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Sample records for cell dynamic evaluation

  1. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Reiko; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori; Tanabe, Kazunari [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan)

    2016-06-15

    We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. (orig.)

  2. Dynamic modeling and evaluation of solid oxide fuel cell - combined heat and power system operating strategies

    Science.gov (United States)

    Nanaeda, Kimihiro; Mueller, Fabian; Brouwer, Jacob; Samuelsen, Scott

    Operating strategies of solid oxide fuel cell (SOFC) combined heat and power (CHP) systems are developed and evaluated from a utility, and end-user perspective using a fully integrated SOFC-CHP system dynamic model that resolves the physical states, thermal integration and overall efficiency of the system. The model can be modified for any SOFC-CHP system, but the present analysis is applied to a hotel in southern California based on measured electric and heating loads. Analysis indicates that combined heat and power systems can be operated to benefit both the end-users and the utility, providing more efficient electric generation as well as grid ancillary services, namely dispatchable urban power. Design and operating strategies considered in the paper include optimal sizing of the fuel cell, thermal energy storage to dispatch heat, and operating the fuel cell to provide flexible grid power. Analysis results indicate that with a 13.1% average increase in price-of-electricity (POE), the system can provide the grid with a 50% operating range of dispatchable urban power at an overall thermal efficiency of 80%. This grid-support operating mode increases the operational flexibility of the SOFC-CHP system, which may make the technology an important utility asset for accommodating the increased penetration of intermittent renewable power.

  3. Dynamic modeling, experimental evaluation, optimal design and control of integrated fuel cell system and hybrid energy systems for building demands

    Science.gov (United States)

    Nguyen, Gia Luong Huu

    Fuel cells can produce electricity with high efficiency, low pollutants, and low noise. With the advent of fuel cell technologies, fuel cell systems have since been demonstrated as reliable power generators with power outputs from a few watts to a few megawatts. With proper equipment, fuel cell systems can produce heating and cooling, thus increased its overall efficiency. To increase the acceptance from electrical utilities and building owners, fuel cell systems must operate more dynamically and integrate well with renewable energy resources. This research studies the dynamic performance of fuel cells and the integration of fuel cells with other equipment in three levels: (i) the fuel cell stack operating on hydrogen and reformate gases, (ii) the fuel cell system consisting of a fuel reformer, a fuel cell stack, and a heat recovery unit, and (iii) the hybrid energy system consisting of photovoltaic panels, fuel cell system, and energy storage. In the first part, this research studied the steady-state and dynamic performance of a high temperature PEM fuel cell stack. Collaborators at Aalborg University (Aalborg, Denmark) conducted experiments on a high temperature PEM fuel cell short stack at steady-state and transients. Along with the experimental activities, this research developed a first-principles dynamic model of a fuel cell stack. The dynamic model developed in this research was compared to the experimental results when operating on different reformate concentrations. Finally, the dynamic performance of the fuel cell stack for a rapid increase and rapid decrease in power was evaluated. The dynamic model well predicted the performance of the well-performing cells in the experimental fuel cell stack. The second part of the research studied the dynamic response of a high temperature PEM fuel cell system consisting of a fuel reformer, a fuel cell stack, and a heat recovery unit with high thermal integration. After verifying the model performance with the

  4. Microbial Cell Dynamics Lab (MCDL)

    Data.gov (United States)

    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...

  5. Manual for Dynamic Triaxial Cell

    DEFF Research Database (Denmark)

    Pedersen, Thomas Schmidt; Ibsen, Lars Bo

    This report is a test report that describes the test setup for a dynamic triaxial cell at the Laboratory for Geotechnique at Aalborg University.......This report is a test report that describes the test setup for a dynamic triaxial cell at the Laboratory for Geotechnique at Aalborg University....

  6. In vitro evaluation of the human gingival fibroblast/gingival mesenchymal stem cell dynamics through perforated guided tissue membranes: cell migration, proliferation and membrane stiffness assay.

    Science.gov (United States)

    Gamal, A Y; Al-Berry, N N; Hassan, A A; Rashed, L A; Iacono, V J

    2017-06-01

    Migration of gingival fibroblasts/gingival mesenchymal stem cells through macro-perforated barrier membranes may allow them to participate positively in periodontal regeneration. The optimal guided tissue membrane perforation diameter that could favor maximum cell migration into the defect area and at the same time act as an occlusive barrier for gingival epithelium and its associated gingival extracellular matrix component is not yet identified. Cultured human gingival fibroblasts/gingival mesenchymal stem cells were placed in the upper chambers of 12-well collagen-coated polytetrafluoroethylene transwells, which were manually perforated with 0.2, 0.4 and 0.7 mm sized pores. The lower chambers of the transwells received blood clot as an attraction medium. The number of cells that have migrated to the lower chambers was calculated. Proliferation of these cells was evaluated using MTT assay. Scanning electron microscopy images were obtained for the lower surfaces of the transwell membranes. Perforated bovine collagen membranes (Tutopatch ® ) were subjected to mechanical testing to determine the tensile strength and modulus of elasticity. Group 3 (0.7 mm) showed significantly higher values for cell migration and proliferation. All groups showed a small degree of extracellular matrix migration through membrane perforations. Scanning electron microscopy evaluation revealed variable numbers of cells in fibrin matrices located mainly around the pore edges. There were non-significant differences between groups regarding mechanical properties. The present study demonstrated that macro-membrane perforations of 0.2, 0.4 and 0.7 mm are suitable pore diameters that could maintain membrane stiffness and allow for cellular migration. However, these membrane perforation diameters did not allow for total gingival connective tissue isolation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Evaluation of phosphopeptide enrichment strategies for quantitative TMT analysis of complex network dynamics in cancer-associated cell signalling

    Directory of Open Access Journals (Sweden)

    Benedetta Lombardi

    2015-03-01

    Full Text Available Defining alterations in signalling pathways in normal and malignant cells is becoming a major field in proteomics. A number of different approaches have been established to isolate, identify and quantify phosphorylated proteins and peptides. In the current report, a comparison between SCX prefractionation versus an antibody based approach, both coupled to TiO2 enrichment and applied to TMT labelled cellular lysates, is described. The antibody strategy was more complete for enriching phosphopeptides and allowed the identification of a large set of proteins known to be phosphorylated (715 protein groups with a minimum number of not previously known phosphorylated proteins (2.

  8. [Effects on proliferation ability of vascular smooth muscle cells by static and/or dynamic cell culture: utility of pre-seeding technique for dynamic cell culture].

    Science.gov (United States)

    Yokomuro, Hiroki; Ozawa, Tsukasa; Fujii, Takeshiro; Shiono, Noritsugu; Watanabe, Yoshinori; Yoshihara, Katsunori; Koyama, Nobuya; Okada, Mitsumasa

    2007-11-01

    Conventional biomaterials are not viable, do not grow, and do not provide contractile effects in cardiac tissue. Foreign synthetic material may become thrombogenic or infected. The most recent cardiac constructs consist of biodegradable material which has the potential to solve these problems. However, dynamic three-dimensional cell culture is necessary because conventional culture is limited to construct tough biografts. Vascular smooth muscle cells derived from rat aorta were seeded to poly-L-lactide-epsilon-capro-lactone copolymer in three groups; static culture group (static cell seeding + static cell culture), dynamic culture group (dynamic cell seeding + dynamic cell culture), and pre-seeding group [static cell seeding and culture for 1 week (pre-seeding) + dynamic cell culture]. The dynamic cell culture system used an original spinner flask. The pre-seeding technique used static cell seeding and culture before dynamic culture. The three groups were evaluated by cell proliferation and histologic studies. Vascular smooth muscle cells could be proliferated in/on the biodegradable materials. The pre-seeding group cells grew much more efficiently than the other groups. Very few cells were found in the biodegradable materials with the dynamic groups. However, there were many cells in the materials with the static culture group and pre-seeding group, especially the pre-seeding group. Dynamic culture is useful for constructing tough biografts by the pre-seeding technique.

  9. Characterization of Collective Cell Migration Dynamics

    Science.gov (United States)

    Lee, Rachel; Yue, Haicen; Rappel, Wouter-Jan; Losert, Wolfgang

    2015-03-01

    During cancer progression, tumor cells invade the surrounding tissue and migrate throughout the body, forming clinically dangerous secondary tumors. This metastatic process begins when cells leave the primary tumor, either as individual cells or collectively migrating groups. Here we present data on the migration dynamics of epithelial sheets composed of many cells. Using quantitative image analysis techniques, we are able to extract motion information from time-lapse images of cell lines with varying malignancy. Adapting metrics originally used to study fluid flows we are able to characterize the migration dynamics of these cell lines. By describing the migration dynamics in great detail, we are able to make a clear comparison of our results to a simulation of collective cell migration. Specifically, we explore whether leader cells are required to describe our expanding sheets of cells and whether the answer depends on individual cell activity.

  10. Epigenetic dynamics across the cell cycle

    DEFF Research Database (Denmark)

    Kheir, Tony Bou; Lund, Anders H.

    2010-01-01

    Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle...... a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle....

  11. Electrorefining cell evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Bronson, M.C.; Thomas, R.L. (ed.)

    1989-04-14

    Operational characteristics of the LANL electrorefining cell, a modified LANL electrorefining cell, and an advanced electrorefining cell (known as the CRAC cell) were determined. Average process yields achieved were: 75% for the LANL cell, 82% for the modified LANL cell, and 86% for the CRAC cell. All product metal from the LANL and modified LANL cells was within foundry specifications. Metal from one run in the CRAC cell exceeded foundry specifications for tantalum. The LANL and modified LANL cells were simple in design and operation, but product separation was more labor intensive than with the CRAC cell. The CRAC cell was more complicated in design but remained relatively simple in operation. A decision analysis concluded that the modified LANL cell was the preferred cell. It was recommended that the modified LANL cell be implemented by the Plutonium Recovery Project at Rocky Flats and that development of the CRAC cell continue. 8 refs., 22 figs., 12 tabs.

  12. 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

  13. Analysis of Cell Cycle Dynamics using Probabilistic Cell Cycle Models

    Science.gov (United States)

    Gurkan-Cavusoglu, Evren; Schupp, Jane E.; Kinsella, Timothy J.; Loparo, Kenneth A.

    2013-01-01

    In this study, we develop asynchronous probabilistic cell cycle models to quantitatively assess the effect of ionizing radiation on a human colon cancer cell line. We use both synchronous and asynchronous cell populations and follow treated cells for up to 2 cell cycle times. The model outputs quantify the changes in cell cycle dynamics following ionizing radiation treatment, principally in the duration of both G1 and G2/M phases. PMID:22254270

  14. RELIABILITY EVALUATION OF PRIMARY CELLS

    African Journals Online (AJOL)

    Dr Obe

    ABSTRACT. Evaluation of the reliability of a primary cell took place in three stages: 192 cells went through a slow-discharged test. A designed experiment was conducted on 144 cells; there were three factors in the experiment: Storage temperature (three levels), thermal shock (two levels) and date code (two levels). 16 cells ...

  15. 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.

  16. Actin microfilament dynamics in locomoting cells

    Science.gov (United States)

    Theriot, Julie A.; Mitchison, Timothy J.

    1991-07-01

    The dynamic behaviour of actin filaments has been directly observed in living, motile cells using fluorescence photoactivation. In goldfish epithelial keratocytes, the actin microfilaments in the lamellipodium remain approximately fixed relative to the substrate as the cell moves over them, regardless of cell speed. The rate of turnover of actin subunits in the lamellipodium is remarkably rapid. Cell movement is directly and tightly coupled to the formation of new actin filaments at the leading edge.

  17. Population dynamics in vasopressin cells.

    Science.gov (United States)

    Leng, Gareth; Brown, Colin; Sabatier, Nancy; Scott, Victoria

    2008-01-01

    Most neurons sense and code change, and when presented with a constant stimulus they adapt, so as to be able to detect a fresh change. However, for some things it is important to know their absolute level; to encode such information, neurons must sustain their response to an unchanging stimulus while remaining able to respond to a change in that stimulus. One system that encodes the absolute level of a stimulus is the vasopressin system, which generates a hormonal signal that is proportional to plasma osmolality. Vasopressin cells sense plasma osmolality and secrete appropriate levels of vasopressin from the neurohypophysis as needed to control water excretion; this requires sustained secretion under basal conditions and the ability to increase (or decrease) secretion should plasma osmolality change. Here we explore the mechanisms that enable vasopressin cells to fulfill this function, and consider how coordination between the cells might distribute the secretory load across the population of vasopressin cells. 2008 S. Karger AG, Basel.

  18. Choosing Cell Fate Through a Dynamic Cell Cycle.

    Science.gov (United States)

    Chen, Xinyue; Hartman, Amaleah; Guo, Shangqin

    2015-01-01

    A close relationship between proliferation and cell fate specification has been well documented in many developmental systems. In addition to the gradual cell fate changes accompanying normal development and tissue homeostasis, it is now commonly appreciated that cell fate could also undergo drastic changes, as illustrated by the induction of pluripotency from many differentiated somatic cell types during the process of Yamanaka reprogramming. Strikingly, the drastic cell fate change induced by Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) is preceded by extensive cell cycle acceleration. Prompted by our recent discovery that progression toward pluripotency from rare somatic cells could bypass the stochastic phase of reprogramming and that a key feature of these somatic cells is an ultrafast cell cycle (~8 h/cycle), we assess whether cell cycle dynamics could provide a general framework for controlling cell fate. Several potential mechanisms on how cell cycle dynamics may impact cell fate determination by regulating chromatin, key transcription factor concentration, or their interactions are discussed. Specific challenges and implications for studying and manipulating cell fate are considered.

  19. Force Dynamics During T Cell Activation

    Science.gov (United States)

    Garcia, David A.; Upadhyaya, Arpita

    T cell activation is an essential step in the adaptive immune response. The binding of the T cell receptor (TCR) with antigen triggers signaling cascades and cell spreading. Physical forces exerted on the TCR by the cytoskeleton have been shown to induce signaling events. While cellular forces are known to depend on the mechanical properties of the cytoskeleton, the biophysical mechanisms underlying force induced activation of TCR-antigen interactions unknown. Here, we use traction force microscopy to measure the force dynamics of activated Jurkat T cells. The movements of beads embedded in an elastic gel serve as a non-invasive reporter of cytoskeletal and molecular motor dynamics. We examined the statistical structure of the force profiles throughout the cell during signaling activation. We found two spatially distinct active regimes of force generation characterized by different time scales. Typically, the interior of the cells was found to be more active than the periphery. Inhibition of myosin motor activity altered the correlation time of the bead displacements indicating additional sources of stochastic force generation. Our results indicate a complex interaction between myosin activity and actin polymerization dynamics in producing cellular forces in immune cells.

  20. Computational fluid dynamics evaluation of excessive dynamic airway collapse.

    Science.gov (United States)

    Taherian, Shahab; Rahai, Hamid; Gomez, Bernardo; Waddington, Thomas; Mazdisnian, Farhad

    2017-12-01

    Excessive dynamic airway collapse, which is often caused by the collapse of the posterior membrane wall during exhalation, is often misdiagnosed with other diseases; stents can provide support for the collapsing airways. The standard pulmonary function tests do not necessarily show change in functional breathing condition for evaluation of these type of diseases. Flow characteristics through a patient's airways with excessive dynamic airway collapse have been numerically investigated. A stent was placed to support the collapsing airway and to improve breathing conditions. Computed tomography images of the patient's pre- and post-stenting were used for generating 3-Dimensional models of the airways, and were imported into a computational fluid dynamics software for simulation of realistic air flow behavior. Unsteady simulations of the inspiratory phase and expiratory phase were performed with patient-specific boundary conditions for pre- and post-intervention cases to investigate the effect of stent placement on flow characteristic and possible improvements. Results of post-stent condition show reduced pressure, velocity magnitude and wall shear stress during expiration. The variation in wall shear stress, velocity magnitude and pressure drop is negligible during inspiration. Although Spirometry tests do not show significant improvements, computational fluid dynamics results show significant improvements in pre- and post-treatment results, suggesting improvement in breathing condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Collective dynamics of cell migration and cell rearrangements

    Science.gov (United States)

    Kabla, Alexandre

    Understanding multicellular processes such as embryo development or cancer metastasis requires to decipher the contributions of local cell autonomous behaviours and long range interactions with the tissue environment. A key question in this context concerns the emergence of large scale coordination in cell behaviours, a requirement for collective cell migration or convergent extension. I will present a few examples where physical and mechanical aspects play a significant role in driving tissue scale dynamics. Geometrical confinement is one of the key external factors influencing large scale coordination during collective migration. Using a combination of in vitro experiments and numerical simulations, we show that the velocity correlation length, measured in unconfined conditions, provides a convenient length scale to predict the dynamic response under confinement. The same length scale can also be used to quantify the influence range of directional cues within the cell population. Heterogeneity within motile cell populations is frequently associated with an increase in their invasive capability and appears to play an important role during cancer metastasis. Using in silico experiments, we studied the way cell invasion is influenced by both the degree of cell coordination and the amount of variability in the motile force of the invading cells. Results suggest that mechanical heterogeneity dramatically enhances the invasion rate through an emerging cooperative process between the stronger and weaker cells, accounting for a number of observed invasion phenotypes. Effective convergent extension requires on a consistent orientation of cell intercalation at the tissue scale, most often in relation with planar cell polarity mechanisms to define the primary axes of deformation. Using a novel modelling approach for cells mechanical interactions, we studied the dynamics of substrate free motile cell populations. Ongoing work shows in particular that nematic order emerges

  2. 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.

  3. Human T Cell Memory: A Dynamic View

    Science.gov (United States)

    Macallan, Derek C.; Borghans, José A. M.; Asquith, Becca

    2017-01-01

    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. PMID:28165397

  4. Dynamics of proteasome distribution in living cells

    NARCIS (Netherlands)

    Reits, E. A.; Benham, A. M.; Plougastel, B.; Neefjes, J.; Trowsdale, J.

    1997-01-01

    Proteasomes are proteolytic complexes involved in non-lysosomal degradation which are localized in both the cytoplasm and the nucleus. The dynamics of proteasomes in living cells is unclear, as is their targeting to proteins destined for degradation. To investigate the intracellular distribution and

  5. 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.

  6. Quantitative evaluation of the reticuloendothelial system function with dynamic MRI.

    Directory of Open Access Journals (Sweden)

    Ting Liu

    Full Text Available To evaluate the reticuloendothelial system (RES function by real-time imaging blood clearance as well as hepatic uptake of superparamagnetic iron oxide nanoparticle (SPIO using dynamic magnetic resonance imaging (MRI with two-compartment pharmacokinetic modeling.Kinetics of blood clearance and hepatic accumulation were recorded in young adult male 01b74 athymic nude mice by dynamic T2* weighted MRI after the injection of different doses of SPIO nanoparticles (0.5, 3 or 10 mg Fe/kg. Association parameter, Kin, dissociation parameter, Kout, and elimination constant, Ke, derived from dynamic data with two-compartment model, were used to describe active binding to Kupffer cells and extrahepatic clearance. The clodrosome and liposome were utilized to deplete macrophages and block the RES function to evaluate the capability of the kinetic parameters for investigation of macrophage function and density.The two-compartment model provided a good description for all data and showed a low sum squared residual for all mice (0.27±0.03. A lower Kin, a lower Kout and a lower Ke were found after clodrosome treatment, whereas a lower Kin, a higher Kout and a lower Ke were observed after liposome treatment in comparison to saline treatment (P<0.005.Dynamic SPIO-enhanced MR imaging with two-compartment modeling can provide information on RES function on both a cell number and receptor function level.

  7. Dynamical properties of water in living cells

    Science.gov (United States)

    Piazza, Irina; Cupane, Antonio; Barbier, Emmanuel L.; Rome, Claire; Collomb, Nora; Ollivier, Jacques; Gonzalez, Miguel A.; Natali, Francesca

    2018-02-01

    With the aim of studying the effect of water dynamics on the properties of biological systems, in this paper, we present a quasi-elastic neutron scattering study on three different types of living cells, differing both in their morphological and tumor properties. The measured scattering signal, which essentially originates from hydrogen atoms present in the investigated systems, has been analyzed using a global fitting strategy using an optimized theoretical model that considers various classes of hydrogen atoms and allows disentangling diffusive and rotational motions. The approach has been carefully validated by checking the reliability of the calculation of parameters and their 99% confidence intervals. We demonstrate that quasi-elastic neutron scattering is a suitable experimental technique to characterize the dynamics of intracellular water in the angstrom/picosecond space/time scale and to investigate the effect of water dynamics on cellular biodiversity.

  8. Dynamic Viscoelasticity of Individual Bacterial Cells

    Science.gov (United States)

    Vadillo-Rodriguez, Virginia; Dutcher, John

    2009-03-01

    We have used an AFM-based approach to probe the mechanical properties of single bacterial cells (gram-negative Escherichia coli K12) by applying a constant compressive force to the cell under fluid conditions while measuring the time-dependent displacement (creep) of a colloidal AFM tip due to the viscoelastic properties of the cell. We observed that the cells exhibited a viscoelastic solid-like behavior with retarded elasticity, i.e. both an instantaneous and a delayed elastic deformation, which is well described by a three-parameter mechanical model. Using the best fit parameter values, we have calculated the dynamic viscoelastic behavior of the cells over a wide range of frequencies based on a numerical time-frequency transform technique and we have compared the calculated behavior with that measured experimentally. Comparison of the results obtained for E. coli with previously reported data on the mechanical properties of others gram-negative cells and their isolated surface layers suggests that the elastic component of the cell viscoelastic response is dominated by the properties of the peptidoglycan layer, whereas the viscous component likely arises from the liquid-like character of the cell membranes.

  9. 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...... and followers etc. In this research we analyze and predict the most likely role a particular node can adapt once a member of the network is either killed or caught. The adaptation is based on computing Bayes posteriori probability of each node and the level of the said node in the network structure....

  10. 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.

  11. Basics elements for modelling the dynamics of cell migration in cell culture

    International Nuclear Information System (INIS)

    FarIas, Ro; Vidal, Cs; Rapacioli, M; Flores, V

    2007-01-01

    This paper introduces some basic elements for modelling the dynamics of cell migration activity over a bi-dimensional substratum. A square matrix, representing the substratum, is implemented in order to generate virtual cells with an initial random uniform distribution, with the ability to freely move within the matrix and to interact with each others by mean of adhesive forces. Two different conditions were examined: A) cells can freely move and after contacting with another cell they both completely inhibit their migration; B) cells that come into contact have the ability to rotate respect to each other without losing their contacts and retaining the ability to move together but at a slower rate, being the decrease in the rate of movement proportional to the number of contacting cells. The dynamics of the migration process in these two conditions was evaluated by recording the evolution of several parameters as a function of time. Minor modifications in some parameters (mobility, intensity of cell-cell and cell-substratum adhesiveness) significantly change the dynamics and the final result of the virtual migrating cells

  12. In vitro evaluation of major in vivo drug metabolic pathways using primary human hepatocytes and HepaRG cells in suspension and a dynamic three-dimensional bioreactor system.

    Science.gov (United States)

    Darnell, Malin; Ulvestad, Maria; Ellis, Ewa; Weidolf, Lars; Andersson, Tommy B

    2012-10-01

    Major human specific metabolites, not detected during in vivo and in vitro preclinical studies, may cause unexpected drug interactions and toxicity in human and delays in clinical programs. Thus, reliable preclinical tools for the detection of major human metabolites are of high importance. The aim of this study was to compare major drug metabolic pathways in HepaRG cells, a human hepatoma cell line, to fresh human hepatocytes, cryopreserved human hepatocytes, and human in vivo data. Furthermore, the maintenance of cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) activities in a dynamic three-dimensional (3D) bioreactor were evaluated over time by using HepaRG cells and human hepatocytes. (14)C-diclofenac and a candidate from AstraZeneca's drug development program, (14)C-AZD6610, which are metabolized by P450 and UGT in vivo, were used as model substrates. The proportion of relevant biotransformation pathways of the investigated drug was clearly different in the various cell systems. The hydroxylation route was favored in primary human hepatocytes, whereas the glucuronidation route was favored in HepaRG cells. The human in vivo metabolite profile of AZD6610 was best represented by human hepatocytes, whereas all major diclofenac metabolites were detected in HepaRG cells. Moreover, the metabolite profiles in cryopreserved and fresh human hepatocytes were essentially the same. The liver bioreactor using both fresh human hepatocytes and HepaRG cells retained biotransformation capacity over 1 week. Thus, the incubation time can be increased from a few hours in suspension to several days in 3D cultures, which opens up for detection of metabolites from slowly metabolized drugs.

  13. Characterizing motility dynamics in human RPE cells

    Science.gov (United States)

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

    2017-02-01

    Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, however, are often compromised in ageing and ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, but while in vivo biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. Recently we addressed this problem by using organelle motility as a novel contrast agent to enhance the RPE cell in conjunction with 3D resolution of adaptive optics-optical coherence tomography (AO-OCT) to section the RPE layer. In this study, we expand on the central novelty of our method - organelle motility - by characterizing the dynamics of the motility in individual RPE cells, important because of its direct link to RPE physiology. To do this, AO-OCT videos of the same retinal patch were acquired at approximately 1 min intervals or less, time stamped, and registered in 3D with sub-cellular accuracy. Motility was quantified by an exponential decay time constant, the time for motility to decorrelate the speckle field across an RPE cell. In two normal subjects, we found the decay time constant to be just 3 seconds, thus indicating rapid motility in normal RPE cells.

  14. 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

  15. Molten carbonate fuel cell: dynamic numerical modeling and experimental investigation

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Elisangela Martins [National Institute for Space Research, Cachoeira Paulista, SP (Brazil). Combustion and Propulsion Lab.], e-mail: elisangela@lcp.inpe.br; Jabbari, Faryar [University of California, Irvine, CA (United States). Mechanical and Aerospace Engineering Dept.], e-mail: fjabbari@uci.edu; Brouwer, Jacob [University of California, Irvine, CA (United States). National Fuel Cell Research Center], e-mail: jb@nfcrc.uci.edu

    2006-07-01

    In this paper, a detailed model incorporating simplified geometric resolution of a molten carbonate fuel cell (MCFC) with detailed and dynamic simulation of all physical, chemical, and electrochemical processes in the stream-wise direction is presented. The model was developed using mass and momentum conservation, electrochemical and chemical reaction mechanisms, and heat transfer. Results from the model are compared with data from an experimental MCFC unit. Furthermore, the model was applied to predict dynamic variations of voltage, current and temperature in an MCFC as it responds to varying load demands. The voltage was evaluated by applying a model developed by Yu h and Selman (1991a, 1991b). The results show that the model can be used to predict voltage and dynamic response characteristics of an MCFC accurately and consistently for a variety of temperatures and pressures. (author)

  16. Dynamic Flow Impacts Cell-Particle Interactions: Sedimentation and Particle Shape Effects.

    Science.gov (United States)

    Björnmalm, Mattias; Faria, Matthew; Chen, Xi; Cui, Jiwei; Caruso, Frank

    2016-10-17

    The interaction of engineered particles with biological systems determines their performance in biomedical applications. Although standard static cell cultures remain the norm for in vitro studies, modern models mimicking aspects of the dynamic in vivo environment have been developed. Herein, we investigate fundamental cell-particle interactions under dynamic flow conditions using a simple and self-contained device together with standard multiwell cell culture plates. We engineer two particle systems and evaluate their cell interactions under dynamic flow, and we compare the results to standard static cell cultures. We find substantial differences between static and dynamic flow conditions and attribute these to particle shape and sedimentation effects. These results demonstrate how standard static assays can be complemented by dynamic flow assays for a more comprehensive understanding of fundamental cell-particle interactions.

  17. Programming microbial population dynamics by engineered cell-cell communication.

    Science.gov (United States)

    Song, Hao; Payne, Stephen; Tan, Cheemeng; You, Lingchong

    2011-07-01

    A major aim of synthetic biology is to program novel cellular behavior using engineered gene circuits. Early endeavors focused on building simple circuits that fulfill simple functions, such as logic gates, bistable toggle switches, and oscillators. These gene circuits have primarily focused on single-cell behaviors since they operate intracellularly. Thus, they are often susceptible to cell-cell variations due to stochastic gene expression. Cell-cell communication offers an efficient strategy to coordinate cellular behavior at the population level. To this end, we review recent advances in engineering cell-cell communication to achieve reliable population dynamics, spanning from communication within single species to multispecies, from one-way sender-receiver communication to two-way communication in synthetic microbial ecosystems. These engineered systems serve as well-defined model systems to better understand design principles of their naturally occurring counterparts and to facilitate novel biotechnology applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Mechanosensing Dynamics of Red blood Cells

    Science.gov (United States)

    Wan, Jiandi

    2015-11-01

    Mechanical stress-induced deformation of human red blood cells (RBCs) plays important physiopathological roles in oxygen delivery, blood rheology, transfusion, and malaria. Recent studies demonstrate that, in response to mechanical deformation, RBCs release adenosine-5'-triphosphate (ATP), suggesting the existence of mechanotransductive pathways in RBCs. Most importantly, the released ATP from RBCs regulates vascular tone and impaired release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. To date, however, the mechanisms of mechanotransductive release of ATP from RBCs remain unclear. Given that RBCs experience shear stresses continuously during the circulation cycle and the released ATP plays a central role in vascular physiopathology, understanding the mechanotransductive release of ATP from RBCs will provide not only fundamental insights to the role of RBCs in vascular homeostasis but also novel therapeutic strategies for red cell dysfunction and vascular disease. This talk describes the main research in my group on integrating microfluidic-based approaches to study the mechanosensing dynamics of RBCs. Specifically, I will introduce a micro?uidic approach that can probe the dynamics of shear-induced ATP release from RBCs with millisecond resolution and provide quantitative understandings of the mechanosensitive ATP release processes in RBCs. Furthermore, I will also describe our recent findings about the roles of the Piezo1 channel, a newly discovered mechanosensitive cation channel in the mechanotransductive ATP release in RBCs. Last, possible functions of RBCs in the regulation of cerebral blood flow will be discussed.

  19. Performance Evaluation of Dynamic Particle Swarm Optimization

    OpenAIRE

    Ms. Hemlata S. Urade; Rahila Patel

    2012-01-01

    In this paper the concept of dynamic particle swarmoptimization is introduced. The dynamic PSO is different fromthe existing PSO’s and some local version of PSO in terms ofswarm size and topology. Experiment conducted for benchmarkfunctions of single objective optimization problem, which showsthe better performance rather the basic PSO. The paper alsocontains the comparative analysis for Simple PSO and DynamicPSO which shows the better result for dynamic PSO rather thansimple PSO.

  20. 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

  1. 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.

  2. The evaluation of vine leaves development dynamic

    Directory of Open Access Journals (Sweden)

    Patrik Burg

    2013-01-01

    Full Text Available This experiment was focused on evaluation of grape vine leaves surface area development of the six varieties on experimental sites in Velke Bilovice and Lednice, in the viticultural conditions of the South Moravia. The dynamic of leaves surface area development was mesured by using device LAM CI–202 (Leaf Area Meter, the device operating on the principle of the scanner and the resulting values are expressed through the leaf area index (LAI. The measurements were carried out in four dates (May, June, July, August during phenological growth stages of growth, flowering, initial development of fruits (Berries pea-sized, berries beginning to touch. Obtained results show, that the greatest increase of the leaves surface area on annual shoots is during phenological growth stages of flowering and during initial development of fruits.To the development of the leaves surface area of the leaves on lateral shoots then occurs after tipping of the top parts of the annual shoots, the main axes of herbaceous shoot are interrupted. During the phenological growth stage of the development of fruits was measured at both sites the largest leaves surface area on the varieties St. Laurent in the variety, Lemberger, Cabernet Moravia and ranged from 2.74 to 4.24 m2 per plant.

  3. Mitochondrial dynamics and the cell cycle

    Directory of Open Access Journals (Sweden)

    Penny M.A. Kianian

    2014-05-01

    Full Text Available Nuclear-mitochondrial (NM communication impacts many aspects of plant development including vigor, sterility and viability. Dynamic changes in mitochondrial number, shape, size, and cellular location takes place during the cell cycle possibly impacting the process itself and leading to distribution of this organelle into daughter cells. The genes that underlie these changes are beginning to be identified in model plants such as Arabidopsis. In animals disruption of the drp1 gene, a homolog to the plant drp3A and drp3B, delays mitochondrial division. This mutation results in increased aneuploidy due to chromosome mis-segregation. It remains to be discovered if a similar outcome is observed in plants. Alloplasmic lines provide an opportunity to understand the communication between the cytoplasmic organelles and the nucleus. Examples of studies in these lines, especially from the extensive collection in wheat, point to the role of mitochondria in chromosome movement, pollen fertility and other aspects of development. Genes involved in NM interaction also are believed to play a critical role in evolution of species and interspecific cross incompatibilities.

  4. 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.

  5. Dynamics evaluation of total IgG, IgG1 and IgG2a in the serum of mice immunized with radioattenuated paracoccidioides brasiliensis yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)]. E-mail: estefaniabio@yahoo.com.br; antero@cdtn.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia]. E-mail: brsgarbi@mono.icb.ufmg.br; goes@mono.icb.ufmg.br

    2007-07-01

    Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans. Up to the moment no vaccine has still been reported. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory we developed radioattenuated yeast cells of P. brasiliensis and the aim of the present work was to evaluate the antibody production dynamics in mice immunized with this cells. Were analyzed the IgG antibodies titers as well as the type of response by analyzing the IgG1 and IgG2a antibody pattern in the course of infection. The mice were divided in two groups that were immunized one time and two times respectively. The mice infected with the virulent P. brasiliensis showed a high level of antibody production while the infection with the radioattenuated yeast did not significantly change the antibody level. The level of IgG raised in both immunized groups after the challenge. In the group immunized one time was not observed a significant difference between the levels of both subclasses when compared with the control. After the challenge of the group immunized two times the IgG2a levels increased significantly when analyzed 90 days post challenge. We concluded that a pattern related to the disease control was apparent in the group submitted to two immunizations. The mice had not developed a totally polarized pattern of TH1/TH2 response but a trend to a TH1 response was evident. (author)

  6. Dynamics evaluation of total IgG, IgG1 and IgG2a in the serum of mice immunized with radioattenuated paracoccidioides brasiliensis yeast cells

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Reis, Bernardo S.; Goes, Alfredo M.

    2007-01-01

    Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans. Up to the moment no vaccine has still been reported. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory we developed radioattenuated yeast cells of P. brasiliensis and the aim of the present work was to evaluate the antibody production dynamics in mice immunized with this cells. Were analyzed the IgG antibodies titers as well as the type of response by analyzing the IgG1 and IgG2a antibody pattern in the course of infection. The mice were divided in two groups that were immunized one time and two times respectively. The mice infected with the virulent P. brasiliensis showed a high level of antibody production while the infection with the radioattenuated yeast did not significantly change the antibody level. The level of IgG raised in both immunized groups after the challenge. In the group immunized one time was not observed a significant difference between the levels of both subclasses when compared with the control. After the challenge of the group immunized two times the IgG2a levels increased significantly when analyzed 90 days post challenge. We concluded that a pattern related to the disease control was apparent in the group submitted to two immunizations. The mice had not developed a totally polarized pattern of TH1/TH2 response but a trend to a TH1 response was evident. (author)

  7. Direct Adaptive Aircraft Control Using Dynamic Cell Structure Neural Networks

    Science.gov (United States)

    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.

  8. 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

  9. Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics

    Science.gov (United States)

    Smith, Quinton; Stukalin, Evgeny; Kusuma, Sravanti; Gerecht, Sharon; Sun, Sean X.

    2015-07-01

    Stem cell differentiation underlies many fundamental processes such as development, tissue growth and regeneration, as well as disease progression. Understanding how stem cell differentiation is controlled in mixed cell populations is an important step in developing quantitative models of cell population dynamics. Here we focus on quantifying the role of cell-cell interactions in determining stem cell fate. Toward this, we monitor stem cell differentiation in adherent cultures on micropatterns and collect statistical cell fate data. Results show high cell fate variability and a bimodal probability distribution of stem cell fraction on small (80-140 μm diameter) micropatterns. On larger (225-500 μm diameter) micropatterns, the variability is also high but the distribution of the stem cell fraction becomes unimodal. Using a stochastic model, we analyze the differentiation dynamics and quantitatively determine the differentiation probability as a function of stem cell fraction. Results indicate that stem cells can interact and sense cellular composition in their immediate neighborhood and adjust their differentiation probability accordingly. Blocking epithelial cadherin (E-cadherin) can diminish this cell-cell contact mediated sensing. For larger micropatterns, cell motility adds a spatial dimension to the picture. Taken together, we find stochasticity and cell-cell interactions are important factors in determining cell fate in mixed cell populations.

  10. 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

  11. Dynamic imaging of cell-free and cell-associated viral capture in mature dendritic cells.

    Science.gov (United States)

    Izquierdo-Useros, Nuria; Esteban, Olga; Rodriguez-Plata, Maria T; Erkizia, Itziar; Prado, Julia G; Blanco, Julià; García-Parajo, Maria F; Martinez-Picado, Javier

    2011-12-01

    Dendritic cells (DCs) capture human immunodeficiency virus (HIV) through a non-fusogenic mechanism that enables viral transmission to CD4(+) T cells, contributing to in vivo viral dissemination. Although previous studies have provided important clues to cell-free viral capture by mature DCs (mDCs), dynamic and kinetic insight on this process is still missing. Here, we used three-dimensional video microscopy and single-particle tracking approaches to dynamically dissect both cell-free and cell-associated viral capture by living mDCs. We show that cell-free virus capture by mDCs operates through three sequential phases: virus binding through specific determinants expressed in the viral particle, polarized or directional movements toward concrete regions of the cell membrane and virus accumulation in a sac-like structure where trapped viral particles display a hindered diffusive behavior. Moreover, real-time imaging of cell-associated viral transfer to mDCs showed a similar dynamics to that exhibited by cell-free virus endocytosis leading to viral accumulation in compartments. However, cell-associated HIV type 1 transfer to mDCs was the most effective pathway, boosted throughout enhanced cellular contacts with infected CD4(+) T cells. Our results suggest that in lymphoid tissues, mDC viral uptake could occur either by encountering cell-free or cell-associated virus produced by infected cells generating the perfect scenario to promote HIV pathogenesis and impact disease progression. © 2011 John Wiley & Sons A/S.

  12. Evaluating Dynamic Analysis Techniques for Program Comprehension

    NARCIS (Netherlands)

    Cornelissen, S.G.M.

    2009-01-01

    Program comprehension is an essential part of software development and software maintenance, as software must be sufficiently understood before it can be properly modified. One of the common approaches in getting to understand a program is the study of its execution, also known as dynamic analysis.

  13. 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.

  14. 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.

  15. Dynamic risk factors: the Kia Marama evaluation.

    Science.gov (United States)

    Hudson, Stephen M; Wales, David S; Bakker, Leon; Ward, Tony

    2002-04-01

    Risk assessment is an essential part of clinical practice. Each of the three aspects of risk (static, stable, and acute dynamic) are important at various points of contact between the man and the systems that are responsible for providing service. Dynamic factors, the typical treatment and supervision targets, have received less research attention than static factors. This paper examined the extent to which pretreatment, posttreatment and change scores were associated with reoffending among men incarcerated for sexually molesting. The results were generally supportive of change in prooffending attitudes as the key to not reoffending and suggested that the perspective-taking component of empathy and the use of fantasy may be important mechanisms. Affect scales generally failed to show any relationship with reoffending, outside decreases in trait and suppressed anger. Moreover, these data suggest that we could improve our assessments and treatment through increased sensitivity to offense pathways.

  16. Cycle length restitution in sinoatrial node cells: a theory for understanding spontaneous action potential dynamics.

    Directory of Open Access Journals (Sweden)

    Patric Glynn

    Full Text Available Normal heart rhythm (sinus rhythm is governed by the sinoatrial node, a specialized and highly heterogeneous collection of spontaneously active myocytes in the right atrium. Sinoatrial node dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, is associated with cardiovascular disease (e.g. heart failure, atrial fibrillation. While tremendous progress has been made in understanding the molecular and ionic basis of automaticity in sinoatrial node cells, the dynamics governing sinoatrial nodel cell synchrony and overall pacemaker function remain unclear. Here, a well-validated computational model of the mouse sinoatrial node cell is used to test the hypothesis that sinoatrial node cell dynamics reflect an inherent restitution property (cycle length restitution that may give rise to a wide range of behavior from regular periodicity to highly complex, irregular activation. Computer simulations are performed to determine the cycle length restitution curve in the computational model using a newly defined voltage pulse protocol. The ability of the restitution curve to predict sinoatrial node cell dynamics (e.g., the emergence of irregular spontaneous activity and susceptibility to termination is evaluated. Finally, ionic and tissue level factors (e.g. ion channel conductances, ion concentrations, cell-to-cell coupling that influence restitution and sinoatrial node cell dynamics are explored. Together, these findings suggest that cycle length restitution may be a useful tool for analyzing cell dynamics and dysfunction in the sinoatrial node.

  17. Nonlinear dynamics, Waddington landscape and stem cells

    Science.gov (United States)

    Tang, Chao

    There are hundreds of different cell types (skin, neuron, muscle, etc.) in human body, all derived from the stem cell and all have the same genetic information. About 60 years ago, Waddington speculated that the different cell types correspond to different minima in a landscape emerged from genetic interactions. Recently, biologists succeeded in transforming one cell type to another by perturbing the genetic interactions in a cell. I will discuss the experiments and a mathematical model of a set of such cell type transformations in mice, in which we can see an actual example of the Waddington landscape and ways to alter it to facilitate cell type transformation - in particular, to reprogram a differentiated cell back into a stem cell.

  18. Evaluation Team Dynamics: Intragroup Ethical Challenges

    Science.gov (United States)

    Urias, David

    2009-01-01

    Ethical challenges associated with the relationships among members of an evaluative team/organization receive less attention. Examples of the kinds of ethical dilemmas that could occur within an evaluation team include an individual taking undeserved credit, transferring blame, making false promises, withholding information, breaching…

  19. 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

  20. 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.

  1. 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.

  2. Evaluation of interaction dynamics of concurrent processes

    Science.gov (United States)

    Sobecki, Piotr; Białasiewicz, Jan T.; Gross, Nicholas

    2017-03-01

    The purpose of this paper is to present the wavelet tools that enable the detection of temporal interactions of concurrent processes. In particular, the determination of interaction coherence of time-varying signals is achieved using a complex continuous wavelet transform. This paper has used electrocardiogram (ECG) and seismocardiogram (SCG) data set to show multiple continuous wavelet analysis techniques based on Morlet wavelet transform. MATLAB Graphical User Interface (GUI), developed in the reported research to assist in quick and simple data analysis, is presented. These software tools can discover the interaction dynamics of time-varying signals, hence they can reveal their correlation in phase and amplitude, as well as their non-linear interconnections. The user-friendly MATLAB GUI enables effective use of the developed software what enables to load two processes under investigation, make choice of the required processing parameters, and then perform the analysis. The software developed is a useful tool for researchers who have a need for investigation of interaction dynamics of concurrent processes.

  3. 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

  4. Water Dynamics in Living Cells and Tumor Cell Migration in Confined Microenvironments

    Science.gov (United States)

    Sun, Sean

    More than 70% of the total mass in living cells is water. In most biological scenarios water serves as a passive medium responsible for solvation and proper functioning of proteins. However, it has been long recognized that there are situations where dynamic transport of water in cells is important. First, cells actively transport water in order to maintain its volume, and because cell volume directly influences cell shape and internal hydrostatic pressure, it is a critical aspect of cell mechanics. Furthermore, cell volume is coupled to protein synthesis which ultimately determines the cell size. Therefore water transport and cell volume dynamics ultimately impact cell growth and division. Second, epithelial cells in organs such as the eye and kidney actively transport water across the cell membrane and the epithelial layer. Indeed, water channels such as aquaporins increase water permeability of the membrane and facilitate this transport. Recent, we have shown that in confined microenvironments, active transport of water is responsible for actin-independent cell movement in confined spaces, especially for cancer cells. These results suggest that cells actively control its water content. The active regulation of water content is a crucial aspect of cell dynamics. We will discuss a theoretical model of cell pressure/volume control. Implications of this model for active cell dynamics in multi-cellular epithelial sheets will be discussed.

  5. 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.

  6. 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

    is constant over time is unclear. Here we analyse the stability of neoantigen-specific T-cell responses and the antigens they recognize in two patients with stage IV melanoma treated by adoptive T-cell transfer. The T-cell-recognized neoantigens can be selectively lost from the tumour cell population, either...... 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...

  7. Adhesion dynamics and durotaxis in migrating cells

    Science.gov (United States)

    Harland, Ben; Walcott, Sam; Sun, Sean X.

    2011-02-01

    When tissue cells are plated on a flexible substrate, durotaxis, the directed migration of cells toward mechanically stiff regions, has been observed. Environmental mechanical signals are not only important in cell migration but also seem to influence all aspects of cell differentiation and development, including the metastatic process in cancer cells. Based on a theoretical model suggesting that this mechanosensation has a mechanical basis, we introduce a simple model of a cell by considering the contraction of F-actin bundles containing myosin motors (stress fibers) mediated by the movement of adhesions. We show that, when presented with a linear stiffness gradient, this simple model exhibits durotaxis. Interestingly, since stress fibers do not form on soft surfaces and since adhesion sliding occurs very slowly on hard surfaces, the model predicts that the expected cell velocity reaches a maximum at an intermediate stiffness. This prediction can be experimentally tested. We therefore argue that stiffness-dependent cellular adaptations (mechanosensation) and durotaxis are intimately related and may share a mechanical basis. We therefore identify the essential physical ingredients, which combined with additional biochemical mechanisms can explain durotaxis and mechanosensation in cells.

  8. Antigen dynamics of follicular dendritic cells

    NARCIS (Netherlands)

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  9. HIV dynamics linked to memory CD4+ T cell homeostasis.

    Science.gov (United States)

    Murray, John M; Zaunders, John; Emery, Sean; Cooper, David A; Hey-Nguyen, William J; Koelsch, Kersten K; Kelleher, Anthony D

    2017-01-01

    The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART). We investigated whether plasma viral level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest changes over the 1st year of ART. Dynamics slowed over the following 2 years so that total HIV DNA levels were equivalent to reported values for individuals after 10 years of ART. The mathematical model reproduced the multiphasic dynamics of pVL, and levels of total, 2-LTR and integrated HIV DNA in both PHI and CHI over 3 years of ART. Under these simulations, residual viremia originated from reactivated latently infected cells where most of these cells arose from clonal expansion within the resting phenotype. Since virion production from clonally expanded cells will not be affected by antiretroviral drugs, simulations of ART intensification had little impact on pVL. HIV DNA decay over the first year of ART followed the loss of activated memory cells (120 day half-life) while the 5.9 year half-life of total HIV DNA after this point mirrored the slower decay of resting memory cells. Simulations had difficulty reproducing the fast early HIV DNA dynamics, including 2-LTR levels peaking at week 12, and the later slow loss of total and 2-LTR HIV DNA, suggesting some ongoing infection. In summary, our modelling indicates that much of the dynamical behavior of HIV can be explained by its impact on memory CD4+ T cell homeostasis.

  10. HIV dynamics linked to memory CD4+ T cell homeostasis.

    Directory of Open Access Journals (Sweden)

    John M Murray

    Full Text Available The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART. We investigated whether plasma viral level (pVL and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI and 8 chronic HIV infected (CHI individuals enrolled on a raltegravir (RAL based regimen, exhibited greatest changes over the 1st year of ART. Dynamics slowed over the following 2 years so that total HIV DNA levels were equivalent to reported values for individuals after 10 years of ART. The mathematical model reproduced the multiphasic dynamics of pVL, and levels of total, 2-LTR and integrated HIV DNA in both PHI and CHI over 3 years of ART. Under these simulations, residual viremia originated from reactivated latently infected cells where most of these cells arose from clonal expansion within the resting phenotype. Since virion production from clonally expanded cells will not be affected by antiretroviral drugs, simulations of ART intensification had little impact on pVL. HIV DNA decay over the first year of ART followed the loss of activated memory cells (120 day half-life while the 5.9 year half-life of total HIV DNA after this point mirrored the slower decay of resting memory cells. Simulations had difficulty reproducing the fast early HIV DNA dynamics, including 2-LTR levels peaking at week 12, and the later slow loss of total and 2-LTR HIV DNA, suggesting some ongoing infection. In summary, our modelling indicates that much of the dynamical behavior of HIV can be explained by its impact on memory CD4+ T cell homeostasis.

  11. Construction of a reconfigurable dynamic logic cell

    Indian Academy of Sciences (India)

    dynamic computer architecture and serve as ingredients of a general-purpose device more flexible than statically wired ... basic logic gates with a single chaotic system. Consider a chaotic element (our chaotic chip or chaotic processor) ..... [9] J N Blakely et al, IEEE J. Quantum Electron. 40, 299 (2004). Pramana – J. Phys.

  12. Moisture evaluation by dynamic thermography data modeling

    Energy Technology Data Exchange (ETDEWEB)

    Bison, P.G.; Grinzato, E.; Marinetti, S. [ITEF-CNR, Padova (Italy)

    1994-12-31

    This paper is the prosecution of previous works on the design of a Non Destructive method for in situ detection of moistened areas in buildings and the evaluation of the water content in porous materials by thermographic analysis. The use of heat transfer model to interpret data allows to improve the measurement accuracy taking into account the actual boundary conditions. The relative increase of computation time is balanced by the additional advantage to optimize the testing procedure of different objects simulating the heat transfer. Two models are tested both analytically and experimentally: (1) the semi-infinite body to evaluate the thermal inertia and water content; (2) the slab to measure the sample`s diffusivity, the dependence of conductivity with the water content and to correct the water content estimation. The fitting of the experimental data on the model is carried out according to the least square method that is linear in the first case and nonlinear in the second. The Levenberg-Marquardt procedure is followed in nonlinear fitting to search in the parameters space the optimum point that minimizes the Chi-square estimator. Experimental results on bricks used in building for restoration activities, are discussed. The water content measured in different hygrometric conditions is compared with known values. A correction on the absorptivity coefficient dependent on water content is introduced.

  13. QuaNCAT: quantitating proteome dynamics in primary cells

    Science.gov (United States)

    Howden, Andrew J.M.; Geoghegan, Vincent; Katsch, Kristin; Efstathiou, Georgios; Bhushan, Bhaskar; Boutureira, Omar; Thomas, Benjamin; Trudgian, David C.; Kessler, Benedikt M.; Dieterich, Daniela C.; Davis, Benjamin G.; Acuto, Oreste

    2013-01-01

    Here we demonstrate that quantitation of stimuli-induced proteome dynamics in primary cells is feasible by combining the power of Bio-Orthogonal Non Canonical Amino acid Tagging (BONCAT) and Stable Isotope Labelling of Amino acids in Cell culture (SILAC). In conjunction with nanoLC-MS/MS QuaNCAT allowed us to monitor the early expression changes of > 600 proteins in primary resting T cells subjected to activation stimuli. PMID:23474466

  14. 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...

  15. Intercellular calcium waves in glial cells with bistable dynamics

    Science.gov (United States)

    Wei, Fang; Shuai, Jianwei

    2011-04-01

    A two-dimensional model is proposed for intercellular calcium (Ca2 +) waves with Ca2 +-induced IP3 regeneration and the diffusion of IP3 through gap junctions. Many experimental observations in glial cells, i.e. responding to local mechanical stimulation, glutamate application, mechanical stimulation followed by ACh application, and glutamate followed by mechanical stimulation, are reproduced and classified by the model. We show that a glial cell model with bistable dynamics, i.e. a Ca2 + oscillation state coexisting with a fixed point, can cause a prolonged plateau of Ca2 + signals in the cells nearby the stimulated cell when the cell network responds to the local mechanical stimulation.

  16. 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)

  17. 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.

  18. Collective Dynamics of Intracellular Water in Living Cells

    Science.gov (United States)

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

    2012-02-01

    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.

  19. Development of a dynamic in vitro model of a stented blood vessel to evaluate the effects of stent strut material selection and surface coating on smooth muscle cell response

    Science.gov (United States)

    Winn, Bradley Huegh

    formation of this new tissue, primarily consisting of VSMCs of the synthetic phenotype and their subsequent extracellular matrix, is the sole causation of in-stent restenosis since the stent serves to prevent elastic recoil and negative remodeling. This doctoral research program is focused on endovascular stent biomaterials science and engineering. Overall, this doctoral project is founded on the hypothesis that smooth muscle cell hyperplasia, as an important causative factor for vascular restenosis following endovascular stent deployment, is triggered by the various effects of stent strut contact on the vessel wall including contact forces and material biocompatibility. In this program, a dynamic in vitro model of a stented blood vessel aimed at evaluating the effect of stent strut material selection, and surface coating on smooth muscle cell response was developed. The in vitro stented artery model was validated through the proliferation of VSMC in contact with stent struts. Additionally, it was demonstrated that, with respect to known biocompatible materials such as Nitinol and 316L stainless steel, DNA synthesis and alpha-actin expression, as indicators of VSMC phenotype, are independent of stent material composition. Furthermore, hydroxyapatite was shown to be a biocompatible stent surface coating with acceptable post-strain integrity. This coating was shown in a feasibility study to be capable of serving as a favorable drug delivery platform able to reliably deliver locally therapeutic doses of bisphosphonates, such as alendronate, to control VSMC proliferation in an in vitro model of a stented blood vessel. This stent coating/drug combination may be effective for reducing restenosis as a result of VSMC hyperplasia in vivo.

  20. Spin glass model for dynamics of cell reprogramming

    Science.gov (United States)

    Pusuluri, Sai Teja; Lang, Alex H.; Mehta, Pankaj; Castillo, Horacio E.

    2015-03-01

    Recent experiments show that differentiated cells can be reprogrammed to become pluripotent stem cells. The possible cell fates can be modeled as attractors in a dynamical system, the ``epigenetic landscape.'' Both cellular differentiation and reprogramming can be described in the landscape picture as motion from one attractor to another attractor. We perform Monte Carlo simulations in a simple model of the landscape. This model is based on spin glass theory and it can be used to construct a simulated epigenetic landscape starting from the experimental genomic data. We re-analyse data from several cell reprogramming experiments and compare with our simulation results. We find that the model can reproduce some of the main features of the dynamics of cell reprogramming.

  1. Intergenerational continuity of cell shape dynamics in Caulobacter crescentus

    Science.gov (United States)

    Wright, Charles S.; Banerjee, Shiladitya; Iyer-Biswas, Srividya; Crosson, Sean; Dinner, Aaron R.; Scherer, Norbert F.

    2015-03-01

    We investigate the intergenerational shape dynamics of single Caulobacter crescentus cells using a novel combination of imaging techniques and theoretical modeling. We determine the dynamics of cell pole-to-pole lengths, cross-sectional widths, and medial curvatures from high accuracy measurements of cell contours. Moreover, these shape parameters are determined for over 250 cells across approximately 10000 total generations, which affords high statistical precision. Our data and model show that constriction is initiated early in the cell cycle and that its dynamics are controlled by the time scale of exponential longitudinal growth. Based on our extensive and detailed growth and contour data, we develop a minimal mechanical model that quantitatively accounts for the cell shape dynamics and suggests that the asymmetric location of the division plane reflects the distinct mechanical properties of the stalked and swarmer poles. Furthermore, we find that the asymmetry in the division plane location is inherited from the previous generation. We interpret these results in terms of the current molecular understanding of shape, growth, and division of C. crescentus.

  2. Dynamic photochemical lipid micropatterning for manipulation of nonadherent mammalian cells.

    Science.gov (United States)

    Yamahira, Shinya; Takasaki, Yumi; Yamaguchi, Satoshi; Sumaru, Kimio; Kanamori, Toshiyuki; Nagamune, Teruyuki

    2014-01-01

    Cell micropatterning methods with stimuli-responsive dynamic surfaces are getting a lot of attention in a wide variety of research fields, ranging from cell engineering to fundamental studies in cell biology. The surface of a slide coated with photo-cleavable poly(ethylene glycol) (PEG)-lipid can be used to spatiotemporally control cell immobilization and release by light irradiation. On the basis of this surface, it is easy to design simple methods for making a fine micropattern of any kind of cell. Furthermore, target cells can be selectively and rapidly released from this surface by light irradiation. In this review, we first describe how to obtain the photo-cleavable PEG-lipid from commercially available compounds through a facile four-step synthesis. Next, as a cell-patterning method, the protocols of coating substrates with the PEG-lipid, irradiating a pattern of light onto the coated substrate, and loading cells onto the irradiated surface are described. These protocols require no expensive equipment and potentially apply to any substrates that can adsorb serum albumin or chemically expose amine moieties on their surfaces. Finally, as an advanced method, cell release from the PEG-lipid surface in microfluidic devices is introduced. We also discuss the advantages and the possible applications of the present dynamic cell-patterning method. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Dynamic quantitative microscopy and nanoscopy of red blood cells in sickle cell disease

    Science.gov (United States)

    Shaked, Natan T.; Satterwhite, Lisa L.; Telen, Marilyn J.; Truskey, George A.; Wax, Adam

    2012-03-01

    We have applied wide-field digital interferometric techniques to quantitatively image sickle red blood cells (RBCs) [1] in a noncontact label-free manner, and measure the nanometer-scale fluctuations in their thickness as an indication of their stiffness. The technique can simultaneously measure the fluctuations for multiple spatial points on the RBC and thus yields a map describing the stiffness of each RBC in the field of view. Using this map, the local rigidity regions of the RBC are evaluated quantitatively. Since wide-field digital interferometry is a quantitative holographic imaging technique rather than one-point measurement, it can be used to simultaneously evaluate cell transverse morphology plus thickness in addition to its stiffness profile. Using this technique, we examine the morphology and dynamics of RBCs from individuals who suffer from sickle cell disease, and find that the sickle RBCs are significantly stiffer than healthy RBCs. Furthermore, we show that the technique is sensitive enough to distinguish various classes of sickle RBCs, including sickle RBCs with visibly-normal morphology, compared to the stiffer crescent-shaped sickle RBCs.

  4. Phosphorylation site dynamics of early T-cell receptor signaling

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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...

  5. Plastids: dynamic components of plant cell development

    Science.gov (United States)

    Guikema, J. A.; Gallegos, G. L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    The gravitropic bending of maize roots, as a response to reorientation of the root within a gravitational field, was examined for sensitivity to exogenous applications of the cytoskeletal inhibitor, cytochalasin D. Agar blocks were impregnated with this inhibitor, and were applied either to the root cap or to the zone of root cell elongation. Root growth was normal with either treatment, if the roots were not repositioned with respect to the gravitational vector. When untreated roots were placed in a horizontal position with respect to gravity, a 40 degree bending response was observed within one hour. This bending also occurred when cytochalasin D was applied at high concentrations to the zone of root cell elongation. However, when cytochalasin D above 40 micrograms/ml was applied to the root cap, roots lost the ability of directional reorientation within the gravitational field, causing a random bending.

  6. 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

  7. Dynamics and 'normal stress' evaluation of dilute suspensions of ...

    Indian Academy of Sciences (India)

    practical applications of the study of the dynamics of small dipolar particles in various linear flows under the .... we evaluated the integral in the interval [0,t −ϵ], whereϵ is chosen to be a very small number. We note that in the ... solve the differential equations using an embedded Runge–Kutta method with adaptive step size.

  8. Field and Laboratory Evaluation of Dynamics in Soil Properties of ...

    African Journals Online (AJOL)

    Dynamics in properties of soils of three land use types (Fallow, Pineapple and Cassava) in Owerri, Southeastern Nigeria were evaluated under field and laboratory incubation conditions. Soil properties varied with time within land use types, with chemical more significantly than physical properties under both conditions.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Sperm cell surface dynamics during activation and fertilization

    NARCIS (Netherlands)

    Boerke, A.|info:eu-repo/dai/nl/304822922

    2013-01-01

    Before the sperm cell can reach the oocyte it needs to be activated and to undergo a series of preparative steps. The sperm surface dynamics was studied in relation to this activation process and the modifications and removal of sperm surface components havebeen investigated. Bicarbonate-induced

  15. Cell state switching factors and dynamical patterning modules ...

    Indian Academy of Sciences (India)

    2009-01-05

    Jan 5, 2009 ... Home; Journals; Journal of Biosciences; Volume 34; Issue 4. Cell state switching factors and dynamical patterning modules: complementary mediators of plasticity in development and evolution. Stuart A Newman Ramray Bhat Nadejda V Mezentseva. Articles Volume 34 Issue 4 October 2009 pp 553-572 ...

  16. Galectin-9: From cell biology to complex disease dynamics

    Indian Academy of Sciences (India)

    Galectins is a family of non-classically secreted, β-galactoside-binding proteins that has recently received considerableattention in the spatio-temporal regulation of surface 'signal lattice' organization, membrane dynamics, cell-adhesionand disease therapeutics. Galectin-9 is a unique member of this family, with two ...

  17. 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.

  18. 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.

  19. Photon Counts Statistics in Leukocyte Cell Dynamics

    Science.gov (United States)

    van Wijk, Eduard; van der Greef, Jan; van Wijk, Roeland

    2011-12-01

    In the present experiment ultra-weak photon emission/ chemiluminescence from isolated neutrophils was recorded. It is associated with the production of reactive oxygen species (ROS) in the "respiratory burst" process which can be activated by PMA (Phorbol 12-Myristate 13-Acetate). Commonly, the reaction is demonstrated utilizing the enhancer luminol. However, with the use of highly sensitive photomultiplier equipment it is also recorded without enhancer. In that case, it can be hypothesized that photon count statistics may assist in understanding the underlying metabolic activity and cooperation of these cells. To study this hypothesis leukocytes were stimulated with PMA and increased photon signals were recorded in the quasi stable period utilizing Fano factor analysis at different window sizes. The Fano factor is defined by the variance over the mean of the number of photon within the observation time. The analysis demonstrated that the Fano factor of true signal and not of the surrogate signals obtained by random shuffling increases when the window size increased. It is concluded that photon count statistics, in particular Fano factor analysis, provides information regarding leukocyte interactions. It opens the perspective to utilize this analytical procedure in (in vivo) inflammation research. However, this needs further validation.

  20. 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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Precharattana, Monamorn; Triampo, Wannapong

    2014-08-01

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

  4. 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...

  5. 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

  6. 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.

  7. Dynamic ray tracing for modeling optical cell manipulation

    Science.gov (United States)

    Sraj, Ihab; Szatmary, Alex C.; Marr, David W. M.; Eggleton, Charles D.

    2010-01-01

    Current methods for predicting stress distribution on a cell surface due to optical trapping forces are based on a traditional ray optics scheme for fixed geometries. Cells are typically modeled as solid spheres as this facilitates optical force calculation. Under such applied forces however, real and non-rigid cells can deform, so assumptions inherent in traditional ray optics methods begin to break down. In this work, we implement a dynamic ray tracing technique to calculate the stress distribution on a deformable cell induced by optical trapping. Here, cells are modeled as three-dimensional elastic capsules with a discretized surface with associated hydrodynamic forces calculated using the Immersed Boundary Method. We use this approach to simulate the transient deformation of spherical, ellipsoidal and biconcave capsules due to external optical forces induced by a single diode bar optical trap for a range of optical powers. PMID:20721060

  8. Physical guidance of the actin cytoskeleton and cell migration dynamics in epithelial cells

    Science.gov (United States)

    Lee, Rachel; Schmidt, B. U. Sebastian; Campanello, Leonard; Hourwitz, Matt J.; Fourkas, John T.; Losert, Wolfgang

    Many cell types have been shown to exhibit contact guidance, in which cells sense and follow the texture of their environment. Contact guidance can lead to persistent directional migration that does not require the coordinated spatial and temporal cues required for guidance cues such as chemical concentration (i.e. chemotaxis). Actin polymerization has been shown to be guided by topographical features (esotaxis) in Dictyostelium discoideum cells, leading to guided cell migration. In this work, we show that actin dynamics are also guided by nanotopography in epithelial MCF10A cells despite large differences in the normal migration behavior of these two cell types. The existence of esotaxis and guided migration across phyla suggests that cytoskeletal dynamics play an important role in texture sensing and directional cell migration.

  9. Evaluation of a novel diffusion cell for in vitro transdermal permeation : effects of injection height, volume and temperature

    NARCIS (Netherlands)

    Bosman, IJ; Avegaart, [No Value; Lawant, AL; Ensing, K; de Zeeuw, RA

    The objective of this study was to evaluate the performance of a new, compact, dynamic diffusion cell for in vitro transdermal permeation. These so-called Kelder-cells were developed as an automated alternative to the static Franz diffusion cells. The new cells were used in combination with the

  10. 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

    of hydrolytic activities, transmission electron microscopy (TEM) 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......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...

  11. 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.

  12. Evaluating Learner Autonomy: A Dynamic Model with Descriptors

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

  14. 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.

  15. 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.

  16. 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).

  17. 3-dimensional forces and molecular dynamics of live cells

    Science.gov (United States)

    Hur, Sung Sik; Li, Yi-Shuan; Park, Joon Seok; Hu, Ying-Li; Chien, Shu

    2010-08-01

    The forces exerted by an adherent cell on a substrate were studied previously only in the two-dimensions (2D) tangential to the substrate surface. We used a novel technique to measure the three-dimensional (3D) stresses exerted by live bovine aortic endothelial cells (BAECs) on polyacrylamide deformable substrate, with particular emphasis on the 3D forces of focal adhesions. On 3D images acquired by confocal microscopy, displacements were determined with imageprocessing programs, and stresses in tangential (XY) and normal (Z) directions were computed by finite element method (FEM). BAECs generated stress in normal direction (Tz) with an order of magnitude comparable to that in tangential direction (Txy). Tz is upward at the cell edge and downward under the nucleus, changing continuously with a sign reversal between cell edge and nucleus edge. With the use of green fluorescent protein (GFP) labeled paxillin, the dynamics of this intracellular molecule were studied concurrently with the measurement of 3D forces. In the dynamic region, including the new lamellapodium forming region in the front and the retracting region in the rear, the tangential forces (Fxy) are correlated with the size of the focal adhesions (FAs) much more strongly than those in the stable region under the nucleus. In the dynamic region, normal force (Fz) was upward and positively correlated with FA size, while Fz in the stable region was downward and negatively correlated with FA size. These findings show the influence of the size of FAs on the 3D forces they exert on the substrate. This technique can be applied to study any adherent type of live cells to assess their biomechanical dynamics in conjunction with biochemical and functional activities, thus elucidating cellular functions in health and disease.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Dynamic Model of High Temperature PEM Fuel Cell Stack Temperature

    DEFF Research Database (Denmark)

    Andreasen, Søren Juhl; Kær, Søren Knudsen

    2007-01-01

    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...... parts, where also the temperatures are measured. The heat balance of the system involves a fuel cell model to describe the heat added by the fuel cells when a current is drawn. Furthermore the model also predicts the temperatures, when heating the stack with external heating elements for start-up, heat...... 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...

  3. Dynamic Enhanced Inter-Cell Interference Coordination for Realistic Networks

    DEFF Research Database (Denmark)

    Pedersen, Klaus I.; Alvarez, Beatriz Soret; Barcos, Sonia

    2016-01-01

    ICIC configuration leads to modest gains, whereas the set of proposed fast dynamic eICIC algorithms result in capacity gains on the order of 35-120% depending on the local environment characteristics. These attractive gains together with the simplicity of the proposed solutions underline the practical relevance...... area. Rather than the classical semi-static and network-wise configuration, the importance of having highly dynamic and distributed mechanisms that are able to adapt to local environment conditions is revealed. We propose two promising cell association algorithms: one aiming at pure load balancing...... and an opportunistic approach exploiting the varying cell conditions. Moreover, an autonomous fast distributed muting algorithm is presented, which is simple, robust, and well suited for irregular network deployments. Performance results for realistic network deployments show that the traditional semi-static e...

  4. 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.

  5. Programmed subcellular release to study the dynamics of cell detachment

    Science.gov (United States)

    Wildt, Bridget

    Cell detachment is central to a broad range of physio-pathological changes however there are no quantitative methods to study this process. Here we report programmed subcellular release, a method for spatially and temporally controlled cellular detachment and present the first quantitative results of the detachment dynamics of 3T3 fibroblasts at the subcellular level. Programmed subcellular release is an in vitro technique designed to trigger the detachment of distinct parts of a single cell from a patterned substrate with both spatial and temporal control. Subcellular release is achieved by plating cells on an array of patterned gold electrodes created by standard microfabrication techniques. The electrodes are biochemically functionalized with an adhesion-promoting RGD peptide sequence that is attached to the gold electrode via a thiol linkage. Each electrode is electrically isolated so that a subcellular section of a single cell spanning multiple electrodes can be released independently. Upon application of a voltage pulse to a single electrode, RGD-thiol molecules on an individual electrode undergo rapid electrochemical desorption that leads to subsequent cell contraction. The dynamics of cell contraction are found to have characteristic induction and contraction times. This thesis presents the first molecular inhibition studies conducted using programmed subcellular release verifying that this technique can be used to study complex signaling pathways critical to cell motility. Molecular level dynamics of focal adhesion proteins and actin stress fibers provide some insight into the complexities associated with triggered cell detachment. In addition to subcellular release, the programmed release of alkanethiols provides a tool for to study the spatially and temporally controlled release of small molecules or particles from individually addressable gold electrodes. Here we report on experiments which determine the dynamics of programmed release using fluorophore

  6. 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...

  7. 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.

  8. Evaluation of robotic surgery skills using dynamic time warping.

    Science.gov (United States)

    Jiang, Jingyu; Xing, Yuan; Wang, Shuxin; Liang, Ke

    2017-12-01

    accompanied with the wide acceptance of robot assisted minimally invasive surgery (RMIS), the demand for efficient and objective surgical skills evaluation method is increased. Recently, with the development of medical engineering technology, several evaluation methods have been proposed. Among them, kinematic analysis, an unsupervised and data-based method, has been accepted by many researchers. However, this method is still limited by the number of metrics and unconvinced scoring system. This paper aims to propose a new evaluation method to assess surgical skills efficiently and objectively. this research proposed an efficient and effective surgical skills evaluation algorithm which used the trajectories of instrument tip and dynamic time warping (DTW) to provide trainees with real-time and summative feedback. The optimum trajectories based on 'Therbligs' theory was designed as a template. DTW algorithm was used to align actual trajectories to optimum trajectories with an evaluating indicator designed to emphasize the crucial motion features in surgical skills evaluation. The real-time feedback was obtained through a sliding time window to help trainees improve learning efficiency. experts (n = 2) and novices (n = 8) were invited to complete the peg transfer tasks and 60 instrument tip trajectories were assessed by the proposed algorithm. Significant differences between different groups were observed (experts' right trajectories versus experts' left trajectories, p = 0.0002; experts' right trajectories versus novices' right trajectories, p = 0.0124). In addition, evaluation results of trajectories with operational mistakes were significantly different from those of others. the proposed evaluation method showed its advantages in distinguishing and evaluating surgical performance. Given its ability to evaluate the performance based on kinematic information, the proposed evaluation method can be further developed in the future. Furthermore, because

  9. Cell transmission model of dynamic assignment for urban rail transit networks.

    Directory of Open Access Journals (Sweden)

    Guangming Xu

    Full Text Available For urban rail transit network, the space-time flow distribution can play an important role in evaluating and optimizing the space-time resource allocation. For obtaining the space-time flow distribution without the restriction of schedules, a dynamic assignment problem is proposed based on the concept of continuous transmission. To solve the dynamic assignment problem, the cell transmission model is built for urban rail transit networks. The priority principle, queuing process, capacity constraints and congestion effects are considered in the cell transmission mechanism. Then an efficient method is designed to solve the shortest path for an urban rail network, which decreases the computing cost for solving the cell transmission model. The instantaneous dynamic user optimal state can be reached with the method of successive average. Many evaluation indexes of passenger flow can be generated, to provide effective support for the optimization of train schedules and the capacity evaluation for urban rail transit network. Finally, the model and its potential application are demonstrated via two numerical experiments using a small-scale network and the Beijing Metro network.

  10. 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

  11. 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.

  12. The effect of EIF dynamics on the cryopreservation process of a size distributed cell population.

    Science.gov (United States)

    Fadda, S; Briesen, H; Cincotti, A

    2011-06-01

    Typical mathematical modeling of cryopreservation of cell suspensions assumes a thermodynamic equilibrium between the ice and liquid water in the extracellular solution. This work investigates the validity of this assumption by introducing a population balance approach for dynamic extracellular ice formation (EIF) in the absence of any cryo-protectant agent (CPA). The population balance model reflects nucleation and diffusion-limited growth in the suspending solution whose driving forces are evaluated in the relevant phase diagram. This population balance description of the extracellular compartment has been coupled to a model recently proposed in the literature [Fadda et al., AIChE Journal, 56, 2173-2185, (2010)], which is capable of quantitatively describing and predicting internal ice formation (IIF) inside the cells. The cells are characterized by a size distribution (i.e. through another population balance), thus overcoming the classic view of a population of identically sized cells. From the comparison of the system behavior in terms of the dynamics of the cell size distribution it can be concluded that the assumption of a thermodynamic equilibrium in the extracellular compartment is not always justified. Depending on the cooling rate, the dynamics of EIF needs to be considered. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. 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.

  14. Myosin II dynamics are regulated by tension in intercalating cells.

    Science.gov (United States)

    Fernandez-Gonzalez, Rodrigo; Simoes, Sérgio de Matos; Röper, Jens-Christian; Eaton, Suzanne; Zallen, Jennifer A

    2009-11-01

    Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin II is stabilized at the cortex in regions of increased tension. Myosin II is recruited in response to an ectopic force and relieving tension leads to a rapid loss of myosin, indicating that tension is necessary and sufficient for cortical myosin localization. These results demonstrate that myosin II dynamics are regulated by tension in a positive feedback loop that leads to multicellular actomyosin cable formation and efficient tissue elongation.

  15. Dynamics of Traction Force Reinforcement in Smooth Muscle Cells

    Science.gov (United States)

    Lin, Yi-Chia; Kramer, Corinne; Chen, Christopher; Reich, Daniel

    2010-03-01

    Mechanical forces influence cell function in various ways. For instance, the force-induced contraction or relaxation of vascular smooth muscle cells (SMCs) is critical to regulating the properties of blood vessels. Here, we study the dynamics of cellular traction forces in SMCs using micro-scale magnetic nanowires together with flexible PDMS micropost arrays. We use dual magnetic tweezers to apply a sinusoidal magnetic torque on nickel nanowires which are internalized by the SMCs. The spatial and temporal responses of the SMCs cultured on the tips of the microposts are recorded by the deflected posts. We observe a global reinforcement of the cells' traction forces upon applying a localized torque via the nanowires. Interestingly, we also find that the contractile response depends on the frequency of the applied stimulation, with a greater percentage of the SMCs showing enhanced reinforcement at lower frequencies.

  16. Computational evaluation of convection schemes in fluid dynamics problems

    Directory of Open Access Journals (Sweden)

    Paulo Laerte Natti

    2012-11-01

    Full Text Available This article provides a computational evaluation of the popular high resolution upwind WACEB, CUBISTA and ADBQUICKEST schemes for solving non-linear fluid dynamics problems. By using the finite difference methodology, the schemes are analyzed and implemented in the context of normalized variables of Leonard. In order to access the performance of the schemes, Riemann problems for 1D Burgers, Euler and shallow water equations are considered. From the numerical results, the schemes are ranked according to their performance in solving these non-linear equations. The best scheme is then applied in the numerical simulation of tridimensional incompressible moving free surface flows.

  17. 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).

  18. 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.

  19. 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.

  20. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal.

    Science.gov (United States)

    Hemberger, Myriam; Dean, Wendy; Reik, Wolf

    2009-08-01

    Cells of the early mammalian embryo, including pluripotent embryonic stem (ES) cells and primordial germ cells (PGCs), are epigenetically dynamic and heterogeneous. During early development, this heterogeneity of epigenetic states is associated with stochastic expression of lineage-determining transcription factors that establish an intimate crosstalk with epigenetic modifiers. Lineage-specific epigenetic modification of crucial transcription factor loci (for example, methylation of the Elf5 promoter) leads to the restriction of transcriptional circuits and the fixation of lineage fate. The intersection of major epigenetic reprogramming and programming events in the early embryo creates plasticity followed by commitment to the principal cell lineages of the early conceptus.

  1. A Novel Automated High-Content Analysis Workflow Capturing Cell Population Dynamics from Induced Pluripotent Stem Cell Live Imaging Data.

    Science.gov (United States)

    Kerz, Maximilian; Folarin, Amos; Meleckyte, Ruta; Watt, Fiona M; Dobson, Richard J; Danovi, Davide

    2016-10-01

    Most image analysis pipelines rely on multiple channels per image with subcellular reference points for cell segmentation. Single-channel phase-contrast images are often problematic, especially for cells with unfavorable morphology, such as induced pluripotent stem cells (iPSCs). Live imaging poses a further challenge, because of the introduction of the dimension of time. Evaluations cannot be easily integrated with other biological data sets including analysis of endpoint images. Here, we present a workflow that incorporates a novel CellProfiler-based image analysis pipeline enabling segmentation of single-channel images with a robust R-based software solution to reduce the dimension of time to a single data point. These two packages combined allow robust segmentation of iPSCs solely on phase-contrast single-channel images and enable live imaging data to be easily integrated to endpoint data sets while retaining the dynamics of cellular responses. The described workflow facilitates characterization of the response of live-imaged iPSCs to external stimuli and definition of cell line-specific, phenotypic signatures. We present an efficient tool set for automated high-content analysis suitable for cells with challenging morphology. This approach has potentially widespread applications for human pluripotent stem cells and other cell types. © 2016 Society for Laboratory Automation and Screening.

  2. 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

  3. Quantifying differences in cell line population dynamics using CellPD.

    Science.gov (United States)

    Juarez, Edwin F; Lau, Roy; Friedman, Samuel H; Ghaffarizadeh, Ahmadreza; Jonckheere, Edmond; Agus, David B; Mumenthaler, Shannon M; Macklin, Paul

    2016-09-21

    The increased availability of high-throughput datasets has revealed a need for reproducible and accessible analyses which can quantitatively relate molecular changes to phenotypic behavior. Existing tools for quantitative analysis generally require expert knowledge. CellPD (cell phenotype digitizer) facilitates quantitative phenotype analysis, allowing users to fit mathematical models of cell population dynamics without specialized training. CellPD requires one input (a spreadsheet) and generates multiple outputs including parameter estimation reports, high-quality plots, and minable XML files. We validated CellPD's estimates by comparing it with a previously published tool (cellGrowth) and with Microsoft Excel's built-in functions. CellPD correctly estimates the net growth rate of cell cultures and is more robust to data sparsity than cellGrowth. When we tested CellPD's usability, biologists (without training in computational modeling) ran CellPD correctly on sample data within 30 min. To demonstrate CellPD's ability to aid in the analysis of high throughput data, we created a synthetic high content screening (HCS) data set, where a simulated cell line is exposed to two hypothetical drug compounds at several doses. CellPD correctly estimates the drug-dependent birth, death, and net growth rates. Furthermore, CellPD's estimates quantify and distinguish between the cytostatic and cytotoxic effects of both drugs-analyses that cannot readily be performed with spreadsheet software such as Microsoft Excel or without specialized computational expertise and programming environments. CellPD is an open source tool that can be used by scientists (with or without a background in computational or mathematical modeling) to quantify key aspects of cell phenotypes (such as cell cycle and death parameters). Early applications of CellPD may include drug effect quantification, functional analysis of gene knockout experiments, data quality control, minable big data generation, and

  4. Dynamic testing of nuclear power plant structures: an evaluation

    International Nuclear Information System (INIS)

    Weaver, H.J.

    1980-02-01

    Lawrence Livermore Laboratory (LLL) evaluated the applications of system identification techniques to the dynamic testing of nuclear power plant structures and subsystems. These experimental techniques involve exciting a structure and measuring, digitizing, and processing the time-history motions that result. The data can be compared to parameters calculated using finite element or other models of the test systems to validate the model and to verify the seismic analysis. This report summarizes work in three main areas: (1) analytical qualification of a set of computer programs developed at LLL to extract model parameters from the time histories; (2) examination of the feasibility of safely exciting nuclear power plant structures and accurately recording the resulting time-history motions; (3) study of how the model parameters that are extracted from the data be used best to evaluate structural integrity and analyze nuclear power plants

  5. Catalysis of protein folding by chaperones accelerates evolutionary dynamics in adapting cell populations.

    Directory of Open Access Journals (Sweden)

    Murat Cetinbaş

    Full Text Available Although molecular chaperones are essential components of protein homeostatic machinery, their mechanism of action and impact on adaptation and evolutionary dynamics remain controversial. Here we developed a physics-based ab initio multi-scale model of a living cell for population dynamics simulations to elucidate the effect of chaperones on adaptive evolution. The 6-loci genomes of model cells encode model proteins, whose folding and interactions in cellular milieu can be evaluated exactly from their genome sequences. A genotype-phenotype relationship that is based on a simple yet non-trivially postulated protein-protein interaction (PPI network determines the cell division rate. Model proteins can exist in native and molten globule states and participate in functional and all possible promiscuous non-functional PPIs. We find that an active chaperone mechanism, whereby chaperones directly catalyze protein folding, has a significant impact on the cellular fitness and the rate of evolutionary dynamics, while passive chaperones, which just maintain misfolded proteins in soluble complexes have a negligible effect on the fitness. We find that by partially releasing the constraint on protein stability, active chaperones promote a deeper exploration of sequence space to strengthen functional PPIs, and diminish the non-functional PPIs. A key experimentally testable prediction emerging from our analysis is that down-regulation of chaperones that catalyze protein folding significantly slows down the adaptation dynamics.

  6. Taming the Trojan horse: optimizing dynamic carrier cell/oncolytic virus systems for cancer biotherapy.

    Science.gov (United States)

    Power, A T; Bell, J C

    2008-05-01

    Live cells offer unique advantages as vehicles for systemic oncolytic virus (OV) delivery. Recent studies from our laboratory and others have shown that virus-infected cells can serve as Trojan horse vehicles to evade antiviral mechanisms encountered in the bloodstream, prevent uptake by off-target tissues and act as microscale factories to produce OV upon arrival in tumor beds. However to be employed effectively, OV-infected cells are best viewed as dynamic biological systems rather than static therapeutic agents. The time-dependent processes of infection and in vivo cell trafficking will inevitably vary depending on which particular OV is being delivered, as well as the type of carrier cells (CC) employed. Understanding these parameters with respect to each unique CC/OV combination will therefore be required in order to effectively evaluate and harness their potential in preclinical study. In the following review, we discuss how early studies of OV delivery led us to investigate the use of cell carriers in our laboratory, and the approaches we are currently undertaking to compare the dynamics of different CC/OV systems. On the basis of these studies and others it is apparent that the success of any cell-based system for OV delivery rests upon the coordinated timing of three sequential phases--(1) ex vivo loading, (2) stealth delivery and (3) virus production at the tumor site. While at the current time, the timing of these processes are coupled to the natural cycle of infection and in vivo trafficking properties innate to each cell virus system, a quantitative delineation of their dynamics will lay the foundation for engineering CC/OV biotherapeutic systems that can be clinically deployed in a highly directed and controlled manner.

  7. Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

    International Nuclear Information System (INIS)

    Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko

    2002-01-01

    Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13±2.4, 6±2.2, and 4±1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

  8. Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

    Energy Technology Data Exchange (ETDEWEB)

    Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko [Tokyo Medical Coll., Ami, Ibaraki (Japan). Kasumigaura Hospital

    2002-07-01

    Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13{+-}2.4, 6{+-}2.2, and 4{+-}1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

  9. 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

  10. Dynamic Response during PEM Fuel Cell Loading-up

    Directory of Open Access Journals (Sweden)

    Jun Gou

    2009-07-01

    Full Text Available A study on the effects of controlling and operating parameters for a Proton Exchange Membrane (PEM fuel cell on the dynamic phenomena during the loading-up process is presented. The effect of the four parameters of load-up amplitudes and rates, operating pressures and current levels on gas supply or even starvation in the flow field is analyzed based accordingly on the transient characteristics of current output and voltage. Experiments are carried out in a single fuel cell with an active area of 285 cm2. The results show that increasing the loading-up amplitude can inevitably increase the possibility of gas starvation in channels when a constant flow rate has been set for the cathode; With a higher operating pressure, the dynamic performance will be improved and gas starvations can be relieved. The transient gas supply in the flow channel during two loading-up mode has also been discussed. The experimental results will be helpful for optimizing the control and operation strategies for PEM fuel cells in vehicles.

  11. 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.

  12. Dynamic subcellular imaging of cancer cell mitosis in the brain of live mice.

    Science.gov (United States)

    Momiyama, Masashi; Suetsugu, Atsushi; Kimura, Hiroaki; Chishima, Takashi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2013-04-01

    The ability to visualize cancer cell mitosis and apoptosis in the brain in real time would be of great utility in testing novel therapies. In order to achieve this goal, the cancer cells were labeled with green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm, such that mitosis and apoptosis could be clearly imaged. A craniotomy open window was made in athymic nude mice for real-time fluorescence imaging of implanted cancer cells growing in the brain. The craniotomy window was reversibly closed with a skin flap. Mitosis of the individual cancer cells were imaged dynamically in real time through the craniotomy-open window. This model can be used to evaluate brain metastasis and brain cancer at the subcellular level.

  13. Dynamic and reversible surface topography influences cell morphology.

    Science.gov (United States)

    Kiang, Jennifer D; Wen, Jessica H; del Álamo, Juan C; Engler, Adam J

    2013-08-01

    Microscale and nanoscale surface topography changes can influence cell functions, including morphology. Although in vitro responses to static topography are novel, cells in vivo constantly remodel topography. To better understand how cells respond to changes in topography over time, we developed a soft polyacrylamide hydrogel with magnetic nickel microwires randomly oriented in the surface of the material. Varying the magnetic field around the microwires reversibly induced their alignment with the direction of the field, causing the smooth hydrogel surface to develop small wrinkles; changes in surface roughness, ΔRRMS , ranged from 0.05 to 0.70 μm and could be oscillated without hydrogel creep. Vascular smooth muscle cell morphology was assessed when exposed to acute and dynamic topography changes. Area and shape changes occurred when an acute topographical change was imposed for substrates exceeding roughness of 0.2 μm, but longer-term oscillating topography did not produce significant changes in morphology irrespective of wire stiffness. These data imply that cells may be able to use topography changes to transmit signals as they respond immediately to changes in roughness. Copyright © 2013 Wiley Periodicals, Inc.

  14. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Rymut, Sharon M; Kampman, Claire M; Corey, Deborah A; Endres, Tori; Cotton, Calvin U; Kelley, Thomas J

    2016-08-01

    High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF. Copyright © 2016 the American Physiological Society.

  15. 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.

  16. 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

  17. Calculated disturbances for evaluation of dynamical properties of freight cars

    Directory of Open Access Journals (Sweden)

    I.A. Mashchenko

    2013-08-01

    defining the standardized factors of the dynamical properties of empty and loaded open cars. Comparison of the calculated factors and experimental data demonstrated its assurance. Originality. The three models of the calculated disturbances that can be used for calculating estimation of the maximal values of the standardized dynamical factors of freight vehicles are proposed. Practical value. The research results ensure an acceptable predicted evaluation of the dynamical properties factors for the designed or refitted vehicles of railway rolling stock, refinement of the values of the certain system parameters at the stage of prototypes, reduction of the expenses for performance trials, etc.

  18. Dynamic evaluation of swallowing disorders with electron-beam tomography

    International Nuclear Information System (INIS)

    Raith, J.; Lindbichler, F.; Kern, R.; Groell, R.; Rienmueller, R.

    1996-01-01

    Three cases preselected by videofluorography were studied to evaluate whether electron beam tomography (EBT) permits more detailed dynamic imaging of swallowing disorders focusing on the mesonasopharyngeal segment, the hypopharynx and the upper esophageal sphincter (UES). Immediately after videofluorographic examination of the oropharyngeal deglutition, EBT is performed. The patient is in a supine position and while the patient swallows a 20 ml bolus of water or diluted iodine containing contrast agent, a sequence of 20 images per level is scanned. The levels, which are determined by using the scout view, are oriented parallel to the hard palate either at the level of the hard palate to image the mesonasopharyngel segment or just above the hyoid bone to focus on the hypopharynx or at the location of the USE. The scan technique is a single-slice cinemode with a slice thickness of 3 mm (exposure time 100 ms, interscan delay 16 ms, 130 kV, 620 mA). The following structural interactions that we have so far been unable to image can be clearly demonstrated with EBT: During normal swallowing, the mesonasopharyngeal segment is completely and symmetrically closed by the soft palate and Passavant's cushion; lateral hypopharyngeal pouches can be located more precisely; and disorders of the UES can be differentiated into functional or morphologically caused disorders (e.g., goiter or cervical osteophytes). Videofluorography and cinematography are still the gold standard in functional evaluation of swallowing disorders. However, EBT permits dynamic imaging of pharyngeal deglutition in a preselected transverse plane and can give useful additional information concerning functional anatomical changes in the pharynx during swallowing. Further clinical evaluation is needed. (orig.) [de

  19. Evaluating sustainability of truck weight regulations: A system dynamics view

    Directory of Open Access Journals (Sweden)

    Pei Liu

    2015-11-01

    Full Text Available Purpose: Targeting the problem of overload trucking in Highway Transportation of iron ore from Caofeidian to Tangshan (HTCT, this paper aims to assess long-term effects of alternative Truck Weight Regulation (TWR policies on sustainability of HTCT. Design/methodology/approach: A system dynamics model was established for policy evaluation. The model, composed of six interrelating modules, is able to simulate policies effects on trucking issues such as freight flow, truck traffic flow, pavement performance, highway transport capacity and trucking time, and further on the Cumulative Economic Cost (CEC including transport cost and time cost of freight owners and the Cumulative Social Cost (CSC including pavement maintenance cost, green house gas emission cost, air pollutants emission cost and traffic accidents cost, so the effects of TWR policies on sustainability of HTCT could be evaluated. Findings: According to different values of overload ratio which a TWR policy allows, alternative TWR policies are classified into three types, which are The Rigid Policy (TRP, The Moderate Policy (TMP and The Tolerant Policy (TTP. Results show that the best policy for sustainability of HTCT depends on the importance of CSC which is expected by the local government. To be specific, (1 if CSC is considered much less important than CEC, the local government should continue implementing the current TTP with the maximum overload ratio; (2 if CSC is considered much more important than CEC, then TRP is recommended; and (3 if CSC is considered slightly more important than CES, TMP with overload ratio of 80% is the best. Practical implications: Conclusions of this paper may help the local government design appropriate TWR policies to achieve sustainability of HTCT. Originality/value: To the best of our knowledge, this is the first effort to evaluate TWR policies on sustainability of regional freight transportation based on system dynamics modeling.

  20. In vivo single cell analysis reveals Gata2 dynamics in cells transitioning to hematopoietic fate.

    Science.gov (United States)

    Eich, Christina; Arlt, Jochen; Vink, Chris S; Solaimani Kartalaei, Parham; Kaimakis, Polynikis; Mariani, Samanta A; van der Linden, Reinier; van Cappellen, Wiggert A; Dzierzak, Elaine

    2018-01-02

    Cell fate is established through coordinated gene expression programs in individual cells. Regulatory networks that include the Gata2 transcription factor play central roles in hematopoietic fate establishment. Although Gata2 is essential to the embryonic development and function of hematopoietic stem cells that form the adult hierarchy, little is known about the in vivo expression dynamics of Gata2 in single cells. Here, we examine Gata2 expression in single aortic cells as they establish hematopoietic fate in Gata2Venus mouse embryos. Time-lapse imaging reveals rapid pulsatile level changes in Gata2 reporter expression in cells undergoing endothelial-to-hematopoietic transition. Moreover, Gata2 reporter pulsatile expression is dramatically altered in Gata2 +/- aortic cells, which undergo fewer transitions and are reduced in hematopoietic potential. Our novel finding of dynamic pulsatile expression of Gata2 suggests a highly unstable genetic state in single cells concomitant with their transition to hematopoietic fate. This reinforces the notion that threshold levels of Gata2 influence fate establishment and has implications for transcription factor-related hematologic dysfunctions. © 2018 Eich et al.

  1. Understanding dynamic changes in live cell adhesion with neutron reflectometry

    Science.gov (United States)

    Junghans, Ann

    Understanding the structure and functionality of biological systems on a nanometer-resolution and short temporal scales is important for solving complex biological problems, developing innovative treatment, and advancing the design of highly functionalized biomimetic materials. For example, adhesion of cells to an underlying substrate plays a crucial role in physiology and disease development, and has been investigated with great interest for several decades. In the talk, we would like to highlight recent advances in utilizing neutron scattering to study bio-related structures in dynamic conditions (e . g . under the shear flow) including in-situ investigations of the interfacial properties of living cells. The strength of neutron reflectometry is its non-pertubative nature, the ability to probe buried interfaces with nanometer resolution and its sensitivity to light elements like hydrogen and carbon. That allows us to study details of cell - substrate interfaces that are not accessible with any other standard techniques. We studied the adhesion of human brain tumor cells (U251) to quartz substrates and their responses to the external mechanical forces. Such cells are isolated within the central nervous system which makes them difficult to reach with conventional therapies and therefore making them highly invasive. Our results reveal changes in the thickness and composition of the adhesion layer (a layer between the cell lipid membrane and the quartz substrate), largely composed of hyaluronic acid and associated proteoglycans, when the cells were subjected to shear stress. Further studies will allow us to determine more conditions triggering changes in the composition of the bio-material in the adhesion layer. This, in turn, can help to identify changes that correlate with tumor invasiveness, which can have significant medical impact for the development of targeted anti-invasive therapies.

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

    OpenAIRE

    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 cell. Therefore, a control-oriented model has been devised in Aspen Plus Dynamics, which accommodates electrochemical, thermal, feed flow and water crossover models in addition to two-phase calculatio...

  3. Charge carrier recombination dynamics in perovskite and polymer solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Paulke, Andreas; Kniepert, Juliane; Kurpiers, Jona; Wolff, Christian M.; Schön, Natalie; Brenner, Thomas J. K.; Neher, Dieter [Institute of Physics and Astronomy, University of Potsdam, Karl-Liebknecht-Str. 24–25, 14476, Potsdam (Germany); Stranks, Samuel D. [Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom); Research Laboratory of Electronics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 (United States); Cavendish Laboratory, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Snaith, Henry J. [Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom)

    2016-03-14

    Time-delayed collection field experiments are applied to planar organometal halide perovskite (CH{sub 3}NH{sub 3}PbI{sub 3}) based solar cells to investigate charge carrier recombination in a fully working solar cell at the nanosecond to microsecond time scale. Recombination of mobile (extractable) charges is shown to follow second-order recombination dynamics for all fluences and time scales tested. Most importantly, the bimolecular recombination coefficient is found to be time-dependent, with an initial value of ca. 10{sup −9} cm{sup 3}/s and a progressive reduction within the first tens of nanoseconds. Comparison to the prototypical organic bulk heterojunction device PTB7:PC{sub 71}BM yields important differences with regard to the mechanism and time scale of free carrier recombination.

  4. The structure and dynamics of patterns of Benard convection cells

    International Nuclear Information System (INIS)

    Rivier, N.; Imperial Coll. of Science and Technology, London; Lausanne Univ.

    1990-08-01

    Benard-Marangoni convection, in containers with large aspect ratio, exhibits space-filling cellular structures, highly deformable, but crystallized. They contain dislocations and grain boundaries generated and moved by elementary topological transformations, and are subjected to a weak shear stress due to the earth's rotation. The cellular structure and its fluctuations are analyzed from a crystallographic viewpoint, by using two complementary approaches. One is a global analysis of cellular structures in cylindrical symmetry. Their structural stability and defect pattern are obtained as topological mode-locking of a continuous structural parameter. The other, a local, molecular dynamics of the cells, gives a realistic parametrization of the forces and the transformations by generalizing the Voronoi cell construction in one extra dimension. 23 refs., 8 figs

  5. Quantitative single cell analysis of cell population dynamics during submandibular salivary gland development and differentiation

    Science.gov (United States)

    Nelson, Deirdre A.; Manhardt, Charles; Kamath, Vidya; Sui, Yunxia; Santamaria-Pang, Alberto; Can, Ali; Bello, Musodiq; Corwin, Alex; Dinn, Sean R.; Lazare, Michael; Gervais, Elise M.; Sequeira, Sharon J.; Peters, Sarah B.; Ginty, Fiona; Gerdes, Michael J.; Larsen, Melinda

    2013-01-01

    Summary Epithelial organ morphogenesis involves reciprocal interactions between epithelial and mesenchymal cell types to balance progenitor cell retention and expansion with cell differentiation for evolution of tissue architecture. Underlying submandibular salivary gland branching morphogenesis is the regulated proliferation and differentiation of perhaps several progenitor cell populations, which have not been characterized throughout development, and yet are critical for understanding organ development, regeneration, and disease. Here we applied a serial multiplexed fluorescent immunohistochemistry technology to map the progressive refinement of the epithelial and mesenchymal cell populations throughout development from embryonic day 14 through postnatal day 20. Using computational single cell analysis methods, we simultaneously mapped the evolving temporal and spatial location of epithelial cells expressing subsets of differentiation and progenitor markers throughout salivary gland development. We mapped epithelial cell differentiation markers, including aquaporin 5, PSP, SABPA, and mucin 10 (acinar cells); cytokeratin 7 (ductal cells); and smooth muscle α-actin (myoepithelial cells) and epithelial progenitor cell markers, cytokeratin 5 and c-kit. We used pairwise correlation and visual mapping of the cells in multiplexed images to quantify the number of single- and double-positive cells expressing these differentiation and progenitor markers at each developmental stage. We identified smooth muscle α-actin as a putative early myoepithelial progenitor marker that is expressed in cytokeratin 5-negative cells. Additionally, our results reveal dynamic expansion and redistributions of c-kit- and K5-positive progenitor cell populations throughout development and in postnatal glands. The data suggest that there are temporally and spatially discreet progenitor populations that contribute to salivary gland development and homeostasis. PMID:23789091

  6. Evaluation of intracerebral hematoma resorption dynamics with computed tomography

    International Nuclear Information System (INIS)

    Strzesniewski, P.; Lasek, W.; Serafin, Z.; Ksiazkiewicz, B.; Wanat-Slupska, E.

    2004-01-01

    High mortality and severe grade of disability observed in patients after intracerebral hemorrhage provide efforts to improve diagnostics and therapy of the hemorrhagic cerebral stroke. An aim of this paper was an evaluation of blood resorption dynamics in patients with intracerebral hematoma, performed with computed tomography of the head and an analysis of clinical significance of this process. An examined group included 133 patients with intracerebral hematoma proven by a CT exam. In 97 patients resorption of the hematoma was measured, based on control scans taken on 15 th and 30 th day on average. Volume of the hemorrhagic foci was measured as well as the width of ventricles and the displacement of medial structures. The mean hematoma volume reached 11,59 ml after 15 days, and 3,16 m after 30 days (average decrease of the volume 0,67 ml/day). There was a significant difference in the rate of resorption between the first (0-15 days) and the second (15-30 days) observation period - 0,78 and 0,62 ml/day respectively. The dynamics of the process was dependent on volume and localization of the hematoma and independent of the grade of displacement and compression of the ventricles. The calculated mean rate of the hematomas resorption enables to schedule control examinations precisely. The significant differences of the dynamics of blood resorption depending on hematomas size and the independence of compression and displacement of ventricular system suggest, that the most important factor in therapeutic decision-making should be a clinical status of the patient. (author)

  7. The role of tridimensional dynamic ultrasound for pelvic floor evaluation.

    Science.gov (United States)

    de la Portilla, Fernando; Rubio Manzanares Dorado, Mercedes; Pino Díaz, Verónica; Vazquez Monchul, Jorge M; Palacios, Carmen; Díaz Pavón, José M; Sánchez Gil, José M; García Cabrera, Ana María

    2015-10-01

    Dynamic endoanal ultrasound has emerged in recent years as a test that could replace the now existing tests in the diagnosis of pelvic floor disorders. The aim of this paper is to determine the usefulness of echodefecography in the diagnosis and evaluation of patients with symptoms of anorrectal obstruction, and show the results obtained after its implementation in a pelvic floor unit, as a complementary tool that could replace conventional defecography. In this retrospective study we analyzed 66 patients with a mean age of 55 years (19-83), 61 women (92%). All dynamic ultrasound was performed in 3 dimensions and was correlated with symptoms and physical findings in the consultation. A descriptive and inferential study was performed to find a kappa correlation between physical examination and echodefecography. The reasons for consultation were: Anorrectal obstruction syndrome 36 patients (54.5%), pelvic organ prolapse 27 patients (40.9%), and anorrectal obstruction syndrome along with pelvic organ prolapse 3 patients (4.5%). The correlation of the 2 groups indicated that echodefecography diagnosed more patients with grade III rectocele, enteroceles, and anismus than the combination of scan-ultrasound-manometry-proctoscopy (Kappa 0.26, 0.38 and 0.21, 95% CI: from 0,07 to 1.00, 0.15 to 1.00 and from 0.12 to 1.00, respectively) (P<.001). Conversely, echodefecography diagnosed less perineal descense (Kappa 0.28, 95% CI: 0.12 to 1.00). Dynamic anal ultrasonography may have a role as a complementary test in patients with pelvic floor disorders, achieving diagnoses that would go undetected by inspection, physical examination and manometry. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. CT anglographic evaluation of pancreatic islet cell tumors

    International Nuclear Information System (INIS)

    Merine, D.S.; Fishman, E.K.; Kuhlman, J.E.; Siegelman, S.S.; Widlus, D.M.; Cameron, J.L.

    1989-01-01

    To increase the accuracy of CT staging of pancreatic cancer, the authors modified the standard techniques for CT angiography (CTA). Six patients with known or suspected pancreatic islet cell tumors were examined by CTA. The catheter was placed in the superior mesenteric artery, and a sequence of dynamic CT scans were obtained while 150 mL of Hypaque-30 was injected at a rate of 2 mL/sec. In addition to clear identification of the pancreatic tumor mass, CTA proved valuable in evaluating liver metastasis (n = 3) and venous thrombosis (n = 2. In one case, a 1-cm functioning insulinoma was demonstrated by CTA after unsuccessful angiographic detection. In all cases, correlation with surgical or biopsy results showed the CTA to be accurate

  9. Nanoscale live cell optical imaging of the dynamics of intracellular microvesicles in neural cells.

    Science.gov (United States)

    Lee, Sohee; Heo, Chaejeong; Suh, Minah; Lee, Young Hee

    2013-11-01

    Recent advances in biotechnology and imaging technology have provided great opportunities to investigate cellular dynamics. Conventional imaging methods such as transmission electron microscopy, scanning electron microscopy, and atomic force microscopy are powerful techniques for cellular imaging, even at the nanoscale level. However, these techniques have limitations applications in live cell imaging because of the experimental preparation required, namely cell fixation, and the innately small field of view. In this study, we developed a nanoscale optical imaging (NOI) system that combines a conventional optical microscope with a high resolution dark-field condenser (Cytoviva, Inc.) and halogen illuminator. The NOI system's maximum resolution for live cell imaging is around 100 nm. We utilized NOI to investigate the dynamics of intracellular microvesicles of neural cells without immunocytological analysis. In particular, we studied direct, active random, and moderate random dynamic motions of intracellular microvesicles and visualized lysosomal vesicle changes after treatment of cells with a lysosomal inhibitor (NH4Cl). Our results indicate that the NOI system is a feasible, high-resolution optical imaging system for live small organelles that does not require complicated optics or immunocytological staining processes.

  10. Evaluation of Dynamic Channel and Power Assignment for Cognitive Networks

    Energy Technology Data Exchange (ETDEWEB)

    Syed A. Ahmad; Umesh Shukla; Ryan E. Irwin; Luiz A. DaSilva; Allen B. MacKenzie

    2011-03-01

    In this paper, we develop a unifying optimization formulation to describe the Dynamic Channel and Power Assignment (DCPA) problem and evaluation method for comparing DCPA algorithms. DCPA refers to the allocation of transmit power and frequency channels to links in a cognitive network so as to maximize the total number of feasible links while minimizing the aggregate transmit power. We apply our evaluation method to five algorithms representative of DCPA used in literature. This comparison illustrates the tradeoffs between control modes (centralized versus distributed) and channel/power assignment techniques. We estimate the complexity of each algorithm. Through simulations, we evaluate the effectiveness of the algorithms in achieving feasible link allocations in the network, as well as their power efficiency. Our results indicate that, when few channels are available, the effectiveness of all algorithms is comparable and thus the one with smallest complexity should be selected. The Least Interfering Channel and Iterative Power Assignment (LICIPA) algorithm does not require cross-link gain information, has the overall lowest run time, and highest feasibility ratio of all the distributed algorithms; however, this comes at a cost of higher average power per link.

  11. 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. Thus, the guanidine-sensitive step in RNA synthesis is important throughout the virus life cycle in cells....... 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...

  12. Dynamics of Red Cells in Spleen: How Does Vesiculation Happen?

    Science.gov (United States)

    Zhu, Qiang; Salehyar, Sara; Cabrales, Pedro; Asaro, Robert

    2016-11-01

    Vesiculation of red blood cells as a result of local separation between lipid bilayer and cytoskeleton is known to happen in vivo, most likely inside spleen where they sustain large mechanical loads during the passage through venus slits. There is, however, little knowledge about the detailed scenario and condition. We address this question via a fluid-cell interaction model by coupling a multiscale model of the cell membrane (including molecular details) with a fluid dynamics model based on boundary-integral equations. A numerical flow channel is created where the cell is driven through a narrow slit by pressure (imitating the transit through venus slits in spleen). The concentration is the occurrence of large dissociation (negative) pressure between the skeleton/membrane connection that promotes separation, a precursor of vesicle formation. Critical levels for the negative pressure are estimated using published data. By following the maximum range of pressure, we conclude that for vesiculation to happen there must be biochemical influences (e.g. binding of degraded haemoglobin) that significantly reduce effective attachment density. This is consistent with reported trends in vesiculation that are believed to occur in cases of various hereditary anemias and during blood storage. Our findings also suggest the criticality of understanding the biochemical phenomena involved with cytoskeleton/membrane attachment.

  13. Evaluation of periventricular radiolucency in hydrocephalus by dynamic CT studies

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Hideki; Bandou, Kuniaki; Miyaoka, Makoto (Fujisawa City Hospital, Kanagawa (Japan))

    1994-06-01

    The association of periventricular radiolucency (PVL) in normal pressure hydrocephalus (NPH) on CT scan is a common finding. However, it is difficult to differentiate NPH from atrophy or infarctions in which shunt surgery does not reverse these conditions. To distinguish NPH from these, we examined PVL by means of dynamic CT (DCT) studies. We investigated 12 elderly patients presenting with gait disturbance, urinary incontinence and mental dysfunction who had both enlarged lateral ventricles and PVL. All patients had laboratory investigations, including radioisotope and CT cisternography and Xenon CBF studies. Nine patients were shunted because of abnormal CSF dynamics. Varying degrees of clinical improvement after surgery were observed in 6 cases. A difference of arrival time (AT) between PVL and thalamus obtained from time-density-curve was calculated in each patient. The AT difference was 6.2[+-]1.5 sec. in the shunt-effective group, and 1.4[+-]1.3 sec. in both, the shunt in effective and ineligible group, this was highly significant (p<0.01). We also measured peak time (PT) in PVL, of the thalamus and anterior cerebral artery, but no significant correlation was obtained. An AT difference between PVL and thalamus obtained from DCT studies is a clinically useful diagnostic tool for the evaluation of NPH. (author).

  14. Evaluation of periventricular radiolucency in hydrocephalus by dynamic CT studies

    International Nuclear Information System (INIS)

    Nakano, Hideki; Bandou, Kuniaki; Miyaoka, Makoto

    1994-01-01

    The association of periventricular radiolucency (PVL) in normal pressure hydrocephalus (NPH) on CT scan is a common finding. However, it is difficult to differentiate NPH from atrophy or infarctions in which shunt surgery does not reverse these conditions. To distinguish NPH from these, we examined PVL by means of dynamic CT (DCT) studies. We investigated 12 elderly patients presenting with gait disturbance, urinary incontinence and mental dysfunction who had both enlarged lateral ventricles and PVL. All patients had laboratory investigations, including radioisotope and CT cisternography and Xenon CBF studies. Nine patients were shunted because of abnormal CSF dynamics. Varying degrees of clinical improvement after surgery were observed in 6 cases. A difference of arrival time (AT) between PVL and thalamus obtained from time-density-curve was calculated in each patient. The AT difference was 6.2±1.5 sec. in the shunt-effective group, and 1.4±1.3 sec. in both, the shunt in effective and ineligible group, this was highly significant (p<0.01). We also measured peak time (PT) in PVL, of the thalamus and anterior cerebral artery, but no significant correlation was obtained. An AT difference between PVL and thalamus obtained from DCT studies is a clinically useful diagnostic tool for the evaluation of NPH. (author)

  15. 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

  16. Evaluating platelet aggregation dynamics from laser speckle fluctuations.

    Science.gov (United States)

    Hajjarian, Zeinab; Tshikudi, Diane M; Nadkarni, Seemantini K

    2017-07-01

    Platelets are key to maintaining hemostasis and impaired platelet aggregation could lead to hemorrhage or thrombosis. We report a new approach that exploits laser speckle intensity fluctuations, emanated from a drop of platelet-rich-plasma (PRP), to profile aggregation. Speckle fluctuation rate is quantified by the speckle intensity autocorrelation, g 2 (t) , from which the aggregate size is deduced. We first apply this approach to evaluate polystyrene bead aggregation, triggered by salt. Next, we assess dose-dependent platelet aggregation and inhibition in human PRP spiked with adenosine diphosphate and clopidogrel. Additional spatio-temporal speckle analyses yield 2-dimensional maps of particle displacements to visualize platelet aggregate foci within minutes and quantify aggregation dynamics. These findings demonstrate the unique opportunity for assessing platelet health within minutes for diagnosing bleeding disorders and monitoring anti-platelet therapies.

  17. Pre- and Postseason Dynamic Ultrasound Evaluation of the Pitching Elbow.

    Science.gov (United States)

    Keller, Robert A; Marshall, Nathan E; Bey, Michael J; Ahmed, Hafeez; Scher, Courtney E; van Holsbeeck, Marnix; Moutzouros, Vasilios

    2015-09-01

    To use ultrasound imaging to document changes over time (i.e., preseason v postseason) in the pitching elbow of high school baseball pitchers. Twenty-two high school pitchers were prospectively followed. Pitchers were evaluated after a 2-month period of relative arm rest via preseason physical exams, dynamic ultrasound imaging of their throwing elbow, and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) assessment. Players were reevaluated within 1 week of their last game. Dynamic ultrasound images were then randomized, blinded to testing time point, and evaluated by 2 fellowship-trained musculoskeletal radiologists. Average pitcher age was 16.9 years. Average pitches thrown was 456.5, maximum velocity 77.7 mph, games pitched 7.3, and days off between starts 6.6. From preseason to postseason, there were significant increases in ulnar collateral ligament (UCL) thickness (P = .02), ulnar nerve cross-sectional area (P = .001), UCL substance heterogeneity (P = .001), and QuickDASH scores (P = .03). In addition, there was a nonsignificant increase in loaded ulnohumeral joint space (P = .10). No pitchers had loose bodies on preseason exam, while 3 demonstrated loose bodies postseason. The increase in UCL thickness was significantly associated with the number of bullpen sessions per week (P = .01). The increase in ulnar nerve cross-sectional area was significantly associated with the number of pitches (P = .04), innings pitched (P = .01), and games pitched (P = .04). The stresses placed on the elbow during only one season of pitching create adaptive changes to multiple structures about the elbow including UCL heterogeneity and thickening, increased ulnohumeral joint space laxity, and enlarged ulnar nerve cross-sectional area. Level II prospective observational study. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  18. Dynamic network data envelopment analysis for university hospitals evaluation

    Directory of Open Access Journals (Sweden)

    Maria Stella de Castro Lobo

    2016-01-01

    Full Text Available ABSTRACT OBJECTIVE To develop an assessment tool to evaluate the efficiency of federal university general hospitals. METHODS Data envelopment analysis, a linear programming technique, creates a best practice frontier by comparing observed production given the amount of resources used. The model is output-oriented and considers variable returns to scale. Network data envelopment analysis considers link variables belonging to more than one dimension (in the model, medical residents, adjusted admissions, and research projects. Dynamic network data envelopment analysis uses carry-over variables (in the model, financing budget to analyze frontier shift in subsequent years. Data were gathered from the information system of the Brazilian Ministry of Education (MEC, 2010-2013. RESULTS The mean scores for health care, teaching and research over the period were 58.0%, 86.0%, and 61.0%, respectively. In 2012, the best performance year, for all units to reach the frontier it would be necessary to have a mean increase of 65.0% in outpatient visits; 34.0% in admissions; 12.0% in undergraduate students; 13.0% in multi-professional residents; 48.0% in graduate students; 7.0% in research projects; besides a decrease of 9.0% in medical residents. In the same year, an increase of 0.9% in financing budget would be necessary to improve the care output frontier. In the dynamic evaluation, there was progress in teaching efficiency, oscillation in medical care and no variation in research. CONCLUSIONS The proposed model generates public health planning and programming parameters by estimating efficiency scores and making projections to reach the best practice frontier.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae

    Science.gov (United States)

    Rego, António; Duarte, Ana M.; Azevedo, Flávio; Sousa, Maria J.; Côrte-Real, Manuela; Chaves, Susana R.

    2014-01-01

    Acetic acid triggers apoptotic cell death in Saccharomyces cerevisiae, similar to mammalian apoptosis. To uncover novel regulators of this process, we analyzed whether impairing MAPK signaling affected acetic acid-induced apoptosis and found the mating-pheromone response and, especially, the cell wall integrity pathways were the major mediators, especially the latter, which we characterized further. Screening downstream effectors of this pathway, namely targets of the transcription factor Rlm1p, highlighted decreased cell wall remodeling as particularly important for acetic acid resistance. Modulation of cell surface dynamics therefore emerges as a powerful strategy to increase acetic acid resistance, with potential application in industrial fermentations using yeast, and in biomedicine to exploit the higher sensitivity of colorectal carcinoma cells to apoptosis induced by acetate produced by intestinal propionibacteria. PMID:28357256

  4. Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background

    Science.gov (United States)

    2017-01-01

    Cell proliferation is the common characteristic of all biological systems. The immune system insures the maintenance of body integrity on the basis of a continuous production of diversified T lymphocytes in the thymus. This involves processes of proliferation, differentiation, selection, death and migration of lymphocytes to peripheral tissues, where proliferation also occurs upon antigen recognition. Quantification of cell proliferation dynamics requires specific experimental methods and mathematical modelling. Here, we assess the impact of genetics and aging on the immune system by investigating the dynamics of proliferation of T lymphocytes across their differentiation through thymus and spleen in mice. Our investigation is based on single-cell multicolour flow cytometry analysis revealing the active incorporation of a thymidine analogue during S phase after pulse-chase-pulse experiments in vivo, versus cell DNA content. A generic mathematical model of state transition simulates through Ordinary Differential Equations (ODEs) the evolution of single cell behaviour during various durations of labelling. It allows us to fit our data, to deduce proliferation rates and estimate cell cycle durations in sub-populations. Our model is simple and flexible and is validated with other durations of pulse/chase experiments. Our results reveal that T cell proliferation is highly heterogeneous but with a specific “signature” that depends upon genetic origins, is specific to cell differentiation stages in thymus and spleen and is altered with age. In conclusion, our model allows us to infer proliferation rates and cell cycle phase durations from complex experimental 5-ethynyl-2'-deoxyuridine (EdU) data, revealing T cell proliferation heterogeneity and specific signatures. PMID:28288157

  5. 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...

  6. Differential dynamics of splicing factor SC35 during the cell cycle

    Indian Academy of Sciences (India)

    Srinivas

    We analysed the dynamics of the splicing factor SC35 in interphase and mitotic cells. In HeLa cells expressing green fluorescent protein (GFP)-SC35, this was localized ... Cell cycle dynamics; FRAP analysis; mitotic interchromatin granules; splicing factor SC35 .... for 1 h at room temperature for single labelling experiments.

  7. 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...

  8. 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...

  9. 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...

  10. Reliability Evaluation of Primary Cells | Anyaka | Nigerian Journal of ...

    African Journals Online (AJOL)

    Evaluation of the reliability of a primary cell took place in three stages: 192 cells went through a slow-discharged test. A designed experiment was conducted on 144 cells; there were three factors in the experiment: Storage temperature (three levels), thermal shock (two levels) and date code (two levels). 16 cells ...

  11. Modeling centrifugal cell washers using computational fluid dynamics.

    Science.gov (United States)

    Kellet, Beth E; Han, Binbing; Dandy, David S; Wickramasinghe, S Ranil

    2004-11-01

    Reinfusion of shed blood during surgery could avoid the need for blood transfusions. Prior to reinfusion of the red blood cells, the shed blood must be washed in order to remove leukocytes, platelets, and other contaminants. Further, the hematocrit of the washed blood must be increased. The feasibility of using computational fluid dynamics (CFD) to guide the design of better centrifuges for processing shed blood is explored here. The velocity field within a centrifuge bowl and the rate of protein removal from the shed blood has been studied. The results obtained indicate that CFD could help screen preliminary centrifuge bowl designs, thus reducing the number of initial experimental tests required when developing new centrifuge bowls. Although the focus of this work is on washing shed blood, the methods developed here are applicable to the design of centrifuge bowls for other blood-processing applications.

  12. Dynamics of phytoplankton blooms in turbulent vortex cells

    DEFF Research Database (Denmark)

    Lindemann, Christian; Visser, Andre; Mariani, Patrizio

    2017-01-01

    Turbulence and coherent circulation structures, such as submesoscale and mesoscale eddies, convective plumes and Langmuir cells, play a critical role in shaping phytoplankton spatial distribution and population dynamics. We use a framework of advection-reaction-diffusion equations to investigate...... the effects of turbulent transport on the phytoplankton population growth and its spatial structure in a vertical two-dimensional vortex flow field. In particular, we focus on how turbulent flow velocities and sinking influence phytoplankton growth and biomass aggregation. Our results indicate that conditions...... in mixing and growth of phytoplankton can drive different vertical spatial structures in the mixed layer, with the depth of the mixed layer being a critical factor to allow coexistence of populations with different sinking speed. With increasing mixed layer depth, positive growth for sinking phytoplankton...

  13. Modeling bacterial population growth from stochastic single-cell dynamics.

    Science.gov (United States)

    Alonso, Antonio A; Molina, Ignacio; Theodoropoulos, Constantinos

    2014-09-01

    A few bacterial cells may be sufficient to produce a food-borne illness outbreak, provided that they are capable of adapting and proliferating on a food matrix. This is why any quantitative health risk assessment policy must incorporate methods to accurately predict the growth of bacterial populations from a small number of pathogens. In this aim, mathematical models have become a powerful tool. Unfortunately, at low cell concentrations, standard deterministic models fail to predict the fate of the population, essentially because the heterogeneity between individuals becomes relevant. In this work, a stochastic differential equation (SDE) model is proposed to describe variability within single-cell growth and division and to simulate population growth from a given initial number of individuals. We provide evidence of the model ability to explain the observed distributions of times to division, including the lag time produced by the adaptation to the environment, by comparing model predictions with experiments from the literature for Escherichia coli, Listeria innocua, and Salmonella enterica. The model is shown to accurately predict experimental growth population dynamics for both small and large microbial populations. The use of stochastic models for the estimation of parameters to successfully fit experimental data is a particularly challenging problem. For instance, if Monte Carlo methods are employed to model the required distributions of times to division, the parameter estimation problem can become numerically intractable. We overcame this limitation by converting the stochastic description to a partial differential equation (backward Kolmogorov) instead, which relates to the distribution of division times. Contrary to previous stochastic formulations based on random parameters, the present model is capable of explaining the variability observed in populations that result from the growth of a small number of initial cells as well as the lack of it compared to

  14. 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...

  15. Dynamic Evaluation of Acrylonitrile Butadiene Styrene Subjected to High-Strain-Rate Compressive Loads

    Science.gov (United States)

    2014-12-01

    Dynamic Evaluation of Acrylonitrile Butadiene Styrene Subjected to High-Strain-Rate Compressive Loads by Alex Peterson, Ed Habtour, Jaret...Army Research Laboratory Aberdeen Proving Ground, MD 21005-5066 ARL-TN-0648 December 2014 Dynamic Evaluation of Acrylonitrile Butadiene ...Dynamic Evaluation of Acrylonitrile Butadiene Styrene Subjected to High-Strain- Rate Compressive Loads 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

  16. Development and Evaluation of a Dynamic, 3-Degree-of-Freedom (DOF) Wind Tunnel Model

    Science.gov (United States)

    2016-11-01

    ARL-CR-0807● NOV 2016 US Army Research Laboratory Development and Evaluation of a Dynamic, 3-Degree-of-Freedom ( DOF ) Wind...ARL-CR-0807 ● NOV 2016 US Army Research Laboratory Development and Evaluation of a Dynamic, 3-Degree-of-Freedom ( DOF ) Wind...Development and Evaluation of a Dynamic, 3-Degree-of-Freedom ( DOF ) Wind Tunnel Model 5a. CONTRACT NUMBER W911-QX-14-C-0016 5b. GRANT NUMBER

  17. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-01-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +- 0.2, compared with an oxygen enhancement ratio of 3.3 +- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD 50 was estimated to be 125 to 150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit

  18. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-01-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit

  19. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-07-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit.

  20. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    Directory of Open Access Journals (Sweden)

    Mazen A. Juratli

    2014-01-01

    Full Text Available Circulating tumor cells (CTCs are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min. These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.

  1. Linking chromatin dynamics, cell fate plasticity, and tissue homeostasis in adult mouse hair follicle stem cells.

    Science.gov (United States)

    Lee, Jayhun; Tumbar, Tudorita

    2017-07-01

    Cellular plasticity for fate acquisition is associated with distinct chromatin states, which include histone modifications, dynamic association of chromatin factors with the DNA, and global chromatin compaction and nuclear organization. While embryonic stem cell (ESC) plasticity in vitro and its link with chromatin states have been characterized in depth, little is known about tissue stem cell plasticity in vivo , during adult tissue homeostasis. Recently, we reported a distinct globally low level of histone H3 K4/9/27me3 in mouse hair follicle stem cells (HFSCs) during quiescence. This occurred at the stage preceding fate acquisition, when HFSC fate plasticity must be at its highest. This hypomethylated state was required for proper skin homeostasis and timely hair cycle. Here, we show both in the live tissue and in cell culture that at quiescence HFSCs have higher exchange rates for core histone H2B when compared with proliferative or differentiated cells. This denoted a hyperdynamic chromatin state, which was previously associated with high cell fate plasticity in ESCs. Moreover, we find that quiescent HFSCs display a higher propensity for de-differentiation in response to Yamanaka's reprogramming factors in vivo . These results further support our recent model in which HFSCs render their chromatin into a specific state at quiescence, which is attuned to higher cell fate plasticity.

  2. Charge carrier dynamics in thin film solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Strothkaemper, Christian

    2013-06-24

    This work investigates the charge carrier dynamics in three different technological approaches within the class of thin film solar cells: radial heterojunctions, the dye solar cell, and microcrystalline CuInSe{sub 2}, focusing on charge transport and separation at the electrode, and the relaxation of photogenerated charge carriers due to recombination and energy dissipation to the phonon system. This work relies mostly on optical-pump terahertz-probe (OPTP) spectroscopy, followed by transient absorption (TA) and two-photon photoemission (2PPE). The charge separation in ZnO-electrode/In{sub 2}S{sub 3}-absorber core/shell nanorods, which represent a model system of a radial heterojunction, is analyzed by OPTP. It is concluded, that the dynamics in the absorber are determined by multiple trapping, which leads to a dispersive charge transport to the electrode that lasts over hundreds of picoseconds. The high trap density on the order of 10{sup 19}/cm{sup 3} is detrimental for the injection yield, which exhibits a decrease with increasing shell thickness. The heterogeneous electron transfer from a series of model dyes into ZnO proceeds on a time-scale of 200 fs. However, the photoconductivity builds up just on a 2-10 ps timescale, and 2PPE reveals that injected electrons are meanwhile localized spatially and energetically at the interface. It is concluded that the injection proceeds through adsorbate induced interface states. This is an important result because the back reaction from long lived interface states can be expected to be much faster than from bulk states. While the charge transport in stoichiometric CuInSe{sub 2} thin films is indicative of free charge carriers, CuInSe{sub 2} with a solar cell grade composition (Cu-poor) exhibits signs of carrier localization. This detrimental effect is attributed to a high density of charged defects and a high degree of compensation, which together create a spatially fluctuating potential that inhibits charge transport. On

  3. MST-312 Alters Telomere Dynamics, Gene Expression Profiles and Growth in Human Breast Cancer Cells.

    Science.gov (United States)

    Gurung, Resham Lal; Lim, Shi Ni; Low, Grace Kah Mun; Hande, M Prakash

    2014-01-01

    Targeting telomerase is a potential cancer management strategy given that it allows unlimited cellular replication in the majority of cancers. Dysfunctional telomeres are recognized as double-strand breaks. However, the status of DNA repair response pathways following telomerase inhibition is not well understood in human breast cancer cells. Here, we evaluated the effects of MST-312, a chemically modified derivative from tea catechin, epigallocatechin gallate, on telomere dynamics and DNA damage gene expression in breast cancer cells. Breast cancer cells MCF-7 and MDA-MB-231 were treated with MST-312, and telomere-telomerase homeostasis, induced DNA damage and gene expression profiling were analyzed. MST-312 decreased telomerase activity and induced telomere dysfunction and growth arrest in breast cancer cells with more profound effects in MDA-MB-231 than in MCF-7 cells. Consistent with these data, the telomere-protective protein TRF2 was downregulated in MDA-MB-231 cells. MST-312 induced DNA damage at telomeres accompanied by reduced expression of DNA damage-related genes ATM and RAD50. Co-treatment with MST-312 and the poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor PJ-34 further enhanced growth reduction as compared to single treatment with MST-312 or PJ-34. Our work demonstrates potential importance for the establishment of antitelomerase cancer therapy using MST-312 along with PARP-1 inhibition in breast cancer therapy. © 2015 S. Karger AG, Basel.

  4. Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro.

    Science.gov (United States)

    Sisino, Giorgia; Zhou, Alex-Xianghua; Dahr, Niklas; Sabirsh, Alan; Soundarapandian, Mangala M; Perera, Ranjan; Larsson-Lekholm, Erik; Magnone, Maria Chiara; Althage, Magnus; Tyrberg, Björn

    2017-01-01

    Pregnancy is associated with increased β-cell proliferation driven by prolactin. Long noncoding RNAs (lncRNA) are the most abundant RNA species in the mammalian genome, yet, their functional importance is mainly elusive. This study tests the hypothesis that lncRNAs regulate β-cell proliferation in response to prolactin in the context of β-cell mass compensation in pregnancy. The expression profile of lncRNAs in mouse islets at day 14.5 of pregnancy was explored by a bioinformatics approach, further confirmed by quantitative PCR at different days of pregnancy, and islet specificity was evaluated by comparing expression in islets versus other tissues. In order to establish the role of the candidate lncRNAs we studied cell proliferation in mouse islets and the MIN6 β-cell line by EdU incorporation and cell count. We found that a group of lncRNAs is differentially regulated in mouse islets at 14.5 days of pregnancy. At different stages of pregnancy, these lncRNAs are dynamically expressed, and expression is prolactin dependent in mouse islets and MIN6 cells. One of those lncRNAs, Gm16308 (Lnc03), is dynamically regulated during pregnancy, prolactin-dependent and islet-enriched. Silencing Lnc03 in primary β-cells and MIN6 cells inhibits, whereas over-expression stimulates, proliferation even in the absence of prolactin, demonstrating that Lnc03 regulates β-cell growth. During pregnancy mouse islet proliferation is correlated with dynamic changes of lncRNA expression. In particular, Lnc03 regulates mouse β-cell proliferation and may be a crucial component of β-cell proliferation in β-cell mass adaptation in both health and disease.

  5. Simultaneous characterization of protein-material and cell-protein interactions using dynamic QCM-D analysis on SAM surfaces.

    Science.gov (United States)

    Kushiro, Keiichiro; Lee, Chih-Hao; Takai, Madoka

    2016-05-24

    Understanding the interactions among materials, proteins and cells is critical for the development of novel biomaterials, and establishing a highly sensitive and quantitative method to standardize these interactions is desired. In this study, quartz crystal microbalance with dissipation (QCM-D) combined with microscopy was utilized to quantitatively monitor the entirety of the cell adhesion processes, starting from the protein adsorption, on various self-assembled monolayer (SAM) surfaces. Although the resulting cell adhesion morphologies were similar on most of the surfaces, the dynamic QCM-D signal patterns were unique on each surface, suggesting different forms of material-protein-cell interactions. The viscoelasticity and the density of the surface-adsorbed fibronectin (FN), as well as the relative exposure of the cell adhesive arginine-glycine-aspartic acid (RGD) motifs, were correlated to the different cell adhesion dynamics and mechanics. Some surfaces exhibited complicated behaviors alluding to the detachment/rearrangement of surface proteins or highly sparse but bioactive proteins that promote a slow adhesion process. This study underscores the potential use of the QCM-D signal pattern as a rule of thumb for delineating different protein-material and cell-protein interactions, and offers a rapid in vitro platform for the dynamic evaluation of protein and cell behaviors on novel biomaterials.

  6. Bone Cells Dynamics during Peri-Implantitis: a Theoretical Analysis

    Directory of Open Access Journals (Sweden)

    Maria Helena Fernandes

    2016-09-01

    Full Text Available Objectives: The present manuscript aims a detailed characterization of the bone cells dynamics during physiological bone remodelling and, subsequently, to address the cellular and molecular mechanisms that play a fundamental role in the immune-inflammatory-induced uncoupled bone remodelling observed in peri-implantitis. Results: An intimate relationship between the immune system and bone is acknowledged to be determinant for bone tissue remodelling and integrity. Due to the close interaction of immune and bone cells, the two systems share a number of surface receptors, cytokines, signalling pathways and transcription factors that are involved in mutual regulatory mechanisms. This physiological equilibrium is disturbed in pathological conditions, as verified in peri-implantitis establishment and development. Activation of the innate and adaptive immune response, challenged by the local bacterial infection, induces the synthesis of high levels of a variety of pro- and anti-inflammatory cytokines that disturb the normal functioning of the bone cells, by uncoupling bone resorption and formation, ending up with a net alveolar bone loss and subsequent implant failure. Most data points to an immune-inflammatory induced osteoclast differentiation and function, as the major underlying mechanism to the uncoupled bone resorption to bone formation. Further, the disturbed functioning of osteoblasts, reflected by the possible expression of a fibro-osteoblastic phenotype, may also play a role. Conclusions: Alveolar bone loss is a hallmark of peri-implantitis. A great deal of data is still needed on the cellular and humoral crosstalk in the context of an integrated view of the osteoimmunologic interplay occurring in the peri-implantitis environment subjacent to the bone loss outcome.

  7. Evaluation of Control Structures for Dynamic Dispatch in Java

    OpenAIRE

    Zendra, Olivier; Driesen, Karel

    2002-01-01

    Dynamic dispatch, or late binding of function calls, is a salient feature of object-oriented programming languages like C++ and Java. It can be costly on deeply pipelined processors, because dynamic calls translate to hard to predict multi-way branch instructions, which are prone to causing pipeline bubbles. Several alternative implementation techniques have been designed in the past in order to perform dynamic dispatch without relying on these expensive branch instructions. Unfortunately it ...

  8. Bladder cancer: Evaluation of staging accuracy using dynamic MRI

    International Nuclear Information System (INIS)

    Rajesh, A.; Sokhi, H.K.; Fung, R.; Mulcahy, K.A.; Bankart, M.J.G.

    2011-01-01

    Aim: To assess the accuracy of magnetic resonance imaging (MRI) in staging bladder cancer and to assess whether dynamic gadolinium-enhanced sequences have any added benefit in staging. Materials and methods: Over a 22 month period, the MRI findings of 100 consecutive patients with histologically proven transitional cell carcinoma (TCC) of the bladder were reviewed. The T stage was assessed independently on T2-weighted imaging alone and in combination with gadolinium-enhanced MRI. The final histological diagnosis was considered the reference standard. Statistical analysis was performed to ascertain stage-by-stage accuracy. Accuracy of MRI in differentiating superficial (≤T1) from invasive (≥T2) and in differentiating organ-confined (≤T2) from non-organ-confined (≥T3) disease was assessed. Results: On a stage-by-stage basis, tumours were correctly staged using MRI in 63% of patients (observed agreement = 0.63, weighted kappa = 0.57). The sensitivity and specificity of MRI to differentiate between superficial (≤T1) from invasive (≥T2) disease was 78.2 and 93.3%. The observed agreement for this group was 85% (kappa = 70%; p < 0.0001). The sensitivity and specificity of MRI to differentiate between organ-confined (≤T2) from non-organ confined (≥T3) disease was 90.5 and 60%. The observed agreement for this group was 89% (kappa = 30%; p < 0.01). Gadolinium-enhanced images improved staging in only three patients. Conclusion: In the present study MRI was found to be a moderately accurate tool in assessing the T stage. Agreement on a stage-by-stage basis was good. Agreement for differentiating between non-invasive versus muscle-invasive disease was good and that for organ-confined versus non-organ-confined disease was fair. Routine use of gadolinium-enhanced images is not routinely required.

  9. Bladder cancer: Evaluation of staging accuracy using dynamic MRI

    Energy Technology Data Exchange (ETDEWEB)

    Rajesh, A., E-mail: arajesh27@hotmail.com [Department of Radiology, University Hospitals of Leicester NHS Trust, Leicester General Hospital (United Kingdom); Sokhi, H.K.; Fung, R.; Mulcahy, K.A. [Department of Radiology, University Hospitals of Leicester NHS Trust, Leicester General Hospital (United Kingdom); Bankart, M.J.G. [Department of Health Sciences, University of Leicester, Leicester (United Kingdom)

    2011-12-15

    Aim: To assess the accuracy of magnetic resonance imaging (MRI) in staging bladder cancer and to assess whether dynamic gadolinium-enhanced sequences have any added benefit in staging. Materials and methods: Over a 22 month period, the MRI findings of 100 consecutive patients with histologically proven transitional cell carcinoma (TCC) of the bladder were reviewed. The T stage was assessed independently on T2-weighted imaging alone and in combination with gadolinium-enhanced MRI. The final histological diagnosis was considered the reference standard. Statistical analysis was performed to ascertain stage-by-stage accuracy. Accuracy of MRI in differentiating superficial ({<=}T1) from invasive ({>=}T2) and in differentiating organ-confined ({<=}T2) from non-organ-confined ({>=}T3) disease was assessed. Results: On a stage-by-stage basis, tumours were correctly staged using MRI in 63% of patients (observed agreement = 0.63, weighted kappa = 0.57). The sensitivity and specificity of MRI to differentiate between superficial ({<=}T1) from invasive ({>=}T2) disease was 78.2 and 93.3%. The observed agreement for this group was 85% (kappa = 70%; p < 0.0001). The sensitivity and specificity of MRI to differentiate between organ-confined ({<=}T2) from non-organ confined ({>=}T3) disease was 90.5 and 60%. The observed agreement for this group was 89% (kappa = 30%; p < 0.01). Gadolinium-enhanced images improved staging in only three patients. Conclusion: In the present study MRI was found to be a moderately accurate tool in assessing the T stage. Agreement on a stage-by-stage basis was good. Agreement for differentiating between non-invasive versus muscle-invasive disease was good and that for organ-confined versus non-organ-confined disease was fair. Routine use of gadolinium-enhanced images is not routinely required.

  10. 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

  11. Murine Mesenchymal Stem Cell Commitment to Differentiation Is Regulated by Mitochondrial Dynamics.

    Science.gov (United States)

    Forni, Maria Fernanda; Peloggia, Julia; Trudeau, Kyle; Shirihai, Orian; Kowaltowski, Alicia J

    2016-03-01

    Mouse skin mesenchymal stem cells (msMSCs) are dermis CD105(+) CD90(+) CD73(+) CD29(+) CD34(-) mesodermal precursors which, after in vitro induction, undergo chondro, adipo, and osteogenesis. Extensive metabolic reconfiguration has been found to occur during differentiation, and the bioenergetic status of a cell is known to be dependent on the quality and abundance of the mitochondrial population, which may be regulated by fusion and fission. However, little is known regarding the impact of mitochondrial dynamics on the differentiation process. We addressed this knowledge gap by isolating MSCs from Swiss female mice, inducing these cells to differentiate into osteo, chondro, and adipocytes and measuring changes in mass, morphology, dynamics, and bioenergetics. Mitochondrial biogenesis was increased in adipogenesis, as evaluated through confocal microscopy, citrate synthase activity, and mtDNA content. The early steps of adipo and osteogenesis involved mitochondrial elongation, as well as increased expression of mitochondrial fusion proteins Mfn1 and 2. Chondrogenesis involved a fragmented mitochondrial phenotype, increased expression of fission proteins Drp1, Fis1, and 2, and enhanced mitophagy. These events were accompanied by profound bioenergetic alterations during the commitment period. Moreover, knockdown of Mfn2 in adipo and osteogenesis and the overexpression of a dominant negative form of Drp1 during chondrogenesis resulted in a loss of differentiation ability. Overall, we find that mitochondrial morphology and its regulating processes of fission/fusion are modulated early on during commitment, leading to alterations in the bioenergetic profile that are important for differentiation. We thus propose a central role for mitochondrial dynamics in the maintenance/commitment of mesenchymal stem cells. © 2015 AlphaMed Press.

  12. Ammonia removal via microbial fuel cell (MFC) dynamic reactor

    Science.gov (United States)

    Alabiad, I.; Ali, U. F. M.; Zakarya, I. A.; Ibrahim, N.; Radzi, R. W.; Zulkurnai, N. Z.; Azmi, N. H.

    2017-06-01

    Landfill leachate is generally known as high-strength wastewater that is difficult to handle and contains dissolved extracts and suspended matter. Microbial fuel cells (MFCs) were designed to treat landfill leachate while continuously producing power (voltage output). Three different anodes were tested in MFC reactors: carbon black, activated carbon, and zinc electrodes. Movements in the MFC reactor during treatment were also a key factor for testing. Results showed a difference in ammonia levels in the three anodes used. The study compared the efficiency of static and dynamic modes of MFC in removing ammonia. Continual leachate movement in the reactor could increase the rate of removal of the ammonia components. The setup provided a viable condition for maximum removal because the reactor movement caused the sludge to disintegrate, which allowed ammonia to separate easily from the parent leachate. Ammonia removal also resulted from the transfer of ammonium through the membrane or from ammonia loss. Constant exchange of ionic content benefited the MFC performance by increasing power production and decreasing internal electrode material resistance. This paper presents the results of the analyses of leachate treatment from the solid waste landfill located in Padang Siding Landfill, Perlis. The performance of ammonia removal was enhanced using different types of electrodes. In both modes, activated carbon performed better than black carbon and zinc. The respective percentages of ammonia removal for activated carbon of dynamic over static were 96.6%, 66.6%, and 92.8% for activated carbon, zinc, and black carbon. The results provide further information on the possibility of using MFCs in landfill leachate treatment systems.

  13. Connecting Research to Teaching: Evaluating and Writing Dynamic Geometry Tasks

    Science.gov (United States)

    Trocki, Aaron

    2014-01-01

    The advent of dynamic geometry software has changed the way students draw, construct, and measure by using virtual tools instead of or along with physical tools. Use of technology in general and of dynamic geometry in particular has gained traction in mathematics education, as evidenced in the Common Core State Standards for Mathematics (CCSSI…

  14. 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

  15. Dynamic Performance Evaluation of a 2-DoF Planar Parallel Mechanism

    Directory of Open Access Journals (Sweden)

    Hao Qi

    2012-12-01

    Full Text Available The acceleration performance function and dynamic performance evaluation combining the acceleration, velocity, gravity and external force of a 2-DoF planar parallel mechanism are presented in this paper. By means of the principle of virtual work, the inverse dynamic model and acceleration performance function of the planar parallel mechanism are setup. Based on the factors in the acceleration performance function, the effect on the acceleration performance of parallel mechanisms is investigated. Then a new method considering the acceleration factor, velocity factor, gravity factor and external force factor for dynamic performance evaluation of the parallel mechanism is introduced, which can evaluate the dynamic performance of high-speed parallel mechanisms more exactly. Based on this method, the evaluation indices used in dynamic optimization are introduced. These indices overcome the limitation of commonly used indices, and lay the foundation for dynamic optimization of parallel mechanisms.

  16. An evaluation of the washout rate in dynamic CT

    International Nuclear Information System (INIS)

    Kawahara, Nobutaka; Sakamoto, Tetsuya; Tanaka, Hiroshi; Sasaki, Masaru; Aruga, Tohru; Mii, Koji; Takakura, Kintomo.

    1986-01-01

    The present authors compared the washout rate in dynamic CT with the mean transit time (MTT), which was calculated using the intra-arterial 99m Tc injection method, in order to evaluate the reliability of the washout rate. Nineteen patients were studied from April through December, 1984 (transit ischemic attack (TIA) and lacunar stroke without angiographical lesion : 9; major trunk stenotic lesions : 4; arteriovenous malformation : 1; subarachnoid hemorrhage : 1; thalamic hemorrhage : 2; brain tumor : 1; posterior fossa arteriosclerosis : 1). In all patients, the rapid washout rate was calculated from the CT number-time curve as the reduction rate of the CT number from the peak value in the rapid washout phase (100 x rapid washout/peak value/sec). The MTT was calculated in 16 patients by the height-over-area method following the intracarotid injection of 99m Tc-DTPA (20 - 30 mCi). These two indices (MTT, washout rate) were then compared, mainly in the perfusion area of the middle cerebral artery of the same hemisphere. Furthermore, regional cerebralblood-flow measurements were made in 9 patients using the 133 Xe intra-arterial injection method. The washout rate and the MTT in patients with TIA and lacunar stroke were 7.90 ± 1.70 %/s and 3.06 ± 0.37 sec respectively. In 3 out of 4 patients with major trunk lesions, the MTT was shortened after extracranial-intracranial bypass surgery, although 1 patient showed post-operative deterioration in the washout rate. The analysis between the MTT and the washout rate showed no statistically significant correlation, and the higher reliability of MTT was confirmed by the significant correlation with rCBF. (J.P.N.)

  17. Higher Cell Probe Lower Bounds for Evaluating Polynomials

    DEFF Research Database (Denmark)

    Larsen, Kasper Green

    2012-01-01

    In this paper, we study the cell probe complexity of evaluating an $n$-degree polynomial $P$ over a finite field $F$ of size at least $n^{1+Omega(1)}$. More specifically, we show that any static data structure for evaluating $P(x)$, where $x in F$, must use $Omega(lg |F|/lg(Sw/nlg|F|))$ cell probes...

  18. The nature and dynamics of spermatogonial stem cells

    NARCIS (Netherlands)

    de Rooij, Dirk G.

    2017-01-01

    Spermatogonial stem cells (SSCs) are crucial for maintaining spermatogenesis throughout life, and understanding how these cells function has important implications for understanding male infertility. Recently, various populations of cells harbouring stem cell-like properties have been identified in

  19. Computational fluid dynamics modeling of proton exchange membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    UM,SUKKEE; WANG,C.Y.; CHEN,KEN S.

    2000-02-11

    A transient, multi-dimensional model has been developed to simulate proton exchange membrane (PEM) fuel cells. The model accounts simultaneously for electrochemical kinetics, current distribution, hydrodynamics and multi-component transport. A single set of conservation equations valid for flow channels, gas-diffusion electrodes, catalyst layers and the membrane region are developed and numerically solved using a finite-volume-based computational fluid dynamics (CFD) technique. The numerical model is validated against published experimental data with good agreement. Subsequently, the model is applied to explore hydrogen dilution effects in the anode feed. The predicted polarization cubes under hydrogen dilution conditions are found to be in qualitative agreement with recent experiments reported in the literature. The detailed two-dimensional electrochemical and flow/transport simulations further reveal that in the presence of hydrogen dilution in the fuel stream, hydrogen is depleted at the reaction surface resulting in substantial kinetic polarization and hence a lower current density that is limited by hydrogen transport from the fuel stream to the reaction site.

  20. 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.

  1. Roles of membrane trafficking in plant cell wall dynamics

    Directory of Open Access Journals (Sweden)

    Kazuo eEbine

    2015-10-01

    Full Text Available The cell wall is one of the characteristic components of plant cells. The cell wall composition differs among cell types and is modified in response to various environmental conditions. To properly generate and modify the cell wall, many proteins are transported to the plasma membrane or extracellular space through membrane trafficking, which is one of the key protein transport mechanisms in eukaryotic cells. Given the diverse composition and functions of the cell wall in plants, the transport of the cell wall components and proteins that are involved in cell wall-related events could be specialized for each cell type, i.e., the machinery for cell wall biogenesis, modification, and maintenance could be transported via different trafficking pathways. In this review, we summarize the recent progress in the current understanding of the roles and mechanisms of membrane trafficking in plant cells and focus on the biogenesis and regulation of the cell wall.

  2. Raman spectral dynamics of single cells in the early stages of growth factor stimulation.

    Science.gov (United States)

    Takanezawa, Sota; Morita, Shin-ichi; Ozaki, Yukihiro; Sako, Yasushi

    2015-05-05

    Cell fates change dynamically in response to various extracellular signals, including growth factors that stimulate differentiation and proliferation. The processes underlying cell-fate decisions are complex and often include large cell-to-cell variations, even within a clonal population in the same environment. To understand the origins of these cell-to-cell variations, we must detect the internal dynamics of single cells that reflect their changing chemical milieu. In this study, we used the Raman spectra of single cells to trace their internal dynamics during the early stages of growth factor stimulation. This method allows nondestructive and inclusive time-series analyses of chemical compositions of the same single cells. Applying a Gaussian mixture model to the major principal components of the single-cell Raman spectra, we detected the dynamics of the chemical states in MCF-7 cancer-derived cells in the absence and presence of differentiation and proliferation factors. The dynamics displayed characteristic variations according to the functions of the growth factors. In the differentiation pathway, the chemical composition changed directionally between multiple states, including both reversible and irreversible state transitions. In contrast, in the proliferation pathway, the chemical composition was homogenized into a single state. The differentiation factor also stimulated fluctuations in the chemical composition, whereas the proliferation factor did not. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. 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.

  4. The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization.

    Directory of Open Access Journals (Sweden)

    Ghanim Ullah

    2015-08-01

    Full Text Available Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little of how cell volume affects neuronal dynamics. We here performed the first detailed study of the effects of cell volume on neuronal dynamics. By incorporating cell swelling together with dynamic ion concentrations and oxygen supply into Hodgkin-Huxley type spiking dynamics, we demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. Our use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial K buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia. We argue that the dynamics of seizures, spreading depression, and anoxic depolarization lie along a continuum of the repertoire of the neuron membrane that can be understood only when the dynamic ion concentrations, oxygen homeostasis,and cell swelling in response to osmotic pressure are taken into consideration. Our results demonstrate the feasibility of a unified framework for a wide range of neuronal behaviors that may be of substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states.

  5. A Comprehensive Fluid Dynamic-Diffusion Model of Blood Microcirculation with Focus on Sickle Cell Disease

    Science.gov (United States)

    Le Floch, Francois; Harris, Wesley L.

    2009-11-01

    A novel methodology has been developed to address sickle cell disease, based on highly descriptive mathematical models for blood flow in the capillaries. Our investigations focus on the coupling between oxygen delivery and red blood cell dynamics, which is crucial to understanding sickle cell crises and is unique to this blood disease. The main part of our work is an extensive study of blood dynamics through simulations of red cells deforming within the capillary vessels, and relies on the use of a large mathematical system of equations describing oxygen transfer, blood plasma dynamics and red cell membrane mechanics. This model is expected to lead to the development of new research strategies for sickle cell disease. Our simulation model could be used not only to assess current researched remedies, but also to spur innovative research initiatives, based on our study of the physical properties coupled in sickle cell disease.

  6. Evaluation of a dynamic dissolution/permeation model

    DEFF Research Database (Denmark)

    Sironi, Daniel; Christensen, Mette; Rosenberg, Jörg

    2017-01-01

    -steady state). To this end, a model case was construed: compacts of pure crystalline hydrocortisone methanolate (HC·MeOH) of slow release rates were prepared, and their dissolution and permeation determined simultaneously in a side-by-side setup, separated by a biomimetic barrier (Permeapad...... dissolution rate and flux influenced each other. Interestingly, for all the dynamic scenarios, the incremental flux values obtained correlated nicely with the corresponding actual donor concentrations. Furthermore, donor depletion was tested using a HC solution. The dynamic interplay between decrease in donor...

  7. EVALUATION OF METALLIC MATERIALS PLASTICITY BY DYNAMIC INDENTATION METHOD

    Directory of Open Access Journals (Sweden)

    V. A. Rudnitsky

    2017-01-01

    Full Text Available The method of plasticity test of metallic materials realized by means of a dynamic dimpling of material by a spherical tip is offered. The measured value of plasticity is defined by a ratio of plastic and complete deformations in the formed indentation which considers influence of an elastic modulus of material. The dependence connecting plasticity and dynamic hardness of materials is received. Experiments on metals from 70 to 380 GPA having an elastic modulus and hardness up to 62 HRC are made.

  8. Dynamic MRI of parathyroid tumors in preoperative evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Seiji; Takano, Hideyuki; Ito, Hisao [Chiba Univ. (Japan). School of Medicine] [and others

    2000-08-01

    Dynamic MRI was compared to enhanced CT and Tc-99m MIBI, in detection of the parathyroid tumors. STIR MR images achieved higher detectability than enhanced CT or Tc-99m MIBI. Time intensity curves were also drawn in the dynamic MRI. A case of adenocarcinoma showed rapid increase and following gradual decrease in intensity, which pattern is considered as malignant in many tumors of the other organs. However, it was not easy to differentiate parathyroid adenomas from thyroid gland or tumors. MRI was considered as one of the useful methods in detection of the parathyroid tumors. MRI may be useful in searching of heterotopic parathyroid tumors. (author)

  9. Modelling and Simulation of the Dynamics of the Antigen-Specific T Cell Response Using Variable Structure Control Theory.

    Directory of Open Access Journals (Sweden)

    Anet J N Anelone

    Full Text Available Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control. In particular, it is shown that the robustness properties of the specific T cell response as observed in experiments can be explained analytically using a VSC perspective. Further, the predictive capacity of the VSC framework to determine the T cell help required to overcome chronic Lymphocytic Choriomeningitis Virus (LCMV infection is demonstrated. The findings demonstrate that studying the immune system using variable structure control theory provides a new framework for evaluating immunological dynamics and experimental observations. A modelling and simulation tool results with predictive capacity to determine how to modify the immune response to achieve healthy outcomes which may have application in drug development and vaccine design.

  10. Modelling and Simulation of the Dynamics of the Antigen-Specific T Cell Response Using Variable Structure Control Theory.

    Science.gov (United States)

    Anelone, Anet J N; Spurgeon, Sarah K

    2016-01-01

    Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC) law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control. In particular, it is shown that the robustness properties of the specific T cell response as observed in experiments can be explained analytically using a VSC perspective. Further, the predictive capacity of the VSC framework to determine the T cell help required to overcome chronic Lymphocytic Choriomeningitis Virus (LCMV) infection is demonstrated. The findings demonstrate that studying the immune system using variable structure control theory provides a new framework for evaluating immunological dynamics and experimental observations. A modelling and simulation tool results with predictive capacity to determine how to modify the immune response to achieve healthy outcomes which may have application in drug development and vaccine design.

  11. Modelling and Simulation of the Dynamics of the Antigen-Specific T Cell Response Using Variable Structure Control Theory

    Science.gov (United States)

    2016-01-01

    Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC) law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control. In particular, it is shown that the robustness properties of the specific T cell response as observed in experiments can be explained analytically using a VSC perspective. Further, the predictive capacity of the VSC framework to determine the T cell help required to overcome chronic Lymphocytic Choriomeningitis Virus (LCMV) infection is demonstrated. The findings demonstrate that studying the immune system using variable structure control theory provides a new framework for evaluating immunological dynamics and experimental observations. A modelling and simulation tool results with predictive capacity to determine how to modify the immune response to achieve healthy outcomes which may have application in drug development and vaccine design. PMID:27861537

  12. Dynamic Simulation of a Proton Exchange Membrane Fuel Cell System For Automotive Applications

    DEFF Research Database (Denmark)

    Rabbani, Raja Abid; Rokni, Masoud

    2012-01-01

    A dynamic model of the PEMFC system is developed to investigate the behaviour and transient response of the fuel cell system for automotive applications. The system accounts for the fuel cell stack with coolant, humidifier, heat exchangers and pumps. Governing equations for fuel cell and humidifier...

  13. Dynamic echocardiography in evaluation of platypnoea?orthodeoxia

    OpenAIRE

    Yastrebov, Konstantin; Sader, Mark; Youssef, George; Nojoumian, Haidy

    2015-01-01

    Platypnoea?orthodeoxia is an infrequent syndrome that is usually associated with positional intracardiac right?to?left shunting. The authors report the case of a patient who presented with deteriorating severe dyspnoea and deoxygenation in the upright position that was partially relieved by recumbent repositioning. Dynamic echocardiography provided insight into the underlying anatomical and pathophysiological mechanisms as well as guidance for definitive therapy.

  14. An Evaluation of Dynamic Web Service Composition Approaches

    NARCIS (Netherlands)

    Khadka, Ravi; van Sinderen, M.J.; van Sinderen, Marten J.; Sapkota, B.; Sapkota, Brahmananda

    2010-01-01

    Web Services composition has received much interest from both the academic researchers and industry to support cross-enterprise application integration. Promising research projects and their prototypes are being developed. At the same time the web service environment is getting more dynamic as

  15. 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.

  16. Evaluation of dynamic fracture toughness for Yong Gwang unit 5 reactor pressure vessel materials (Baseline Tests)

    Energy Technology Data Exchange (ETDEWEB)

    Chi Se Hwan; Kim, Joo Hag; Hong, Jun Hwa; Kwon, Sun Chil; Lee, Bong Sang [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-10-01

    The dynamic fracture toughness (K{sub d}) of intermediate shell and its weld in SA 508 CI. 3 Yong Gwang 5 reactor pressure vessel was determined and evaluated. Precracked thirty six Charpy specimens were tested by using an instrumented impact tester. The purpose of present work is to evaluate and confirm the un-irradiated dynamic fracture toughness and to provide pre-irradiation baseline data for future evaluation on dynamic fracture toughness change during operation. 18 refs., 5 figs., 5 tabs. (Author)

  17. Static and Dynamic Facial Cues Differentially Affect the Consistency of Social Evaluations.

    Science.gov (United States)

    Hehman, Eric; Flake, Jessica K; Freeman, Jonathan B

    2015-08-01

    Individuals are quite sensitive to others' appearance cues when forming social evaluations. Cues such as facial emotional resemblance are based on facial musculature and thus dynamic. Cues such as a face's structure are based on the underlying bone and are thus relatively static. The current research examines the distinction between these types of facial cues by investigating the consistency in social evaluations arising from dynamic versus static cues. Specifically, across four studies using real faces, digitally generated faces, and downstream behavioral decisions, we demonstrate that social evaluations based on dynamic cues, such as intentions, have greater variability across multiple presentations of the same identity than do social evaluations based on static cues, such as ability. Thus, although evaluations of intentions vary considerably across different instances of a target's face, evaluations of ability are relatively fixed. The findings highlight the role of facial cues' consistency in the stability of social evaluations. © 2015 by the Society for Personality and Social Psychology, Inc.

  18. Dynamics of NKT-Cell Responses to Chlamydial Infection.

    Science.gov (United States)

    Shekhar, Sudhanshu; Joyee, Antony George; Yang, Xi

    2015-01-01

    Natural killer T (NKT) cells have gained great attention owing to their critical functional roles in immunity to various pathogens. In this review, we provide an overview of the current knowledge on the role of NKT cells in host defense against and pathogenesis due to Chlamydia, which is an intracellular bacterial pathogen that poses a threat to the public health worldwide. Accumulating evidence has demonstrated that NKT cells, particularly invariant NKT (iNKT) cells, play a crucial role in host defense against chlamydial infections, especially in C. pneumoniae infection. iNKT cells can promote type-1 protective responses to C. pneumoniae by inducing enhanced production of IL-12 by dendritic cells (DCs), in particular CD8α+ DCs, which promote the differentiation of naive T cells into protective IFN-γ-producing Th1/Tc1 type CD4+/CD8+ T cells. This iNKT-cell-mediated modulation of DC function is largely dependent upon CD40-CD40L interaction, IFN-γ production, and cell-to-cell contact. In addition, iNKT cells modulate the function of natural killer cells. NKT cells may be also involved in the pathogenesis of some chlamydial diseases by inducing different patterns of cytokine production. A better understanding of NKT-cell biology will enable us to rationally design prophylactic and therapeutic tools to combat infectious diseases.

  19. Measuring the Dynamic Parameters of MCF7 Cell Microtubules

    Science.gov (United States)

    Winton, Carly; Shojania Feizabadi, Mitra

    2013-03-01

    Microtubules are the key component of the cytoskeleton. They are intrinsically dynamic displaying dynamic instability in which they randomly switch between a phase of growing and shrinking, both in vitro and in vivo. This dynamic is specified by the following parameters: growing rate, shrinking rate, frequency of catastrophe, and frequency of rescue. In this work, we will present our primary results in which we measured the dynamic parameters of a single microtubule polymerized from MCF7 tubulin in vitro. The results are significant since the MCF7 microtubules are non-neural mammalian consisting of different beta tubulin isotypes in their structures as compared to neural mammalian microtubules, such as bovine brain. The unique dynamic parameters of individual MCF7 microtubules in vitro, which are reported for the first time, indicate that non-neural microtubules can be fundamentally different from neural microtubules.

  20. 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.

  1. 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)

  2. Dynamics of dye release from nanocarriers of different types in model cell membranes and living cells

    Directory of Open Access Journals (Sweden)

    Tkacheva T. N.

    2014-07-01

    Full Text Available Aim. To study the dynamics of lipophilic content release from nanocarriers of different types, organic molecular ensembles and inorganic nanoparticles (NPs in vitro experiments. Methods. Two-channel ratiometric fluorescence detection method based on Forster Resonance Energy Transfer, fluorescent spectroscopy and micro-spectroscopy have been used. Results. It has been found that the profiles of lipophilic dyes release from organic nanocarriers (PC liposomes and SDS micelles and inorganic ones (GdYVO4:Eu3+ and CeO2 NPs are well fitted by the first-order reaction kinetics in both model cell membranes and living cells (rat hepatocytes. The dye release constants (K and half-lives (t1/2 were analyzed. Conclusions. GdYVO4:Eu3+ and CeO2 NPs have been shown to provide faster lipophilic content release in model cell membranes as compared to PC liposomes. Negatively charged or lipophilic compounds added into nanocarriers can decrease the rate of lipophilic dyes release. Specific interaction of GdYVO4:Eu3+ NPs with rat hepatocytes has been observed.

  3. Evaluating the use of cell phone messaging for community Ebola ...

    African Journals Online (AJOL)

    community Ebola syndromic surveillance cell phone alert system by the Moyamba District Health Management Team in ... Cite as: Jia K, Mohamed K. Evaluating the use of cell phone messaging for community Ebola syndromic surveillance in high risked settings in ... The first case of Ebola Hemorrhagic Fever (EHF) in Si-.

  4. Investigation of dynamic morphological changes of cancer cells during photoimmuno therapy (PIT) by low-coherence quantitative phase microscopy

    Science.gov (United States)

    Ogawa, Mikako; Yamauchi, Toyohiko; Iwai, Hidenao; Magata, Yasuhiro; Choyke, Peter L.; Kobayashi, Hisataka

    2014-03-01

    We have reported a new molecular-targeted cancer phototherapy, photoimmunotherapy (PIT), which killed implanted tumors in mice without side-effects. To understand the mechanism of cell killing with PIT, three-dimentional dynamic low-coherence quantitative phase microscopy (3D LC-QPM), a device developed by Hamamatsu Photonics K.K, was used to detect morphologic changes in cancer cells during PIT. 3T3/HER2 cells were incubated with anti-HER2 trastuzumab-IR700 (10 μg/mL, 0.1 μM as IR700) for 24 hours, then, three-dimensionally imaged with the LC-QPM during the exposure of two different optically filtered lights for excitation of IR700 (500-780 nm) and imaging (780-950 nm). For comparison with traditional PDT, the same experiments were performed with Photofrin (10 and 1 μM). Serial changes in the cell membrane were readily visualized on 3D LC-QPM. 3T3/HER2 cells began to swell rapidly after exposure to 500-780 nm light excitation. The cell volume reached a maximum within 1 min after continuous exposure, and then the cells appeared to burst. This finding suggests that PIT damages the cell membrane by photo-reaction inducing an influx of water into the cell causing swelling and bursting of the cells. Interestingly, even after only 5 seconds of light exposure, the cells demonstrated swelling and bursting albeit more slowly, implying that sufficient cumulative damage occurs on the cell membrane to induce lethal damage to cells even at minimal light exposure. Similar but non-selective membrane damage was shown in PDT-treated cells Photofrin. Thus, PIT induces sufficient damage to the cell membrane within 5 seconds to induce rapid necrotic cell death which can be observed directly with 3D LC-QPM. Further investigation is needed to evaluate the biochemical mechanisms underlying PIT-induced cellular membrane damage.

  5. Endogenous Ion Dynamics in Cell Motility and Tissue Regeneration

    International Nuclear Information System (INIS)

    Özkucur, N; Perike, S; Epperlein, H H; Funk, R H W

    2011-01-01

    Directional cell migration is an essential process, including regeneration of tissues, wound healing, and embryonic development. Cells achieve persistent directional migration by polarizing the spatiotemporal components involved in the morphological polarity. Ion transporter proteins situated at the cell membrane generates small electric fields that can induce directional cell motility. Besides them, externally applied direct current electric fields induce similar kind of responses as cell orientation and directional migration. However, the bioelectric mechanisms that lead to cellular directedness are poorly understood. Therefore, understanding the bioelectric signaling cues can serve as a powerful modality in controlling the cell behaviour, which can contribute additional insights for development and regeneration.

  6. Feasibility of dynamic MRI for evaluating velopharyngeal insufficiency in children

    International Nuclear Information System (INIS)

    Drissi, C.; Mitrofanoff, M.; Talandier, C.; Falip, C.; Couls, V. le; Adamsbaum, C.

    2011-01-01

    To demonstrate the feasibility of dynamic MRI with near-real-time temporal resolution for analysing velopharyngeal closure. Eleven children and young adults (seven girls, four boys, mean age: 8.4 years) with suspected velopharyngeal insufficiency (VPI), and one healthy volunteer underwent MRI (1.5 Tesla) using T2 fast imaging sequences. Imaging was done without any sedation at rest and during various phonations in the axial and sagittal planes. Images were analysed by two radiologists, a plastic surgeon and a speech therapist. The MRI examinations were well tolerated by even the youngest patient. A qualitative analysis found that the sagittal dynamic sequences during phonation were in relation to the clinical data in all patients. A quantitative analysis enabled calculation of the elevation angle of the soft palate in relation to the hard palate, the velar eminence angle and the percentage of reduction of the antero-posterior diameter of the pharyngeal lumen. Dynamic MRI is a non-invasive, rapid and repeatable method. It can be considered a complementary tool to endoscopy and fluoroscopy, particularly in children, for assessing VPI without any sedation or radiation exposure. (orig.)

  7. Large stationary fuel cell systems: Status and dynamic requirements

    Science.gov (United States)

    Bischoff, Manfred

    Molten carbonate fuel cell demonstrations to-date, have been able to show the highest fuel-to-electricity conversion efficiencies (>50%) of any stand-alone fuel cell type. The primary developer of this type of fuel cell in United States is Fuel Cell Energy Corporation (FCE), the developer and manufacturer of the Direct FuelCell ™ concept. FCE and MTU CFC Solutions in Germany, a licensee of FCE have demonstrated carbonate fuel cells from 10 kW to 2 MW of electrical output on a variety of fuels. IHI in Japan are also developing carbonate fuel cells for stationary power and have recently successfully demonstrated the technology in Kawagoe, Japan. In Italy, Ansaldo fuel cell have demonstrated a 100 kW carbonate fuel cell in Milan. In Korea, the Ministry of Commerce, Industry and Energy has committed to install 300 fuel cell units, sized 250 kW to 1 MW, for distributed power generation by 2012. Carbonate fuel cell technology is more fuel flexible than lower temperature fuel cell technologies and is well suited for on-site stationary CHP applications as well as to marine, military, and traction applications. The present paper gives an overview about the commercialisation efforts for the molten carbonate fuel cell technology.

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

    Energy Technology Data Exchange (ETDEWEB)

    Xie Yong E-mail: xie813@263.net; Xu Jianxue; Hu Sanjue; Kang Yanmei; Yang Hongjun; Duan Yubin

    2004-10-01

    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.

  9. Dynamic properties of independent chromatin domains measured by correlation spectroscopy in living cells.

    NARCIS (Netherlands)

    M. Wachsmuth (Malte); T.A. Knoch (Tobias); K. Rippe (Karsten)

    2016-01-01

    textabstractBackground: Genome organization into subchromosomal topologically associating domains (TADs) is linked to cell-type-specific gene expression programs. However, dynamic properties of such domains remain elusive, and it is unclear how domain plasticity modulates genomic accessibility for

  10. 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.

  11. Primer and interviews: The dynamic stem cell niche.

    Science.gov (United States)

    Kiefer, Julie C

    2011-03-01

    A stem cell niche is a microenvironment that supports self-renewal of a population of stem cells, and their production of differentiated cells. While the definition evokes images of a stem cell Shangri-La-where a serene stem cell pool nestles within a niche that shelters and sustains it-the reality is much more tumultuous. Niches are subject to an ever-changing maelstrom of environmental factors, the ravages of old age, and the sly tactics of disease. Presented here is a basic overview of the different ways in which stem cell niches respond to local and systemic environments, and their impact on stem cell behavior. The primer culminates with a discussion of the topic with stem cell and niche biologists D. Leanne Jones, Ph.D., and Tudorita Tumbar, Ph.D. Copyright © 2011 Wiley-Liss, Inc.

  12. Evaluation of a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay (Keystone Sym)

    Science.gov (United States)

    Our goal is to establish an in vitro model system to evaluate chemical effects using a single stem cell culture technique that would improve throughput and provide quantitative markers of differentiation and cell number. To this end, we have used an adherent cell differentiation ...

  13. Plant cortical microtubule dynamics and cell division plane orientation

    NARCIS (Netherlands)

    Chakrabortty, Bandan

    2017-01-01

    This thesis work aimed at a better understanding of the molecular basis of oriented cell division in plant cell. As, the efficiency of plant morphogenesis depends on oriented cell division, this work should contribute  towards a fundamental understanding of the  molecular basis of

  14. Cell state switching factors and dynamical patterning modules ...

    Indian Academy of Sciences (India)

    Prakash

    this, other DPMs (defined as physical forces and processes pertinent to the scale of the aggregates mobilized by a ... Adhesion; cell polarity; lateral inhibition; physical mechanisms of morphogenesis ...... micromass culture of 5-day leg bud apical zone limb mesenchymal cells, visualized by staining with Alcian blue. The cells ...

  15. T-cell dynamics in chronic viral infection

    NARCIS (Netherlands)

    Veel, E.M.

    2014-01-01

    In this thesis we investigate how chronic HIV and CMV infections impact on the human T-cell compartment. How untreated HIV infection affects the turnover of human CD4+ and CD8+ T cells is described in chapter 2. In this chapter, T-cell turnover in untreated HIV infected individuals is compared to

  16. Dynamic Thermal Model And Control Of A Pem Fuel Cell System

    DEFF Research Database (Denmark)

    Liso, Vincenzo; Nielsen, Mads Pagh

    2013-01-01

    A lumped parameter dynamic model is developed for predicting the stack performance, temperatures of the exit reactant gases and coolant liquid outlet in a proton-exchange membrane fuel cell (PEMFC) system. The air compressor, humidifier and cooling heat exchanger models are integrated to study...... the performance of the thermal system, especially when investigating applications that have highly dynamic operating conditions....

  17. Manganese induces mitochondrial dynamics impairment and apoptotic cell death: a study in human Gli36 cells.

    Science.gov (United States)

    Alaimo, Agustina; Gorojod, Roxana M; Miglietta, Esteban A; Villarreal, Alejandro; Ramos, Alberto J; Kotler, Mónica L

    2013-10-25

    Manganese (Mn) is an essential trace element due to its participation in many physiological processes. However, overexposure to this metal leads to a neurological disorder known as Manganism whose clinical manifestations and molecular mechanisms resemble Parkinson's disease. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity being the mitochondria the most affected organelles. The aim of this study was to investigate the possible mitochondrial dynamics alterations in Mn-exposed human astrocytes. Therefore, we employed Gli36 cells which express the astrocytic markers GFAP and S100B. We demonstrated that Mn triggers the mitochondrial apoptotic pathway revealed by increased Bax/Bcl-2 ratio, by the loss of mitochondrial membrane potential and by caspase-9 activation. This apoptotic program may be in turn responsible of caspase-3/7 activation, PARP-1 cleavage, chromatin condensation and fragmentation. In addition, we determined that Mn induces deregulation in mitochondria-shaping proteins (Opa-1, Mfn-2 and Drp-1) expression levels in parallel with the disruption of the mitochondrial network toward to an exacerbated fragmentation. Since mitochondrial dynamics is altered in several neurodegenerative diseases, these proteins could become future targets to be considered in Manganism treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Chaotic Dynamics of Red Blood Cells in a Sinusoidal Flow

    Science.gov (United States)

    Dupire, Jules; Abkarian, Manouk; Viallat, Annie

    2010-04-01

    We show that the motion of individual red blood cells in an oscillating moderate shear flow is described by a nonlinear system of three coupled oscillators. Our experiments reveal that the cell tank treads and tumbles either in a stable way with synchronized cell inclination, membrane rotation and hydrodynamic oscillations, or in an irregular way, very sensitively to initial conditions. By adapting our model described previously, we determine the theoretical diagram for the red cell motion in a sinusoidal flow close to physiological shear stresses and flow variation frequencies and reveal large domains of chaotic motions. Finally, fitting our observations allows a characterization of cell viscosity and membrane elasticity.

  19. Optimization of cell motility evaluation in scratch assay

    Directory of Open Access Journals (Sweden)

    Gotsulyak N. Ya.

    2014-05-01

    Full Text Available A scratch test is one of the most popular methods of classical cell migration assay in a monolayer culture. At the same time, the scratch assay has some disadvantages that can be easily corrected. Aim. Optimization the existent scratch assay on the base of detection of scratch wound surface area and the length of the field of observation which is more objective and less time consuming. Methods. Scratch assay. Results. The modification of scratch assay enables to perform measurement more accurately and rapidly. This approach is more simple and eliminates the main disadvantages of the classical method. Conclusions. The procedure of scratch wound width measurement calculated on the base of detection of cell free area and the length of the field of observation is more effective than the classical wound healing assay. It will be useful for the estimation of cell migration dynamics in monolayer culture for a wide range of live cell based experiments.

  20. 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

  1. 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

  2. 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

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

    Science.gov (United States)

    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.

  4. 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

  5. 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.

  6. Probabilistic evaluation approach for nonlinear vehicle-bridge dynamic performances

    Science.gov (United States)

    Jin, Zhibin; Pei, Shiling; Li, Xiaozhen; Qiang, Shizhong

    2015-03-01

    Railroad vehicle and bridge coupled lateral vibration problems are traditionally solved through detailed nonlinear models in time domain using limited samples to represent rail irregularity. Ideally, a random vibration and reliability based approach should be implemented because of the random nature of the excitation process. In this study, vehicle-bridge coupled dynamic equation was derived using the principle of virtual work utilizing a linearized wheel-rail contact equation. This simplification enables the calculation of the system random lateral responses through the pseudo-excitation method. By applying rail irregularity as random excitations to the system, this study utilized an explicit linearization method to avoid iterative solution at each time step of the integration. The results from the linearized method were validated through comparison with results obtained from Monte-Carlo simulations. By applying the linearized approach to probabilistic assessment of the vehicle-bridge system reliability, it was shown that system probability of exceedance of admissible limits increases with train speed and reduces with increased bridge self-weight. It is concluded that the proposed approach provides a viable efficient alternative to investigate the random dynamic characteristics of vehicle-bridge system especially in the lateral direction, which is dominated by the random rail irregularities.

  7. Dynamic Performance Characteristic Tests of Real Scale Lead Rubber Bearing for the Evaluation of Performance Criteria

    International Nuclear Information System (INIS)

    Kim, Min Kyu; Kim, Jung-Han; Choi, In-Kil

    2014-01-01

    Dynamic characteristic tests of full scale lead rubber bearing were performed for the evaluation of performance criteria of isolation system for nuclear power plants. For the dynamic test for a full scale rubber bearing, two 1500mm diameter lead rubber bearings were manufactured. The viewpoints of this dynamic test are determination of an ultimate shear strain level of lead rubber bearing, behavior of rubber bearing according to static and dynamic input motion, sinusoidal and random (earthquake) motion, and 1-dimentional and 2-dimensional input motion. In this study, seismic isolation device tests were performed for the evaluation of performance criteria of isolation system. Through this test, it can be recognized that in the case of considering a mechanical property test, dynamic and multi degree of loading conditions should be determined. But these differences should be examined how much affect to the global structural behavior

  8. BC Transit Fuel Cell Bus Project: Evaluation Results Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-02-01

    This report evaluates a fuel cell electric bus demonstration led by British Columbia Transit (BC Transit) in Whistler, Canada. BC Transit is collaborating with the California Air Resources Board and the U.S. Department of Energy's National Renewable Energy Laboratory to evaluate the buses in revenue service. This evaluation report covers two years of revenue service data on the buses from April 2011 through March 2013.

  9. Improving dynamic performance of proton-exchange membrane fuel cell system using time delay control

    Science.gov (United States)

    Kim, Young-Bae

    Transient behaviour is a key parameter for the vehicular application of proton-exchange membrane (PEM) fuel cell. The goal of this presentation is to construct better control technology to increase the dynamic performance of a PEM fuel cell. The PEM fuel cell model comprises a compressor, an injection pump, a humidifier, a cooler, inlet and outlet manifolds, and a membrane-electrode assembly. The model includes the dynamic states of current, voltage, relative humidity, stoichiometry of air and hydrogen, cathode and anode pressures, cathode and anode mass flow rates, and power. Anode recirculation is also included with the injection pump, as well as anode purging, for preventing anode flooding. A steady-state, isothermal analytical fuel cell model is constructed to analyze the mass transfer and water transportation in the membrane. In order to prevent the starvation of air and flooding in a PEM fuel cell, time delay control is suggested to regulate the optimum stoichiometry of oxygen and hydrogen, even when there are dynamical fluctuations of the required PEM fuel cell power. To prove the dynamical performance improvement of the present method, feed-forward control and Linear Quadratic Gaussian (LQG) control with a state estimator are compared. Matlab/Simulink simulation is performed to validate the proposed methodology to increase the dynamic performance of a PEM fuel cell system.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. Statistical dynamics of spatial-order formation by communicating cells

    OpenAIRE

    Olimpio, Eduardo P.; Dang, Yiteng; Youk, Hyun

    2017-01-01

    Communicating cells can coordinate their gene expressions to form spatial patterns. 'Secrete-and-sense cells' secrete and sense the same molecule to do so and are ubiquitous. Here we address why and how these cells, from disordered beginnings, can form spatial order through a statistical mechanics-type framework for cellular communication. Classifying cellular lattices by 'macrostate' variables - 'spatial order paramete' and average gene-expression level - reveals a conceptual picture: cellul...

  14. Dissecting mechanisms of mouse embryonic stem cells heterogeneity through a model-based analysis of transcription factor dynamics.

    Science.gov (United States)

    Herberg, Maria; Glauche, Ingmar; Zerjatke, Thomas; Winzi, Maria; Buchholz, Frank; Roeder, Ingo

    2016-04-01

    Pluripotent mouse embryonic stem cells (mESCs) show heterogeneous expression levels of transcription factors (TFs) involved in pluripotency regulation, among them Nanog and Rex1. The expression of both TFs can change dynamically between states of high and low activity, correlating with the cells' capacity for self-renewal. Stochastic fluctuations as well as sustained oscillations in gene expression are possible mechanisms to explain this behaviour, but the lack of suitable data hampered their clear distinction. Here, we present a systems biology approach in which novel experimental data on TF heterogeneity is complemented by an agent-based model of mESC self-renewal. Because the model accounts for intracellular interactions, cell divisions and heredity structures, it allows for evaluating the consistency of the proposed mechanisms with data on population growth and on TF dynamics after cell sorting. Our model-based analysis revealed that a bistable, noise-driven network model fulfils the minimal requirements to consistently explain Nanog and Rex1 expression dynamics in heterogeneous and sorted mESC populations. Moreover, we studied the impact of TF-related proliferation capacities on the frequency of state transitions and demonstrate that cellular genealogies can provide insights into the heredity structures of mESCs. © 2016 The Author(s).

  15. A durable and biocompatible ascorbic acid-based covalent coating method of polydimethylsiloxane for dynamic cell culture.

    Science.gov (United States)

    Leivo, Joni; Virjula, Sanni; Vanhatupa, Sari; Kartasalo, Kimmo; Kreutzer, Joose; Miettinen, Susanna; Kallio, Pasi

    2017-07-01

    Polydimethylsiloxane (PDMS) is widely used in dynamic biological microfluidic applications. As a highly hydrophobic material, native PDMS does not support cell attachment and culture, especially in dynamic conditions. Previous covalent coating methods use glutaraldehyde (GA) which, however, is cytotoxic. This paper introduces a novel and simple method for binding collagen type I covalently on PDMS using ascorbic acid (AA) as a cross-linker instead of GA. We compare the novel method against physisorption and GA cross-linker-based methods. The coatings are characterized by immunostaining, contact angle measurement, atomic force microscopy and infrared spectroscopy, and evaluated in static and stretched human adipose stem cell (hASC) cultures up to 13 days. We found that AA can replace GA as a cross-linker in the covalent coating method and that the coating is durable after sonication and after 6 days of stretching. Furthermore, we show that hASCs attach and proliferate better on AA cross-linked samples compared with physisorbed or GA-based methods. Thus, in this paper, we provide a new PDMS coating method for studying cells, such as hASCs, in static and dynamic conditions. The proposed method is an important step in the development of PDMS-based devices in cell and tissue engineering applications. © 2017 The Author(s).

  16. 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.

  17. Evaluating management regimes for European beech forests using dynamic programming

    Directory of Open Access Journals (Sweden)

    Juan Torres Rojo

    2014-12-01

    Full Text Available Aim of study: This contribution describes a systematic search method for identifying optimum thinning regimes for beech forests (Fagus sylvatica L. by using a combination of optimization heuristics and a simple whole stand growth prediction model. Area of study: Data to build the model come from standard and management forest inventories as well as yield tables from the Northern and Western part of Germany and from southern and central Denmark.Material and Methods: Growth projections are made from equations to project basal area and top height.  The remaining stand variables are recovered from additional equations fitted from forest inventory data or acquired from other authors.  Mortality is estimated through an algorithm based on the maximum density line. The optimization routine uses a two-state dynamic programming model. Thinning type is defined by the NG index, which describes the ratio of the proportion of removed trees and basal area with respect to the same proportion  before thinning. Main results: Growth equations fitted from inventory data show high goodness of fit with R2 values larger than 0.85 and high significance levels for the parameter estimates. The mortality algorithm converges quickly providing mortality estimates within the expected range.Research Highlights: The combination of a simple growth and yield model within a Dynamic Programming framework in conjunction with NG values as indicators of thinning type yield good estimates of practical thinning schedules compared to thinning recommendations provided by diverse authors.Keywords: beech (Fagus sylvatica L.; NG ratio; thinning optimization; growth and yield simulation; mortality.

  18. Nonlinear dynamics of the membrane potential of a bursting pacemaker cell

    Science.gov (United States)

    González-Miranda, J. M.

    2012-03-01

    This article presents the results of an exploration of one two-parameter space of the Chay model of a cell excitable membrane. There are two main regions: a peripheral one, where the system dynamics will relax to an equilibrium point, and a central one where the expected dynamics is oscillatory. In the second region, we observe a variety of self-sustained oscillations including periodic oscillation, as well as bursting dynamics of different types. These oscillatory dynamics can be observed as periodic oscillations with different periodicities, and in some cases, as chaotic dynamics. These results, when displayed in bifurcation diagrams, result in complex bifurcation structures, which have been suggested as relevant to understand biological cell signaling.

  19. 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.

  20. Power output and carrier dynamics studies of perovskite solar cells under working conditions.

    Science.gov (United States)

    Yu, Man; Wang, Hao-Yi; Hao, Ming-Yang; Qin, Yujun; Fu, Li-Min; Zhang, Jian-Ping; Ai, Xi-Cheng

    2017-08-02

    Perovskite solar cells have emerged as promising photovoltaic systems with superb power conversion efficiency. For the practical application of perovskite devices, the greatest concerns are the power output density and the related dynamics under working conditions. In this study, the working conditions of planar and mesoscopic perovskite solar cells are simulated and the power output density evolutions with the working voltage are highlighted. The planar device exhibits higher capability of outputting power than the mesoscopic one. The transient photoelectric conversion dynamics are investigated under the open circuit, short circuit and working conditions. It is found that the power output and dynamic processes are correlated intrinsically, which suggests that the power output is the competitive result of the charge carrier recombination and transport. The present work offers a unique view to elucidating the relationship between the power output and the charge carrier dynamics for perovskite solar cells in a comprehensive manner, which would be beneficial to their future practical applications.

  1. Multivariable control system for dynamic PEM fuel cell model

    International Nuclear Information System (INIS)

    Tanislav, Vasile; Carcadea, Elena; Capris, Catalin; Culcer, Mihai; Raceanu, Mircea

    2010-01-01

    Full text: The main objective of this work was to develop a multivariable control system of robust type for a PEM fuel cells assembly. The system will be used in static and mobile applications for different values of power, generated by a fuel cell assembly of up to 10 kW. Intermediate steps were accomplished: a study of a multivariable control strategy for a PEM fuel cell assembly; a mathematic modeling of mass and heat transfer inside of fuel cell assembly, defining the response function to hydrogen and oxygen/air mass flow and inlet pressure changes; a testing stand for fuel cell assembly; experimental determinations of transient response for PEM fuel cell assembly, and more others. To define the multivariable control system for a PEM fuel cell assembly the parameters describing the system were established. Also, there were defined the generic mass and energy balance equations as functions of derivative of m i , in and m i , out , representing the mass going into and out from the fuel cell, while Q in is the enthalpy and Q out is the enthalpy of the unused reactant gases and heat produced by the product, Q dis is the heat dissipated to the surroundings, Q c is the heat taken away from the stack by active cooling and W el is the electricity generated. (authors)

  2. Phosphorylation dynamics during early differentiation of human embryonic stem cells

    NARCIS (Netherlands)

    van Hoof, D.; Munoz, J.; Braam, S.R.; Pinkse, M.W.H.; Linding, R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2009-01-01

    Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during

  3. Dynamic changes in mouse hematopoietic stem cell numbers during aging

    NARCIS (Netherlands)

    de Haan, G; Van Zant, G

    1999-01-01

    To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The

  4. Mapping of spatiotemporal heterogeneous particle dynamics in living cells

    NARCIS (Netherlands)

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

    2009-01-01

    Colloidal particles embedded in the cytoplasm of living mammalian cells have been found to display remarkable heterogeneity in their amplitude of motion. However, consensus on the significance and origin of this phenomenon is still lacking. We conducted experiments on Hmec-1 cells loaded with about

  5. Flagellar waveform dynamics of freely swimming algal cells

    NARCIS (Netherlands)

    Kurtuldu, H.; Tam, D.; Hosoi, A.E.; Johnson, K.A.; Gollub, J.P.

    2013-01-01

    We present quantitative measurements of time-dependent flagellar waveforms for freely swimming biflagellated algal cells, for both synchronous and asynchronous beating. We use the waveforms in conjunction with resistive force theory as well as a singularity method to predict a cell's time-dependent

  6. Coherent dynamics of exciatable coupled beta-cells

    DEFF Research Database (Denmark)

    Sørensen, Mads P; Petersen, Mette Vesterager; Aslanidi, Oleg

    2004-01-01

    Propagation of excitation waves through a cluster of insulin-secreting beta-cells (a pancreatic islet of Langerhans) is modelled, and the results are related to recent image analysis experiments.......Propagation of excitation waves through a cluster of insulin-secreting beta-cells (a pancreatic islet of Langerhans) is modelled, and the results are related to recent image analysis experiments....

  7. 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...

  8. 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)

  9. 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

  10. Differential dynamics of splicing factor SC35 during the cell cycle

    Indian Academy of Sciences (India)

    We analysed the dynamics of the splicing factor SC35 in interphase and mitotic cells. In HeLa cells expressing green fluorescent protein (GFP)-SC35, this was localized in speckles during interphase and dispersed in metaphase. In telophase, GFP-SC35 was highly enriched within telophase nuclei and also detected in ...

  11. 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

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

    NARCIS (Netherlands)

    Füllgrabe, Anja; Joost, Simon; Are, Alexandra; Jacob, Tina; Sivan, Unnikrishnan; Haegebarth, Andrea; Linnarsson, Sten; Simons, Benjamin D; Clevers, Hans; Toftgård, Rune; Kasper, Maria

    2015-01-01

    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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Evaluation of reflection interference contrast microscope images of living cells.

    Science.gov (United States)

    Beck, K; Bereiter-Hahn, J

    1981-03-01

    Reflection contrast microscope methods are generally used for studies of those portions of the cell that are turned towards the glass coverslip, to comprehend the structure of the cytoskeleton and the dynamics of cell movement, as well as formation of cell-glass contacts. In incident illumination only reflected light contributes to picture formation. The intensity of which in the case of observation of unstained cells is small because of small refraction differences. To overcome this problem a reflection contrast system was developed by Leitz according to Ploem [49], in which by using contrast preserving measures the reflection becomes prominent in comparison with the lens reflexes. The emerging pictures are a result of interferences of reflections at glass-cell, cell-culture medium and culture medium-cell interfaces. According to Fresnel's equations the reflected intensity depends on the differences of the particular refractive indices and the thickness of the layers, which determine the phase of interfering beams. In idealized systems of thin films the reflected intensity is a measure for their optical constants. Relative reflection measurements from glass-cell areas is comparison with the known glass-medium reflection, can therefore be revealing as far as refraction index, cell-glass distance or cell thickness are concerned. The estimates by Bereiter-Hahn et al. [15] were made in the assumption of vertical illumination neglecting its actual conical shape: the comparison of two Fresnel functions of cytological relevant measurements show - in accordance with Gingell and Todd [24] - that this is only permitted under certain conditions, depending on the required accuracy of the measurements; an incidence angle of about 30 degrees leads to an error of about 10%, an angle of 50 degrees to more than 50%.

  16. Evaluation of The Virtual Cells Software: a Teaching Tool

    Directory of Open Access Journals (Sweden)

    C.C.P. da Silva

    2005-07-01

    Full Text Available Studies show that the use of games and interactive materials  at schools is a good educational strategy, motivating students to create mental  outlines and developing the reasoning and facilitating  the learn- ing. In this context, the Scientific Dissemination Coordination of the Center  for Structural Molecular Biotechnology  (CBME,  developed  a series of educational materials  destined  to the  elementary and high  schools,  universities  and  general  public.   Among  these,  we highlighted  the  Virtual  Cells soft- ware that was developed  with  the  aim of helping  in the  understanding of the  basic concepts  of cell types,  their  structures, organelles  and  specific functions.   Characterized by its  interactive  interface, this  software shows eukaryotes  and prokaryotes cells images, where organelles are shown as dynamic structures. In addition, it presents exercises in another  step that reinforce the comprehension  of Cy- tology.  A speaker  narrates the  resources  offered by the  program  and  the  necessary  steps  for its use. During  the  stage  of development of the  software,  students and  teachers of public and  private  high schools from Sao Carlos  city, Sao Paulo  State,  were invited  to register their  opinions  regarding  the language and content of the software in order to help us in the improvement of it.  After this stage, the Scientific Dissemination Coordination of CBME organized a series of workshops, where 120 individuals evaluated the software (students and teachers  of high school and others undergraduate students. For this evaluation, a questionnaire was elaborated based on the international current literature in the area of sciences teaching  and it was applied  after the interactive section with the software.  The analysis of the results demonstrated that most of the individuals  considered the software of easy

  17. Cell diversity and network dynamics in photosensitive human brain organoids.

    Science.gov (United States)

    Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z; Sherwood, John L; Min Yang, Sung; Berger, Daniel R; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin P; Boyden, Edward S; Lichtman, Jeff W; Williams, Ziv M; McCarroll, Steven A; Arlotta, Paola

    2017-05-04

    In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.

  18. QSSPN: dynamic simulation of molecular interaction networks describing gene regulation, signalling and whole-cell metabolism in human cells.

    Science.gov (United States)

    Fisher, Ciarán P; Plant, Nicholas J; Moore, J Bernadette; Kierzek, Andrzej M

    2013-12-15

    Dynamic simulation of genome-scale molecular interaction networks will enable the mechanistic prediction of genotype-phenotype relationships. Despite advances in quantitative biology, full parameterization of whole-cell models is not yet possible. Simulation methods capable of using available qualitative data are required to develop dynamic whole-cell models through an iterative process of modelling and experimental validation. We formulate quasi-steady state Petri nets (QSSPN), a novel method integrating Petri nets and constraint-based analysis to predict the feasibility of qualitative dynamic behaviours in qualitative models of gene regulation, signalling and whole-cell metabolism. We present the first dynamic simulations including regulatory mechanisms and a genome-scale metabolic network in human cell, using bile acid homeostasis in human hepatocytes as a case study. QSSPN simulations reproduce experimentally determined qualitative dynamic behaviours and permit mechanistic analysis of genotype-phenotype relationships. The model and simulation software implemented in C++ are available in supplementary material and at http://sysbio3.fhms.surrey.ac.uk/qsspn/.

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

    Science.gov (United States)

    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

  20. Particle dynamics and particle-cell interaction in microfluidic systems

    Science.gov (United States)

    Stamm, Matthew T.

    Particle-laden flow in a microchannel resulting in aggregation of microparticles was investigated to determine the dependence of the cluster growth rate on the following parameters: suspension void fraction, shear strain rate, and channel-height to particle-diameter ratio. The growth rate of an average cluster was found to increase linearly with suspension void fraction, and to obey a power-law relationships with shear strain rate as S 0.9 and channel-height to particle-diameter ratio as (h/d )--3.5. Ceramic liposomal nanoparticles and silica microparticles were functionalized with antibodies that act as targeting ligands. The bio-functionality and physical integrity of the cerasomes were characterized. Surface functionalization allows cerasomes to deliver drugs with selectivity and specificity that is not possible using standard liposomes. The functionalized particle-target cell binding process was characterized using BT-20 breast cancer cells. Two microfluidic systems were used; one with both species in suspension, the other with cells immobilized inside a microchannel and particle suspension as the mobile phase. Effects of incubation time, particle concentration, and shear strain rate on particle-cell binding were investigated. With both species in suspension, the particle-cell binding process was found to be reasonably well-described by a first-order model. Particle desorption and cellular loss of binding affinity in time were found to be negligible; cell-particle-cell interaction was identified as the limiting mechanism in particle-cell binding. Findings suggest that separation of a bound particle from a cell may be detrimental to cellular binding affinity. Cell-particle-cell interactions were prevented by immobilizing cells inside a microchannel. The initial stage of particle-cell binding was investigated and was again found to be reasonably well-described by a first-order model. For both systems, the time constant was found to be inversely proportional to

  1. Dynamically constrained pipeline for tracking neural progenitor cells

    DEFF Research Database (Denmark)

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

    2013-01-01

    tracking methods are fundamental building blocks of setting up multi purpose pipelines. Segmentation by discriminative dictionary learning and a graph formulated tracking method constraining the allowed topology changes are combined here to accommodate for highly irregular cell shapes and movement patterns...... pipeline by tracking pig neural progenitor cells through a time lapse experiment consisting of 825 images collected over 69 hours. Each step of the tracking pipeline is validated separately by comparison with manual annotations. The number of tracked cells increase from approximately 350 to 650 during...

  2. Evaluation of two human dental pulp stem cell cryopreservation methods.

    Science.gov (United States)

    Munévar, Juan C; Gutiérrez, Nicole; Jiménez, Nury T; Lafaurie, Gloria I

    2015-01-01

    Dental pulp is a promising source of mesenchymal stem cells for use in cell therapy and regenerative medicine. Methods for storing stem cells with minimum compromise of cell viability, differentiation capacity and function should be developed for clinical and research applications. The aim of this study was to evaluate whether human dental pulp stem cells (hDPSCs) isolated and cryopreserved for 1, 7 and 30 days maintain viability and expression of specific stem cell markers. Human dental pulp stem cells were isolated from 23 healthy patients aged 18 to 31 years. Dental pulp was enzymatically dissociated, and CD105+ cells were separated using the Miltenyi™ system. The hDPSCs were cryopreserved using the Kamath and Papaccio methods. Post-cryopreservation viability was measured by flow cytometry (7AAD) and by the expression of the phenotype markers CD105+/ CD73+, CD34-/CD45-. The Papaccio method showed greater cell viability for cells that had been frozen for 30 days (59.5%) than the Kamath method (56.2%), while the Kamath method provided better results for 1 day (65.5%) and 7 days (56%). Post-cryopreservation expression of the markers CD105+/CD34- was greater after 1 and 7 days with the Kamath method and CD105+/CD45- were expressed after all 3 cryopreservation times. There was greater expression of CD73+ in the hDPSCs after 1 and 7 days with the Kamath method, and after 30 days with the Papaccio method. These results suggest that hDPSCs express mesenchymal stem cell markers after cryopreservation. However, cryopreservation time may affect marker expression, probably by altering the spatialconfiguration of cell membrane proteins or by compromising cells at a certain level of differentiation.

  3. Size and Dynamics of Caveolae Studied Using Nanoparticles in Living Endothelial Cells

    OpenAIRE

    Wang, Zhenjia; Tiruppathi, Chinnaswamy; Minshall, Richard D.; Malik, Asrar B.

    2009-01-01

    Caveolae are plasma membrane invaginations prominent in all endothelial cells lining blood vessels. Caveolae characteristically bud to form free cytoplasmic vesicles capable of transporting carrier proteins such as albumin through the cell. However, caveolae size distribution and dynamics in living endothelial cells and ability of caveolae to internalize nanoparticles are not well understood. We demonstrate here the design of a dual-color nanoparticle pair to measure non-invasively caveolae s...

  4. Dynamics of cell aggregates fusion: Experiments and simulations

    Science.gov (United States)

    Thomas, Gilberto L.; Mironov, Vladimir; Nagy-Mehez, Agnes; Mombach, José C. M.

    2014-02-01

    Fusion of cell tissues is an ubiquitous phenomenon and has important technological applications including tissue biofabrication. In this work we present experimental results of aggregates fusion using adipose derived stem cells (ADSC) and a three dimensional computer simulation of the process using the cellular Potts model with aggregates reaching 10,000 cells. We consider fusion of round aggregates and monitor the dimensionless neck area of contact between the two aggregates to characterize the process, as done for the coalescence of liquid droplets and polymers. Both experiments and simulations show that the evolution of this quantity obeys a power law in time. We also study quantitatively individual cell motion with the simulation and it corresponds to an anomalous diffusion.

  5. Stem cell dynamics in the hair follicle niche

    Science.gov (United States)

    Rompolas, Panteleimon; Greco, Valentina

    2014-01-01

    Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

  6. The Ultrastructural Dynamics of Parasite-Host Cell Interactions as ...

    African Journals Online (AJOL)

    layered pellicle, conoid, polar ring, microtubules and rhoptries. The parasites can be maintained continuously in vitro in a variety of mammalian cell lines and their requirements for growth have been previously established. Evidence of active host ...

  7. 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.

  8. Evaluation of the Terrestrial Ecosystem Formation and Diversity in a Modified Dynamic Global Vegetation Model

    Science.gov (United States)

    Zeng, X.; Shao, P.; Song, X.

    2010-12-01

    Terrestrial ecosystem formation and diversity have great impact on the stability and frangibility of ecosystem. It is important that Dynamic Global Vegetation Models (DGVMs) can capture these essential properties so that they can correctly simulate the succession and transition of terrestrial ecosystem in company with the global climate change. Previous studies have shown that DGVMs can roughly reproduce the spatial distributions of different vegetation types as well as the dependence of the vegetation distribution on climate conditions, however, the capability of DGVMs to reproduce the global vegetation distribution and ecosystem formation has not been fully evaluated. This study is based on our modified DGVM coupled with the Community Land Model (CLM-DGVM). The modified CLM-DGVM can simulate 12 plant functional types (PFTs) besides the bare soil. It allows two or more PFTs coexisting in a grid cell, in contrast to the DGVMs which tend to generate the ecosystem with single dominant plant functional type and hence lose the functional diversity of ecosystem. Our results show that the density distributions of fractional coverage (DDFC) of three vegetation categories (e.g., forest, grassland, and shrubland) and PFTs are different with the observation. In particular, the model overestimates the DDFC over regions with tree coverage larger than 70%, but underestimates the DDFC over regions with tree coverage less than 40%. Furthermore, the functional diversity of PFTs in each gridcell is generally lower than that in the observation. Sensitivity tests show that substantial changes in the terrestrial ecosystem usually occur within the areas where two or more PFTs coexist with comparable fractions, i.e., and the functional diversity is high. These results imply that current CLM-DGVM may not be able to appropriately produce the averaged amplitude and spatial pattern of the transition in global ecosystem. Therefore, we suggest that extensive studies are required to improve

  9. A Modified NK Cell Degranulation Assay Applicable for Routine Evaluation of NK Cell Function

    Directory of Open Access Journals (Sweden)

    Snehal Shabrish

    2016-01-01

    Full Text Available Natural killer (NK cells play important role in innate immunity against tumors and viral infections. Studies show that lysosome-associated membrane protein-1 (LAMP-1, CD107a is a marker for degranulation of NK and cytotoxic T cells and its expression is a sensitive marker for the cytotoxic activity determination. The conventional methods of determination of CD107a on NK cells involve use of peripheral blood mononuclear cells (PBMC or pure NK cells and K562 cells as stimulants. Thus, it requires large volume of blood sample which is usually difficult to obtain in pediatric patients and patients with cytopenia and also requires specialized laboratory for maintaining cell line. We have designed a flow cytometric assay to determine CD107a on NK cells using whole blood, eliminating the need for isolation of PBMC or isolate NK cells. This assay uses phorbol-12-myristate-13-acetate (PMA and calcium ionophore (Ca2+-ionophore instead of K562 cells for stimulation and thus does not require specialized cell culture laboratory. CD107a expression on NK cells using modified NK cell degranulation assay compared to the conventional assay was significantly elevated (p<0.0001. It was also validated by testing patients diagnosed with familial hemophagocytic lymphohistiocytosis (FHL with defect in exocytosis. This assay is rapid, cost effective, and reproducible and requires significantly less volume of blood which is important for clinical evaluation of NK cells.

  10. Evaluation of GLUT-1 in the granular cell tumour and congenital granular cell epulis.

    Science.gov (United States)

    Souto, Giovanna Ribeiro; Caldeira, Patrícia Carlos; Johann, Aline Cristina Batista Rodrigues; Andrade Marigo, Helenicede; Souza, Suzana Cantanhede Orsini Machadode; Mesquita, Ricardo Alves

    2013-07-01

    The glucose transporter type 1 (GLUT-1) protein is a useful marker for perineurial cells. Because of the possible neuroectodermal histogenesis of the granular cell tumour and congenital granular cell epulis, the aim of this study was to assess the immunoexpression of GLUT-1 protein in granular cell tumour and congenital granular cell epulis to aid in clarifying their histogenesis. The protocol of this study was approved by the Committee of Bioethics in Research at Universidade Federal Minas Gerais. Six cases of granular cell tumour and three cases of congenital granular cell epulis were submitted to immunohistochemistry for GLUT-1 and S-100 using the streptavidin-biotin standard protocol. Five cases of granular cell tumour were located on the tongue and one case on the upper lip. All cases of congenital granular cell epulis were observed in the alveolar ridge of newborns. All lesions evaluated proved to be immunonegative for GLUT-1. S-100 was found to be positive in all granular cell tumours and negative in congenital granular cell epulis. Neither granular cell tumour nor congenital granular cell epulis is directly related to perineurial cells. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Evaluating road surface conditions using dynamic tire pressure sensor

    Science.gov (United States)

    Zhao, Yubo; Wu, H. Felix; McDaniel, J. Gregory; Wang, Ming L.

    2014-03-01

    In order to best prioritize road maintenance, the level of deterioration must be known for all roads in a city's network. Pavement Condition Index (PCI) and International Roughness Index (IRI) are two standard methods for obtaining this information. However, IRI is substantially easier to measure. Significant time and money could be saved if a method were developed to estimate PCI from IRI. This research introduces a new method to estimate IRI and correlate IRI with PCI. A vehicle-mounted dynamic tire pressure sensor (DTPS) system is used. The DTPS measures the signals generated from the tire/road interaction while driving. The tire/road interaction excites surface waves that travel through the road. DTPS, which is mounted on the tire's valve stem, measures tire/road interaction by analyzing the pressure change inside the tire due to the road vibration, road geometry and tire wall vibration. The road conditions are sensible to sensors in a similar way to human beings in a car. When driving on a smooth road, tire pressure stays almost constant and there are minimal changes in the DTPS data. When driving on a rough road, DTPS data changes drastically. IRI is estimated from the reconstructed road profile using DTPS data. In order to correlate IRI with PCI, field tests were conducted on roads with known PCI values in the city of Brockton, MA. Results show a high correlation between the estimated IRI values and the known PCI values, which suggests that DTPS-based IRI can provide accurate predictions of PCI.

  12. Membrane dynamics and interactions in measles virus dendritic cell infections.

    Science.gov (United States)

    Avota, Elita; Koethe, Susanne; Schneider-Schaulies, Sibylle

    2013-02-01

    Viral entry, compartmentalization and transmission depend on the formation of membrane lipid/protein microdomains concentrating receptors and signalosomes. Dendritic cells (DCs) are prime targets for measles virus (MV) infection, and this interaction promotes immune activation and generalized immunosuppression, yet also MV transport to secondary lymphatics where transmission to T cells occurs. In addition to MV trapping, DC-SIGN interaction can enhance MV uptake by activating cellular sphingomyelinases and, thereby, vertical surface transport of its entry receptor CD150. To exploit DCs as Trojan horses for transport, MV promotes DC maturation accompanied by mobilization, and restrictions of viral replication in these cells may support this process. MV-infected DCs are unable to support formation of functional immune synapses with conjugating T cells and signalling via viral glycoproteins or repulsive ligands (such as semaphorins) plays a key role in the induction of T-cell paralysis. In the absence of antigen recognition, MV transmission from infected DCs to T cells most likely involves formation of polyconjugates which concentrate viral structural proteins, viral receptors and with components enhancing either viral uptake or conjugate stability. Because DCs barely support production of infectious MV particles, these organized interfaces are likely to represent virological synapses essential for MV transmission. © 2012 Blackwell Publishing Ltd.

  13. Protein Availability and Satellite Cell Dynamics in Skeletal Muscle.

    Science.gov (United States)

    Shamim, Baubak; Hawley, John A; Camera, Donny M

    2018-03-20

    Human skeletal muscle satellite cells are activated in response to both resistance and endurance exercise. It was initially proposed that satellite cell proliferation and differentiation were only required to support resistance exercise-induced hypertrophy. However, satellite cells may also play a role in muscle fibre remodelling after endurance-based exercise and extracellular matrix regulation. Given the importance of dietary protein, particularly branched chain amino acids, in supporting myofibrillar and mitochondrial adaptations to both resistance and endurance-based training, a greater understanding of how protein intake impacts satellite cell activity would provide further insight into the mechanisms governing skeletal muscle remodelling with exercise. While many studies have investigated the capacity for protein ingestion to increase post-exercise rates of muscle protein synthesis, few investigations have examined the role for protein ingestion to modulate satellite cell activity. Here we review the molecular mechanisms controlling the activation of satellite cells in response to mechanical stress and protein intake in both in vitro and in vivo models. We provide a mechanistic framework that describes how protein ingestion may enhance satellite activity and promote exercise adaptations in human skeletal muscle.

  14. Evaluation of Instrumentation and Dynamic Thermal Ratings for Overhead Lines

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, A. [New York Power Authority, White Plains, NY (United States)

    2013-01-31

    In 2010, a project was initiated through a partnership between the Department of Energy (DOE) and the New York Power Authority (NYPA) to evaluate EPRI's rating technology and instrumentation that can be used to monitor the thermal states of transmission lines and provide the required real-time data for real-time rating calculations. The project included the installation and maintenance of various instruments at three 230 kV line sites in northern New York. The instruments were monitored, and data collection and rating calculations were performed for about a three year period.

  15. Evaluation of cell cytotoxic effect on herbal extracts mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Soo; Gwon, Hui Jeong; Choi, Bo Ram; Lim, Youn Mook; Nho, Young Chang [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2009-12-15

    Herbal extracts (HE) such as Houttuynia cordata Thunb., Eucommia ulimoides, Plantago asiatica var., Morus alba L., and Ulmus davidiana var., are known to suppress an atopic dermatitis like skin lesions. In this study, to evaluate the cell cytotoxicity effect on L929, HaCaT and HMC-1 cell by the HE, the herbs were extracted with distilled water (at 75 .deg. C) and then the HE mixtures were freeze-dried for 5 days and sterilized with {gamma}-rays. The cytotoxicity was measured by Cell Counting Kit-8 (CCK-8) assay. The result showed that the HE mixtures did not significantly affect cell viability and had no toxicity on the cells. These findings indicate that the HE mixtures can be used as a potential therapeutic agent.

  16. Surfactant uptake dynamics in mammalian cells elucidated with quantitative coherent anti-stokes Raman scattering microspectroscopy.

    Directory of Open Access Journals (Sweden)

    Masanari Okuno

    Full Text Available The mechanism of surfactant-induced cell lysis has been studied with quantitative coherent anti-Stokes Raman scattering (CARS microspectroscopy. The dynamics of surfactant molecules as well as intracellular biomolecules in living Chinese Hamster Lung (CHL cells has been examined for a low surfactant concentration (0.01 w%. By using an isotope labeled surfactant having CD bonds, surfactant uptake dynamics in living cells has been traced in detail. The simultaneous CARS imaging of the cell itself and the internalized surfactant has shown that the surfactant molecules is first accumulated inside a CHL cell followed by a sudden leak of cytosolic components such as proteins to the outside of the cell. This finding indicates that surfactant uptake occurs prior to the cell lysis, contrary to what has been believed: surface adsorption of surfactant molecules has been thought to occur first with subsequent disruption of cell membranes. Quantitative CARS microspectroscopy enables us to determine the molecular concentration of the surfactant molecules accumulated in a cell. We have also investigated the effect of a drug, nocodazole, on the surfactant uptake dynamics. As a result of the inhibition of tubulin polymerization by nocodazole, the surfactant uptake rate is significantly lowered. This fact suggests that intracellular membrane trafficking contributes to the surfactant uptake mechanism.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Modelling and simulation of fuel cell dynamics for electrical energy usage of Hercules airplanes.

    Science.gov (United States)

    Radmanesh, Hamid; Heidari Yazdi, Seyed Saeid; Gharehpetian, G B; Fathi, S H

    2014-01-01

    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.

  19. 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.

  20. 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. PMID:24302883

  1. 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.

  2. Evaluation of glass transition temperature and dynamic mechanical properties of autopolymerized hard direct denture reline resins.

    Science.gov (United States)

    Takase, Kazuma; Watanabe, Ikuya; Kurogi, Tadafumi; Murata, Hiroshi

    2015-01-01

    This study assessed methods for evaluation of glass transition temperature (Tg) of autopolymerized hard direct denture reline resins using dynamic mechanical analysis and differential scanning calorimetry in addition to the dynamic mechanical properties. The Tg values of 3 different reline resins were determined using a dynamic viscoelastometer and differential scanning calorimeter, and rheological parameters were also determined. Although all materials exhibited higher storage modulus and loss modulus values, and a lower loss tangent at 37˚C with a higher frequency, the frequency dependence was not large. Tg values obtained by dynamic mechanical analysis were higher than those by differential scanning calorimetry and higher frequency led to higher Tg, while more stable Tg values were also obtained by that method. These results suggest that dynamic mechanical analysis is more advantageous for characterization of autopolymerized hard direct denture reline resins than differential scanning calorimetry.

  3. Single Molecule Spectroelectrochemistry of Interfacial Charge Transfer Dynamics In Hybrid Organic Solar Cell

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Shanlin [Univ. of Alabama, Tuscaloosa, AL (United States)

    2014-11-16

    Our research under support of this DOE grant is focused on applied and fundamental aspects of model organic solar cell systems. Major accomplishments are: 1) we developed a spectroelectorchemistry technique of single molecule single nanoparticle method to study charge transfer between conjugated polymers and semiconductor at the single molecule level. The fluorescence of individual fluorescent polymers at semiconductor surfaces was shown to exhibit blinking behavior compared to molecules on glass substrates. Single molecule fluorescence excitation anisotropy measurements showed the conformation of the polymer molecules did not differ appreciably between glass and semiconductor substrates. The similarities in molecular conformation suggest that the observed differences in blinking activity are due to charge transfer between fluorescent polymer and semiconductor, which provides additional pathways between states of high and low fluorescence quantum efficiency. Similar spectroelectrochemistry work has been done for small organic dyes for understand their charge transfer dynamics on various substrates and electrochemical environments; 2) We developed a method of transferring semiconductor nanoparticles (NPs) and graphene oxide (GO) nanosheets into organic solvent for a potential electron acceptor in bulk heterojunction organic solar cells which employed polymer semiconductor as the electron donor. Electron transfer from the polymer semiconductor to semiconductor and GO in solutions and thin films was established through fluorescence spectroscopy and electroluminescence measurements. Solar cells containing these materials were constructed and evaluated using transient absorption spectroscopy and dynamic fluorescence techniques to understand the charge carrier generation and recombination events; 3) We invented a spectroelectorchemistry technique using light scattering and electroluminescence for rapid size determination and studying electrochemistry of single NPs in an

  4. Dynamics of Acute Local Inflammatory Response after Autologous Transplantation of Muscle-Derived Cells into the Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Anna Burdzinska

    2014-01-01

    Full Text Available The vast majority of myoblasts transplanted into the skeletal muscle die within the first week after injection. Inflammatory response to the intramuscular cell transfer was studied in allogeneic but not in autologous model. The aim of this study was to evaluate immune reaction to autotransplantation of myogenic cells and to assess its dynamics within the first week after injection. Muscle-derived cells or medium alone was injected into the intact skeletal muscles in autologous model. Tissue samples were collected 1, 3, and 7 days after the procedure. Our analysis revealed the peak increase of the gene expression of all evaluated cytokines (Il-1α, Il-1β, Il-6, Tgf-β, and Tnf-α at day 1. The mRNA level of analyzed cytokines normalized in subsequent time points. The increase of Il-β gene expression was further confirmed at the protein level. Analysis of the tissue sections revealed rapid infiltration of injected cell clusters with neutrophils and macrophages. The inflammatory infiltration was almost completely resolved at day 7. The survived cells were able to participate in the muscle regeneration process. Presented results demonstrate that autotransplanted muscle-derived cells induce classical early immune reaction in the site of injection which may contribute to cellular graft elimination.

  5. 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

  6. Mechanical model of geometric cell and topological algorithm for cell dynamics from single-cell to formation of monolayered tissues with pattern.

    Directory of Open Access Journals (Sweden)

    Sëma Kachalo

    Full Text Available 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

  7. Phase Diagram and Breathing Dynamics of Red Blood Cell Motion in Shear Flow

    Science.gov (United States)

    Bagchi, Prosenjit; Yazdani, Alireza

    2011-11-01

    We present phase diagrams of red blood cell dynamics in shear flow using three-dimensional numerical simulations. By considering a wide range of shear rate and interior-to-exterior fluid viscosity ratio, it is shown that the cell dynamics is often more complex than the well-known tank-treading, tumbling and swinging motion, and is characterized by an extreme variation of the cell shape. We identify such complex shape dynamics as `breathing' dynamics. During the breathing motion, the cell either completely aligns with the flow direction and the membrane folds inward forming two cusps, or, it undergoes large swinging motion while deep, crater-like dimples periodically emerge and disappear. At lower bending rigidity, the breathing motion occurs over a wider range of shear rates, and is often characterized by the emergence of a quad-concave shape. The effect of the breathing dynamics on the tank-treading-to-tumbling transition is illustrated by detailed phase diagrams which appear to be more complex and richer than those of vesicles. In a remarkable departure from classical theory of nondeformable cells, we find that there exists a critical viscosity ratio below which the transition is dependent on shear rate only. Supported by NSF.

  8. Evaluation of a recombinant yeast cell estrogen screening assay.

    OpenAIRE

    Coldham, N G; Dave, M; Sivapathasundaram, S; McDonnell, D P; Connor, C; Sauer, M J

    1997-01-01

    A wide range of chemicals with diverse structures derived from plant and environmental origins are reported to have hormonal activity. The potential for appreciable exposure of humans to such substances prompts the need to develop sensitive screening methods to quantitate and evaluate the risk to the public. Yeast cells transformed with plasmids encoding the human estrogen receptor and an estrogen responsive promoter linked to a reporter gene were evaluated for screening compounds for estroge...

  9. 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

  10. Toxic effects of cadmium on flatworm stem cell dynamics: A transcriptomic and ultrastructural elucidation of underlying mechanisms.

    Science.gov (United States)

    Plusquin, Michelle; De Mulder, Katrien; Van Belleghem, Frank; DeGheselle, Olivier; Pirotte, Nicky; Willems, Maxime; Cuypers, Ann; Salvenmoser, Willi; Ladurner, Peter; Artois, Tom; Smeets, Karen

    2016-10-01

    Stem cells or undifferentiated cells can cope more easily with external stresses. To evaluate the impact of toxic compounds on stem cell dynamics in vivo, in relation to other biological responses, we use the carcinogenic element cadmium and the regenerating model organism Macrostomum lignano. Through both BrdU and anti-histone H3 immunostainings, cadmium-induced effects were investigated at different stages of the stem cell cycle. A 24-h exposure to 100 and 250 μM CdCl2 significantly decreased the number of stem cells (neoblasts) in mitosis, whereas the number of cells in the S phase remained unchanged. After this short-term exposure, the ultrastructure of the neoblasts was minimally affected in contrast to the epidermal tissues. These results were supported by gene expression data: transcripts of cdc2 and pig3 were significantly upregulated during all treatments. Both genes are involved in the cell cycle progression and are transcribed in the gonadal region, where stem cells are highly represented. Based on a substantial increase in gene expression of heat shock proteins (HSP) and their high activity in the gonadal region, we hypothesize that these proteins are key players in the protection of stem cells against external stresses. Apart from the strong HSP induction, other protective processes including cell division, apoptosis and anti-oxidative defence, were also activated. We, therefore, conclude that the protection of stem cells against external stressors may be based on the interplay between stem cell maintenance, i.e. repair and recovery through division, on one hand and apoptosis on the other hand. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1217-1228, 2016. © 2015 Wiley Periodicals, Inc.

  11. 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

  12. Dynamic data evaluation for solid-liquid equilibria

    DEFF Research Database (Denmark)

    Cunico, Larissa; Ceriani, Roberta; Kang, Jeong Won

    The accuracy and reliability of the measured data sets to be used in regression of model parameters is an important issue related to modeling of phase equilibria. It is clear that good parameters for any model cannot be obtained from low quality data. A thermodynamic consistency test for solid...... studies considering the methodology proposed for SLE thermodynamic consistency tests and data from open literature and databases such as NIST-TDE®, DIPPR® and DECHEMA® are presented. The SLE consistency test and data evaluation is performed in a software containing option for data analysis, model analysis......-liquid systems using a relation between the solid and liquid activity coefficients for systems containing metals [1], where the data from the two phases are given were proposed. However, as consistency tests based on the Gibbs–Duhem equation are not feasible, new consistency tests have been developed [2]. Some...

  13. Evaluation of dynamic behavior of waffle slab to gym center

    Directory of Open Access Journals (Sweden)

    Yuri Cláudio Vieira da Costa

    Full Text Available In Brazil, the use of reinforced concrete waffle slab in multi-story buildings is widespread nowadays. These buildings are projected for different purposes such as fitness centers, supermarkets, parking garages, offices and residential units. Simple activities as walking, skipping and jumping can generate vibrations in these slabs. Vibrations can cause inconvenience in persons, questions about structure´s safety, and collapse risk that it is determined by its intensity of vibrations. The objective of this paper is evaluating the behavior of reinforced concrete waffle slabs due to the human rhythmic activities. Slabs are modeled by finite elements method using the SAP2000 program. The results are verified according to Brazilian and international codes. The waffle slabs are submitted to high-levels of acceleration and velocity generating discomfort in users.

  14. Evaluating Stem Cell Response to a Spider Silk Scaffold

    Science.gov (United States)

    Hafner, Katherine Lee

    Micropatterning on a surface using fibers, channels, and troughs, can act as an effective means of inducing cell attachment and alignment. These morphological and pattern changes as a response to physical cues can impact the potential that a cell has to differentiate into a different cell line. This thesis evaluated the response of human dental pulp stem cells (DPSCs), and other cell types, to spider dragline silk fibers, a potential scaffold material for tissue regeneration, and further observed the effects of morphology, orientation, and composition of silk on the adherence of cells. Several cell lines were studied in this thesis, including adipose derived stem cells (ADSCs), osteoblasts (7F2s), and fibroblasts (3T3s), but DPSCs were the main cell type of interest. This is due to the fact that DPSCs are a proposed source of stem cells for nerve regeneration based on their close embryonic origin to neurons and the ease with which DPSCs can be obtained from a donor. The cells' morphologies and spread patterns were characterized after they were plated onto Nephila clavipes dragline fibers in media. The inclusion of 3T3s and 7F2s in this study allowed for both direct comparisons to prior published work and a qualitative comparison to the morphology of the DPSCs. After twelve days, the DPSCs exhibited greater relative alignment and adherence to the spider dragline fibers than the 3T3s and 7F2s when silk was wrapped in an aligned orientation rather than a random orientation. The impact of a common sterilization method (ultraviolet light) on the spider dragline fiber surface and subsequent cell response to this modified surface was also characterized. Exposure of the silk to ultraviolet light did not have a measureable effect on cell alignment, but it did eliminate bacterial growth and changed fiber surface roughness. Spiders' exposure to stressful environments did not have an effect on silk to impair cell alignment or adhesion, and synthetic recombinant protein silk

  15. Dynamics of Proliferative and Quiescent Stem Cells in Liver Homeostasis and Injury.

    Science.gov (United States)

    Cao, Wanlu; Chen, Kan; Bolkestein, Michiel; Yin, Yuebang; Verstegen, Monique M A; Bijvelds, Marcel J C; Wang, Wenshi; Tuysuz, Nesrin; Ten Berge, Derk; Sprengers, Dave; Metselaar, Herold J; van der Laan, Luc J W; Kwekkeboom, Jaap; Smits, Ron; Peppelenbosch, Maikel P; Pan, Qiuwei

    2017-10-01

    Adult liver stem cells are usually maintained in a quiescent/slow-cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. We studied LGR5-positive stem cells using diphtheria toxin receptor and green fluorescent protein (GFP) knock-in mice. In these mice, LGR5-positive cells specifically coexpress diphtheria toxin receptor and the GFP reporter. Lineage-tracing experiments were performed in mice in which LGR5-positive stem cells and their daughter cells expressed a yellow fluorescent protein/mTmG reporter. Slow-cycling stem cells were investigated using GFP-based, Tet-on controlled transgenic mice. We studied the dynamics of both stem cell populations during liver homeostasis and injury induced by carbon tetrachloride. Stem cells were isolated from mouse liver and organoid formation assays were performed. We analyzed hepatocyte and cholangiocyte lineage differentiation in cultured organoids. We did not detect LGR5-expressing stem cells in livers of mice at any stage of a lifespan, but only following liver injury induced by carbon tetrachloride. In the liver stem cell niche, where the proliferating LGR5 + cells are located, we identified a quiescent/slow-cycling cell population, called label-retaining cells (LRCs). These cells were present in the homeostatic liver, capable of retaining the GFP label over 1 year, and expressed a panel of progenitor/stem cell markers. Isolated single LRCs were capable of forming organoids that could be carried in culture, expanded for months, and differentiated into hepatocyte and cholangiocyte lineages in vitro, demonstrating their bona fide stem cell properties. More interestingly, LRCs responded to liver injury and gave rise to LGR5-expressing stem cells, as well as

  16. 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.

  17. Cell Sorting of Neural Stem and Progenitor Cells from the Adult Mouse Subventricular Zone and Live-imaging of their Cell Cycle Dynamics.

    Science.gov (United States)

    Daynac, Mathieu; Morizur, Lise; Kortulewski, Thierry; Gauthier, Laurent R; Ruat, Martial; Mouthon, Marc-André; Boussin, François D

    2015-09-14

    Neural stem cells (NSCs) in the subventricular zone of the lateral ventricles (SVZ) sustain olfactory neurogenesis throughout life in the mammalian brain. They successively generate transit amplifying cells (TACs) and neuroblasts that differentiate into neurons once they integrate the olfactory bulbs. Emerging fluorescent activated cell sorting (FACS) techniques have allowed the isolation of NSCs as well as their progeny and have started to shed light on gene regulatory networks in adult neurogenic niches. We report here a cell sorting technique that allows to follow and distinguish the cell cycle dynamics of the above-mentioned cell populations from the adult SVZ with a LeX/EGFR/CD24 triple staining. Isolated cells are then plated as adherent cells to explore in details their cell cycle progression by time-lapse video microscopy. To this end, we use transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice in which cells are red-fluorescent during G1 phase due to a G1 specific red-Cdt1 reporter. This method has recently revealed that proliferating NSCs progressively lengthen their G1 phase during aging, leading to neurogenesis impairment. This method is easily transposable to other systems and could be of great interest for the study of the cell cycle dynamics of brain cells in the context of brain pathologies.

  18. Viscoelastic and dynamic properties of embryonic stem cells

    DEFF Research Database (Denmark)

    Ritter, Christine

    . The fluctuations of lipid granules both within the nucleus and in the cytoplasm of Epi- andPrE-primed cells were measured for 3 s and the microrheological scaling exponent a was extractedfrom the power spectrum of the recorded time series. Actin was disrupted with latrunculin B andthe effect of the disruption...... on the cells’ viscoelasticity was determined. To assess the effect of actindisruption on gene expression, time-lapse microscopy was employed to follow single, LatB treated,PrE-primed cells over a course of 24h, and qPCR was used to determine the effect on the expressionof Nanog, a pluripotency marker, and Gata......6, another marker for the primitive endoderm. The underlyingdiffusive process was determined by means of the ensemble and time averaged mean squareddisplacement, the amplitude scatter, higher order moments and the velocity autocorrelation func-tion.It was found that PrE-primed cells were...

  19. Switching and programming dynamics in phase-change memory cells

    Science.gov (United States)

    Ielmini, D.; Mantegazza, D.; Lacaita, A. L.; Pirovano, A.; Pellizzer, F.

    2005-11-01

    Emerging phase-change memory (PCM) technology for non-volatile applications presents many potential advantages in terms of scalability, endurance and program/read speed. While several integration issues have still to be solved before achieving volume-production stage, the fundamental physics of chalcogenide switching and phase-change behaviour has still to be comprehensively understood. This paper provides an in-depth analysis of the switching and programming transient in PCM cells. It is shown that the cell parasitic capacitance can lead to a marked current overshoot in the programming transient. As evidenced by experiments, this overshoot is able to melt and quench the active material as in a reset operation. The parasitic reset results in a series distribution of crystalline and amorphous phases after program. The analysis of array cell capacitance instead indicates that no parasitic reset is to be expected, allowing for a localized crystallization during program, as previously obtained by numerical simulations.

  20. Dynamic imaging for CAR-T-cell therapy.

    Science.gov (United States)

    Emami-Shahri, Nia; Papa, Sophie

    2016-04-15

    Chimaeric antigen receptor (CAR) therapy is entering the mainstream for the treatment of CD19(+)cancers. As is does we learn more about resistance to therapy and the role, risks and management of toxicity. In solid tumour CAR therapy research the route to the clinic is less smooth with a wealth of challenges facing translating this, potentially hugely valuable, therapeutic option for patients. As we strive to understand our successes, and navigate the challenges, having a clear understanding of how adoptively transferred CAR-T-cells behavein vivoand in human trials is invaluable. Harnessing reporter gene imaging to enable detection and tracking of small numbers of CAR-T-cells after adoptive transfer is one way by which we can accomplish this. The compatibility of certain reporter gene systems with tracers available routinely in the clinic makes this approach highly useful for future appraisal of CAR-T-cell success in humans. © 2016 Authors; published by Portland Press Limited.

  1. Dynamics of Ras Complexes Observed in Living Cells

    Directory of Open Access Journals (Sweden)

    Xiangyong Li

    2012-07-01

    Full Text Available K-Ras works as a switch in many important intracellular signaling pathways and plays important roles in cell growth, proliferation, differentiation and carcinogenesis. For signal transduction from K-Ras to Raf1, the best-characterized effector of K-Ras, the general view is that Ras recruits Raf1 from the cytoplasm to the cell membrane. To elucidate this process, we constructed a series of fusion proteins (including Raf1 and K-Ras fused with either fluorescent proteins or fluorescent protein fragments to compare subcellular localizations of these proteins. Bimolecular fluorescence complementation (BiFC and a co-transfection system were used. In the BiFC system, the K-Ras/Raf1 complexes were mainly located in the cell membrane, while the Raf1 control was uniformly distributed in the cytoplasm. However, the complexes of Raf1 and K-RasC185S, a K-Ras mutant which loses membrane-localization, were also able to accumulate in the cell membrane. In contrast, an apparent cytosolic distribution pattern was observed in cells co-transfected with mcerulean-Raf1 and EGFP-K-RasC185S, suggesting that the membrane localization of K-Ras/Raf1 complexes is not entirely dependent on K-Ras, and that other factors, such as the irreversible conformation formed between K-Ras and Raf1 may play a role. This study sheds light on the interaction between K-Ras and Raf1 and provides a practical method to elucidate the mechanism underlying K-Ras and Raf1 binding to the cell membrane.

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

    Science.gov (United States)

    Nassour, Mayssa; Idoux-Gillet, Ysia; Selmi, Abdelkader; Côme, Christophe; Faraldo, Maria-Luisa M; Deugnier, Marie-Ange; Savagner, Pierre

    2012-01-01

    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 provide

  3. 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

  4. Spin-cast bulk heterojunction solar cells: A dynamical investigation

    KAUST Repository

    Chou, Kang Wei

    2013-02-22

    Spin-coating is extensively used in the lab-based manufacture of organic solar cells, including most of the record-setting solution-processed cells. We report the first direct observation of photoactive layer formation as it occurs during spin-coating. The study provides new insight into mechanisms and kinetics of bulk heterojunction formation, which may be crucial for its successful transfer to scalable printing processes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. 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.

  6. Chromatin interaction of TATA-binding protein is dynamically regulated in human cells.

    Science.gov (United States)

    de Graaf, Petra; Mousson, Florence; Geverts, Bart; Scheer, Elisabeth; Tora, Laszlo; Houtsmuller, Adriaan B; Timmers, H Th Marc

    2010-08-01

    Gene transcription in mammalian cells is a dynamic process involving regulated assembly of transcription complexes on chromatin in which the TATA-binding protein (TBP) plays a central role. Here, we investigate the dynamic behaviour of TBP by a combination of fluorescence recovery after photobleaching (FRAP) and biochemical assays using human cell lines of different origin. The majority of nucleoplasmic TBP and other TFIID subunits associate with chromatin in a highly dynamic manner. TBP dynamics are regulated by the joint action of the SNF2-related BTAF1 protein and the NC2 complex. Strikingly, both BTAF1 and NC2 predominantly affect TBP dissociation rates, leaving the association rate unchanged. Chromatin immunoprecipitation shows that BTAF1 negatively regulates TBP and NC2 binding to active promoters. Our results support a model for a BTAF1-mediated release of TBP-NC2 complexes from chromatin.

  7. Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach

    Science.gov (United States)

    Pizzolato, Nicola; Valenti, Davide; Adorno, Dominique Persano; Spagnolo, Bernardo

    2009-09-01

    The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modelled therapies. We show how the patient response to the therapy changes when a high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a fraction of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.

  8. The control of mesenchymal stem cell differentiation using dynamically tunable surface microgrooves.

    Science.gov (United States)

    Gong, Tao; Zhao, Kun; Yang, Guang; Li, Jinrong; Chen, Hongmei; Chen, Yuping; Zhou, Shaobing

    2014-10-01

    Many studies have demonstrated the potential to modulate stem cell differentiation by using static material substrate surfaces. However, cells actually grow in a dynamically diverse microenvironment in vivo. The regulated signals to the differentiation provided by these materials should not be passive or static but be active and dynamic. To mimic the endogenous cell culture microenvironment, a novel system is designed to realize the dynamic change of the surface geometries as well as a resultant mechanical force using a thermally activated four-stage shape memory polymer. The parallel microgroove surface patterns are fabricated via thermal embossing lithography on the polymer substrate surface. The dynamic microgroove surfaces accompanying with the mechanical force can effectively and significantly regulate the shape and the cytoskeletal arrangement of rBMSC compared with the static patterned and non-patterned surfaces. Cellular and molecular analyses reveal that the spatiotemporally programmed regulation of cell shape is more viable to coax lineage-specific differentiation of stem cell in contrast to the general reports with the static surfaces. Therefore, this study provides a facile strategy in designing and manufacturing an artificial substrate with a mimic natural cellular environment to precisely direct the cell differentiation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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.

  10. EB1 and cytoplasmic dynein mediate protrusion dynamics for efficient 3-dimensional cell migration.

    Science.gov (United States)

    Jayatilaka, Hasini; Giri, Anjil; Karl, Michelle; Aifuwa, Ivie; Trenton, Nicholaus J; Phillip, Jude M; Khatau, Shyam; Wirtz, Denis

    2018-03-01

    Microtubules have long been implicated to play an integral role in metastatic disease, for which a critical step is the local invasion of tumor cells into the 3-dimensional (3D) collagen-rich stromal matrix. Here we show that cell migration of human cancer cells uses the dynamic formation of highly branched protrusions that are composed of a microtubule core surrounded by cortical actin, a cytoskeletal organization that is absent in cells on 2-dimensional (2D) substrates. Microtubule plus-end tracking protein End-binding 1 and motor protein dynein subunits light intermediate chain 2 and heavy chain 1, which do not regulate 2D migration, critically modulate 3D migration by affecting RhoA and thus regulate protrusion branching through differential assembly dynamics of microtubules. An important consequence of this observation is that the commonly used cancer drug paclitaxel is 100-fold more effective at blocking migration in a 3D matrix than on a 2D matrix. This work reveals the central role that microtubule dynamics plays in powering cell migration in a more pathologically relevant setting and suggests further testing of therapeutics targeting microtubules to mitigate migration.-Jayatilaka, H., Giri, A., Karl, M., Aifuwa, I., Trenton, N. J., Phillip, J. M., Khatau, S., Wirtz, D. EB1 and cytoplasmic dynein mediate protrusion dynamics for efficient 3-dimensional cell migration.

  11. 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.

  12. Scheduling Performance Evaluation of Logistics Service Supply Chain Based on the Dynamic Index Weight

    Directory of Open Access Journals (Sweden)

    Weihua Liu

    2014-01-01

    Full Text Available Scheduling is crucial to the operation of logistics service supply chain (LSSC, so scientific performance evaluation method is required to evaluate the scheduling performance. Different from general project performance evaluation, scheduling activities are usually continuous and multiperiod. Therefore, the weight of scheduling performance evaluation index is not unchanged, but dynamically varied. In this paper, the factors that influence the scheduling performance are analyzed in three levels which are strategic environment, operating process, and scheduling results. Based on these three levels, the scheduling performance evaluation index system of LSSC is established. In all, a new performance evaluation method proposed based on dynamic index weight will have three innovation points. Firstly, a multiphase dynamic interaction method is introduced to improve the quality of quantification. Secondly, due to the large quantity of second-level indexes and the requirements of dynamic weight adjustment, the maximum attribute deviation method is introduced to determine weight of second-level indexes, which can remove the uncertainty of subjective factors. Thirdly, an adjustment coefficient method based on set-valued statistics is introduced to determine the first-level indexes weight. In the end, an application example from a logistics company in China is given to illustrate the effectiveness of the proposed method.

  13. A dynamic biomechanical evaluation of lifting maximum acceptable loads.

    Science.gov (United States)

    Freivalds, A; Chaffin, D B; Garg, A; Lee, K S

    1984-01-01

    A biomechanical evaluation of the job-related stresses imposed upon a worker is a potential means of reducing the high incidence rates of manual material handling injuries in industry. A biomechanical model consisting of seven rigid links joined at six articulations has been developed for this purpose. Using data from cinematographic analysis of lifting motions the model calculates: (1) body position from articulation angles, (2) angular velocities and accelerations, (3) inertial moments and forces, and (4) reactive moments and forces at each articulation, including the L5/S1 joint. Results indicated effects of the common task variables. Larger load and box sizes increased the rise times and peak values of both vertical ground reaction forces and predicted L5/S1 compressive forces. However, boxes with handles resulted in higher L5/S1 compressive forces than for boxes without handles. Also, in lifting the larger boxes the subjects did not sufficiently compensate with reduced box weights in order to maintain uniform L5/S1 compressive forces. Smoothed and rectified EMG of erector spinae muscles correlated significantly with L5/S1 compressive forces, while predicted and measured vertical ground reaction forces also correlated significantly, indicating the validity of the model as a tool for predicting job physical stresses.

  14. Evaluation of the Redesign of an Undergraduate Cell Biology Course

    Science.gov (United States)

    McEwen, Laura April; Harris, dik; Schmid, Richard F.; Vogel, Jackie; Western, Tamara; Harrison, Paul

    2009-01-01

    This article offers a case study of the evaluation of a redesigned and redeveloped laboratory-based cell biology course. The course was a compulsory element of the biology program, but the laboratory had become outdated and was inadequately equipped. With the support of a faculty-based teaching improvement project, the teaching team redesigned the…

  15. The dynamic cytoskeleton of the developing male germ cell.

    Science.gov (United States)

    Sperry, Ann O

    2012-05-01

    Mammalian spermatogenesis is characterised by dramatic cellular change to transform the non-polar spermatogonium into a highly polarised and functional spermatozoon. The acquisition of cell polarity is a requisite step for formation of viable sperm. The polarity of the spermatozoon is clearly demonstrated by the acrosome at the apical pole of the cell and the flagellum at the opposite end. Spermatogenesis consists of three basic phases: mitosis, meiosis and spermiogenesis. The final phase represents the period of greatest cellular change where cell-type specific organelles such as the acrosome and the flagellum form, the nucleus migrates to the plasma membrane and elongates, chromatin condenses and residual cytoplasm is removed. An important feature of spermatogenesis is the change in the cytoskeleton that occurs throughout this pathway. In this review, the author will provide an overview of these transformations and provide insight into possible modes of regulation of these rearrangements during spermatogenesis. Although primary focus will be given to the microtubule cytoskeleton, the importance of actin filaments to the cellular transformation of the male germ cell will also be discussed. Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France.

  16. Cell state switching factors and dynamical patterning modules ...

    Indian Academy of Sciences (India)

    Prakash

    Plasticity (i.e. stochastic or condition-dependent variability) of developmental outcome in multicellular organisms is due to two principal mechanisms. The first is largely, though not entirely, a function of differential gene expression and is based on the capacity of individual cells to switch between alternative states under ...

  17. Galectin-9: From cell biology to complex disease dynamics

    Indian Academy of Sciences (India)

    2016-07-16

    Jul 16, 2016 ... properties and functions in both physiological and pathological settings, such as during development, immune .... These findings sug- gest that each CRD has the potential to form oligomers to exert its activity. The recombinant chimeric proteins consisting of two ...... cell and prolongs survival of skin graft.

  18. Particle and Blood Cell Dynamics in Oscillatory Flows Final Report

    International Nuclear Information System (INIS)

    Restrepo, Juan M.

    2008-01-01

    Our aim has been to uncover fundamental aspects of the suspension and dislodgement of particles in wall-bounded oscillatory flows, in flows characterized by Reynolds numbers encompassing the situation found in rivers and near shores (and perhaps in some industrial processes). Our research tools are computational and our coverage of parameter space fairly broad. Computational means circumvent many complications that make the measurement of the dynamics of particles in a laboratory setting an impractical task, especially on the broad range of parameter space we plan to report upon. The impact of this work on the geophysical problem of sedimentation is boosted considerably by the fact that the proposed calculations can be considered ab-initio, in the sense that little to no modeling is done in generating dynamics of the particles and of the moving fluid: we use a three-dimensional Navier Stokes solver along with straightforward boundary conditions. Hence, to the extent that Navier Stokes is a model for an ideal incompressible isotropic Newtonian fluid, the calculations yield benchmark values for such things as the drag, buoyancy, and lift of particles, in a highly controlled environment. Our approach will be to make measurements of the lift, drag, and buoyancy of particles, by considering progressively more complex physical configurations and physics.

  19. Evaluating the Dynamical Stability of Outer Solar System Objects in the Presence of Planet Nine

    OpenAIRE

    Becker, Juliette; Adams, Fred; Khain, Tali; Hamilton, Stephanie; Gerdes, David

    2017-01-01

    We evaluate the dynamical stability of a selection of outer solar system objects in the presence of the proposed new Solar System member Planet Nine. We use a Monte Carlo suite of numerical N-body integrations to construct a variety of orbital elements of the new planet and evaluate the dynamical stability of eight Trans-Neptunian objects (TNOs) in the presence of Planet Nine. These simulations show that some combinations of orbital elements ($a,e$) result in Planet Nine acting as a stabilizi...

  20. American Fuel Cell Bus Project Evaluation. Second Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-09-01

    This report presents results of the American Fuel Cell Bus (AFCB) Project, a demonstration of fuel cell electric buses operating in the Coachella Valley area of California. The prototype AFCB was developed as part of the Federal Transit Administration's (FTA's) National Fuel Cell Bus Program. Through the non-profit consortia CALSTART, a team led by SunLine Transit Agency and BAE Systems developed a new fuel cell electric bus for demonstration. SunLine added two more AFCBs to its fleet in 2014 and another in 2015. FTA and the AFCB project team are collaborating with the U.S. Department of Energy (DOE) and DOE's National Renewable Energy Laboratory to evaluate the buses in revenue service. This report summarizes the performance results for the buses through June 2015.

  1. Regulatory effects on the population dynamics and wave propagation in a cell lineage model.

    Science.gov (United States)

    Wang, Mao-Xiang; Ma, Yu-Qiang; Lai, Pik-Yin

    2016-03-21

    We consider the interplay of cell proliferation, cell differentiation (and de-differentiation), cell movement, and the effect of feedback regulations on the population and propagation dynamics of different cell types in a cell lineage model. Cells are assumed to secrete and respond to negative feedback molecules which act as a control on the cell lineage. The cell densities are described by coupled reaction-diffusion partial differential equations, and the propagating wave front solutions in one dimension are investigated analytically and by numerical solutions. In particular, wavefront propagation speeds are obtained analytically and verified by numerical solutions of the equations. The emphasis is on the effects of the feedback regulations on different stages in the cell lineage. It is found that when the progenitor cell is negatively regulated, the populations of the cell lineage are strongly down-regulated with the steady growth rate of the progenitor cell being driven to zero beyond a critical regulatory strength. An analytic expression for the critical regulation strength in terms of the model parameters is derived and verified by numerical solutions. On the other hand, if the inhibition is acting on the differentiated cells, the change in the population dynamics and wave propagation speed is small. In addition, it is found that only the propagating speed of the progenitor cells is affected by the regulation when the diffusion of the differentiated cells is large. In the presence of de-differentiation, the effect on down-regulating the progenitor population is weakened and there is no effect on the propagation speed due to regulation, suggesting that the effect of regulatory control is diminished by de-differentiation pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 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

    . 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......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...... 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...

  3. Functional evaluation indicates physical losses after hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Clarissa Vasconcellos de Souza

    2012-01-01

    Full Text Available OBJECTIVE: To perform a function evaluation of patients before and after hematopoietic stem cell transplantation. METHODS: From November 2008 to November 2010, 29 female (58% and 21 male patients (42% with median age of 48 years (range: 24-67 were enrolled in this study. Data collection was performed before and after autologous or allogeneic hematopoietic stem cell transplantation. Evaluation instruments included the 2-minute walking test to evaluate gait performance with assessment of the oxygen saturation, heart rate and Borg Scale before and after the test; grip strength for strength evaluation, Schober Test for spine mobility testing and maximum and adapted activity scores of the Human Activity Profile questionnaire to test functionality in daily activities. RESULTS: Fifty patients were evaluated at baseline; six did not undergo hematopoietic stem cell transplantation (three died, one refused and two were excluded. Thus 44/50 (88% - 21 allogeneic and 23 autologous transplantations were performed. Only 33 of the 44 patients (75% performed evaluations after transplantation (nine died and two were excluded. Of the patients who performed both evaluations, significantly lower values were found in the evaluation after transplantation for the 2-minute walking test (p-value = 0.004, grip strength of both right and left hands (p-value = 0.004 and p-value < 0.0001, respectively, the Schober Test, and maximum and adapted activity scores (p-value < 0.0001. The heart rate was higher (p-value = 0.01 before the 2-minute walking test and oxygen saturation was higher (p-value = 0.02 after. CONCLUSION: Statistical differences indicate functional impairment after transplantation showing physical losses in this population.

  4. Dual Control Cell Reaction Ensemble Molecular Dynamics: A Method for Simulations of Reactions and Adsorption in Porous Materials

    National Research Council Canada - National Science Library

    Lisal, Martin; Brennan, John K; Smith, William R; Siperstein, Flor R

    2006-01-01

    .... The method, termed the dual control cell reaction ensemble molecular dynamics method, allows for the calculation of both equilibrium and nonequilibrium transport properties in porous materials...

  5. OCT4: dynamic DNA binding pioneers stem cell pluripotency.

    Science.gov (United States)

    Jerabek, Stepan; Merino, Felipe; Schöler, Hans Robert; Cojocaru, Vlad

    2014-03-01

    OCT4 was discovered more than two decades ago as a transcription factor specific to early embryonic development. Early studies with OCT4 were descriptive and looked at determining the functional roles of OCT4 in the embryo as well as in pluripotent cell lines derived from embryos. Later studies showed that OCT4 was one of the transcription factors in the four-factor cocktail required for reprogramming somatic cells into induced pluripotent stem cells (iPSCs) and that it is the only factor that cannot be substituted in this process by other members of the same protein family. In recent years, OCT4 has emerged as a master regulator of the induction and maintenance of cellular pluripotency, with crucial roles in the early stages of differentiation. Currently, mechanistic studies look at elucidating the molecular details of how OCT4 contributes to establishing selective gene expression programs that define different developmental stages of pluripotent cells. OCT4 belongs to the POU family of proteins, which have two conserved DNA-binding domains connected by a variable linker region. The functions of OCT4 depend on its ability to recognize and bind to DNA regulatory regions alone or in cooperation with other transcription factors and on its capacity to recruit other factors required to regulate the expression of specific sets of genes. Undoubtedly, future iPSC-based applications in regenerative medicine will benefit from understanding how OCT4 functions. Here we provide an integrated view of OCT4 research conducted to date by reviewing the different functional roles for OCT4 and discussing the current progress in understanding their underlying molecular mechanisms. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. © 2013.

  6. 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.

  7. Evaluation of high-energy lithium thionyl chloride primary cells

    Science.gov (United States)

    Frank, H. A.

    1980-02-01

    An advanced commercial primary lithium cell (LiSoCl2) was evaluated in order to establish baseline data for improved lithium batteries for aerospace applications. The cell tested had nominal capacity of 6 Ah. Maximum energy density at low rates (less than C/30, where C is the cell capacity in amp-hrs and 30 corresponds to a 30 hr discharge time) was found to be near 300 Wh/kg. An equation which predicts the operating voltage of these cells as a function of current and state of charge is presented. Heat generation rates of these cells were determined as a function of current in a calorimeter. It was found that heat rates could be theoretically predicted with some degree of accuracy at currents less than 1 amp or the C/6 rate. No explosions were observed in the cells during the condition of overdischarge or reversal nor during high rate discharge. It was found, however, that the cells can vent when overdischarge currents are greater than C/30 and when discharge rates are greater than 1.5C.

  8. Evaluation of Isolation Methods for Circulating Tumor Cells (CTCs

    Directory of Open Access Journals (Sweden)

    Galatea Kallergi

    2016-11-01

    Full Text Available Background: Detection of CTCs is a poor prognostic factor for many cancer types; however, their very low frequency represents an obstacle for their detection. The objective of the current study was to compare the performance of commonly used methods for CTCs isolation. Methods: The evaluated methods using spiking experiments of MCF7, SKBR3 and MDA MB-231 breast cancer cell lines were (i ficoll density gradient separation (DGS, (ii red blood cell lysis (Erythrolysis isolation, (iii positive immunomagnetic selection (EpCAM Dynal beads, (iv two different negative immunomagnetic separation systems (Dynal vs Miltenyi CD45 beads as well as (v the Cell Search platform and (vi the ISET system. Results: The recovery rates of Erythrolysis and DGS were 39% and 24%, respectively. Magnetic isolations are ranked from the worse to the best recovery rate as follows:, Myltenyi-anti-CD45 microbeads (24%; Dynal-anti-EpCAM beads (75%; Dynabeads-anti-CD45 (97%. CTCs isolation from blood samples using the CellSearch and ISET systems revealed that the recovery rate for Cell Search and ISET was 52% and 95%, respectively. Conclusions: Dynal-anti-CD45 beads have the best recovery rate compared to other magnetic methods. Furthermore the recovery rate of ISET was higher compared to Cell Search, especially for the more aggressive MDA-MB 231 cell line.

  9. Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program.

    Science.gov (United States)

    Khacho, Mireille; Clark, Alysen; Svoboda, Devon S; Azzi, Joelle; MacLaurin, Jason G; Meghaizel, Cynthia; Sesaki, Hiromi; Lagace, Diane C; Germain, Marc; Harper, Mary-Ellen; Park, David S; Slack, Ruth S

    2016-08-04

    Regulated mechanisms of stem cell maintenance are key to preventing stem cell depletion and aging. While mitochondrial morphology plays a fundamental role in tissue development and homeostasis, its role in stem cells remains unknown. Here, we uncover that mitochondrial dynamics regulates stem cell identity, self-renewal, and fate decisions by orchestrating a transcriptional program. Manipulation of mitochondrial structure, through OPA1 or MFN1/2 deletion, impaired neural stem cell (NSC) self-renewal, with consequent age-dependent depletion, neurogenesis defects, and cognitive impairments. Gene expression profiling revealed ectopic expression of the Notch self-renewal inhibitor Botch and premature induction of transcription factors that promote differentiation. Changes in mitochondrial dynamics regulate stem cell fate decisions by driving a physiological reactive oxygen species (ROS)-mediated process, which triggers a dual program to suppress self-renewal and promote differentiation via NRF2-mediated retrograde signaling. These findings reveal mitochondrial dynamics as an upstream regulator of essential mechanisms governing stem cell self-renewal and fate decisions through transcriptional programming. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. 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.

  11. ZnO nanostructure-modified QCM for dynamic monitoring of cell adhesion and proliferation.

    Science.gov (United States)

    Reyes, Pavel Ivanoff; Duan, Ziqing; Lu, Yicheng; Khavulya, Dmitry; Boustany, Nada

    2013-03-15

    Noninvasive examination of live cell function in real-time is essential in advancing the understanding of the dynamic progression of cell's biological processes. We present a dynamic and noninvasive method of monitoring the adhesion and proliferation of bovine aortic endothelial cells (BAEC) using a ZnO nanostructure-modified quartz crystal microbalance (ZnOnano-QCM) biosensor. The ZnOnano-QCM biosensor consists of a conventional QCM with ZnO nanostructures directly grown on its sensing electrode deployed in-situ of a standard cell culture environment. Cell adhesion to the ZnO surfaces with various morphologies is studied and the optimal morphology is chosen for the BAEC adhesion. The ZnOnano-QCM biosensor displays enhanced sensitivity compared to the standard QCM sensor with ~10 times higher frequency shift and motional inductance, and ~4 times higher measured motional resistance at full confluency. The dynamic motional resistance and inductance relating to the cells' viscoelastic properties during growth are extracted from the measured time-evolving acoustic spectra. The Butterworth-Van-Dyck (BVD) model is adapted for the ZnOnano-QCM biosensor system and is used to correlate the measured time-evolving acoustic spectra with the motional characteristics of cell attachment and proliferation. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. 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

  13. A nonlinear dynamics approach for incorporating wind-speed patterns into wind-power project evaluation.

    Science.gov (United States)

    Huffaker, Ray; Bittelli, Marco

    2015-01-01

    Wind-energy production may be expanded beyond regions with high-average wind speeds (such as the Midwest U.S.A.) to sites with lower-average speeds (such as the Southeast U.S.A.) by locating favorable regional matches between natural wind-speed and energy-demand patterns. A critical component of wind-power evaluation is to incorporate wind-speed dynamics reflecting documented diurnal and seasonal behavioral patterns. Conventional probabilistic approaches remove patterns from wind-speed data. These patterns must be restored synthetically before they can be matched with energy-demand patterns. How to accurately restore wind-speed patterns is a vexing problem spurring an expanding line of papers. We propose a paradigm shift in wind power evaluation that employs signal-detection and nonlinear-dynamics techniques to empirically diagnose whether synthetic pattern restoration can be avoided altogether. If the complex behavior of observed wind-speed records is due to nonlinear, low-dimensional, and deterministic system dynamics, then nonlinear dynamics techniques can reconstruct wind-speed dynamics from observed wind-speed data without recourse to conventional probabilistic approaches. In the first study of its kind, we test a nonlinear dynamics approach in an application to Sugarland Wind-the first utility-scale wind project proposed in Florida, USA. We find empirical evidence of a low-dimensional and nonlinear wind-speed attractor characterized by strong temporal patterns that match up well with regular daily and seasonal electricity demand patterns.

  14. Scientific considerations for the regulatory evaluation of cell therapy products.

    Science.gov (United States)

    Petricciani, John; Hayakawa, Takao; Stacey, Glyn; Trouvin, Jean-Hugues; Knezevic, Ivana

    2017-11-01

    Cell therapy involves the administration of a viable somatic cell preparation to a patient for the treatment of a disease or traumatic damage. Because cell therapies are complex and very different from traditional biological products, they present significant challenges for regulatory authorities, manufacturers, developers, health care providers, and patients involved in their application. Like other emerging areas of biomedical research and development, there are many issues where regulatory views and decisions among countries and regions may differ due to minimal scientific evidence to support safety and efficacy, and lack of experience with these novel treatments. A brief overview of the current regulatory landscape for cell-based therapies is presented, and the need for a global effort to develop a set of common principles that may serve to facilitate the regulatory evaluation and market availability of these products is identified. In addition, a number of elements that could form a core consensus package of requirements for evaluating human cell therapy products is presented in the supplemental material which should be read in conjunction with the manuscript. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Evaluation of JRR-4 neutron beam using tumor cells

    International Nuclear Information System (INIS)

    Yamamoto, Kazuyoshi; Kumada, Hiroaki; Torii, Yoshiya; Kishi, Toshiaki; Horiguchi, Yoji

    2001-03-01

    For preparation of irradiation plan of boron-neutron capture therapy (BNCT), not only the physical dose is important, but also weighted factors or RBE are also necessary on the evaluation of the effect on the organism. Physical dose calculated by dose evaluation system (JCDS : JAERI Computational Dosimetry System) must appropriately carry out the weighting by various cells like tumor, central nerve, glia, and the vascular in proportion to JRR-4 each irradiation mode. In-vitro biological experiment which used 9L gliosarcoma and C6 glioma in the head water phantom was carried out in order to evaluate these effect. Neutron beam characteristics of JRR-4 were also evaluated from the functions of survival fraction of these cells. As a result of the evaluation, it became clear that the dose evaluation calculated from physical dose of the boron and nitrogen carried out in traditional BNCT of Japan using thermal neutron is applicable for thermal and epi-thermal mixed neutron beam. (author)

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

    Directory of Open Access Journals (Sweden)

    Ryusuke Yokoyama

    2016-11-01

    Full Text Available 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.

  17. 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)

  18. A system dynamics evaluation model: implementation of health information exchange for public health reporting.

    Science.gov (United States)

    Merrill, Jacqueline A; Deegan, Michael; Wilson, Rosalind V; Kaushal, Rainu; Fredericks, Kimberly

    2013-06-01

    To evaluate the complex dynamics involved in implementing electronic health information exchange (HIE) for public health reporting at a state health department, and to identify policy implications to inform similar implementations. Qualitative data were collected over 8 months from seven experts at New York State Department of Health who implemented web services and protocols for querying, receipt, and validation of electronic data supplied by regional health information organizations. Extensive project documentation was also collected. During group meetings experts described the implementation process and created reference modes and causal diagrams that the evaluation team used to build a preliminary model. System dynamics modeling techniques were applied iteratively to build causal loop diagrams representing the implementation. The diagrams were validated iteratively by individual experts followed by group review online, and through confirmatory review of documents and artifacts. Three casual loop diagrams captured well-recognized system dynamics: Sliding Goals, Project Rework, and Maturity of Resources. The findings were associated with specific policies that address funding, leadership, ensuring expertise, planning for rework, communication, and timeline management. This evaluation illustrates the value of a qualitative approach to system dynamics modeling. As a tool for strategic thinking on complicated and intense processes, qualitative models can be produced with fewer resources than a full simulation, yet still provide insights that are timely and relevant. System dynamics techniques clarified endogenous and exogenous factors at play in a highly complex technology implementation, which may inform other states engaged in implementing HIE supported by federal Health Information Technology for Economic and Clinical Health (HITECH) legislation.

  19. 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.

  20. 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.

  1. Process-oriented statistical-dynamical evaluation of LM precipitation forecasts

    Directory of Open Access Journals (Sweden)

    A. Claußnitzer

    2008-04-01

    Full Text Available The objective of this study is the scale dependent evaluation of precipitation forecasts of the Lokal-Modell (LM from the German Weather Service in relation to dynamical and cloud parameters. For this purpose the newly designed Dynamic State Index (DSI is correlated with clouds and precipitation. The DSI quantitatively describes the deviation and relative distance from a stationary and adiabatic solution of the primitive equations. A case study and statistical analysis of clouds and precipitation demonstrates the availability of the DSI as a dynamical threshold parameter. This confirms the importance of imbalances of the atmospheric flow field, which dynamically induce the generation of rainfall.

  2. An evaluation of biosurveillance grid--dynamic algorithm distribution across multiple computer nodes.

    Science.gov (United States)

    Tsai, Ming-Chi; Tsui, Fu-Chiang; Wagner, Michael M

    2007-10-11

    Performing fast data analysis to detect disease outbreaks plays a critical role in real-time biosurveillance. In this paper, we described and evaluated an Algorithm Distribution Manager Service (ADMS) based on grid technologies, which dynamically partition and distribute detection algorithms across multiple computers. We compared the execution time to perform the analysis on a single computer and on a grid network (3 computing nodes) with and without using dynamic algorithm distribution. We found that algorithms with long runtime completed approximately three times earlier in distributed environment than in a single computer while short runtime algorithms performed worse in distributed environment. A dynamic algorithm distribution approach also performed better than static algorithm distribution approach. This pilot study shows a great potential to reduce lengthy analysis time through dynamic algorithm partitioning and parallel processing, and provides the opportunity of distributing algorithms from a client to remote computers in a grid network.

  3. An Evaluation of Biosurveillance Grid—Dynamic Algorithm Distribution Across Multiple Computer Nodes

    Science.gov (United States)

    Tsai, Ming-Chi; Tsui, Fu-Chiang; Wagner, Michael M.

    2007-01-01

    Performing fast data analysis to detect disease outbreaks plays a critical role in real-time biosurveillance. In this paper, we described and evaluated an Algorithm Distribution Manager Service (ADMS) based on grid technologies, which dynamically partition and distribute detection algorithms across multiple computers. We compared the execution time to perform the analysis on a single computer and on a grid network (3 computing nodes) with and without using dynamic algorithm distribution. We found that algorithms with long runtime completed approximately three times earlier in distributed environment than in a single computer while short runtime algorithms performed worse in distributed environment. A dynamic algorithm distribution approach also performed better than static algorithm distribution approach. This pilot study shows a great potential to reduce lengthy analysis time through dynamic algorithm partitioning and parallel processing, and provides the opportunity of distributing algorithms from a client to remote computers in a grid network. PMID:18693936

  4. 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.

  5. Lineage correlations of single cell division time as a probe of cell-cycle dynamics.

    Science.gov (United States)

    Sandler, Oded; Mizrahi, Sivan Pearl; Weiss, Noga; Agam, Oded; Simon, Itamar; Balaban, Nathalie Q

    2015-03-26

    Stochastic processes in cells are associated with fluctuations in mRNA, protein production and degradation, noisy partition of cellular components at division, and other cell processes. Variability within a clonal population of cells originates from such stochastic processes, which may be amplified or reduced by deterministic factors. Cell-to-cell variability, such as that seen in the heterogeneous response of bacteria to antibiotics, or of cancer cells to treatment, is understood as the inevitable consequence of stochasticity. Variability in cell-cycle duration was observed long ago; however, its sources are still unknown. A central question is whether the variance of the observed distribution originates from stochastic processes, or whether it arises mostly from a deterministic process that only appears to be random. A surprising feature of cell-cycle-duration inheritance is that it seems to be lost within one generation but to be still present in the next generation, generating poor correlation between mother and daughter cells but high correlation between cousin cells. This observation suggests the existence of underlying deterministic factors that determine the main part of cell-to-cell variability. We developed an experimental system that precisely measures the cell-cycle duration of thousands of mammalian cells along several generations and a mathematical framework that allows discrimination between stochastic and deterministic processes in lineages of cells. We show that the inter- and intra-generation correlations reveal complex inheritance of the cell-cycle duration. Finally, we build a deterministic nonlinear toy model for cell-cycle inheritance that reproduces the main features of our data. Our approach constitutes a general method to identify deterministic variability in lineages of cells or organisms, which may help to predict and, eventually, reduce cell-to-cell heterogeneity in various systems, such as cancer cells under treatment.

  6. Comparison of static model and dynamic model for the evaluation of station blackout sequences

    International Nuclear Information System (INIS)

    Lee, Kwang-Nam; Kang, Sun-Koo; Hong, Sung-Yull.

    1992-01-01

    Station blackout is one of major contributors to the core damage frequency (CDF) in many PSA studies. Since station blackout sequence exhibits dynamic features, accurate calculation of CDF for the station blackout sequence is not possible with event tree/fault tree (ET/FT) method. Although the integral method can determine accurate CDF, it is time consuming and is difficult to evaluate various alternative AC source configuration and sensitivities. In this study, a comparison is made between static model and dynamic model and a new methodology which combines static model and dynamic model is provided for the accurate quantification of CDF and evaluation of improvement alternatives. Results of several case studies show that accurate calculation of CDF is possible by introducing equivalent mission time. (author)

  7. Bioluminescent system for dynamic imaging of cell and animal behavior

    Energy Technology Data Exchange (ETDEWEB)

    Hara-Miyauchi, Chikako [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198 (Japan); Department of Biophysics and Biochemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo 113-8510 (Japan); Tsuji, Osahiko [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582 (Japan); Hanyu, Aki [Division of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo 135-8550 (Japan); Okada, Seiji [Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Yasuda, Akimasa [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582 (Japan); Fukano, Takashi [Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198 (Japan); Akazawa, Chihiro [Department of Biophysics and Biochemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo 113-8510 (Japan); Nakamura, Masaya [Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582 (Japan); Imamura, Takeshi [Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295 (Japan); Core Research for Evolutional Science and Technology, The Japan Science and Technology Corporation, Tokyo 135-8550 (Japan); Matsuzaki, Yumi [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Okano, Hirotaka James, E-mail: hjokano@jikei.ac.jp [Department of Physiology, Keio University School of Medicine, Tokyo 160-8582 (Japan); Division of Regenerative Medicine Jikei University School of Medicine, Tokyo 150-8461 (Japan); and others

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer We combined a yellow variant of GFP and firefly luciferase to make ffLuc-cp156. Black-Right-Pointing-Pointer ffLuc-cp156 showed improved photon yield in cultured cells and transgenic mice. Black-Right-Pointing-Pointer ffLuc-cp156 enabled video-rate bioluminescence imaging of freely-moving animals. Black-Right-Pointing-Pointer ffLuc-cp156 mice enabled tracking real-time drug delivery in conscious animals. -- Abstract: The current utility of bioluminescence imaging is constrained by a low photon yield that limits temporal sensitivity. Here, we describe an imaging method that uses a chemiluminescent/fluorescent protein, ffLuc-cp156, which consists of a yellow variant of Aequorea GFP and firefly luciferase. We report an improvement in photon yield by over three orders of magnitude over current bioluminescent systems. We imaged cellular movement at high resolution including neuronal growth cones and microglial cell protrusions. Transgenic ffLuc-cp156 mice enabled video-rate bioluminescence imaging of freely moving animals, which may provide a reliable assay for drug distribution in behaving animals for pre-clinical studies.

  8. Bioluminescent system for dynamic imaging of cell and animal behavior

    International Nuclear Information System (INIS)

    Hara-Miyauchi, Chikako; Tsuji, Osahiko; Hanyu, Aki; Okada, Seiji; Yasuda, Akimasa; Fukano, Takashi; Akazawa, Chihiro; Nakamura, Masaya; Imamura, Takeshi; Matsuzaki, Yumi; Okano, Hirotaka James

    2012-01-01

    Highlights: ► We combined a yellow variant of GFP and firefly luciferase to make ffLuc-cp156. ► ffLuc-cp156 showed improved photon yield in cultured cells and transgenic mice. ► ffLuc-cp156 enabled video-rate bioluminescence imaging of freely-moving animals. ► ffLuc-cp156 mice enabled tracking real-time drug delivery in conscious animals. -- Abstract: The current utility of bioluminescence imaging is constrained by a low photon yield that limits temporal sensitivity. Here, we describe an imaging method that uses a chemiluminescent/fluorescent protein, ffLuc-cp156, which consists of a yellow variant of Aequorea GFP and firefly luciferase. We report an improvement in photon yield by over three orders of magnitude over current bioluminescent systems. We imaged cellular movement at high resolution including neuronal growth cones and microglial cell protrusions. Transgenic ffLuc-cp156 mice enabled video-rate bioluminescence imaging of freely moving animals, which may provide a reliable assay for drug distribution in behaving animals for pre-clinical studies.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Dynamic Evaluation of Two Decades of CMAQ Simulations over the Continental United States (book chapter)

    Science.gov (United States)

    This paper focuses on dynamic evaluation of the CMAQ model over the continental United States using multi-decadal simulations for the period from 1990 to 2010 to examine how well the changes in observed ozone air quality induced by variations in meteorology and/or emissions are s...

  11. Evaluation of Student Models on Current Socio-Scientific Topics Based on System Dynamics

    Science.gov (United States)

    Nuhoglu, Hasret

    2014-01-01

    This study aims to 1) enable primary school students to develop models that will help them understand and analyze a system, through a learning process based on system dynamics approach, 2) examine and evaluate students' models related to socio-scientific issues using certain criteria. The research method used is a case study. The study sample…

  12. Time-Varying Dynamic Properties of Offshore Wind Turbines Evaluated by Modal Testing

    DEFF Research Database (Denmark)

    Damgaard, Mads; Andersen, J. K. F.; Ibsen, Lars Bo

    2014-01-01

    resonance of the wind turbine structure. In this paper, free vibration tests and a numerical Winkler type approach are used to evaluate the dynamic properties of a total of 30 offshore wind turbines located in the North Sea. Analyses indicate time-varying eigenfrequencies and damping ratios of the lowest...

  13. Evaluation of the readsorption of plutonium and americium in dynamic fractionations of environmental solid samples

    DEFF Research Database (Denmark)

    Petersen, Roongrat; Hou, Xiaolin; Hansen, Elo Harald

    2008-01-01

    extractions. The degree of readsorption in dynamic and conventional batch extraction systems are compared and evaluated by using a double-spiking technique. A high degree of readsorption of plutonium and americium (>75%) was observed in both systems, and they also exhibited similar distribution patterns...

  14. Comparison of growth kinetics between static and dynamic cultures of human induced pluripotent stem cells.

    Science.gov (United States)

    Kato, Yuma; Kim, Mee-Hae; Kino-Oka, Masahiro

    2018-02-02

    Understanding the fundamental mechanisms that govern the growth kinetics of human induced pluripotent stem cells (hiPSCs) contributes to culture design strategies to improve large-scale production. Two hiPSC lines (Tic and 253G1) were cultured under static and dynamic suspension conditions, and growth kinetics were compared during early (24-48 h), middle (48-72 h), and late (72-96 h) stages. In 2D static culture, similar growth profiles were observed for both hiPSC lines. However, there were significant differences in growth profile patterns and aggregate morphologies between hiPSC lines grown in 3D static and dynamic cultures. Based on immunostaining comparing the two hiPSC lines, surface distribution of collagen type I was observed in aggregates of the Tic line, but not in those of the 253G1 line. Compared to that in 3D static culture, the numbers of cells at 96 h were significantly decreased in 3D dynamic culture. The apparent specific growth rate (μ app ) of the Tic line was maintained continuously throughout culture, whereas that of the 253G1 line decreased gradually with culture until the late phase, at which time this parameter was reduced to μ app  = (0.85 ± 0.71) × 10 -2  h -1 . This indicates that during the growth of hiPSCs in 3D dynamic culture, cells were damaged by liquid flow, which disrupted the cell-synthesized extracellular matrix (ECM). These results demonstrate that cell-synthesized ECM is an important factor affecting cell growth and morphology, and that changes to the ECM within aggregates lead to reduced growth abilities in dynamic culture. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  15. 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.

  16. Dissect the Dynamic Molecular Circuits of Cell Cycle Control through Network Evolution Model

    Directory of Open Access Journals (Sweden)

    Yang Peng

    2017-01-01

    Full Text Available The molecular circuits of cell cycle control serve as a key hub to integrate from endogenous and environmental signals into a robust biological decision driving cell growth and division. Dysfunctional cell cycle control is highlighted in a wide spectrum of human cancers. More importantly the mainstay anticancer treatment such as radiation therapy and chemotherapy targets the hallmark of uncontrolled cell proliferation in cancer cells by causing DNA damage, cell cycle arrest, and cell death. Given the functional importance of cell cycle control, the regulatory mechanisms that drive the cell division have been extensively investigated in a huge number of studies by conventional single-gene approaches. However the complexity of cell cycle control renders a significant barrier to understand its function at a network level. In this study, we used mathematical modeling through modern graph theory and differential equation systems. We believe our network evolution model can help us understand the dynamic cell cycle control in tumor evolution and optimizing dosing schedules for radiation therapy and chemotherapy targeting cell cycle.

  17. 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.

  18. Multiple-Trapping Model for the Charge Recombination Dynamics in Mesoporous-Structured Perovskite Solar Cells.

    Science.gov (United States)

    Wang, Hao-Yi; Wang, Yi; Hao, Ming-Yang; Qin, Yujun; Fu, Li-Min; Guo, Zhi-Xin; Ai, Xi-Cheng; Zhang, Jian-Ping

    2017-12-22

    The photovoltaic performance of organic-inorganic hybrid perovskite solar cells has reached a bottleneck after rapid development in last few years. Further breakthrough in this field requires deeper understanding of the underlying mechanism of the photoelectric conversion process in the device, especially the dynamics of charge-carrier recombination. Originating from dye-sensitized solar cells (DSSCs), mesoporous-structured perovskite solar cells (MPSCs) have shown many similarities to DSSCs with respect to their photoelectric dynamics. Herein, by applying the multiple-trapping model of the charge-recombination dynamic process for DSSCs in MPSCs, with rational modification, a novel physical model is proposed to describe the dynamics of charge recombination in MPSCs that exhibits good agreement with experimental data. Accordingly, the perovskite- and TiO 2 -dominating charge-recombination processes are assigned and their relationships with the trap-state distribution are also discussed. An optimal balance between these two dynamic processes is required to improve the performance of mesoporous-structured perovskite devices. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Harnessing Cell Dynamic Responses on Magnetoelectric Nanocomposite Films to Promote Osteogenic Differentiation.

    Science.gov (United States)

    Tang, Bolin; Zhuang, Junjun; Wang, Liming; Zhang, Bo; Lin, Suya; Jia, Fei; Dong, Lingqing; Wang, Qi; Cheng, Kui; Weng, Wenjian

    2018-03-07

    The binding of cell integrins to proteins adsorbed on the material surface is a highly dynamic process critical for guiding cellular responses. However, temporal dynamic regulation of adsorbed proteins to meet the spatial conformation requirement of integrins for a certain cellular response remains a great challenge. Here, an active CoFe 2 O 4 /poly(vinylidene fluoride-trifluoroethylene) nanocomposite film, which was demonstrated to be an obvious surface potential variation (Δ V ≈ 93 mV) in response to the applied magnetic field intensity (0-3000 Oe), was designed to harness the dynamic binding of integrin-adsorbed proteins by in situ controlling of the conformation of adsorbed proteins. Experimental investigation and molecular dynamics simulation confirmed the surface potential-induced conformational change in the adsorbed proteins. Cells cultured on nanocomposite films indicated that cellular responses in different time periods (adhesion, proliferation, and differentiation) required distinct magnetic field intensity, and synthetically programming the preferred magnetic field intensity of each time period could further enhance the osteogenic differentiation through the FAK/ERK signaling pathway. This work therefore provides a distinct concept that dynamically controllable modulation of the material surface property fitting the binding requirement of different cell time periods would be more conducive to achieving the desired osteogenic differentiation.

  20. Cellular volume regulation and substrate stiffness modulate the detachment dynamics of adherent cells

    Science.gov (United States)

    Yang, Yuehua; Jiang, Hongyuan

    2018-03-01

    Quantitative characterizations of cell detachment are vital for understanding the fundamental mechanisms of cell adhesion. Experiments have found that cell detachment shows strong rate dependence, which is mostly attributed to the binding-unbinding kinetics of receptor-ligand bond. However, our recent study showed that the cellular volume regulation can significantly regulate the dynamics of adherent cell and cell detachment. How this cellular volume regulation contributes to the rate dependence of cell detachment remains elusive. Here, we systematically study the role of cellular volume regulation in the rate dependence of cell detachment by investigating the cell detachments of nonspecific adhesion and specific adhesion. We find that the cellular volume regulation and the bond kinetics dominate the rate dependence of cell detachment at different time scales. We further test the validity of the traditional Johnson-Kendall-Roberts (JKR) contact model and the detachment model developed by Wyart and Gennes et al (W-G model). When the cell volume is changeable, the JKR model is not appropriate for both the detachments of convex cells and concave cells. The W-G model is valid for the detachment of convex cells but is no longer applicable for the detachment of concave cells. Finally, we show that the rupture force of adherent cells is also highly sensitive to substrate stiffness, since an increase in substrate stiffness will lead to more associated bonds. These findings can provide insight into the critical role of cell volume in cell detachment and might have profound implications for other adhesion-related physiological processes.

  1. Models of dynamic extraction of lipid tethers from cell membranes

    International Nuclear Information System (INIS)

    Nowak, Sarah A; Chou, Tom

    2010-01-01

    When a ligand that is bound to an integral membrane receptor is pulled, the membrane and the underlying cytoskeleton can deform before either the membrane delaminates from the cytoskeleton or the ligand detaches from the receptor. If the membrane delaminates from the cytoskeleton, it may be further extruded and form a membrane tether. We develop a phenomenological model for this process by assuming that deformations obey Hooke's law up to a critical force at which the cell membrane locally detaches from the cytoskeleton and a membrane tether forms. We compute the probability of tether formation and show that tethers can be extruded only within an intermediate range of force loading rates and pulling velocities. The mean tether length that arises at the moment of ligand detachment is computed as are the force loading rates and pulling velocities that yield the longest tethers

  2. BC Transit Fuel Cell Bus Project Evaluation Results: Second Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Post, M.

    2014-09-01

    Second report evaluating a fuel cell electric bus (FCEB) demonstration led by British Columbia Transit (BC Transit) in Whistler, Canada. BC Transit is collaborating with the California Air Resources Board and the U.S. Department of Energy's National Renewable Energy Laboratory to evaluate the buses in revenue service. NREL published its first report on the demonstration in February 2014. This report is an update to the previous report; it covers 3 full years of revenue service data on the buses from April 2011 through March 2014 and focuses on the final experiences and lessons learned.

  3. 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.

  4. Live imaging reveals the progenitors and cell dynamics of limb regeneration.

    Science.gov (United States)

    Alwes, Frederike; Enjolras, Camille; Averof, Michalis

    2016-10-25

    Regeneration is a complex and dynamic process, mobilizing diverse cell types and remodelling tissues over long time periods. Tracking cell fate and behaviour during regeneration in active adult animals is especially challenging. Here, we establish continuous live imaging of leg regeneration at single-cell resolution in the crustacean Parhyale hawaiensis . By live recordings encompassing the first 4-5 days after amputation, we capture the cellular events that contribute to wound closure and morphogenesis of regenerating legs with unprecedented resolution and temporal detail. Using these recordings we are able to track cell lineages, to generate fate maps of the blastema and to identify the progenitors of regenerated epidermis. We find that there are no specialized stem cells for the epidermis. Most epidermal cells in the distal part of the leg stump proliferate, acquire new positional values and contribute to new segments in the regenerating leg.

  5. Cytotoxicity evaluation of silica nanoparticles using fish cell lines.

    Science.gov (United States)

    Vo, Nguyen T K; Bufalino, Mary R; Hartlen, Kurtis D; Kitaev, Vladimir; Lee, Lucy E J

    2014-01-01

    Nanoparticles (NPs) have extensive industrial, biotechnological, and biomedical/pharmaceutical applications, leading to concerns over health risks to humans and biota. Among various types of nanoparticles, silica nanoparticles (SiO2 NPs) have become popular as nanostructuring, drug delivery, and optical imaging agents. SiO2 NPs are highly stable and could bioaccumulate in the environment. Although toxicity studies of SiO2 NPs to human and mammalian cells have been reported, their effects on aquatic biota, especially fish, have not been significantly studied. Twelve adherent fish cell lines derived from six species (rainbow trout, fathead minnow, zebrafish, goldfish, haddock, and American eel) were used to comparatively evaluate viability of cells by measuring metabolic impairment using Alamar Blue. Toxicity of SiO2 NPs appeared to be size-, time-, temperature-, and dose-dependent as well as tissue-specific. However, dosages greater than 100 μg/mL were needed to achieve 24 h EC50 values (effective concentrations needed to reduce cell viability by 50%). Smaller SiO2 NPs (16 nm) were relatively more toxic than larger sized ones (24 and 44 nm) and external lining epithelial tissue (skin, gills)-derived cells were more sensitive than cells derived from internal tissues (liver, brain, intestine, gonads) or embryos. Higher EC50 values were achieved when toxicity assessment was performed at higher incubation temperatures. These findings are in overall agreement with similar human and mouse cell studies reported to date. Thus, fish cell lines could be valuable for screening emerging contaminants in aquatic environments including NPs through rapid high-throughput cytotoxicity bioassays.

  6. Isotropic averaging for cell-dynamical-system simulation of spinodal ...

    Indian Academy of Sciences (India)

    HOT stands for higher order terms. Substituting the above in (1) we get. ¯ψ0 =ψ0 + 1. 2 n. ∑ i 1. ∂2ψ. ∂x2 i. 0. Á. ∂Ω x2 i ds. Á. ∂Ω. ds+HOT. In order to evaluate the integral in the above equation, we express the variables x1,x2, ...,xn on the surface of the 'sphere' in terms of the angles θ1,θ2, ...,θn 1, by x1 =ε cosθ1.

  7. American Fuel Cell Bus Project Evaluation: Third Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States); Jeffers, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-05-01

    This report presents results of the American Fuel Cell Bus (AFCB) Project, a demonstration of fuel cell electric buses operating in the Coachella Valley area of California. The prototype AFCB, which was developed as part of the Federal Transit Administration's (FTA) National Fuel Cell Bus Program, was delivered to SunLine in November 2011 and was put in revenue service in mid-December 2011. Two new AFCBs with an upgraded design were delivered in June/July of 2014 and a third new AFCB was delivered in February 2015. FTA and the AFCB project team are collaborating with the U.S. Department of Energy (DOE) and DOE's National Renewable Energy Laboratory to evaluate the buses in revenue service. This report covers the performance of the AFCBs from July 2015 through December 2016.

  8. 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…

  9. Optimization of a new flow design for solid oxide cells using computational fluid dynamics modelling

    DEFF Research Database (Denmark)

    Duhn, Jakob Dragsbæk; Jensen, Anker Degn; Wedel, Stig

    2016-01-01

    Design of a gas distributor to distribute gas flow into parallel channels for Solid Oxide Cells (SOC) is optimized, with respect to flow distribution, using Computational Fluid Dynamics (CFD) modelling. The CFD model is based on a 3d geometric model and the optimized structural parameters include...

  10. Tracking the Dynamic Folding and Unfolding of RNA G-Quadruplexes in Live Cells.

    Science.gov (United States)

    Chen, Xiu-Cai; Chen, Shuo-Bin; Dai, Jing; Yuan, Jia-Hao; Ou, Tian-Miao; Huang, Zhi-Shu; Tan, Jia-Heng

    2018-04-16

    Because of the absence of methods for tracking RNA G-quadruplex dynamics, especially the folding and unfolding of this attractive structure in live cells, understanding of the biological roles of RNA G-quadruplexes is so far limited. Herein, we report a new red-emitting fluorescent probe, QUMA-1, for the selective, continuous, and real-time visualization of RNA G-quadruplexes in live cells. The applications of QUMA-1 in several previously intractable applications, including live-cell imaging of the dynamic folding, unfolding, and movement of RNA G-quadruplexes and the visualization of the unwinding of RNA G-quadruplexes by RNA helicase have been demonstrated. Notably, our real-time results revealed the complexity of the dynamics of RNA G-quadruplexes in live cells. We anticipate that the further application of QUMA-1 in combination with appropriate biological and imaging methods to explore the dynamics of RNA G-quadruplexes will uncover more information about the biological roles of RNA G-quadruplexes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Computational fluid dynamics characterization of a novel mixed cell raceway design

    Science.gov (United States)

    Computational fluid dynamics (CFD) analysis was performed on a new type of mixed cell raceway (MCR) that incorporates longitudinal plug flow using inlet and outlet weirs for the primary fraction of the total flow. As opposed to regular MCR wherein vortices are entirely characterized by the boundary ...

  12. 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

  13. 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)

  14. 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

  15. 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

  16. Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice

    Science.gov (United States)

    Hayes, N. L.; Nowakowski, R. S.

    2002-01-01

    The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'.

  17. Towards the rational design of synthetic cells with prescribed population dynamics

    Science.gov (United States)

    Dalchau, Neil; Smith, Matthew J.; Martin, Samuel; Brown, James R.; Emmott, Stephen; Phillips, Andrew

    2012-01-01

    The rational design of synthetic cell populations with prescribed behaviours is a long-standing goal of synthetic biology, with the potential to greatly accelerate the development of biotechnological applications in areas ranging from medical research to energy production. Achieving this goal requires well-characterized components, modular implementation strategies, simulation across temporal and spatial scales and automatic compilation of high-level designs to low-level genetic parts that function reliably inside cells. Many of these steps are incomplete or only partially understood, and methods for integrating them within a common design framework have yet to be developed. Here, we address these challenges by developing a prototype framework for designing synthetic cells with prescribed population dynamics. We extend the genetic engineering of cells (GEC) language, originally developed for programming intracellular dynamics, with cell population factors such as cell growth, division and dormancy, together with spatio-temporal simulation methods. As a case study, we use our framework to design synthetic cells with predator–prey interactions that, when simulated, produce complex spatio-temporal behaviours such as travelling waves and spatio-temporal chaos. An analysis of our design reveals that environmental factors such as density-dependent dormancy and reduced extracellular space destabilize the population dynamics and increase the range of genetic variants for which complex spatio-temporal behaviours are possible. Our findings highlight the importance of considering such factors during the design process. We then use our analysis of population dynamics to inform the selection of genetic parts, which could be used to obtain the desired spatio-temporal behaviours. By identifying, integrating and automating key stages of the design process, we provide a computational framework for designing synthetic systems, which could be tested in future laboratory studies

  18. Dynamics, ultrastructure and gene expression of human in vitro organized testis cells from testicular sperm extraction biopsies.

    Science.gov (United States)

    von Kopylow, Kathrein; Schulze, Wolfgang; Salzbrunn, Andrea; Schaks, Matthias; Schäfer, Elke; Roth, Beate; Schlatt, Stefan; Spiess, Andrej-Nikolai

    2018-03-01

    ) (STAR), undifferentiated spermatogonia (FGFR3), differentiating spermatogonia/spermatocytes (DDX4) and postmeiotic germ cells (PRM1). Single clusters from four patients and a pool of eight larger clusters from another patient were manually picked and subjected to quantitative real-time PCR to evaluate the presence of SC (SOX9, AR), LC (INSL3, STAR, HSD3B1), peritubular myoid cells (ACTA2), fibroblasts (FSP1), endothelial cells (CD34), macrophages (CD68), undifferentiated spermatogonia (FGFR3), differentiating spermatogonia/spermatocytes (DDX4) and postmeiotic germ cells (PRM1). Finally, an ultrastructural investigation was conducted based on TEM of clusters from six different patients, among them 3-month cultivated large clusters from two patients. Quantitative PCR-based analysis of single-picked testicular cell clusters identified SC, peritubular myoid cells, endothelial cells, fibroblasts, macrophages, spermatids and LC after 1, 2 or 3 weeks or 3 months of cultivation. Immunofluorescence positivity for SC and peritubular myoid cells corroborated the presence of these two kinds of testis niche cells. In addition, round as well as elongated spermatids were frequently encountered in 1 and 2 weeks old clusters. Transmission electron microscopical classification confirmed all these cell types together with a few spermatogonia. Macrophages were found to be of the proinflammatory M1 subtype, as revealed by CD68+/CD163-/IL6+ expression. Time-lapse imaging uncovered the specific dynamics of cluster fusion and enlargement, which could be prevented by addition of protein kinase inhibitor K252a. N/A. Cell composition of the clusters varied based on the spermatogenic state of the TESE patient. Although spermatids could be observed with all applied methods, spermatogonia were only detected by TEM in single cases. Hence, a direct maintenance of these germ cell types by our system in its current state cannot be postulated. Moreover, putative dedifferentiation and malignant

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

    Science.gov (United States)

    Fox, Grace E; Li, Meng; Zhao, Fang; Tsien, Joe Z

    2017-01-01

    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.

  20. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Chen Tianxiang

    2012-01-01

    Full Text Available Abstract Background Intratumoral and circulating regulatory T cells (Tregs have been shown to be critical in the pathogenesis of hepatocellular carcinoma (HCC. However there is limited knowledge on the alterations of regulatory B cells (Bregs. We here investigated perioperative dynamic alterations of peripheral circulating Tregs and Bregs in HCC patients to reveal the relationship between regulatory lymphocytes and its clinical implications. Methods 36 patients with HCC, 6 with chronic hepatitis B infection and 10 healthy donors were enrolled for this study. Frequencies of peripheral Tregs and Bregs were measured by flow cytometry with antibodies against CD4, CD25, CD127, CD19 and IL-10 before, and after radical surgery. Then, clinical informatics of HCC patients was achieved through Digital Evaluation Score System (DESS for the assessment of disease severity. Finally, we analysed correlations between digitalized clinical features and kinetics of circulating regulatory lymphocytes. Results Level of circulating CD4+CD25+CD127- Tregs in HCC patients was significantly lower than that in healthy donors and patients with chronic hepatitis B infection before surgery, but was increased after surgery. Preoperative level of CD19+ IL-10+ Bregs in HCC patients was also significantly lower than the other groups. However it dramatically was elevated right after surgery and remained elevated compared to controls (about 7 days after surgery, P = 0.04. Frequency of circulating Tregs was correlated with circulating leukocytes, ferritin, and clinical features suggesting tumor aggressiveness including portal vein thrombosis, hepatic vein involvement and advanced clinical stages. Frequency of circulating Bregs was associated with Hepatitis B e Antigen (HBeAg and Hepatitis B virus (HBV DNA copy number. In addition, DESS was significantly and positively correlated with other staging systems. Conclusion Frequencies of peripheral Tregs and Bregs in HCC patients

  3. 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

    in experimental single-cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single-cell observations and validation...... and description of cell cultivations, where average cell behaviors observed experimentally now are interpreted as a potential joint result of various co-existing single-cell behaviors, rather than a unique response common to all cells in the cultivation.......Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro-environmental conditions. A major development...

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    David S. Domozych

    2014-11-01

    Full Text Available Penium margaritaceum is a new and valuable unicellular model organism for studying plant cell wall structure and developmental dynamics. This charophyte has a cell wall composition remarkably similar to the primary cell wall of many higher plants and clearly-defined inclusive zones containing specific polymers. Penium has a simple cylindrical phenotype with a distinct region of focused wall synthesis. Specific polymers, particularly pectins, can be identified using monoclonal antibodies raised against polymers of higher plant cell walls. Immunofluorescence-based labeling is easily performed using live cells that subsequently can be returned to culture and monitored. This feature allows for rapid assessment of wall expansion rates and identification of multiple polymer types in the wall microarchitecture during the cell cycle. Cryofixation by means of spray freezing provides excellent transmission electron microscopy imaging of the cell, including its elaborate endomembrane and cytoskeletal systems, both integral to cell wall development. Penium’s fast growth rate allows for convenient microarray screening of various agents that alter wall biosynthesis and metabolism. Finally, recent successful development of transformed cell lines has allowed for non-invasive imaging of proteins in cells and for RNAi reverse genetics that can be used for cell wall biosynthesis studies.

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

    Science.gov (United States)

    Domozych, David S

    2014-11-18

    Penium margaritaceum is a new and valuable unicellular model organism for studying plant cell wall structure and developmental dynamics. This charophyte has a cell wall composition remarkably similar to the primary cell wall of many higher plants and clearly-defined inclusive zones containing specific polymers. Penium has a simple cylindrical phenotype with a distinct region of focused wall synthesis. Specific polymers, particularly pectins, can be identified using monoclonal antibodies raised against polymers of higher plant cell walls. Immunofluorescence-based labeling is easily performed using live cells that subsequently can be returned to culture and monitored. This feature allows for rapid assessment of wall expansion rates and identification of multiple polymer types in the wall microarchitecture during the cell cycle. Cryofixation by means of spray freezing provides excellent transmission electron microscopy imaging of the cell, including its elaborate endomembrane and cytoskeletal systems, both integral to cell wall development. Penium's fast growth rate allows for convenient microarray screening of various agents that alter wall biosynthesis and metabolism. Finally, recent successful development of transformed cell lines has allowed for non-invasive imaging of proteins in cells and for RNAi reverse genetics that can be used for cell wall biosynthesis studies.

  7. Cell-scale dynamic recycling and cortical flow of the actin–myosin cytoskeleton for rapid cell migration

    Directory of Open Access Journals (Sweden)

    Shigehiko Yumura

    2012-11-01

    Actin and myosin II play major roles in cell migration. Whereas pseudopod extension by actin polymerization has been intensively researched, less attention has been paid to how the rest of the actin cytoskeleton such as the actin cortex contributes to cell migration. In this study, cortical actin and myosin II filaments were simultaneously observed in migrating Dictyostelium cells under total internal reflection fluorescence microscopy. The cortical actin and myosin II filaments remained stationary with respect to the substratum as the cells advanced. However, fluorescence recovery after photobleaching experiments and direct observation of filaments showed that they rapidly turned over. When the cells were detached from the substratum, the actin and myosin filaments displayed a vigorous retrograde flow. Thus, when the cells migrate on the substratum, the cortical cytoskeleton firmly holds the substratum to generate the motive force instead. The present studies also demonstrate how myosin II localizes to the rear region of the migrating cells. The observed dynamic turnover of actin and myosin II filaments contributes to the recycling of their subunits across the whole cell and enables rapid reorganization of the cytoskeleton.

  8. Structural constraints and dynamics of bacterial cell wall architecture

    Directory of Open Access Journals (Sweden)

    Miguel Angel De Pedro

    2015-05-01

    Full Text Available The peptidoglycan wall (PG is a unique structure which confers physical strength and defined shape to bacteria. It consists of a net-like macromolecule of peptide interlinked glycan chains overlying the cell membrane. The structure and layout of the PG dictates that the wall has to be continuously modified as bacteria go through division, morphological differentiation and adaptive responses. The PG is poorly known in structural terms. However, to understand morphogenesis a precise knowledge of glycan strand arrangement and of local effects of the different kinds of subunits is essential. The scarcity of data led to a conception of the PG as a regular, highly ordered structure which strongly influenced growth models. Here, we review the structure of the PG to define a more realistic conceptual framework. We discuss the consequences of the plasticity of murein architecture in morphogenesis and try to define a set of minimal structural constraints that must be fulfilled by any model to be compatible with present day information.

  9. Using Speckle Dynamics for Comparison of the Metabolic Activity of Different Cell Cultures

    Science.gov (United States)

    Vladimirov, A. P.; Malygin, A. S.; Mikhailova, Yu. A.; Borodin, E. M.; Bakharev, A. A.; Poryvaeva, A. P.

    2015-01-01

    The dynamics of speckles in the image plane of a monolayer of cells cultivated on a glass substrate has been recorded. Cell cultures HEL-3, L-41, and Vero were selected as the objects of research. The digitized value of the radiation intensity I in one pixel and the parameter η characterizing the change in the intensity distribution on an 10 × 10 pixel area was recorded for 24 hours. The multiple determinacy coefficient of three cell cultures, which was obtained from the time dependences of η, was equal to 0.94.

  10. 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.

  11. Clinicopathological evaluation of radiation induced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meibodi Naser

    2008-01-01

    Full Text Available Background: Development of skin neoplasms is one of the most important chronic complications of radiation therapy. Basal cell carcinoma (BCC is the most frequent carcinoma occurring at the region of the body to which radiotherapy was delivered. Aim: The aim of this study was to evaluate clinical and histological aspects of basal cell carcinoma in patients with a history of radiotherapy. Materials and Methods: Medical records and microscopic slides of 80 patients with basal cell carcinoma who had received radiotherapy (1996-2006 were reviewed in pathology department of Imam Reza hospital of Mashhad, Iran. Collected data were analyzed statistically using descriptive test. Results: 60 men and 20 women were included, majority of them in their sixties. Plaque was the most common clinical pattern of basal cell carcinoma. Fifty one percent of the patients had pigmented and 42.5% had multiple lesions. Scalp was the most common site of involvement. Histologically, macronodular and pigmented carcinoma were the most predominant forms of basal cell carcinoma. Discussion: Majority of patients had scalp involvement and multiple lesions. Nodular and pigmented forms were the most common histological findings. We suggest the need for close supervision in patients with a history of radio therapy in the past.

  12. Cell-cycle research with synchronous cultures: an evaluation

    Science.gov (United States)

    Helmstetter, C. E.; Thornton, M.; Grover, N. B.

    2001-01-01

    The baby-machine system, which produces new-born Escherichia coli cells from cultures immobilized on a membrane, was developed many years ago in an attempt to attain optimal synchrony with minimal disturbance of steady-state growth. In the present article, we put forward a model to describe the behaviour of cells produced by this method, and provide quantitative evaluation of the parameters involved, at each of four different growth rates. Considering the high level of selection achievable with this technique and the natural dispersion in interdivision times, we believe that the output of the baby machine is probably close to optimal in terms of both quality and persistence of synchrony. We show that considerable information on events in the cell cycle can be obtained from populations with age distributions very much broader than those achieved with the baby machine and differing only modestly from steady state. The data presented here, together with the long and fruitful history of findings employing the baby-machine technique, suggest that minimisation of stress on cells is the single most important factor for successful cell-cycle analysis.

  13. Proton exchange fuel cell : the design, construction and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Heinzen, M.R.; Simoes, G.C.; Da Silva, L. [Univ. do Vale do Itajai, Sao Jose, SC (Brazil). Lab. de Pesquisa em Energia; Fiori, M.A.; Paula, M.M.S. [Univ. do Extremo Sul Catarinense, Santa Catarina (Brazil). Lab. de Sintese de Complexos Multifuncionais; Benavides, R. [Centro de Investigacion en Quimica Aplicada, Coahuila (Mexico)

    2010-07-15

    Polymer electrolyte membrane fuel cells (PEMFC) convert the chemical energy stored in the fuel directly into electrical energy without intermediate steps. The PEMFC operates at a relatively low operating temperature making it a good choice for mobile applications, but a high power density is needed in order to decrease the total weight of the vehicles. This paper presented a simple methodology to construct a PEMFC-type fuel cell, with particular reference to the gaseous diffuser, cell structure, the fixing plate, mounting bracket, gas distribution plates, and the membrane electrode assembly (MEA). The geometric design and meshing of the PEMFC were also described. The electrode was made using graphite with flow-field geometry. The PEMFC was tested for 100 hour of continuous work, during which time the current and voltage produced were monitored in order to evaluate the performance of the PEMFC. The materials used in the preparation of the fuel cell proved to be suitable. There was no loss of efficiency during the tests. The most relevant aspects affecting the PEMFC design were examined in an effort to optimize the performance of the cell. 13 refs., 6 figs.

  14. A Dynamic Precision Evaluation Method for the Star Sensor in the Stellar-Inertial Navigation System.

    Science.gov (United States)

    Lu, Jiazhen; Lei, Chaohua; Yang, Yanqiang

    2017-06-28

    Integrating the advantages of INS (inertial navigation system) and the star sensor, the stellar-inertial navigation system has been used for a wide variety of applications. The star sensor is a high-precision attitude measurement instrument; therefore, determining how to validate its accuracy is critical in guaranteeing its practical precision. The dynamic precision evaluation of the star sensor is more difficult than a static precision evaluation because of dynamic reference values and other impacts. This paper proposes a dynamic precision verification method of star sensor with the aid of inertial navigation device to realize real-time attitude accuracy measurement. Based on the gold-standard reference generated by the star simulator, the altitude and azimuth angle errors of the star sensor are calculated for evaluation criteria. With the goal of diminishing the impacts of factors such as the sensors' drift and devices, the innovative aspect of this method is to employ static accuracy for comparison. If the dynamic results are as good as the static results, which have accuracy comparable to the single star sensor's precision, the practical precision of the star sensor is sufficiently high to meet the requirements of the system specification. The experiments demonstrate the feasibility and effectiveness of the proposed method.

  15. Evaluating the Dynamics of Aircraft Crew Skill Development by Using the Results of Discrete Exercise Marking

    Directory of Open Access Journals (Sweden)

    Lešinskis Aloizs

    2017-08-01

    Full Text Available Aircraft crew training corresponds to the interactive learning models of sensorimotor skill acquisition, and the dynamics of skill acquirement can be approximated by the exponential trend. A model of 5-grade assessment of separate exercises is offered. It helps to calculate a resulting evaluation, in accordance with which the progress level of a discrete exercise is evaluated. Such an evaluation forms one of the points for the analytical construction of a learning curve using the Gaussian method. Possible applications of the learning curve are covered.

  16. Dynamic Organization of Chromatin Domains Revealed by Super-Resolution Live-Cell Imaging.

    Science.gov (United States)

    Nozaki, Tadasu; Imai, Ryosuke; Tanbo, Mai; Nagashima, Ryosuke; Tamura, Sachiko; Tani, Tomomi; Joti, Yasumasa; Tomita, Masaru; Hibino, Kayo; Kanemaki, Masato T; Wendt, Kerstin S; Okada, Yasushi; Nagai, Takeharu; Maeshima, Kazuhiro

    2017-07-20

    The eukaryotic genome is organized within cells as chromatin. For proper information output, higher-order chromatin structures can be regulated dynamically. How such structures form and behave in various cellular processes remains unclear. Here, by combining super-resolution imaging (photoactivated localization microscopy [PALM]) and single-nucleosome tracking, we developed a nuclear imaging system to visualize the higher-order structures along with their dynamics in live mammalian cells. We demonstrated that nucleosomes form compact domains with a peak diameter of ∼160 nm and move coherently in live cells. The heterochromatin-rich regions showed more domains and less movement. With cell differentiation, the domains became more apparent, with reduced dynamics. Furthermore, various perturbation experiments indicated that they are organized by a combination of factors, including cohesin and nucleosome-nucleosome interactions. Notably, we observed the domains during mitosis, suggesting that they act as building blocks of chromosomes and may serve as information units throughout the cell cycle. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Dynamics of an HIV-1 infection model with cell mediated immunity

    Science.gov (United States)

    Yu, Pei; Huang, Jianing; Jiang, Jiao

    2014-10-01

    In this paper, we study the dynamics of an improved mathematical model on HIV-1 virus with cell mediated immunity. This new 5-dimensional model is based on the combination of a basic 3-dimensional HIV-1 model and a 4-dimensional immunity response model, which more realistically describes dynamics between the uninfected cells, infected cells, virus, the CTL response cells and CTL effector cells. Our 5-dimensional model may be reduced to the 4-dimensional model by applying a quasi-steady state assumption on the variable of virus. However, it is shown in this paper that virus is necessary to be involved in the modeling, and that a quasi-steady state assumption should be applied carefully, which may miss some important dynamical behavior of the system. Detailed bifurcation analysis is given to show that the system has three equilibrium solutions, namely the infection-free equilibrium, the infectious equilibrium without CTL, and the infectious equilibrium with CTL, and a series of bifurcations including two transcritical bifurcations and one or two possible Hopf bifurcations occur from these three equilibria as the basic reproduction number is varied. The mathematical methods applied in this paper include characteristic equations, Routh-Hurwitz condition, fluctuation lemma, Lyapunov function and computation of normal forms. Numerical simulation is also presented to demonstrate the applicability of the theoretical predictions.

  18. An evaluation of dynamic mutuality measurements and methods in cyclic time series

    Science.gov (United States)

    Xia, Xiaohua; Huang, Guitian; Duan, Na

    2010-12-01

    Several measurements and techniques have been developed to detect dynamic mutuality and synchronicity of time series in econometrics. This study aims to compare the performances of five methods, i.e., linear regression, dynamic correlation, Markov switching models, concordance index and recurrence quantification analysis, through numerical simulations. We evaluate the abilities of these methods to capture structure changing and cyclicity in time series and the findings of this paper would offer guidance to both academic and empirical researchers. Illustration examples are also provided to demonstrate the subtle differences of these techniques.

  19. 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)

  20. Dual-trap Raman tweezers for probing dynamics and heterogeneity of interacting microbial cells

    Science.gov (United States)

    Li, Yan; Wang, Guiwen; Yao, Hui-Lu; Liu, Junxian; Li, Yong-Qing

    2010-11-01

    We report on development of dual-trap Raman tweezers for monitoring cellular dynamics and heterogeneity of interacting living cells suspended in a liquid medium. Dual-beam optical tweezers were combined with Raman spectroscopy, which allows capturing two cells that are in direct contact or closely separated by a few micrometers and simultaneously acquiring their Raman spectra with an imaging CCD spectrograph. As a demonstration, we recorded time-lapse Raman spectra of budding yeast cells held in dual traps for over 40 min to monitor the dynamic growth in a nutrient medium. We also monitored two germinating Bacillus spores after the initiation with L-alanine and observed their heterogeneity in the release of CaDPA under identical microenvironment.

  1. 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.

  2. 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.

  3. 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.

  4. Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells

    Directory of Open Access Journals (Sweden)

    Carla Marchetti

    2015-01-01

    Full Text Available Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (Olea europaea L., is believed to have therapeutic potentials for various diseases, including tumors. We obtained an oleuropein-enriched fraction, consisting of 60% w/w oleuropein, from olive leaves, and assessed its effects on intracellular Ca2+ and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca2+ dynamics and cell viability were studied in the REN mesothelioma cell line, using fura-2 microspectrofluorimetry and MTT assay, respectively. Fura-2-loaded cells, transiently exposed to the oleuropein-enriched fraction, showed dose-dependent transient elevations of cytosolic Ca2+ concentration (Ca2+i. Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca2+ channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca2+ channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC50 of 22 μg/mL oleuropein. Data suggest that our oleuropein-enriched fraction from olive leaf extract could have pharmacological application in malignant mesothelioma anticancer therapy, possibly by targeting T-type Ca2+ channels and thereby dysregulating intracellular Ca2+ dynamics.

  5. The dynamic influence of cells on the formation of stable emulsions in organic-aqueous biotransformations.

    Science.gov (United States)

    Collins, Jonathan; Grund, Marcel; Brandenbusch, Christoph; Sadowski, Gabriele; Schmid, Andreas; Bühler, Bruno

    2015-07-01

    Emulsion stability plays a crucial role for mass transfer and downstream processing in organic-aqueous bioprocesses based on whole microbial cells. In this study, emulsion stability dynamics and the factors determining them during two-liquid phase biotransformation were investigated for stereoselective styrene epoxidation catalyzed by recombinant Escherichia coli. Upon organic phase addition, emulsion stability rapidly increased correlating with a loss of solubilized protein from the aqueous cultivation broth and the emergence of a hydrophobic cell fraction associated with the organic-aqueous interface. A novel phase inversion-based method was developed to isolate and analyze cellular material from the interface. In cell-free experiments, a similar loss of aqueous protein did not correlate with high emulsion stability, indicating that the observed particle-based emulsions arise from a convergence of factors related to cell density, protein adsorption, and bioreactor conditions. During styrene epoxidation, emulsion destabilization occurred correlating with product-induced cell toxification. For biphasic whole-cell biotransformations, this study indicates that control of aqueous protein concentrations and selective toxification of cells enables emulsion destabilization and emphasizes that biological factors and related dynamics must be considered in the design and modeling of respective upstream and especially downstream processes.

  6. Hybrid Spreading Mechanisms and T Cell Activation Shape the Dynamics of HIV-1 Infection

    Science.gov (United States)

    Zhang, Changwang; Zhou, Shi; Groppelli, Elisabetta; Pellegrino, Pierre; Williams, Ian; Borrow, Persephone; Chain, Benjamin M.; Jolly, Clare

    2015-01-01

    HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts. The contribution of this hybrid spreading mechanism, which is also a characteristic of some important computer worm outbreaks, to HIV-1 progression in vivo remains unknown. Here we present a new mathematical model that explicitly incorporates the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the consequences for HIV-1 pathogenenesis. The model captures the major phases of the HIV-1 infection course of a cohort of treatment naive patients and also accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading is critical to seed and establish infection, and that cell-to-cell spread and increased CD4+ T cell activation are important for HIV-1 progression. Notably, the model predicts that cell-to-cell spread becomes increasingly effective as infection progresses and thus may present a considerable treatment barrier. Deriving predictions of various treatments’ influence on HIV-1 progression highlights the importance of earlier intervention and suggests that treatments effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS. This study suggests that hybrid spreading is a fundamental feature of HIV infection, and provides the mathematical framework incorporating this feature with which to evaluate future therapeutic strategies. PMID:25837979

  7. 3D/4D multiscale imaging in acute lymphoblastic leukemia cells: visualizing dynamics of cell death

    Science.gov (United States)

    Sarangapani, Sreelatha; Mohan, Rosmin Elsa; Patil, Ajeetkumar; Lang, Matthew J.; Asundi, Anand

    2017-06-01

    Quantitative phase detection is a new methodology that provides quantitative information on cellular morphology to monitor the cell status, drug response and toxicity. In this paper the morphological changes in acute leukemia cells treated with chitosan were detected using d'Bioimager a robust imaging system. Quantitative phase image of the cells was obtained with numerical analysis. Results show that the average area and optical volume of the chitosan treated cells is significantly reduced when compared with the control cells, which reveals the effect of chitosan on the cancer cells. From the results it can be attributed that d'Bioimager can be used as a non-invasive imaging alternative to measure the morphological changes of the living cells in real time.

  8. 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.

  9. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. Dynamic Resource Partitioning for Downlink Femto-to-Macro-Cell Interference Avoidance

    Directory of Open Access Journals (Sweden)

    Zubin Bharucha

    2010-01-01

    Full Text Available Femto-cells consist of user-deployed Home Evolved NodeBs (HeNBs that promise substantial gains in system spectral efficiency, coverage, and data rates due to an enhanced reuse of radio resources. However, reusing radio resources in an uncoordinated, random fashion introduces potentially destructive interference to the system, both, in the femto and macro layers. An especially critical scenario is a closed-access femto-cell, cochannel deployed with a macro-cell, which imposes strong downlink interference to nearby macro user equipments (UEs that are not permitted to hand over to the femto-cell. In order to maintain reliable service of macro-cells, it is imperative to mitigate the destructive femto-cell to macro-cell interference. The contribution in this paper focuses on mitigating downlink femto-cell to macro-cell interference through dynamic resource partitioning, in the way that HeNBs are denied access to downlink resources that are assigned to macro UEs in their vicinity. By doing so, interference to the most vulnerable macro UEs is effectively controlled at the expense of a modest degradation in femto-cell capacity. The necessary signaling is conveyed through downlink high interference indicator (DL-HII messages over the wired backbone. Extensive system level simulations demonstrate that by using resource partitioning, for a sacrifice of 4% of overall femto downlink capacity, macro UEs exposed to high HeNB interference experience a tenfold boost in capacity.

  12. Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation

    Science.gov (United States)

    Kesavan, Gokul; Lieven, Oliver; Mamidi, Anant; Öhlin, Zarah Löf; Johansson, Jenny Kristina; Li, Wan-Chun; Lommel, Silvia; Greiner, Thomas Uwe; Semb, Henrik

    2014-01-01

    Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell delamination and differentiation. These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression of fate-determining transcription factors, such as Isl1 and MafA. Mechanistically, we demonstrate that genetic ablation of N-WASP in β cells expressing constitutively active Cdc42 partially restores both delamination and β cell differentiation. These findings elucidate how junctional actin dynamics via Cdc42/N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis. PMID:24449844

  13. Label-free profiling of cell dynamics: A sequence of impedance-based assays to estimate tumor cell invasiveness in vitro.

    Science.gov (United States)

    Láng, Orsolya; Kőhidai, László; Wegener, Joachim

    2017-10-01

    Dynamic properties of cancer cells, most notably their ability to migrate, have been correlated successfully with their invasive nature in vivo. To establish a stronger experimental basis for such a correlation we subjected five different cancer cell lines of well-defined metastatic potential to a sequence of three independent assays reporting on three different aspects of cell dynamics, namely (1) the kinetics of cell spreading, (2) cell shape fluctuations, and (3) cell migration. The sequentially applied assays correspond to different measuring modes of the well-established ECIS technique that is based on non-invasive and label-free impedance readings of planar gold-film electrodes that serve as the growth substrate for the cells under study. Every individual assay returned a characteristic parameter describing the behavior of the cell lines in that particular assay quantitatively. The parameters of all three assays were ranked to establish individual profiles of cell dynamics for every cell line that correlate favorably with the cells' invasive properties. The sequence of impedance-based assays described here requires only small cell populations (< 10.000 cells), it is highly automated and easily adapted to 96-well formats. It provides an in-depth dynamic profile of adherent cells that might be useful in other areas besides cancer research as well. Copyright © 2017. Published by Elsevier Inc.

  14. Tip cells act as dynamic cellular anchors in the morphogenesis of looped renal tubules in Drosophila.

    Science.gov (United States)

    Weavers, Helen; Skaer, Helen

    2013-11-11

    Tissue morphogenesis involves both the sculpting of tissue shape and the positioning of tissues relative to one another in the body. Using the renal tubules of Drosophila, we show that a specific distal tubule cell regulates both tissue architecture and position in the body cavity. Focusing on the anterior tubules, we demonstrate that tip cells make transient contacts with alary muscles at abdominal segment boundaries, moving progressively forward as convergent extension movements lengthen the tubule. Tip cell anchorage antagonizes forward-directed, TGF-β-guided tubule elongation, thereby ensuring the looped morphology characteristic of renal tubules from worms to humans. Distinctive tip cell exploratory behavior, adhesion, and basement membrane clearing underlie target recognition and dynamic interactions. Defects in these features obliterate tip cell anchorage, producing misshapen and misplaced tubules with impaired physiological function. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Nanoparticle-Mediated Mechanical Destruction of Cell Membranes: A Coarse-Grained Molecular Dynamics Study.

    Science.gov (United States)

    Zhang, Liuyang; Zhao, Yiping; Wang, Xianqiao

    2017-08-16

    The effects of binding mode, shape, binding strength, and rotational speed of actively rotating nanoparticles on the integrity of cell membranes have been systematically studied using dissipative particle dynamics simulations. With theoretical analyses of lipid density, surface tension, stress distribution, and water permeation, we demonstrate that the rotation of nanoparticles can provide a strong driving force for membrane rupture. The results show that nanoparticles embedded inside a cell membrane via endocytosis are more capable of producing large membrane deformations under active rotation than nanoparticles attached on the cell membrane surface. Nanoparticles with anisotropic shapes produce larger deformation and have a higher rupture efficiency than those with symmetric shapes. Our findings provide useful design guidelines for a general strategy based on utilizing mechanical forces to rupture cell membranes and therefore destroy the integrity of cells.

  16. 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.

  17. 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)

  18. 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.

  19. A novel method of evaluating dynamic measurement uncertainty utilizing digital filters

    International Nuclear Information System (INIS)

    Hessling, J P

    2009-01-01

    For every measurement, a measurement uncertainty should be associated with the estimate of the measurand. In particular, this applies to all the common non-stationary transient dynamic measurements made with linear time-invariant measurement systems, despite the present standard treatment providing little guidance for this case. To complete recent studies on the estimation and correction of the systematic dynamic error, the remaining evaluation of measurement uncertainty is addressed here. A method based on digital filtering will be utilized to find the generically time-dependent dynamic contribution to the uncertainty. It will be shown that the widely accepted approach to calculate the stationary uncertainty can be extended to transient measurements, provided some complementary techniques are used and the sensitivity is generalized to be a time-dependent signal instead of a constant. For illustration, the method is applied to the same measurement system analysed in the related published studies

  20. Evaluation of bio-inspired morphing concepts with regard to aircraft dynamics and performance

    Science.gov (United States)

    Wickenheiser, Adam M.; Garcia, Ephrahim; Waszak, Martin

    2004-07-01

    This paper will discuss the application of various bio-inspired morphing concepts to unmanned aerial vehicle (UAV) designs. Several analysis tools will be introduced to calculate the aerodynamic benefits, dynamic response, and mission-level benefits of morphing shape changes. Empirical relations are employed to calculate the effects of various geometry changes on the aerodynamics of the vehicle. A six-degree-of-freedom simulation will evaluate the stability and dynamic response of each vehicle configuration as well as "snapshots" of the morphing change. Subsequently, an aircraft performance analysis will be conducted for various shape configurations. Specifically, the performance of a bio-inspired wing is compared to conventional designs. The aircraft dynamic improvements that morphing technologies introduce will be discussed.

  1. A Study of Developing a System Dynamics Model for the Learning Effectiveness Evaluation

    Directory of Open Access Journals (Sweden)

    Tian-Syung Lan

    2013-01-01

    Full Text Available This study used the research method of system dynamics and applied the Vensim software to develop a learning effectiveness evaluation model. This study developed four cause-and-effect chains affecting learning effectiveness, including teachers’ teaching enthusiasm, family involvement, school’s implementation of scientific activities, and creative teaching method, as well as the system dynamics model based on the four cause-and-effect chains. Based on the developed system dynamic model, this study performed simulation to investigate the relationship among family involvement, learning effectiveness, teaching achievement, creative teaching method, and students’ learning interest. The results of this study verified that there are positive correlations between family involvement and students’ learning effectiveness, as well as students’ learning effectiveness and teachers’ teaching achievements. The results also indicated that the use of creative teaching method is able to increase students’ learning interest and learning achievement.

  2. Microfilament dynamics during cell movement and chemotaxis monitored using a GFP-actin fusion protein.

    Science.gov (United States)

    Westphal, M; Jungbluth, A; Heidecker, M; Mühlbauer, B; Heizer, C; Schwartz, J M; Marriott, G; Gerisch, G

    1997-03-01

    The microfilament system in the cortex of highly motile cells, such as neutrophils and cells of the eukaryotic microorganism Dictyostelium discoideum, is subject to rapid re-organization, both spontaneously and in response to external signals. In particular, actin polymerization induced by a gradient of chemoattractant leads to local accumulation of filamentous actin and protrusion of a 'leading edge' of the cell in the direction of the gradient. In order to study the dynamics of actin in these processes, actin was tagged at its amino terminus with green fluorescent protein (GFP) and observed with fluorescence microscopy in living cells of D. discoideum. Purified GFP-actin was capable of copolymerizing with actin. In the transfected cells of D. discoideum studied, GFP-actin made up 10-20% of the total actin. Microfilaments containing GFP-actin were capable of generating force with myosin in an in vitro assay. Observations of single living cells using fluorescence microscopy showed that the fusion protein was enriched in cell projections, including filopodia and leading edges, and that the fusion protein reflected the dynamics of the microfilament system in cells that were freely moving, being chemotactically stimulated, or aggregated. When confocal sections of fixed cells containing GFP-actin were labeled with fluorescent phalloidin, which binds only to filamentous actin, there was a correlation between the areas of GFP-actin and phalloidin fluorescence, but there were distinct sites in which GFP-actin was more prominent. Double labeling with GFP-actin and other probes provides an indication of the various states of actin in motile cells. A major portion of the actin assemblies visualized using GFP-actin are networks or bundles of filamentous actin. Other clusters of GFP-actin might represent stores of monomeric actin in the form of complexes with actin-sequestering proteins.

  3. Time scales in epigenetic dynamics and phenotypic heterogeneity of embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Masaki Sasai

    Full Text Available A remarkable feature of the self-renewing population of embryonic stem cells (ESCs is their phenotypic heterogeneity: Nanog and other marker proteins of ESCs show large cell-to-cell variation in their expression level, which should significantly influence the differentiation process of individual cells. The molecular mechanism and biological implication of this heterogeneity, however, still remain elusive. We address this problem by constructing a model of the core gene-network of mouse ESCs. The model takes account of processes of binding/unbinding of transcription factors, formation/dissolution of transcription apparatus, and modification of histone code at each locus of genes in the network. These processes are hierarchically interrelated to each other forming the dynamical feedback loops. By simulating stochastic dynamics of this model, we show that the phenotypic heterogeneity of ESCs can be explained when the chromatin at the Nanog locus undergoes the large scale reorganization in formation/dissolution of transcription apparatus, which should have the timescale similar to the cell cycle period. With this slow transcriptional switching of Nanog, the simulated ESCs fluctuate among multiple transient states, which can trigger the differentiation into the lineage-specific cell states. From the simulated transitions among cell states, the epigenetic landscape underlying transitions is calculated. The slow Nanog switching gives rise to the wide basin of ESC states in the landscape. The bimodal Nanog distribution arising from the kinetic flow running through this ESC basin prevents transdifferentiation and promotes the definite decision of the cell fate. These results show that the distribution of timescales of the regulatory processes is decisively important to characterize the fluctuation of cells and their differentiation process. The analyses through the epigenetic landscape and the kinetic flow on the landscape should provide a guideline to

  4. Evaluation of cell proliferation rate in non-dysplastic leukoplakias.

    Science.gov (United States)

    Hildebrand, Laura-de Campos; Carrard, Vinicius-Coelho; Lauxen, Isabel-da Silva; de Quadros, Onofre-Francisco; Chaves, Anna-Cecília-Moraes; Sant' Ana-Filho, Manoel

    2010-03-01

    Analyze whether the most frequent cases of non-dysplastic leukoplakias, hyperkeratosis (H), acanthosis (A), and hyperkeratosis with acanthosis (HA) have similar cell proliferation rates and to compare them with epithelial dysplastic (ED) leukoplakias and normal oral epithelium (NOE). The sample comprised 10 cases of normal oral epithelium, 10 cases of hyperkeratosis, 10 cases of acanthosis, 10 cases of hyperkeratosis with acanthosis and 10 cases of epithelial dysplasia. The mean number of AgNORs per nucleus (mAgNOR) and the mean percentage of cells with 1, 2, 3 and 4 or more AgNORs per nucleus (pAgNOR) were recorded. The results of mAgNOR showed differences between disorders in the evaluation of the basal layer, of the parabasal layer, and in the overall evaluation. mAgNOR and pAgNOR=2 increased progressively from normal oral epithelium to hyperkeratosis with acanthosis, hyperkeratosis, acanthosis and epithelial dysplasia (pdysplastic leukoplakias and this group presented a higher proliferative behavior when compared to normal oral epithelium. It may be suggested that non-dysplastic leukoplakias had different characteristics regarding cell proliferation rates and sometimes showed a proliferative behavior similar to that found in epithelial dysplasia. More studies should be conduced to increase knowledge about the biological profile of non-dysplastic leukoplakias, especially as it pertains to acanthosis.

  5. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells.

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-03-29

    The 'neural plate border' of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

  6. Experimental Design to Evaluate Directed Adaptive Mutation in Mammalian Cells

    Science.gov (United States)

    Chiaro, Christopher R; May, Tobias

    2014-01-01

    Background We describe the experimental design for a methodological approach to determine whether directed adaptive mutation occurs in mammalian cells. Identification of directed adaptive mutation would have profound practical significance for a wide variety of biomedical problems, including disease development and resistance to treatment. In adaptive mutation, the genetic or epigenetic change is not random; instead, the presence and type of selection influences the frequency and character of the mutation event. Adaptive mutation can contribute to the evolution of microbial pathogenesis, cancer, and drug resistance, and may become a focus of novel therapeutic interventions. Objective Our experimental approach was designed to distinguish between 3 types of mutation: (1) random mutations that are independent of selective pressure, (2) undirected adaptive mutations that arise when selective pressure induces a general increase in the mutation rate, and (3) directed adaptive mutations that arise when selective pressure induces targeted mutations that specifically influence the adaptive response. The purpose of this report is to introduce an experimental design and describe limited pilot experiment data (not to describe a complete set of experiments); hence, it is an early report. Methods An experimental design based on immortalization of mouse embryonic fibroblast cells is presented that links clonal cell growth to reversal of an inactivating polyadenylation site mutation. Thus, cells exhibit growth only in the presence of both the countermutation and an inducing agent (doxycycline). The type and frequency of mutation in the presence or absence of doxycycline will be evaluated. Additional experimental approaches would determine whether the cells exhibit a generalized increase in mutation rate and/or whether the cells show altered expression of error-prone DNA polymerases or of mismatch repair proteins. Results We performed the initial stages of characterizing our system

  7. First steps towards fuel cells testing harmonisation: Procedures and parameters for single cell performance evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Lunghi, P. [Department of Industrial Engineering, University of Perugia, Via Duranti 93, Perugia (Italy); Ubertini, S. [Department of Mechanical Engineering, University of Rome ' ' Tor Vergata' ' , Via di Torvergata, 110, Rome (Italy)

    2004-01-01

    The great interest in Fuel Cell Systems, combined with the innovation of the device itself, has led to a huge developmental effort to make the steps necessary for future FC plant commissioning. The clearest and most effective way to evaluate the performance of a fuel cell is to measure it directly and, since few fuel cell test rigs are available at the moment, standard experimental procedures have not been realized so far. Our research group is currently performing single cell testing at the University of Perugia fuel cell laboratory and particular emphasis has been put on the definition of procedures and the testing of parameterisation. The work team strongly believes that this is the key to effective system testing and reliable performance evaluation. In this work, the test parameterisation developed by the team, and the resulting advanced control procedure used for a single MCFC experimental characterization are presented. Efforts have been dedicated to obtain some relevant non-dimensional parameters to allow an easy understanding of the results and quick comparisons with other tests under different operating conditions, or with results obtained on different cells eventually tested in different laboratories. The authors strongly emphasise this topic to avoid the data that developers and research institutions collect being of no practical use due to a lack of shared rules. (Abstract Copyright [2003], Wiley Periodicals, Inc.)

  8. Advances in stem cells and regenerative medicine: single-cell dynamics, new models and translational perspectives.

    Science.gov (United States)

    Twigger, Alecia-Jane; Scheel, Christina H

    2017-09-01

    An international cohort of over 300 stem cell biologists came together in Heidelberg, Germany in May 2017 as delegates of the 'Advances in Stem Cells and Regenerative Medicine' conference run through the European Molecular Biology Organization. This Meeting Review highlights the novel insights into stem cell regulation, new technologies aiding in discovery and exciting breakthroughs in the field of regenerative medicine that emerged from the meeting. © 2017. Published by The Company of Biologists Ltd.

  9. A dynamic vulnerability evaluation model to smart grid for the emergency response

    Science.gov (United States)

    Yu, Zhen; Wu, Xiaowei; Fang, Diange

    2018-01-01

    Smart grid shows more significant vulnerability to natural disasters and external destroy. According to the influence characteristics of important facilities suffered from typical kinds of natural disaster and external destroy, this paper built a vulnerability evaluation index system of important facilities in smart grid based on eight typical natural disasters, including three levels of static and dynamic indicators, totally forty indicators. Then a smart grid vulnerability evaluation method was proposed based on the index system, including determining the value range of each index, classifying the evaluation grade standard and giving the evaluation process and integrated index calculation rules. Using the proposed evaluation model, it can identify the most vulnerable parts of smart grid, and then help adopting targeted emergency response measures, developing emergency plans and increasing its capacity of disaster prevention and mitigation, which guarantee its safe and stable operation.

  10. 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

  11. Particle-in-Cell Code BEAMPATH for Beam Dynamics Simulations in Linear Accelerators and Beamlines

    Energy Technology Data Exchange (ETDEWEB)

    Batygin, Y.

    2004-10-28

    A code library BEAMPATH for 2 - dimensional and 3 - dimensional space charge dominated beam dynamics study in linear particle accelerators and beam transport lines is developed. The program is used for particle-in-cell simulation of axial-symmetric, quadrupole-symmetric and z-uniform beams in a channel containing RF gaps, radio-frequency quadrupoles, multipole lenses, solenoids and bending magnets. The programming method includes hierarchical program design using program-independent modules and a flexible combination of modules to provide the most effective version of the structure for every specific case of simulation. Numerical techniques as well as the results of beam dynamics studies are presented.

  12. Dynamic quantitative visualization of single cell alignment and migration and matrix remodeling in 3-D collagen hydrogels under mechanical force.

    Science.gov (United States)

    Pang, Yonggang; Wang, Xiaoli; Lee, Dongkeun; Greisler, Howard P

    2011-05-01

    We developed a live imaging system enabling dynamic visualization of single cell alignment induced by external mechanical force in a 3-D collagen matrix. The alignment dynamics and migration of smooth muscle cells (SMCs) were studied by time lapse differential interference contrast and/or phase contrast microscopy. Fluorescent and reflection confocal microcopy were used to study the SMC morphology and the microscale collagen matrix remodeling induced by SMCs. A custom developed program was used to quantify the cell migration and matrix remodeling. Our system enables cell concentration-independent alignment eliminating cell-to-cell interference and enables dynamic cell tracking, high magnification observation and rapid cell alignment accomplished in a few hours compared to days in traditional models. We observed that cells sense and response to the mechanical signal before cell spreading. Under mechanical stretch the migration directionality index of SMCs is 46.3% more than those cells without external stretch; the dynamic direction of cell protrusion is aligned to that of the mechanical force; SMCs showed directional matrix remodeling and the alignment index calculated from the matrix in front of cell protrusions is about 3 fold of that adjacent to cell bodies. Our results indicate that the mechanism of cell alignment is directional cell protrusion. Mechano-sensing, directionality in cell protrusion dynamics, cell migration and matrix remodeling are highly integrated. Our system provides a platform for studying the role of mechanical force on the cell matrix interactions and thus finds strategies to optimize selected properties of engineered tissues. Published by Elsevier Ltd.

  13. Real time imaging of mRNA expression dynamics in live cells using protein complementation methods

    Science.gov (United States)

    Meller, Amit

    2009-03-01

    Traditional methods for mRNA quantification in cells, such as northern blots, quantitative PCR or microarrays assays, require cell lysis and therefore do not preserve its dynamics. These methods cannot be used to probe the spatio-temporal localization of mRNA in cells, which provide useful information for a wide range biomolecular process, including RNA metabolizim, expression kinetics and RNA interference. To probe mRNA dynamics in live prokaryotic and eukaryotic cells, we develop a method, which exploit the strong affinity of the eukaryotic initiation factor 4A (eIF4A) to specific RNA aptamers. Two parts of the eIF4A are fused to a split Green Fluorescence Protein (GFP), and are expressed in the cells at high abundance. However, only when the RNA apatmer is also present, the two protein parts complement and become fluorescent. Thus, the fluorescent background remains low, allowing us to directly image the expression of mRNA molecules in live e-coli cells from its early onset, over hours. We find that the expression kinetics can be classified in one out of at least three forms, which also display distinct spatial distributions. I will discuss the possible biological origin for these distributions and their time evolution.

  14. A cell multipole based domain decomposition algorithm for molecular dynamics simulation of systems of arbitrary shape

    Science.gov (United States)

    Lakshminarasimhulu, Pasupulati; Madura, Jeffry D.

    2002-04-01

    A domain decomposition algorithm for molecular dynamics simulation of atomic and molecular systems with arbitrary shape and non-periodic boundary conditions is described. The molecular dynamics program uses cell multipole method for efficient calculation of long range electrostatic interactions and a multiple time step method to facilitate bigger time steps. The system is enclosed in a cube and the cube is divided into a hierarchy of cells. The deepest level cells are assigned to processors such that each processor has contiguous cells and static load balancing is achieved by redistributing the cells so that each processor has approximately same number of atoms. The resulting domains have irregular shape and may have more than 26 neighbors. Atoms constituting bond angles and torsion angles may straddle more than two processors. An efficient strategy is devised for initial assignment and subsequent reassignment of such multiple-atom potentials to processors. At each step, computation is overlapped with communication greatly reducing the effect of communication overhead on parallel performance. The algorithm is tested on a spherical cluster of water molecules, a hexasaccharide and an enzyme both solvated by a spherical cluster of water molecules. In each case a spherical boundary containing oxygen atoms with only repulsive interactions is used to prevent evaporation of water molecules. The algorithm shows excellent parallel efficiency even for small number of cells/atoms per processor.

  15. Size and dynamics of caveolae studied using nanoparticles in living endothelial cells.

    Science.gov (United States)

    Wang, Zhenjia; Tiruppathi, Chinnaswamy; Minshall, Richard D; Malik, Asrar B

    2009-12-22

    Caveolae are plasma membrane invaginations prominent in all endothelial cells lining blood vessels. Caveolae characteristically bud to form free cytoplasmic vesicles capable of transporting carrier proteins such as albumin through the cell. However, caveolae size distribution and dynamics in living endothelial cells and ability of caveolae to internalize nanoparticles are not well understood. We demonstrate here the design of a dual-color nanoparticle pair to measure noninvasively caveolae size and dynamics. First, we coated nanoparticles with BSA (bovine serum albumin) to address whether albumin promoted their delivery. Albumin has been shown to bind to protein on endothelial cell surface localized in caveolae and activate albumin endocytosis. Imaging of BSA-coated nanoparticles varying from 20 to 100 nm in diameter in endothelial cells demonstrated that caveolae-mediated nanoparticle uptake was dependent on albumin coating of particles. We also showed that caveolae could accommodate up to 100 nm diameter nanoparticles, a size larger than the diameter of typical caveolae, suggesting compliant property of caveolae. Together, our results show the feasibility of tracking multicolored nanoparticles in living endothelial cells and potential usefulness for designing therapeutic nanoparticle cargo to cross the limiting vessel wall endothelial barrier.

  16. Development and performance evaluation of a dynamic phantom for biological dosimetry of moving targets

    Science.gov (United States)

    Gemmel, A.; Bert, C.; Saito, N.; von Neubeck, C.; Iancu, G.; K-Weyrather, W.; Durante, M.; Rietzel, E.

    2010-06-01

    A dynamic phantom has been developed to allow for measurement of 3D cell survival distributions and the corresponding distributions of the RBE-weighted dose (RBED) in the presence of motion. The phantom consists of two 96-microwell plates holding Chinese hamster ovary cells inside a container filled with culture medium and is placed on a movable stage. Basic biological properties of the phantom were investigated without irradiation and after irradiation with a carbon ion beam, using both a stationary (reference) exposure and exposure during motion of the phantom perpendicular to the beam with beam tracking. There was no statistically significant difference between plating efficiency measured in the microwells with and without motion (0.75) and values reported in the literature. Mean differences between measured and calculated cell survival for these two irradiation modes were within ±5% of the target dose of 6 Gy (RBE).

  17. 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.

  18. Dynamic expression of the translational machinery during Bacillus subtilis life cycle at a single cell level.

    Directory of Open Access Journals (Sweden)

    Alex Rosenberg

    Full Text Available The ability of bacteria to responsively regulate the expression of translation components is crucial for rapid adaptation to fluctuating environments. Utilizing Bacillus subtilis (B. subtilis as a model organism, we followed the dynamics of the translational machinery at a single cell resolution during growth and differentiation. By comprehensive monitoring the activity of the major rrn promoters and ribosomal protein production, we revealed diverse dynamics between cells grown in rich and poor medium, with the most prominent dissimilarities exhibited during deep stationary phase. Further, the variability pattern of translational activity varied among the cells, being affected by nutrient availability. We have monitored for the first time translational dynamics during the developmental process of sporulation within the two distinct cellular compartments of forespore and mother-cell. Our study uncovers a transient forespore specific increase in expression of translational components. Finally, the contribution of each rrn promoter throughout the bacterium life cycle was found to be relatively constant, implying that differential expression is not the main purpose for the existence of multiple rrn genes. Instead, we propose that coordination of the rrn operons serves as a strategy to rapidly fine tune translational activities in a synchronized fashion to achieve an optimal translation level for a given condition.

  19. Quantifying histone and RNA polymerase II post-translational modification dynamics in mother and daughter cells.

    Science.gov (United States)

    Stasevich, Timothy J; Sato, Yuko; Nozaki, Naohito; Kimura, Hiroshi

    2014-12-01

    Post-translational histone modifications are highly correlated with transcriptional activity, but the relative timing of these marks and their dynamic interplay during gene regulation remains controversial. To shed light on this problem and clarify the connections between histone modifications and transcription, we demonstrate how FabLEM (Fab-based Live Endogenous Modification labeling) can be used to simultaneously track histone H3 Lysine 9 acetylation (H3K9ac) together with RNA polymerase II Serine 2 and Serine 5 phosphorylation (RNAP2 Ser2ph/Ser5ph) in single living cells and their progeny. We provide a detailed description of the FabLEM methodology, including helpful tips for preparing and loading fluorescently conjugated antigen binding fragments (Fab) into cells for optimal results. We also introduce simple procedures for analyzing and visualizing FabLEM data, including color-coded scatterplots to track correlations between modifications through the cell cycle and temporal cross-correlation analysis to dissect modification dynamics. Using these methods, we find significant correlations that span cell generations, with a relatively strong correlation between H3K9ac and Ser5ph that appears to peak a few hours before mitosis and may reflect the bookmarking of genes for efficient re-initiation following mitosis. The techniques we have developed are broadly applicable and should help clarify how histone modifications dynamically contribute to gene regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. 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.

  1. Definition and dynamic control of a continuous chromatography process independent of cell culture titer and impurities.

    Science.gov (United States)

    Chmielowski, Rebecca A; Mathiasson, Linda; Blom, Hans; Go, Daniel; Ehring, Hanno; Khan, Heera; Li, Hong; Cutler, Collette; Lacki, Karol; Tugcu, Nihal; Roush, David

    2017-12-01

    Advances in cell culture technology have enabled the production of antibody titers upwards of 30g/L. These highly productive cell culture systems can potentially lead to productivity bottlenecks in downstream purification due to lower column loadings, especially in the primary capture chromatography step. Alternative chromatography solutions to help remedy this bottleneck include the utilization of continuous processing systems such as periodic counter-current chromatography (PCC). Recent studies have provided methods to optimize and improve the design of PCC for cell culture titers up to about 3g/L. This paper defines a continuous loading strategy for PCC that is independent of cell culture background and encompasses cell culture titers up to about 31g/L. Initial experimentation showed a challenge with determining a difference in change in UV280nm signal (ie. ΔUV) between cell culture feed and monoclonal antibody (mAb) concentration. Further investigation revealed UV280nm absorbance of the cell culture feedstock without antibody was outside of the linear range of detection for a given cell pathlength. Additional experimentation showed the difference in ΔUV for various cell culture feeds can be either theoretically predicted by Beer's Law given a known absorbance of the media background and impurities or experimentally determined using various UV280nm cell pathlengths. Based on these results, a 0.35mm pathlength at UV280nm was chosen for dynamic control to overcome the background signal. The pore diffusion model showed good agreement with the experimental frontal analysis data, which resulted in definition of a ΔUV setpoint range between 20 and 70% for 3C-PCC experiments. Product quality of the elution pools was acceptable between various cell culture feeds and titers up to about 41g/L. Results indicated the following ΔUV setpoints to achieve robust dynamic control and maintain 3C-PCC yield: ∼20-45% for titers greater than 10g/L depending on UV absorbance of

  2. Evaluation of seismic behavior of soils under nuclear containment structures via dynamic centrifuge test

    International Nuclear Information System (INIS)

    Ha, Jeong Gon; Kim, Dong-Soo

    2014-01-01

    Highlights: • A series of dynamic centrifuge tests were performed for NPP structure to investigate the soil–foundation-structure interaction with various soil conditions from loose sand to weathered rock. • SFSI phenomena for NPP structure were observed directly using experimental method. • Effect of the soil stiffness and nonlinear characteristics on SFSI was estimated. • There are comparisons of the control motions for seismic design of a NPP structure. • Subsoil condition, earthquake intensity and control motion affected to seismic load. - Abstract: To evaluate the earthquake loads for the seismic design of a nuclear containment structure, it is necessary to consider the soil–foundation-structure interaction (SFSI) due to their interdependent behavior. Especially, understanding the effects of soil stiffness under the structure and the location of control motion to SFSI are very important. Motivated by these requirements, a series of dynamic centrifuge tests were performed with various soil conditions from loose sand to weathered rock (WR), as well as different seismic intensities for the bedrock motion. The different amplification characteristics in peak-accelerations profile and effects of soil-nonlinearity in response spectrum were observed. The dynamic behaviors were compared between surface of free-field and foundation of the structure for the evaluation of the control motion for seismic design. It was found that dynamic centrifuge test has potentials to estimate the seismic load considering SFSI

  3. The experimental evaluation of the dynamics of fluid-loaded microplates

    International Nuclear Information System (INIS)

    Wu, Zhangming; Wright, Mike T; Ma, Xianghong

    2010-01-01

    An experimental testing system for the study of the dynamic behavior of fluid-loaded rectangular micromachined silicon plates is designed and presented in this paper. In this experimental system, the base-excitation technique combined with pseudo-random signal and cross-correlation analysis is applied to test fluid-loaded microstructures. Theoretical model is also derived to reveal the mechanism of such an experimental system in the application of testing fluid-loaded microstructures. The dynamic experiments cover a series of testings of various microplates with different boundary conditions and dimensions, both in air and immersed in water. This paper is the first that demonstrates the ability and performances of base excitation in the application of dynamic testing of microstructures that involves a natural fluid environment. Traditional modal analysis approaches are used to evaluate natural frequencies, modal damping and mode shapes from the experimental data. The obtained experimental results are discussed and compared with theoretical predictions. This research experimentally determines the dynamic characteristics of the fluid-loaded silicon microplates, which can contribute to the design of plate-based microsystems. The experimental system and testing approaches presented in this paper can be widely applied to the investigation of the dynamics of microstructures and nanostructures.

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

    Science.gov (United States)

    Schmidt, Esther D; Dorn, August

    2004-11-01

    The male germline stem cells (GSCs) of the milkweed bug present an extraordinary structural polarity that is, to our knowledge, unequalled by any other type of stem cells. They consist of a perikaryon and numerous projections arising from the cell pole directed toward the apical cells, the proposed niche of the GSCs. The projections can traverse a considerable distance until their terminals touch the apical cells. From hatching until death, the GSC projections undergo conspicuous changes, the sequence of which has been deduced from observations of all developmental stages. Projection formation starts from lobular cell protrusions showing trabecular ingrowths of the cell membrane. Finger-like projections result from a process of growth and "carving out". The newly formed projections contain mostly only free ribosomes other than a few mitochondria. A stereotyped degradation process commences in the projection terminals: profiles of circular, often concentric, cisternae of rough endoplasmic reticulum appear and turn into myelin bodies, whereas mitochondria become more numerous. The cytoplasm vesiculates, lysosomal bodies appear, and mitochondria become swollen. At the same time, the projection terminals are segregated by