-related voltage dynamics of a polymer-electrolyte-membrane fuel cell stack

Science.gov (United States)

Meiler, M.; Andre, D.; Schmid, O.; Hofer, E. P.

Intelligent energy management is a cost-effective key path to realize efficient automotive drive trains [R. O'Hayre, S.W. Cha, W. Colella, F.B. Prinz. Fuel Cell Fundamentals, John Wiley & Sons, Hoboken, 2006]. To develop operating strategy in fuel cell drive trains, precise and computational efficient models of all system components, especially the fuel cell stack, are needed. Should these models further be used in diagnostic or control applications, then some major requirements must be fulfilled. First, the model must predict the mean fuel cell voltage very precisely in all possible operating conditions, even during transients. The model output should be as smooth as possible to support best efficient optimization strategies of the complete system. At least, the model must be computational efficient. For most applications, a difference between real fuel cell voltage and model output of less than 10 mV and 1000 calculations per second will be sufficient. In general, empirical models based on system identification offer a better accuracy and consume less calculation resources than detailed models derived from theoretical considerations [J. Larminie, A. Dicks. Fuel Cell Systems Explained, John Wiley & Sons, West Sussex, 2003]. In this contribution, the dynamic behaviour of the mean cell voltage of a polymer-electrolyte-membrane fuel cell (PEMFC) stack due to variations in humidity of cell's reactant gases is investigated. The validity of the overall model structure, a so-called general Hammerstein model (or Uryson model), was introduced recently in [M. Meiler, O. Schmid, M. Schudy, E.P. Hofer. Dynamic fuel cell stack model for real-time simulation based on system identification, J. Power Sources 176 (2007) 523-528]. Fuel cell mean voltage is calculated as the sum of a stationary and a dynamic voltage component. The stationary component of cell voltage is represented by a lookup-table and the dynamic voltage by a parallel placed, nonlinear transfer function. A

Dynamics of Corticosteroid Receptors: Lessons from Live Cell Imaging

International Nuclear Information System (INIS)

Nishi, Mayumi

2011-01-01

Adrenal corticosteroids (cortisol in humans or corticosterone in rodents) exert numerous effects on the central nervous system that regulates the stress response, mood, learning and memory, and various neuroendocrine functions. Corticosterone (CORT) actions in the brain are mediated via two receptor systems: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). It has been shown that GR and MR are highly colocalized in the hippocampus. These receptors are mainly distributed in the cytoplasm without hormones and translocated into the nucleus after treatment with hormones to act as transcriptional factors. Thus the subcellular dynamics of both receptors are one of the most important issues. Given the differential action of MR and GR in the central nervous system, it is of great consequence to clarify how these receptors are trafficked between cytoplasm and nucleus and their interactions are regulated by hormones and/or other molecules to exert their transcriptional activity. In this review, we focus on the nucleocytoplasmic and subnuclear trafficking of GR and MR in neural cells and non-neural cells analyzed by using molecular imaging techniques with green fluorescent protein (GFP) including fluorescence recovery after photobleaching (FRAP) and fluorescence resonance energy transfer (FRET), and discuss various factors affecting the dynamics of these receptors. Furthermore, we discuss the future directions of in vivo molecular imaging of corticosteroid receptors at the whole brain level

Cell damage evaluation of mammalian cells in cell manipulation by amplified femtosecond ytterbium laser

Science.gov (United States)

Hong, Z.-Y.; Iino, T.; Hagihara, H.; Maeno, T.; Okano, K.; Yasukuni, R.; Hosokawa, Y.

2018-03-01

A micrometer-scale explosion with cavitation bubble generation is induced by focusing a femtosecond laser in an aqueous solution. We have proposed to apply the explosion as an impulsive force to manipulate mammalian cells especially in microfluidic chip. Herein, we employed an amplified femtosecond ytterbium laser as an excitation source for the explosion and evaluated cell damage in the manipulation process to clarify the application potential. The damage of C2C12 myoblast cell prepared as a representative mammalian cell was investigated as a function of distance between cell and laser focal point. Although the cell received strong damage on the direct laser irradiation condition, the damage sharply decreased with increasing distance. Since the threshold distance, above which the cell had no damage, was consistent with radius of the cavitation bubble, impact of the cavitation bubble would be a critical factor for the cell damage. The damage had strong nonlinearity in the pulse energy dependence. On the other hand, cell position shift by the impact of the cavitation bubble was almost proportional to the pulse energy. In balance between the cell viability and the cell position shift, we elucidated controllability of the cell manipulation in microfluidic chip.

Solid-State NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization

International Nuclear Information System (INIS)

Takahashi, Hiroki; Bardet, Michel; De Paepe, Gael; Hediger, Sabine; Ayala, Isabel; Simorre, Jean-Pierre

2013-01-01

Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool. (authors)

Solid-state NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization.

Science.gov (United States)

Takahashi, Hiroki; Ayala, Isabel; Bardet, Michel; De Paëpe, Gaël; Simorre, Jean-Pierre; Hediger, Sabine

2013-04-03

Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool.

Perivascular epithelioid cell tumour: Dynamic CT, MRI and clinicopathological characteristics—Analysis of 32 cases and review of the literature

International Nuclear Information System (INIS)

Tan, Y.; Zhang, H.; Xiao, E.-H.

2013-01-01

Aim: To evaluate the dynamic computed tomography (CT), magnetic resonance imaging (MRI), and clinicopathological characteristics of perivascular epithelioid cell tumours (PEComas), thus improving the diagnosis of the tumour. Materials and methods: A retrospective analysis was undertaken of the dynamic CT, MRI, and clinicopathological characteristics of 32 PEComas diagnosed at histopathology during the period 1 January 2005 to 1 March 2012 at two hospitals. Results: The age of the patients ranged from 14–80 years (mean 43.3 years). There were more women in this group (19/32). Solitary tumours were identified in kidney (n = 16), liver (n = 7), gynaecological organs (n = 2), retroperitoneal soft tissue (n = 2), lung (n = 2), palate (n = 1), left groin (n = 1). One patient had multiple tumours in the liver, kidney, and retroperitoneal soft tissue. Dynamic CT (32 cases) and MRI (15 cases) demonstrated tumours that were of low density or hypointense on T1-weighted imaging (WI) and hyperintense on T2WI; some were isodense with fat (CT: 10/32; MRI: 6/15). The tumours usually had well-defined borders and were of a regular shape (CT: 26/32; MRI: 12/15). Tumour diameters ranged from 1.5–18 cm (mean 5.1 cm). Most tumours (CT: 21/32, MRI: 10/15) enhanced heterogeneously and significantly on arterial and venous phases. Tumours appeared slightly hypodense on delayed CT imaging, although some (6/32) had delayed enhancement. The expression rate of HMB-45 (human melanoma black monoclonal antibody) was 100% (32/32). Histological classification in 22 cases (22/32) was epithelioid angiomyolipoma (AML), three (3/32) were clear cell “sugar” tumours (CCSTs), two (2/32) were lymphangioleiomyomatosis (LAM), and two (2/32) were clear cell myomelanocytic tumours of the falciform ligament/ligamentum teres (CCMMT). Three tumours did not have a specific classification. Conclusion: Knowledge of dynamic CT, MRI, and clinicopathological characteristics could help improve the diagnosis of

Cell layer level generalized dynamic modeling of a PEMFC stack using VHDL-AMS language

Energy Technology Data Exchange (ETDEWEB)

Gao, Fei; Blunier, Benjamin; Miraoui, Abdellatif; El-Moudni, Abdellah [Transport and Systems Laboratory (SeT) - EA 3317/UTBM, University of Technology of Belfort-Montbeliard, Rue Thierry Mieg, 90000 Belfort (France)

2009-07-15

A generalized, cell layer scale proton exchange membrane fuel cell (PEMFC) stack dynamic model is presented using VHDL-AMS (IEEE standard Very High Speed Integrated Circuit Hardware Description Language-Analog and Mixed-Signal Extensions) modeling language. A PEMFC stack system is a complex energy conversion system that covers three main energy domains: electrical, fluidic and thermal. The first part of this work shows the performance and the advantages of VHDL-AMS language when modeling such a complex system. Then, using the VHDL-AMS modeling standards, an electrical domain model, a fluidic domain model and a thermal domain model of the PEMFC stack are coupled and presented together. Thus, a complete coupled multi-domain fuel cell stack 1-D dynamic model is given. The simulation results are then compared with a Ballard 1.2 kW NEXA fuel cell system, and show a great agreement between the simulation and experimentation. This complex multi-domain VHDL-AMS stack model can be used for a model based control design or a Hardware-In-the-Loop application. (author)

The study of sheath flow dark zone phenomenon in dynamic individual cells scattering measurement

Science.gov (United States)

Zhang, Lu; Zhao, Hong; Wang, Xiaopin; Zhang, Weiguang

2008-09-01

Dynamic cells scattering is one of the most efficient approaches exploring in measurements of cells size, morphology and growth states. This technique can be widely applied in real-time detection for pharmaceutical industry, food industry, liquor industry and other biological fields. A novel method named dynamic individual cells scattering measurement is designed in this paper, which can make cells pass through quartz glass measurement zone one by one with sheath flow driving force. During the experiments, an obvious phenomenon has been found which is called sheath flow dark zone phenomenon (SFDZ). Under the influence of SFDZ, sheath flow forming detection becomes very difficult. In this paper, the causes giving rise to SFDZ have been analyzed. And an improved method is put forward, in which the orifice inside the measurement zone is set as an optical system. Then the illuminating system is redesigned. In this way, almost all the illuminating light can enter orifice so that the total reflection energy decreases substantially. A comparison experiments have been done, which proves the efficiency of this redesigned optical system and its sound effects on SFDZ avoiding.

Dynamic Pedagogy for Effective Training of Youths in Cell Phone Maintenance

Science.gov (United States)

Ogbuanya, T. C.; Jimoh, Bakare

2015-01-01

The study determined dynamic pedagogies for effective training of youths in cell phone maintenance. The study was conducted in Enugu State of Nigeria. Four research questions were developed while four null hypotheses formulated were tested at 0.05 level of significance. A survey research design was adopted for the study. The population for the…

Macroscopic Dynamic Modeling of Sequential Batch Cultures of Hybridoma Cells: An Experimental Validation

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Laurent Dewasme

2017-02-01

Full Text Available Hybridoma cells are commonly grown for the production of monoclonal antibodies (MAb. For monitoring and control purposes of the bioreactors, dynamic models of the cultures are required. However these models are difficult to infer from the usually limited amount of available experimental data and do not focus on target protein production optimization. This paper explores an experimental case study where hybridoma cells are grown in a sequential batch reactor. The simplest macroscopic reaction scheme translating the data is first derived using a maximum likelihood principal component analysis. Subsequently, nonlinear least-squares estimation is used to determine the kinetic laws. The resulting dynamic model reproduces quite satisfactorily the experimental data, as evidenced in direct and cross-validation tests. Furthermore, model predictions can also be used to predict optimal medium renewal time and composition.

Maximal Fluctuations of Confined Actomyosin Gels: Dynamics of the Cell Nucleus.

Science.gov (United States)

Rupprecht, J-F; Singh Vishen, A; Shivashankar, G V; Rao, M; Prost, J

2018-03-02

We investigate the effect of stress fluctuations on the stochastic dynamics of an inclusion embedded in a viscous gel. We show that, in nonequilibrium systems, stress fluctuations give rise to an effective attraction towards the boundaries of the confining domain, which is reminiscent of an active Casimir effect. We apply this generic result to the dynamics of deformations of the cell nucleus, and we demonstrate the appearance of a fluctuation maximum at a critical level of activity, in agreement with recent experiments [E. Makhija, D. S. Jokhun, and G. V. Shivashankar, Proc. Natl. Acad. Sci. U.S.A. 113, E32 (2016)PNASA60027-842410.1073/pnas.1513189113].

Dynamic analysis of CO₂ labeling and cell respiration using membrane-inlet mass spectrometry.

Science.gov (United States)

Yang, Tae Hoon

2014-01-01

Here, we introduce a mass spectrometry-based analytical method and relevant technical details for dynamic cell respiration and CO2 labeling analysis. Such measurements can be utilized as additional information and constraints for model-based (13)C metabolic flux analysis. Dissolved dynamics of oxygen consumption and CO2 mass isotopomer evolution from (13)C-labeled tracer substrates through different cellular processes can be precisely measured on-line using a miniaturized reactor system equipped with a membrane-inlet mass spectrometer. The corresponding specific rates of physiologically relevant gases and CO2 mass isotopomers can be quantified within a short-term range based on the liquid-phase dynamics of dissolved fermentation gases.

An Îto stochastic differential equations model for the dynamics of the MCF-7 breast cancer cell line treated by radiotherapy.

Science.gov (United States)

Oroji, Amin; Omar, Mohd; Yarahmadian, Shantia

2016-10-21

In this paper, a new mathematical model is proposed for studying the population dynamics of breast cancer cells treated by radiotherapy by using a system of stochastic differential equations. The novelty of the model is essentially in capturing the concept of the cell cycle in the modeling to be able to evaluate the tumor lifespan. According to the cell cycle, each cell belongs to one of three subpopulations G, S, or M, representing gap, synthesis and mitosis subpopulations. Cells in the M subpopulation are highly radio-sensitive, whereas cells in the S subpopulation are highly radio-resistant. Therefore, in the process of radiotherapy, cell death rates of different subpopulations are not equal. In addition, since flow cytometry is unable to detect apoptotic cells accurately, the small changes in cell death rate in each subpopulation during treatment are considered. Subsequently, the proposed model is calibrated using experimental data from previous experiments involving the MCF-7 breast cancer cell line. Consequently, the proposed model is able to predict tumor lifespan based on the number of initial carcinoma cells. The results show the effectiveness of the radiation under the condition of stability, which describes the decreasing trend of the tumor cells population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Color opponency in cone-driven horizontal cells in carp retina. Aspecific pathways between cones and horizontal cells

NARCIS (Netherlands)

Kamermans, M.; van Dijk, B. W.; Spekreijse, H.

1991-01-01

The spectral and dynamic properties of cone-driven horizontal cells in carp retina were evaluated with silent substitution stimuli and/or saturating background illumination. The aim of this study was to describe the wiring underlying the spectral sensitivity of these cells. We will present

Robust Optimization Approach for Design for a Dynamic Cell Formation Considering Labor Utilization: Bi-objective Mathematical Mode

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Hiwa Farughi

2016-05-01

Full Text Available In this paper, robust optimization of a bi-objective mathematical model in a dynamic cell formation problem considering labor utilization with uncertain data is carried out. The robust approach is used to reduce the effects of fluctuations of the uncertain parameters with regards to all the possible future scenarios. In this research, cost parameters of the cell formation and demand fluctuations are subject to uncertainty and a mixed-integer programming (MIP model is developed to formulate the related robust dynamic cell formation problem. Then the problem is transformed into a bi-objective linear one. The first objective function seeks to minimize relevant costs of the problem including machine procurement and relocation costs, machine variable cost, inter-cell movement and intra-cell movement costs, overtime cost and labor shifting cost between cells, machine maintenance cost, inventory, holding part cost. The second objective function seeks to minimize total man-hour deviations between cells or indeed labor utilization of the modeled.

Primary lithium-thionyl chloride cell evaluation

Science.gov (United States)

Zolla, A. E.; Waterhouse, R.; Debiccari, D.; Griffin, G. L.

1980-08-01

A test program was conducted to evaluate the Altus 1350AH cell performance against the Minuteman Survival Ground Power requirements. Twelve cells of the 17 inch diameter, 1-3/8 inch heights were fabricated and tested during this study. Under discharge rates varying from C/100 to C/400 at ambient temperature, the volumetric and gravimetric energy density performance requirements of 15 watt hours per cubic inch and 150 watt hours per pound were exceeded in all cases. All other performance requirements of voltage, current, configuration, capacity volume, weight, electrolyte leakage (none), and maintainability (none required), were met or exceeded. The abuse testing demonstrated the Altus Cell's ability to safely withstand short circuit by external shorting, short circuit by penetration with a conductive object, forced discharge, and forced charging of a cell. Disposal of discharged cells by incineration is an environmentally safe and efficient method of disposal.

Griseofulvin stabilizes microtubule dynamics, activates p53 and inhibits the proliferation of MCF-7 cells synergistically with vinblastine