Science.gov

Sample records for cellular parameters final

  1. Estimating cellular parameters through optimization procedures: elementary principles and applications.

    PubMed

    Kimura, Akatsuki; Celani, Antonio; Nagao, Hiromichi; Stasevich, Timothy; Nakamura, Kazuyuki

    2015-01-01

    Construction of quantitative models is a primary goal of quantitative biology, which aims to understand cellular and organismal phenomena in a quantitative manner. In this article, we introduce optimization procedures to search for parameters in a quantitative model that can reproduce experimental data. The aim of optimization is to minimize the sum of squared errors (SSE) in a prediction or to maximize likelihood. A (local) maximum of likelihood or (local) minimum of the SSE can efficiently be identified using gradient approaches. Addition of a stochastic process enables us to identify the global maximum/minimum without becoming trapped in local maxima/minima. Sampling approaches take advantage of increasing computational power to test numerous sets of parameters in order to determine the optimum set. By combining Bayesian inference with gradient or sampling approaches, we can estimate both the optimum parameters and the form of the likelihood function related to the parameters. Finally, we introduce four examples of research that utilize parameter optimization to obtain biological insights from quantified data: transcriptional regulation, bacterial chemotaxis, morphogenesis, and cell cycle regulation. With practical knowledge of parameter optimization, cell and developmental biologists can develop realistic models that reproduce their observations and thus, obtain mechanistic insights into phenomena of interest.

  2. Estimating cellular parameters through optimization procedures: elementary principles and applications

    PubMed Central

    Kimura, Akatsuki; Celani, Antonio; Nagao, Hiromichi; Stasevich, Timothy; Nakamura, Kazuyuki

    2015-01-01

    Construction of quantitative models is a primary goal of quantitative biology, which aims to understand cellular and organismal phenomena in a quantitative manner. In this article, we introduce optimization procedures to search for parameters in a quantitative model that can reproduce experimental data. The aim of optimization is to minimize the sum of squared errors (SSE) in a prediction or to maximize likelihood. A (local) maximum of likelihood or (local) minimum of the SSE can efficiently be identified using gradient approaches. Addition of a stochastic process enables us to identify the global maximum/minimum without becoming trapped in local maxima/minima. Sampling approaches take advantage of increasing computational power to test numerous sets of parameters in order to determine the optimum set. By combining Bayesian inference with gradient or sampling approaches, we can estimate both the optimum parameters and the form of the likelihood function related to the parameters. Finally, we introduce four examples of research that utilize parameter optimization to obtain biological insights from quantified data: transcriptional regulation, bacterial chemotaxis, morphogenesis, and cell cycle regulation. With practical knowledge of parameter optimization, cell and developmental biologists can develop realistic models that reproduce their observations and thus, obtain mechanistic insights into phenomena of interest. PMID:25784880

  3. Cellular senescence: many roads, one final destination.

    PubMed

    Saab, Raya

    2010-04-13

    Cellular senescence is a tumor-suppressor mechanism that has been shown to occur in response to multiple signals, including oncogenic stress, DNA damage, oxidative stress, telomere shortening, and other tumor-promoting insults. Over the past decade, much has been uncovered regarding the phenotype of this tumor-suppressor response and the underlying pathways necessary for its establishment. However, we have also learned that the intricate details of signaling pathways underlying senescence as a tumor-suppressor response are very much context dependent. In addition, cross-talk among pathways, and negative and positive feedback loops, all complicate our understanding of this process. This short review attempts to summarize what is known to date regarding senescence in tumor suppression, both in vitro and in vivo. Further insights into pathways necessary for senescence will hopefully identify appropriate targets for interventions to not only induce senescence as a treatment of cancerous lesions, but also to maintain this state in premalignant lesions in an effort to prevent progression to cancer.

  4. Ito equations out of domino cellular automaton with efficiency parameters

    NASA Astrophysics Data System (ADS)

    Czechowski, Zbigniew; Białecki, Mariusz

    2012-06-01

    Ito equations are derived for simple stochastic cellular automaton with parameters describing efficiencies for avalanche triggering and cell occupation. Analytical results are compared with the numerical one obtained from the histogram method. Good agreement for various parameters supports the wide applicability of the Ito equation as a macroscopic model of some cellular automata and complex natural phenomena which manifest random energy release. Also, the paper is an example of effectiveness of histogram procedure as an adequate method of nonlinear modeling of time series.

  5. Evolving cellular automata to perform computations. Final technical report

    SciTech Connect

    Crutchfield, J.P.; Mitchell, M.

    1998-04-01

    The overall goals of the project are to determine the usefulness of genetic algorithms (GAs) in designing spatially extended parallel systems to perform computational tasks and to develop theoretical frameworks both for understanding the computation in the systems evolved by the GA and for understanding the evolutionary process which successful systems are designed. In the original proposal the authors scheduled the first year of the project to be devoted to experimental grounding. During the first year they developed the simulation and graphics software necessary for doing experiments and analysis on one dimensional cellular automata (CAs), and they performed extensive experiments and analysis concerning two computational tasks--density classification and synchronization. Details of these experiments and results, and a list of resulting publications, were given in the 1994--1995 report. The authors scheduled the second year to be devoted to theoretical development. (A third year, to be funded by the National Science Foundation, will be devoted to applications.) Accordingly, most of the effort during the second year was spent on theory, both of GAs and of the CAs that they evolve. A central notion is that of the computational strategy of a CA, which they formalize in terms of domains, particles, and particle interactions. This formalization builds on the computational mechanics framework developed by Crutchfield and Hanson for understanding intrinsic computation in spatially extended dynamical systems. They have made significant progress in the following areas: (1) statistical dynamics of GAs; (2) formalizing particle based computation in cellular automata; and (3) computation in two-dimensional CAs.

  6. Effect of hyperthermic water bath on parameters of cellular immunity.

    PubMed

    Blazícková, S; Rovenský, J; Koska, J; Vigas, M

    2000-01-01

    Effects of hyperthermic water bath on selected immune parameters (lymphocyte subpopulations, natural killer (NK) cell counts and their activity) were studied in a group of 10 volunteers. Application of hyperthermic water bath (both topical and whole-body) was followed by a significant reduction of relative B lymphocyte counts. Whole-body hyperthermic water bath reduced relative total T lymphocyte counts, increased relative CD8+ T lymphocyte and NK cell counts and increased NK activity. Whole-body hyperthermic bath increased somatotropic hormone (STH) activity in eight out of 10 volunteers; higher relative counts of CD8+ lymphocytes and NK cells were observed compared with the group of volunteers not responding to hyperthermic water bath by STH secretion. In five volunteers STH was released in response to local hyperthermic water bath and the NK activity of lymphocytes also increased but their relative counts did not. The results suggest that these increases in CD8+ lymphocyte and NK cell counts are probably dependent on increased STH production.

  7. Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures

    PubMed Central

    Murugan, Karmani; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2015-01-01

    Cellular internalization and trans-barrier transport of nanoparticles can be manipulated on the basis of the physicochemical and mechanical characteristics of nanoparticles. Research has shown that these factors significantly influence the uptake of nanoparticles. Dictating these characteristics allows for the control of the rate and extent of cellular uptake, as well as delivering the drug-loaded nanosystem intra-cellularly, which is imperative for drugs that require a specific cellular level to exert their effects. Additionally, physicochemical characteristics of the nanoparticles should be optimal for the nanosystem to bypass the natural restricting phenomena of the body and act therapeutically at the targeted site. The factors at the focal point of emerging smart nanomedicines include nanoparticle size, surface charge, shape, hydrophobicity, surface chemistry, and even protein and ligand conjugates. Hence, this review discusses the mechanism of internalization of nanoparticles and ideal nanoparticle characteristics that allow them to evade the biological barriers in order to achieve optimal cellular uptake in different organ systems. Identifying these parameters assists with the progression of nanomedicine as an outstanding vector of pharmaceuticals. PMID:25834433

  8. [The influence of solcoseryl on population and cellular parameters of HeLa and RD cultures].

    PubMed

    Magakian, Iu A; Karalian, Z A; Karalova, E M; Abroian, L O; Akopian, L A; Gasparian, M G; Dzhagatspanian, N G; Semerdzhian, Z B; Ter-Pogosian, Z R

    2010-01-01

    Changes of population and cellular parameters of HeLa and RD cultures after introducing of solcoseryl in culture medium were studied by methods of scanning cytophotometry and cytomorphometry. Monolayer density, proliferation activity, the number of dead cells in a monolayer, the number of nucleoli in nuclei and distribution of cells in the populations by this parameter, RNA and DNA masses in nuclei and nucleoli, total volumes and surface areas of the nuclei and nucleoli were determined. It has been shown that solcoseryl differently affects the cultures both on population and on cellular levels of their organization. The results of multi-parametric analysis of the influence of solseryl on the cultures allow considering it as a biologically active compound with the features typical for cell and cell population growth regulating factors.

  9. ESTIM: A parameter estimation computer program: Final report

    SciTech Connect

    Hills, R.G.

    1987-08-01

    The computer code, ESTIM, enables subroutine versions of existing simulation codes to be used to estimate model parameters. Nonlinear least squares techniques are used to find the parameter values that result in a best fit between measurements made in the simulation domain and the simulation code's prediction of these measurements. ESTIM utilizes the non-linear least square code DQED (Hanson and Krogh (1982)) to handle the optimization aspects of the estimation problem. In addition to providing weighted least squares estimates, ESTIM provides a propagation of variance analysis. A subroutine version of COYOTE (Gartling (1982)) is provided. The use of ESTIM with COYOTE allows one to estimate the thermal property model parameters that result in the best agreement (in a least squares sense) between internal temperature measurements and COYOTE's predictions of these internal temperature measurements. We demonstrate the use of ESTIM through several example problems which utilize the subroutine version of COYOTE.

  10. Engineering parameters for environmental remediation technologies. Final report

    SciTech Connect

    Kikkeri, S.R.

    1996-06-01

    This document identifies engineering parameters and establishes ranges of values for 33 environmental remediation technologies. The main purpose is to provide U.S. Coast Guard (USCG) civil engineering personnel with summarized information regarding matrix characteristics and design parameters that are applicable to each of the technologies. This information is intended to guide USCG personnel when making decisions regarding the selection of appropriate remediation technologies. This document has been developed to be used as a companion document to the Remediation Technologies Screening Matrix and Reference Guide (EPN542/B-94/013).

  11. Estimating genetic and phenotypic parameters of cellular immune-associated traits in dairy cows.

    PubMed

    Denholm, Scott J; McNeilly, Tom N; Banos, Georgios; Coffey, Mike P; Russell, George C; Bagnall, Ainsley; Mitchell, Mairi C; Wall, Eileen

    2017-04-01

    Data collected from an experimental Holstein-Friesian research herd were used to determine genetic and phenotypic parameters of innate and adaptive cellular immune-associated traits. Relationships between immune-associated traits and production, health, and fertility traits were also investigated. Repeated blood leukocyte records were analyzed in 546 cows for 9 cellular immune-associated traits, including percent T cell subsets, B cells, NK cells, and granulocytes. Variance components were estimated by univariate analysis. Heritability estimates were obtained for all 9 traits, the highest of which were observed in the T cell subsets percent CD4(+), percent CD8(+), CD4(+):CD8(+) ratio, and percent NKp46(+) cells (0.46, 0.41, 0.43 and 0.42, respectively), with between-individual variation accounting for 59 to 81% of total phenotypic variance. Associations between immune-associated traits and production, health, and fertility traits were investigated with bivariate analyses. Strong genetic correlations were observed between percent NKp46(+) and stillbirth rate (0.61), and lameness episodes and percent CD8(+) (-0.51). Regarding production traits, the strongest relationships were between CD4(+):CD8(+) ratio and weight phenotypes (-0.52 for live weight; -0.51 for empty body weight). Associations between feed conversion traits and immune-associated traits were also observed. Our results provide evidence that cellular immune-associated traits are heritable and repeatable, and the noticeable variation between animals would permit selection for altered trait values, particularly in the case of the T cell subsets. The associations we observed between immune-associated, health, fertility, and production traits suggest that genetic selection for cellular immune-associated traits could provide a useful tool in improving animal health, fitness, and fertility.

  12. Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production.

    PubMed

    Vistica, D T; Skehan, P; Scudiero, D; Monks, A; Pittman, A; Boyd, M R

    1991-05-15

    The hydrogen acceptor 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) is commonly utilized to estimate cellular viability in drug screening protocols. The present investigation was prompted, in part, by observations that reduction of MTT to its colored reaction product, MTT formazan, varied between cell lines and with culture age. A correlation was established between the D-glucose concentration of the culture medium at the time of assay and the production of MTT formazan for cell lines representing seven tumor histologies. A decrease in the concentration of D-glucose from culture medium was accompanied by a decrease in MTT specific activity (MTT formazan/microgram cell protein) for a number of cell lines. Cells which extensively metabolized D-glucose exhibited the greatest reduction in MTT specific activity. Further evidence that the D-glucose concentration of the culture medium played an important role in MTT reduction was provided by experiments which demonstrated that transfer of cells to a glucose-free medium (L-15) was accompanied by an immediate decrease in MTT reduction which was pH independent. These studies suggested that cellular transport and constant metabolism of glucose were required for maximum MTT reduction. Decreases in the cellular concentration of the reduced pyridine nucleotides NADH and NADPH were accompanied by concomitant decreases in MTT formazan production. MTT formazan varied significantly among cell lines in both the kinetics of its formation and the degree of saturability exhibited. Apparent IC50 values for Adriamycin varied, in a cell line-specific manner, with MTT exposure time. These results indicate that MTT specific activity is significantly influenced by a number of parameters and suggest that assay conditions should be established which minimize their effects.

  13. Effects of temperature on cellular and biochemical parameters in the crab Carcinus aestuarii (Crustacea, Decapoda).

    PubMed

    Matozzo, Valerio; Gallo, Chiara; Marin, Maria Gabriella

    2011-06-01

    The effects of temperature on cellular and biochemical parameters of the crab Carcinus aestuarii were evaluated. Crabs were kept for 7 days at 4, 17 (reference value) and 30 °C (salinity of 35 psu), and total haemocyte count (THC), haemocyte volume, haemocyte proliferation, phenoloxidase (PO) activity in both haemocyte lysate (HL) and cell-free haemolymph (CFH), CFH total protein and glucose levels, superoxide dismutase (SOD) and catalase (CAT) activities in both gills and digestive gland were evaluated. The lowest and the highest temperature significantly decreased THC, whereas haemocyte volume and haemolymph glucose concentration did not differ significantly among experimental conditions. Haemolymph protein concentration significantly reduced in crabs maintained at 30 °C, when compared with that of animals kept at 4 and 17 °C. Haemocyte proliferation increased significantly in crabs kept at 4 and 30 °C, when compared with that of crabs held at 17 °C. Likewise, a significantly higher PO activity was recorded in CFH from crabs kept at 4 and 30 °C, than in control crabs. Conversely, PO activity did not vary significantly in HL. With regard to antioxidant enzyme activities, a significant decrease in CAT activity was observed in gills from crabs kept at 4 °C, when compared to that of crabs kept at 17 °C and 30 °C. Results obtained demonstrated that the highest and lowest temperature tested influenced crab biological responses, and indicated that C. aestuarii modulated its cellular and biochemical parameters (mainly haemocyte proliferation, CFH protein concentrations and CFH PO activity) in order to cope with temperature. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Research on some parameters of cellular immune response in soldiers undergoing basic training--preliminary report.

    PubMed

    Karpiński, J; Kidawa, Z; Kocur, E; Zeman, K; Rogulski, B; Wołkanin, P; Pokoca, L; Fornalczyk-Wachowska, E; Paśnik, J; Kaczmarek, P

    2001-01-01

    On the basis of available reports it can be stated that physical stress causes changes in distribution and activity of many components of the immune system. It is believed that psychophysical stress in soldiers can influence their immune system depressively and in consequence increase the risk of upper respiratory tract infections. Therefore, it was decided to conduct studies aimed at the estimation of the influence of military training on the some parameters of cellular immune response. The study group consisted of 40 draft aged from 18 to 23 years. The research was conducted in the first 8 weeks of service, in the period of the most intense draft stress adaptation. The participants were divide into 2 groups, A and B respectively, 20 soldiers each. Group A derived from an assault unit. Their training induced strenuous physical stress. Group B derived from a support unit. Their training required less physical effort then one of group A. Performed examinations involved: lymphocyte percentage count, lymphocyte proliferative response to mitogen, CD69 antigen expression on T lymphocyte surface, delayed hypersensitivity reaction with CMI Multitest. All assessments were done twice at 8 weeks interval. After 8 weeks of training in the A group a statistically significant increase in the percentage of lymphocytes revealing antigens of the II Class Main Histocompatibility Complex (MHC) was found. In addition, in this group a statistically significant decrease in the value of lymphocyte stimulation index, a statistically significant increase in the percentage of cells revealing CD69 antigen expression after PHA stimulation were observed. During investigated period in the B group following statistically significant changes were found: an increase in the percentage of CD3+ and CD4+ cells, a decrease in the percentage of CD16+CD56+ and an increase in the CD4+ to CD8+ ratio. The obtained results show that military service conditions influence some parameters of the cellular

  15. Simultaneous model discrimination and parameter estimation in dynamic models of cellular systems

    PubMed Central

    2013-01-01

    Background Model development is a key task in systems biology, which typically starts from an initial model candidate and, involving an iterative cycle of hypotheses-driven model modifications, leads to new experimentation and subsequent model identification steps. The final product of this cycle is a satisfactory refined model of the biological phenomena under study. During such iterative model development, researchers frequently propose a set of model candidates from which the best alternative must be selected. Here we consider this problem of model selection and formulate it as a simultaneous model selection and parameter identification problem. More precisely, we consider a general mixed-integer nonlinear programming (MINLP) formulation for model selection and identification, with emphasis on dynamic models consisting of sets of either ODEs (ordinary differential equations) or DAEs (differential algebraic equations). Results We solved the MINLP formulation for model selection and identification using an algorithm based on Scatter Search (SS). We illustrate the capabilities and efficiency of the proposed strategy with a case study considering the KdpD/KdpE system regulating potassium homeostasis in Escherichia coli. The proposed approach resulted in a final model that presents a better fit to the in silico generated experimental data. Conclusions The presented MINLP-based optimization approach for nested-model selection and identification is a powerful methodology for model development in systems biology. This strategy can be used to perform model selection and parameter estimation in one single step, thus greatly reducing the number of experiments and computations of traditional modeling approaches. PMID:23938131

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

    NASA Astrophysics Data System (ADS)

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

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

  17. Biochemical indicators of thermal stress: selected genetic and physiological parameters. Final report

    SciTech Connect

    Powers, D.A.

    1983-05-01

    The model species Fundulus heteroclitus was sampled from the intake and thermally elevated discharge water of five power plants and twenty-five other areas in the Chesapeake Bay which are not associated with power plants. Genetic and physiological measurements were made on sampled populations and differences correlated with environmental temperature, oxygen and/or salinity. Finally, attempts to sort out some of these variables were made by employing laboratory experiments at the whole organism, cellular, and biochemical levels.

  18. Trabecular bone structural parameters evaluated using dental cone-beam computed tomography: cellular synthetic bones.

    PubMed

    Ho, Jung-Ting; Wu, Jay; Huang, Heng-Li; Chen, Michael Y c; Fuh, Lih-Jyh; Hsu, Jui-Ting

    2013-11-09

    This study compared the adequacy of dental cone beam computed tomography (CBCT) and micro computed tomography (micro-CT) in evaluating the structural parameters of trabecular bones. The cellular synthetic bones in 4 density groups (Groups 1-4: 0.12, 0.16, 0.20, and 0.32 g/cm3) were used in this study. Each group comprised 8 experimental specimens that were approximately 1 cm3. Dental CBCT and micro-CT scans were conducted on each specimen to obtain independent measurements of the following 4 trabecular bone structural parameters: bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th.), and trabecular separation (Tb.Sp.). Wilcoxon signed ranks tests were used to compare the measurement variations between the dental CBCT and micro-CT scans. A Spearman analysis was conducted to calculate the correlation coefficients (r) of the dental CBCT and micro-CT measurements. Of the 4 groups, the BV/TV and Tb.Th. measured using dental CBCT were larger compared with those measured using micro-CT. By contrast, the BS/BV measured using dental CBCT was significantly less compared with those measured using micro-CT. Furthermore, in the low-density groups (Groups 1 and 2), the Tb.Sp. measured using dental CBCT was smaller compared with those measured using micro-CT. However, the Tb.Sp. measured using dental CBCT was slightly larger in the high-density groups (Groups 3 and 4) than it was in the low density groups. The correlation coefficients between the BV/TV, BS/BV, Tb.Th., and Tb.Sp. values measured using dental CBCT and micro-CT were 0.9296 (p < .001), 0.8061 (p < .001), 0.9390 (p < .001), and 0.9583 (p < .001), respectively. Although the dental CBCT and micro-CT approaches exhibited high correlations, the absolute values of BV/TV, BS/BV, Tb.Th., Tb.Sp. differed significantly between these measurements. Additional studies must be conducted to evaluate using dental CBCT in clinical practice.

  19. Arrhenius parameter determination as a function of heating method and cellular microenvironment based on spatial cell viability analysis.

    PubMed

    Whitney, Jon; Carswell, William; Rylander, Nichole

    2013-06-01

    Predictions of injury in response to photothermal therapy in vivo are frequently made using Arrhenius parameters obtained from cell monolayers exposed to laser or water bath heating. However, the impact of different heating methods and cellular microenvironments on Arrhenius predictions has not been thoroughly investigated. This study determined the influence of heating method (water bath and laser irradiation) and cellular microenvironment (cell monolayers and tissue phantoms) on Arrhenius parameters and spatial viability. MDA-MB-231 cells seeded in monolayers and sodium alginate phantoms were heated with a water bath for 3-20 min at 46, 50, and 54 °C or laser irradiated (wavelength of 1064 nm and fluences of 40 W/cm(2) or 3.8 W/cm(2) for 0-4 min) in combination with photoabsorptive carbon nanohorns. Spatial viability was measured using digital image analysis of cells stained with calcein AM and propidium iodide and used to determine Arrhenius parameters. The influence of microenvironment and heating method on Arrhenius parameters and capability of parameters derived from more simplistic experimental conditions (e.g. water bath heating of monolayers) to predict more physiologically relevant systems (e.g. laser heating of phantoms) were assessed. Arrhenius predictions of the treated area (<1% viable) under-predicted the measured areas in photothermally treated phantoms by 23 mm(2) using water bath treated cell monolayer parameters, 26 mm(2) using water bath treated phantom parameters, 27 mm(2) using photothermally treated monolayer parameters, and 0.7 mm(2) using photothermally treated phantom parameters. Heating method and cellular microenvironment influenced Arrhenius parameters, with heating method having the greater impact.

  20. 2012 Gordon Research Conference on Cellular and Molecular Fungal Biology, Final Progress Report

    SciTech Connect

    Berman, Judith

    2012-06-22

    The Gordon Research Conference on Cellular and Molecular Fungal Biology was held at Holderness School, Holderness New Hampshire, June 17 - 22, 2012. The 2012 Gordon Conference on Cellular and Molecular Fungal Biology (CMFB) will present the latest, cutting-edge research on the exciting and growing field of molecular and cellular aspects of fungal biology. Topics will range from yeast to filamentous fungi, from model systems to economically important organisms, and from saprophytes and commensals to pathogens of plants and animals. The CMFB conference will feature a wide range of topics including systems biology, cell biology and morphogenesis, organismal interactions, genome organisation and regulation, pathogenesis, energy metabolism, biomass production and population genomics. The Conference was well-attended with 136 participants. Gordon Research Conferences does not permit publication of meeting proceedings.

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

    PubMed

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

    2011-07-01

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

  2. Evaluation of silver nanospheres on viability and innate cellular parameters of gilthead seabream (Sparus aurata L.) head-kidney leucocytes.

    PubMed

    Guardiola, F A; Logothetis, P; Meseguer, J; Esteban, M A

    2017-08-16

    The increasing use of nanomaterials, e.g. nanosilver, has lead to concerns about environmental contamination and possible toxic effects on aquatic organisms. Here, we present evidence for the impact of silver nanospheres (AgNSs) on fish innate immune cells after in vitro exposure. AgNSs of 20, 50 or 100 nm in diameter were tested with the smallest ones (20 nm) clearly having the most deleterious effects, after an exposure period of 30 min, followed by the medium-sized ones; the NSs of 100 nm had no impact. The effective concentration was determined at 10 μg ml(-1) while lower concentrations (1, 2.5 or 5 μg ml(-1)) were ineffective. Head-kidney mixed leucocyte population showed significant viability reduction which was attributable to diminished viability of macrophages/monocytes and lymphocytes only whereas granulocytes' viability was not affected at the above exposure regime. Furthermore, cellular respiratory burst activity, phagocytic capacity and phagocytic ability were all reduced, with the first two parameters exhibiting the sharper reductions. Finally, transmission electron microscopy revealed that the AgNSs' internalization was brought about via phagocytosis, pinocytosis, receptor-mediated endocytosis and macropinocytosis; also, that cell death could be effected in either an apoptotic or a necrotic manner. It is concluded that AgNSs are potentially very noxious for the teleost fish immune system as they can adversely affect the function and viability of the head-kidney leucocytes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Advanced Cellular and Biomolecular Imaging at Lehigh University, (PA) Final Scientific/Technical Report

    SciTech Connect

    Cassimeris, Lynne, U.

    2010-09-10

    Lehigh University is establishing an interdisciplinary program in high resolution cellular and subcellular biological imaging for a range of applications including improved cancer detection. The completed DOE project added to Lehigh?s bio-imaging infrastructure through acquisition of a new confocal microscope system as well as upgrades to two pieces of existing equipment. Bio-imaging related research at Lehigh was also supported through two seed grants for initiation of new projects.

  4. On a three-parameter quantum battle of the sexes cellular automaton

    NASA Astrophysics Data System (ADS)

    Alonso-Sanz, Ramón

    2013-05-01

    The dynamics of a spatial quantum formulation of the iterated battle of the sexes game is studied in this work. The game is played in the cellular automata manner, i.e., with local and synchronous interaction. The effect of spatial structure is assessed when allowing the players to adopt quantum strategies that are no restricted to any particular subset of the possible strategies.

  5. Dynamic Contrast Enhanced MRI Parameters and Tumor Cellularity in a Rat Model of Cerebral Glioma at 7T

    PubMed Central

    Aryal, Madhava P.; Nagaraja, Tavarekere N.; Keenan, Kelly A.; Bagher-Ebadian, Hassan; Panda, Swayamprava; Brown, Stephen L.; Cabral, Glauber; Fenstermacher, Joseph D.; Ewing, James R.

    2013-01-01

    Purpose To test the hypothesis that a non-invasive dynamic contrast enhanced MRI (DCE-MRI) derived interstitial volume fraction (ve) and/or distribution volume (VD) were correlated with tumor cellularity in cerebral tumor. Methods T1-weighted DCE-MRI studies were performed in 18 athymic rats implanted with U251 xenografts. After DCE-MRI, sectioned brain tissues were stained with Hematoxylin and Eosin for cell counting. Using a Standard Model (SM) analysis and Logan graphical plot, DCE-MRI image sets during and after the injection of a gadolinium contrast agent were used to estimate the parameters plasma volume (vp), forward transfer constant (Ktrans), ve, and VD. Results Mean parameter values in regions where the SM was selected as the best model were: (mean ± S.D.): vp = (0.81±0.40)%, Ktrans = (2.09±0.65) ×10−2 min−1, ve = (6.65±1.86)%, and VD = (7.21±1.98)%. The Logan-estimated VD was strongly correlated with the SM’s vp+ve (r = 0.91, p < 0.001). The parameters, ve and/or VD, were significantly correlated with tumor cellularity (r ≥ −0.75, p < 0.001 for both). Conclusion These data suggest that tumor cellularity can be estimated non-invasively by DCE-MRI, thus supporting its utility in assessing tumor pathophysiology. PMID:23878070

  6. Biological (molecular and cellular) markers of toxicity. Final report, September 15, 1988 - September 14, 1991

    SciTech Connect

    Shugart, L. R.; D'Surney, S. J.; Gettys-Hull, C.; Greeley, Jr, M. S.

    1991-12-15

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO{sup 6}-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O{sup 6}-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP.

  7. Heritability of growth curve parameters and heritability of final size: a simulation study.

    PubMed

    Gebhardt-Henrich, S G

    1992-01-01

    Simulations of nestling growth in Great Tits (Parus major) were used to show the consequences genetic variation in the parameters of growth curves could have on the amount of genetic variation in final body weight. This was done for the case of good environmental conditions (i.e. adequate food supply), and for poor environmental conditions (food limitation). A three-parameter process-error growth model based on the Richards curve (Brisbin et al., 1986) was used. The three parameters were the asymptote, the shape, and the time to complete approximately 95% of growth. In simulations, where only the asymptotic value was heritable, genetic variation in final weight was larger under good conditions than under poor conditions. Food limitations decreased the amount of genetic variation and the heritability estimate of final size. Similarly, sib competition, (based on body size differences of nestlings within broods) combined with food limitations lowered heritabilities. Sib competition under good conditions had no effect on heritabilities. In contrast, when the time to complete approximately 95% of growth was heritable, heritabilities for final size were not lower under poor conditions either without or in the presence of sib competition. This model suggests that different amounts of genetic variation in final size under good and poor conditions could be linked to the amount of genetic variation present in the growth curve parameters. The results agreed with an empirical study on body weight in a passerine bird, the Great Tit, where only the asymptote displayed heritable variation and more genetic variance was expressed under good conditions.

  8. Cellular energy metabolism. Final technical report, May 1, 1987--April 30, 1991

    SciTech Connect

    Glaser, M.

    1991-06-01

    Studies have been carried out on adenylate kinase which is an important enzyme in determining the concentrations of the adenine nucleotides. An efficient method has been developed to clone mutant adenylate kinase genes in E. coli. Site-specific mutagenesis of the wild type gene also has been used to obtain forms of adenylate kinase with altered amino acids. The wild type and mutant forms of adenylate kinase have been overexpressed and large quantities were readily isolated. The kinetic and fluorescence properties of the different forms of adenylate kinase were characterized. This has led to a new model for the location of the AMP and ATP bindings sites on the enzyme and a proposal for the mechanism of substrate inhibition. Crystals of the wild type enzyme were obtained that diffract to at least 2.3 {angstrom} resolution. Experiments were also initiated to determine the function of adenylate kinase in vivo. In one set of experiments, E. coli strains with mutations in adenylate kinase showed large changes in cellular nucleotides after reaching the stationary phase in a low phosphate medium. This was caused by selective proteolytic degradation of the mutant adenylate kinase caused by phosphate starvation.

  9. Final Design and Performance Parameters of the Payloads PYREX, PHLUX and RESPECT on EXPERT

    NASA Astrophysics Data System (ADS)

    Lein, Sebastian; Steinbeck, Andreas; Preci, Arianit; Fertig, Markus; Herdrich, Georg; Röser, Hans-Peter; Auweter-Kurtz, Monika

    An overview of the IRS payload development for ESA's EXPERT mission is given. The final design and performance parameters of the payloads PYREX, PHLUX and RESPECT are described. PYREX is a sensor system measuring the thermal protection system (TPS) rear side temperature. PHLUX is a catalysis based experiment to determine the dissociation degree of the boundary layer. RESPECT applies optical emission spectroscopy to measure spectrally resolved the radiation onto a TPS surface.

  10. Cellular, particle and environmental parameters influencing attachment in surface waters: a review.

    PubMed

    Liao, C; Liang, X; Soupir, M L; Jarboe, L R

    2015-08-01

    Effective modelling of the fate and transport of water-borne pathogens is needed to support federally required pollution-reduction plans, for water quality improvement planning, and to protect public health. Lack of understanding of microbial-particle interactions in water bodies has sometimes led to the assumption that bacteria move in surface waters not associated with suspended mineral and organic particles, despite a growing body of evidence suggesting otherwise. Limited information exists regarding the factors driving interactions between micro-organisms and particles in surface waters. This review discusses cellular, particle and environmental factors potentially influencing interactions and in-stream transport. Bacterial attachment in the aquatic environment can be influenced by properties of the cell such as genetic predisposition and physiological state, surface structures such as flagella and fimbriae, the hydrophobicity and electrostatic charge of the cell surface, and the presence of outer-membrane proteins and extracellular polymeric substances. The mechanisms and degree of attachment are also affected by characteristics of mineral and organic particles including the size, surface area, charge and hydrophobicity. Environmental conditions such as the solution chemistry and temperature are also known to play an important role. Just as the size and surface of chemical particles can be highly variable, bacterial attachment mechanisms are also diverse.

  11. Number of Nanoparticles per Cell through a Spectrophotometric Method - A key parameter to Assess Nanoparticle-based Cellular Assays

    PubMed Central

    Unciti-Broceta, Juan D.; Cano-Cortés, Victoria; Altea-Manzano, Patricia; Pernagallo, Salvatore; Díaz-Mochón, Juan J.; Sánchez-Martín, Rosario M.

    2015-01-01

    Engineered nanoparticles (eNPs) for biological and biomedical applications are produced from functionalised nanoparticles (NPs) after undergoing multiple handling steps, giving rise to an inevitable loss of NPs. Herein we present a practical method to quantify nanoparticles (NPs) number per volume in an aqueous suspension using standard spectrophotometers and minute amounts of the suspensions (up to 1 μL). This method allows, for the first time, to analyse cellular uptake by reporting NPs number added per cell, as opposed to current methods which are related to solid content (w/V) of NPs. In analogy to the parameter used in viral infective assays (multiplicity of infection), we propose to name this novel parameter as multiplicity of nanofection. PMID:25976173

  12. Number of Nanoparticles per Cell through a Spectrophotometric Method - A key parameter to Assess Nanoparticle-based Cellular Assays.

    PubMed

    Unciti-Broceta, Juan D; Cano-Cortés, Victoria; Altea-Manzano, Patricia; Pernagallo, Salvatore; Díaz-Mochón, Juan J; Sánchez-Martín, Rosario M

    2015-05-15

    Engineered nanoparticles (eNPs) for biological and biomedical applications are produced from functionalised nanoparticles (NPs) after undergoing multiple handling steps, giving rise to an inevitable loss of NPs. Herein we present a practical method to quantify nanoparticles (NPs) number per volume in an aqueous suspension using standard spectrophotometers and minute amounts of the suspensions (up to 1 μL). This method allows, for the first time, to analyse cellular uptake by reporting NPs number added per cell, as opposed to current methods which are related to solid content (w/V) of NPs. In analogy to the parameter used in viral infective assays (multiplicity of infection), we propose to name this novel parameter as multiplicity of nanofection.

  13. Effects of 60-day bed rest with and without exercise on cellular and humoral immunological parameters

    PubMed Central

    Hoff, Paula; Belavý, Daniel L; Huscher, Dörte; Lang, Annemarie; Hahne, Martin; Kuhlmey, Anne-Kathrin; Maschmeyer, Patrick; Armbrecht, Gabriele; Fitzner, Rudolf; Perschel, Frank H; Gaber, Timo; Burmester, Gerd-Rüdiger; Straub, Rainer H; Felsenberg, Dieter; Buttgereit, Frank

    2015-01-01

    Exercise at regular intervals is assumed to have a positive effect on immune functions. Conversely, after spaceflight and under simulated weightlessness (e.g., bed rest), immune functions can be suppressed. We aimed to assess the effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on immunological parameters and to investigate the effect of exercise (resistive exercise with and without vibration) on these changes. Twenty-four physically and mentally healthy male volunteers (20–45 years) performed resistive vibration exercise (n=7), resistance exercise without vibration (n=8) or no exercise (n=9) within 60 days of bed rest. Blood samples were taken 2 days before bed rest, on days 19 and 60 of bed rest. Composition of immune cells was analyzed by flow cytometry. Cytokines and neuroendocrine parameters were analyzed by Luminex technology and ELISA/RIA in plasma. General changes over time were identified by paired t-test, and exercise-dependent effects by pairwise repeated measurements (analysis of variance (ANOVA)). With all subjects pooled, the number of granulocytes, natural killer T cells, hematopoietic stem cells and CD45RA and CD25 co-expressing T cells increased and the number of monocytes decreased significantly during the study; the concentration of eotaxin decreased significantly. Different impacts of exercise were seen for lymphocytes, B cells, especially the IgD+ subpopulation of B cells and the concentrations of IP-10, RANTES and DHEA-S. We conclude that prolonged bed rest significantly impacts immune cell populations and cytokine concentrations. Exercise was able to specifically influence different immunological parameters. In summary, our data fit the hypothesis of immunoprotection by exercise and may point toward even superior effects by resistive vibration exercise. PMID:25382740

  14. Effects of 60-day bed rest with and without exercise on cellular and humoral immunological parameters.

    PubMed

    Hoff, Paula; Belavý, Daniel L; Huscher, Dörte; Lang, Annemarie; Hahne, Martin; Kuhlmey, Anne-Kathrin; Maschmeyer, Patrick; Armbrecht, Gabriele; Fitzner, Rudolf; Perschel, Frank H; Gaber, Timo; Burmester, Gerd-Rüdiger; Straub, Rainer H; Felsenberg, Dieter; Buttgereit, Frank

    2015-07-01

    Exercise at regular intervals is assumed to have a positive effect on immune functions. Conversely, after spaceflight and under simulated weightlessness (e.g., bed rest), immune functions can be suppressed. We aimed to assess the effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on immunological parameters and to investigate the effect of exercise (resistive exercise with and without vibration) on these changes. Twenty-four physically and mentally healthy male volunteers (20-45 years) performed resistive vibration exercise (n=7), resistance exercise without vibration (n=8) or no exercise (n=9) within 60 days of bed rest. Blood samples were taken 2 days before bed rest, on days 19 and 60 of bed rest. Composition of immune cells was analyzed by flow cytometry. Cytokines and neuroendocrine parameters were analyzed by Luminex technology and ELISA/RIA in plasma. General changes over time were identified by paired t-test, and exercise-dependent effects by pairwise repeated measurements (analysis of variance (ANOVA)). With all subjects pooled, the number of granulocytes, natural killer T cells, hematopoietic stem cells and CD45RA and CD25 co-expressing T cells increased and the number of monocytes decreased significantly during the study; the concentration of eotaxin decreased significantly. Different impacts of exercise were seen for lymphocytes, B cells, especially the IgD(+) subpopulation of B cells and the concentrations of IP-10, RANTES and DHEA-S. We conclude that prolonged bed rest significantly impacts immune cell populations and cytokine concentrations. Exercise was able to specifically influence different immunological parameters. In summary, our data fit the hypothesis of immunoprotection by exercise and may point toward even superior effects by resistive vibration exercise.

  15. Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus.

    PubMed

    Fassbinder, Till; Saunders, Ute; Mickholz, Eva; Jung, Elisabeth; Becker, Heidemarie; Schlüter, Bernhard; Jacobi, Annett Marita

    2015-04-03

    Disease activity and therapy show an impact on cellular and serological parameters in patients with systemic lupus erythematosus (SLE). This study was performed to compare the influence of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) therapy on these parameters in patients with flaring, organ-threatening disease. SLE patients currently receiving CYC (n = 20), MMF (n = 25) or no immunosuppressive drugs (n = 22) were compared using a cross-sectional design. Median disease activity and daily corticosteroid dose were similar in these treatment groups. Concurrent medication, organ manifestations, and disease activity were recorded, and cellular and serological parameters were determined by routine diagnostic tests or flow cytometric analysis. In addition follow-up data were obtained from different sets of patients (CYC n = 24; MMF n = 23). Although both drugs showed a significant effect on disease activity and circulating B cell subsets, only MMF reduced circulating plasmablasts and plasma cells as well as circulating free light chains within three months of induction therapy. Neither MMF nor CYC were able to reduce circulating memory B cells. MMF lowered IgA levels more markedly than CYC. We did not observe a significant difference in the reduction of IgG levels or anti-dsDNA antibodies comparing patients receiving MMF or CYC. In contrast to MMF, induction therapy with CYC was associated with a significant increase of circulating CD8+ effector T cells and plasmacytoid dendritic cells (PDCs) after three months. The results indicate differences between MMF and CYC with regard to the mechanism of action. MMF, but not CYC, treatment leads to a fast and enduring reduction of surrogate markers of B cell activation, such as circulating plasmablasts, plasma cells and free light chains but a comparable rate of hypogammaglobulinemia.

  16. [Evaluation of selected parameters of cellular immunity in children with osteosarcoma at diagnosis].

    PubMed

    Markiewicz, Katarzyna; Zeman, Krzysztof; Kozar, Agata; Gołębiowska-Wawrzyniak, Maria; Woźniak, Wojciech

    2012-01-01

    The causes of osteosarcoma (OS) and effector mechanisms of the immune response against OS and other neoplastic diseases remain unknown. According to current knowledge, the major role is attributed to cytotoxic T lymphocytes, NK, NKT and Tăä lymphocytes, which are engaged directly in the destruction of the tumour cells. Helper T lymphocytes (CD4+) and indirectly B lymphocytes are of special importance. There is sparse data on the state and efficiency of the immune system in children with neoplastic disease, with bone tumours in particular. THE AIM OF THE STUDY was the evaluation of selected elements of cellular immunity in children with osteosarcoma at the time of diagnosis. The study was performed on a group of 44 children with osteosarcoma, aged from 6 to 20 years (median 15.0 years). The control group consisted of 22 children of the same age (median 14.5 years) without the diagnosis of neoplastic disease and active inflammatory state. T lymphocytes with their subpopulations, activated T lymphocytes (CD3+/HLA-DR+), B lymphocytes, NK and NKT cells were analyzed in peripheral blood using the flow cytometry method. Examinations were performed before the therapy - in the diagnostic period. A lower number of peripheral blood lymphocyte population in children with osteosarcoma at diagnosis, compared to the control group was observed. The differences concerned T lymphocytes CD3+(1609.0 vs 3038.0 kom/μl, p<0.001) CD4+(598.0 vs 1071.0 kom/l; p<0.001) and their cytotoxic subpopulation CD8+ (386.0 vs. 866.0 cells/μL; p<0.001), activated T lymphocytes CD3+/HLA-DR+(39.0 vs. 81.0 cells/μL; p<0.025), B lymphocytes CD19+(205.0 vs. 381.0 cells/μL; p<0.025) and NK cells (161.0 vs. 339.0 cells/μL; p<0.005). The number and percentage of peripheral blood lymphocytes in children and youth with osteosarcoma at diagnosis is over 50% lower compared to the patients without neoplastic disease. 1. The general analysis of peripheral blood without differentiating lymphocyte

  17. Gas Transport Parameters for Landfill Final Cover Soil: Measurements and Model Modification by Dry Bulk Density

    NASA Astrophysics Data System (ADS)

    Wickramarachchi, P. N.; Kawamoto, K.; Hamamoto, S.; Nagamori, M.; Moldrup, P.; Komatsu, T.

    2011-12-01

    Landfill sites have been emerging in greenhouse warming scenarios as a significant source of atmospheric methane (CH4). Until recently, landfill management strategies have mainly addressed the problem of preventing groundwater contamination and reduction of leachate generation. Being one of the largest sources of anthropogenic CH4 emission, the final cover system should also be designed for minimizing the greenhouse gases migration into the atmosphere or the areas surrounding the landfill while securing the hydraulic performance. Compared to the intensive research efforts on hydraulic performances of landfill final cover soil, few studies about gas transport characteristics of landfill cover soils have been done. However, recent soil-gas studies implied that the effects of soil physical properties such as bulk density (i.e., compaction level), soil particle size are key parameters to understand landfill gaseous performance. The gas exchange through the final cover soils is controlled by advective and diffusive gas transport. Air permeability (ka) governs the advective gas transport while the soil-gas diffusion coefficient (Dp) governs diffusive gas transport. In this study, the effects of compaction level and particle size fraction effects on ka and Dp for landfill final cover soil was investigated. The disturbed soil samples were taken from landfill final cover in Japan. A compaction tests were performed for the soil samples with two different size fractions (< 35 mm and < 2.0 mm). In the compaction tests at field water content , the soil samples were repacked into soil cores (i.d. 15-cm, length 12-cm, 2120 cm3) at two different compaction levels [(MP):2700 kN/m2 and (SP):600 kN/m2]. After the compaction tests, ka and Dp were measured and then samples were saturated and subsequently drained at different soil-water matric potential of 0.98, 2.94, 9.81, 1235 kPa and with air-dried and oven-dried conditions. Results showed that measured Dp and ka values for the

  18. Experimental study on detonation parameters and cellular structures of fuel cloud

    NASA Astrophysics Data System (ADS)

    Xie, Li-Feng; Li, Bin; Zhang, Yu-Lei

    2012-04-01

    In this paper, detonation parameters of fuel cloud, such as propylene oxide (PO), isopropyl nitrate (IPN), hexane, 90# oil and decane were measured in a self-designed and constructed vertical shock tube. Results show that the detonation pressure and velocity of PO increase to a peak value and then decrease smoothly with increasing equivalence ratio. Several nitrate sensitizers were added into PO to make fuel mixtures, and test results indicated that the additives can efficiently enhance detonation velocity and pressure of fuel cloud and one type of additive n-propyl nitrate (NPN) played the best in the improvement. The critical initiation energy that directly initiated detonation of all the test liquid fuel clouds showed a U-shape curve relationship with equivalence ratios. The optimum concentration lies on the rich-fuel side ( ϕ > 1). The critical initiation energy is closely related to molecular structure and volatility of fuels. IPN and PO have similar critical values while that of alkanes are larger. Detonation cell sizes of PO were respectively investigated at 25°C, 35°C and 50°C with smoked foil technique. The cell width shows a U-shape curve relationship with equivalence ratios at all temperatures. The minimal cell width also lies on the rich-fuel side ( ϕ > 1). The cell width of PO vapor is slightly larger than that of PO cloud. Therefore, the detonation reaction of PO at normal temperature is controlled by gas phase reaction.

  19. Effects of stepwise nitrogen depletion on carotenoid content, fluorescence parameters and the cellular stoichiometry of Chlorella vulgaris

    NASA Astrophysics Data System (ADS)

    Zhang, Ping; Li, Zhe; Lu, Lunhui; Xiao, Yan; Liu, Jing; Guo, Jinsong; Fang, Fang

    2017-06-01

    Stressful conditions can stimulate the accumulation of carotenoids in some microalgae. To obtain more knowledge of the stress response, we studied the effects of different N concentrations on unicellular content of carotenoids using Raman spectroscopic technique; cellular stoichiometric changes and the fluorescence parameters of Chlorella vulgaris were concomitantly studied. Initially, we optimized the Raman scattering conditions and demonstrated the feasibility of unicellular carotenoid analysis by Raman spectroscopic technique. The results showed that an integration time of 10 s, laser power at 0.1 mW and an accumulation time of 1 were the optimum conditions, and the peak height at 1523 cm- 1 scaled linearly with the carotenoid content in the range of 0.625-1440 mg/L with a recovery rate of 97% 103%. In the experiment, seven different nitrogen levels ranging from 0 to 2.48 × 105 μg/L were imposed. Samples were taken at the start, exponential phase and end of the experiment. The results showed that nitrogen stress can facilitate the synthesis of carotenoids, while at the same time, excessive nitrogen stress led to lower proliferative and photosynthetic activity. Compared with carotenoids, chlorophylls were more sensitive to nitrogen stress; it declined dramatically as stress processed. There existed no significant differences for Fv/Fm among different nitrogen levels during the exponential phase, while in the end, it declined and a significant difference appeared between cells in 2.48 × 105 μg/L N and other experimental levels. Photosynthetic efficiency, namely the C/N mole ratio in algal cells, didnot significantly change during the exponential phase; however, apparent increases ultimately occurred, except for the stable C/N in BG11 medium. This increase matched well with the carotenoid decline, indicating that an increasing cellular C/N mole ratio can be used as an indicator of excessive stress in carotenoid production. Besides, there also existed an inverse

  20. Dynamic contrast enhanced MRI parameters and tumor cellularity in a rat model of cerebral glioma at 7T

    NASA Astrophysics Data System (ADS)

    Aryal, Madhava Prasad

    -MRI-derived parameters and cell counting showed that the ve and VD were strongly correlated with tumor cellularity (r ≥ -0.75, p < 0.001 for both), however, no correlation was observed for Ktrans and vp. To conclude, this result supports the clinical utility of DCE-MRI-derived parameters for detection, staging, and evaluation of the therapeutic response on various tumors.

  1. Definition of a parameter for a typical specific absorption rate under real boundary conditions of cellular phones in a GSM networkd

    NASA Astrophysics Data System (ADS)

    Gerhardt, D.

    2003-05-01

    Using cellular phones the specific absorption rate (SAR) as a physical value must observe established and internationally defined levels to guarantee human protection. To assess human protection it is necessary to guarantee safety under worst-case conditions (especially maximum transmitting power) using cellular phones. To evaluate the exposure to electromagnetic fields under normal terms of use of cellular phones the limitations of the specific absorption rate must be pointed out. In a mobile radio network normal terms of use of cellular phones, i.e. in interconnection with a fixed radio transmitter of a mobile radio network, power control of the cellular phone as well as the antenna diagram regarding a head phantom are also significant for the real exposure. Based on the specific absorption rate, the antenna diagram regarding a head phantom and taking into consideration the power control a new parameter, the typical absorption rate (SARtyp), is defined in this contribution. This parameter indicates the specific absorption rate under average normal conditions of use. Constant radio link attenuation between a cellular phone and a fixed radio transmitter for all mobile models tested was assumed in order to achieve constant field strength at the receiving antenna of the fixed radio transmitter as a result of power control. The typical specific absorption rate is a characteristic physical value of every mobile model. The typical absorption rate was calculated for 16 different mobile models and compared with the absorption rate at maximum transmitting power. The results confirm the relevance of the definition of this parameter (SARtyp) as opposed to the specific absorption rate as a competent and applicable method to establish the real mean exposure from a cellular phone in a mobile radio network. The typical absorption rate provides a parameter to assess electromagnetic fields of a cellular phone that is more relevant to the consumer.

  2. A summary of the sources of input parameter values for the Waste Isolation Pilot Plant final porosity surface calculations

    SciTech Connect

    Butcher, B.M.

    1997-08-01

    A summary of the input parameter values used in final predictions of closure and waste densification in the Waste Isolation Pilot Plant disposal room is presented, along with supporting references. These predictions are referred to as the final porosity surface data and will be used for WIPP performance calculations supporting the Compliance Certification Application to be submitted to the U.S. Environmental Protection Agency. The report includes tables and list all of the input parameter values, references citing their source, and in some cases references to more complete descriptions of considerations leading to the selection of values.

  3. Patient Protection and Affordable Care Act; HHS notice of benefit and payment parameters for 2016. Final rule.

    PubMed

    2015-02-27

    This final rule sets forth payment parameters and provisions related to the risk adjustment, reinsurance, and risk corridors programs; cost sharing parameters and cost-sharing reductions; and user fees for Federally-facilitated Exchanges. It also finalizes additional standards for the individual market annual open enrollment period for the 2016 benefit year, essential health benefits, qualified health plans, network adequacy, quality improvement strategies, the Small Business Health Options Program, guaranteed availability, guaranteed renewability, minimum essential coverage, the rate review program, the medical loss ratio program, and other related topics.

  4. Studies on the control of plant cell enlargement by cellular parameters. Final report, July 1, 1987--June 30, 1990

    SciTech Connect

    Cleland, R.E.

    1991-12-06

    The overall goal of this grant was to conduct research that would illuminate the mechanisms by which the plant hormone auxin induces plant cells to enlarge. A large body of knowledge already existed concerning this process. To begin with, it had been demonstrated, primarily by this laboratory during previous grant periods, that the effect of auxin is to cause a loosening of the cell wall, which is followed by turgor-driven wall expansion and water uptake. The wall contains a series of load-bearing wall bonds which must be cleaved in order to loosen the wall. The identification of these load-bearing bonds is one goal of this research. We proposed that an initial action of auxin is to cause cells to excrete protons, and that the resulting acidification of the apoplast activated enzymes responsible for wall loosening. Evidence has been obtained that indicates that the proton excretion is due to an enhanced activity of the plasma membrane H{sup +} {minus}ATPase. A critical question is how auxin activates this enzyme. The third project concerned the role of wall calcium as part of load-bearing wall bonds. It has long been thought that apoplastic calcium crosslinks carboxyl groups in the wall pectic substances and stiffens the walls. We examined the role of calcium-bridges as load-bearing bonds in soybean hypocotyl cell walls in two ways. The first was to measure the viscoelastic extensibility of walls after addition of exogenous calcium or removal of endogenous calcium. The second approach was to determine if removal of wall calcium from walls while under tension resulted in wall extension, as predicted if the calcium-bridges were load-bearing bonds.

  5. TGLF Recalibration for ITER Standard Case Parameters FY2015: Theory and Simulation Performance Target Final Report

    SciTech Connect

    Candy, J.

    2015-12-01

    flows that fit the GYRO simulations, the parameters of the model had to be tuned to each case. A physics basis for the zonal flow model was lacking. Electron energy transport at short wavelength: A secondary issue – the high-k electron energy flux – was initially assumed to be independent of the zonal flow effect. However, detailed studies of the fluctuation spectra from recent multiscale (electron and ion scale) GYRO simulations provided a critical new insight into the role of zonal flows. The multiscale simulations suggested that advection by the zonal flows strongly suppressed electron-scale turbulence. Radial shear of the zonal E×B fluctuation could not compete with the large electron-scale linear growth rate, but the kx-mixing rate of the E×B advection could. This insight led to a preliminary new model for the way zonal flows saturate both electron- and ion-scale turbulence. It was also discovered that the strength of the zonal E×B velocity could be computed from the linear growth rate spectrum. The new saturation model (SAT1), which replaces the original model (SAT0), was fit to the multiscale GYRO simulations as well as the ion-scale GYRO simulations used to calibrate the original SAT0 model. Thus, SAT1 captures the physics of both multiscale electron transport and zonal-flow stabilization. In future work, the SAT1 model will require significant further testing and (expensive) calibration with nonlinear multiscale gyrokinetic simulations over a wider variety of plasma conditions – certainly more than the small set of scans about a single C-Mod L-mode discharge. We believe the SAT1 model holds great promise as a physics-based model of the multiscale turbulent transport in fusion devices. Correction to ITER performance predictions: Finally, the impact of the SAT1model on the ITER hybrid case is mixed. Without the electron-scale contribution to the fluxes, the Dimits shift makes a significant improvement in the predicted fusion power as

  6. Final Technical Report - Integrated Hydrogeophysical and Hydrogeologic Driven Parameter Upscaling for Dual-Domain Transport Modeling

    SciTech Connect

    Shafer, John M

    2012-11-05

    The three major components of this research were: 1. Application of minimally invasive, cost effective hydrogeophysical techniques (surface and borehole), to generate fine scale (~1m or less) 3D estimates of subsurface heterogeneity. Heterogeneity is defined as spatial variability in hydraulic conductivity and/or hydrolithologic zones. 2. Integration of the fine scale characterization of hydrogeologic parameters with the hydrogeologic facies to upscale the finer scale assessment of heterogeneity to field scale. 3. Determination of the relationship between dual-domain parameters and practical characterization data.

  7. Patient Protection and Affordable Care Act; HHS notice of benefit and payment parameters for 2015. Final rule.

    PubMed

    2014-03-11

    This final rule sets forth payment parameters and oversight provisions related to the risk adjustment, reinsurance, and risk corridors programs; cost sharing parameters and cost-sharing reductions; and user fees for Federally-facilitated Exchanges. It also provides additional standards with respect to composite premiums, privacy and security of personally identifiable information, the annual open enrollment period for 2015, the actuarial value calculator, the annual limitation in cost sharing for stand-alone dental plans, the meaningful difference standard for qualified health plans offered through a Federally-facilitated Exchange, patient safety standards for issuers of qualified health plans, and the Small Business Health Options Program.

  8. The final COS-B database: In-flight calibration of instrumental parameters

    NASA Technical Reports Server (NTRS)

    Strong, A. W.; Bloemen, J. B. G. M.; Buccheri, R.; Hermsen, W.; Lebrun, F.; Mayer-Hasselwander, H. A.

    1985-01-01

    A method for the determination of temporal variation of sensitivity is designed to find a set of parameters which lead to maximum consistency between the intensities derived from different observation periods. This method is briefly described and the resulting sensitivity and background variations presented.

  9. Machine learning of parameter control doctrine for sensor and communication systems. Final report

    SciTech Connect

    Kamen, R.B.; Dillard, R.A.

    1988-07-01

    Artificial-intelligence approaches to learning were reviewed for their potential contributions to the construction of a system to learn parameter-control doctrine. Separate learning tasks were isolated and several levels of related problems were distinguished. Formulas for providing the learning system with measures of its performance were derived for four kinds of targets.

  10. Machine self-teaching methods for parameter optimization. Final report, October 1984-August 1986

    SciTech Connect

    Dillard, R.A.

    1986-12-01

    The problem of determining near-optimum parameter-control logic is addressed for cases where a sensor or communication system is highly flexible and the logic cannot be determined analytically. A system that supports human-like learning of optimum parameters is outlined. The major subsystems are (1) a simulation system (described for a radar example), (2) a performance monitoring system, (3) the learning system, and (4) the initial knowledge used by all subsystems. The initial knowledge is expressed modularly as specifications (e.g., radar constraints, performance measures, and target characteristics), relationships (among parameters, intermediate measures, and component performance measures), and formulas. The intent of the learning system is to relieve the human from the very tedious trial-and-error process of examining performance, selecting and applying curve-fitting methods, and selecting the next trial set of parameters. A learning system to design a simple radar meeting specific performance constraints is described in detail, for experimental purposes, in generic object-based code.

  11. Variational optimization of sub-grid scale convection parameters. Final report

    SciTech Connect

    Zivkovic-Rothman, M.

    1997-11-25

    Under the DOE CHAMMP/CLIMATE Program, a convective scheme was developed for use in climate models. The purpose of the present study was to develop an adjoint model of its tangent-linear model. the convective scheme was integrated within a single column model which provides radiative-convective equilibrium solutions applicable to climate models. The main goal of this part of the project was to develop an adjoint of the scheme to facilitate the optimization of its convective parameters. For that purpose, adjoint sensitivities were calculated with the adjoint code. Parameter optimization was based on TOGA COARE data which were also used in this study to obtain integrations of the nonlinear and tangent-linear models as well as the integrations of the adjoint model. Some inadequacies of the inner IFA data array were found, and did not permit a single numerical integration during the entire 4 months of data. However, reliable monthly radiative-convective equilibrium solutions and associated adjoint sensitivities were obtained and used to bring about the parameter optimization.

  12. Final Report: Geoelectrical Measurement of Multi-Scale Mass Transfer Parameters

    SciTech Connect

    Haggerty, Roy; Day-Lewis, Fred; Singha, Kamini; Johnson, Timothy; Binley, Andrew; Lane, John

    2014-03-20

    Mass transfer affects contaminant transport and is thought to control the efficiency of aquifer remediation at a number of sites within the Department of Energy (DOE) complex. An improved understanding of mass transfer is critical to meeting the enormous scientific and engineering challenges currently facing DOE. Informed design of site remedies and long-term stewardship of radionuclide-contaminated sites will require new cost-effective laboratory and field techniques to measure the parameters controlling mass transfer spatially and across a range of scales. In this project, we sought to capitalize on the geophysical signatures of mass transfer. Previous numerical modeling and pilot-scale field experiments suggested that mass transfer produces a geoelectrical signature—a hysteretic relation between sampled (mobile-domain) fluid conductivity and bulk (mobile + immobile) conductivity—over a range of scales relevant to aquifer remediation. In this work, we investigated the geoelectrical signature of mass transfer during tracer transport in a series of controlled experiments to determine the operation of controlling parameters, and also investigated the use of complex-resistivity (CR) as a means of quantifying mass transfer parameters in situ without tracer experiments. In an add-on component to our grant, we additionally considered nuclear magnetic resonance (NMR) to help parse mobile from immobile porosities. Including the NMR component, our revised study objectives were to: 1. Develop and demonstrate geophysical approaches to measure mass-transfer parameters spatially and over a range of scales, including the combination of electrical resistivity monitoring, tracer tests, complex resistivity, nuclear magnetic resonance, and materials characterization; and 2. Provide mass-transfer estimates for improved understanding of contaminant fate and transport at DOE sites, such as uranium transport at the Hanford 300 Area. To achieve our objectives, we implemented a 3

  13. The effect of muscle, cooking method and final internal temperature on quality parameters of beef roast.

    PubMed

    Modzelewska-Kapituła, Monika; Dąbrowska, Ewa; Jankowska, Barbara; Kwiatkowska, Aleksandra; Cierach, Marek

    2012-06-01

    The aim of the study was to evaluate the influence of cooking conditions (dry air and steam) and final internal temperature (75, 85, 95°C) on the physico-chemical properties of beef infraspinatus (INF) and semimembranosus (SEM) muscles as well as their tenderness and juiciness. Cooking method and temperature influenced moisture, total collagen content in cooked meat and cooking loss, whereas muscle type affected fat, total collagen content and cooking loss. Warner-Bratzler shear force values were affected by cooking method, which also influenced juiciness of roasts. Temperature affected tenderness and juiciness, whereas muscle type influenced juiciness. The most desirable tenderness had INF heated in steam and dry air to 95°C. Processing SEM in dry air to 85 and 95°C lowered the juiciness of the roasts. There were significant correlations between physico-chemical, sensorial and image attributes, however high accuracy of prediction (r(2)>0.8) was achieved only for SEM muscle.

  14. Patient Protection and Affordable Care Act; HHS Notice of Benefit and Payment Parameters for 2017. Final rule.

    PubMed

    2016-03-08

    This final rule sets forth payment parameters and provisions related to the risk adjustment, reinsurance, and risk corridors programs; cost-sharing parameters and cost-sharing reductions; and user fees for Federally-facilitated Exchanges. It also provides additional amendments regarding the annual open enrollment period for the individual market for the 2017 and 2018 benefit years; essential health benefits; cost sharing; qualified health plans; Exchange consumer assistance programs; network adequacy; patient safety; the Small Business Health Options Program; stand-alone dental plans; third-party payments to qualified health plans; the definitions of large employer and small employer; fair health insurance premiums; student health insurance coverage; the rate review program; the medical loss ratio program; eligibility and enrollment; exemptions and appeals; and other related topics.

  15. Filtered Rayleigh scattering diagnostic for multi-parameter thermal-fluids measurements : LDRD final report.

    SciTech Connect

    Beresh, Steven Jay; Grasser, Thomas W.; Kearney, Sean Patrick; Schefer, Robert W.

    2004-01-01

    Simulation-based life-cycle-engineering and the ASCI program have resulted in models of unprecedented size and fidelity. The validation of these models requires high-resolution, multi-parameter diagnostics. Within the thermal-fluids disciplines, the need for detailed, high-fidelity measurements exceeds the limits of current engineering sciences capabilities and severely tests the state of the art. The focus of this LDRD is the development and application of filtered Rayleigh scattering (FRS) for high-resolution, nonintrusive measurement of gas-phase velocity and temperature. With FRS, the flow is laser-illuminated and Rayleigh scattering from naturally occurring sources is detected through a molecular filter. The filtered transmission may be interpreted to yield point or planar measurements of three-component velocities and/or thermodynamic state. Different experimental configurations may be employed to obtain compromises between spatial resolution, time resolution, and the quantity of simultaneously measured flow variables. In this report, we present the results of a three-year LDRD-funded effort to develop FRS combustion thermometry and Aerosciences velocity measurement systems. The working principles and details of our FRS opto-electronic system are presented in detail. For combustion thermometry we present 2-D, spatially correlated FRS results from nonsooting premixed and diffusion flames and from a sooting premixed flame. The FRS-measured temperatures are accurate to within {+-}50 K (3%) in a premixed CH4-air flame and within {+-}100 K for a vortex-strained diluted CH4-air diffusion flame where the FRS technique is severely tested by large variation in scattering cross section. In the diffusion flame work, FRS has been combined with Raman imaging of the CH4 fuel molecule to correct for the local light scattering properties of the combustion gases. To our knowledge, this is the first extension of FRS to nonpremixed combustion and the first use of joint FRS

  16. Deoxynivalenol and its metabolite deepoxy-deoxynivalenol: multi-parameter analysis for the evaluation of cytotoxicity and cellular effects.

    PubMed

    Springler, Alexandra; Hessenberger, Sabine; Reisinger, Nicole; Kern, Corinna; Nagl, Veronika; Schatzmayr, Gerd; Mayer, Elisabeth

    2017-02-01

    The mycotoxin deoxynivalenol (DON) contaminates agricultural commodities worldwide, posing health threats to humans and animals. Associated with DON are derivatives, such as deepoxy-deoxynivalenol (DOM-1), produced by enzymatic transformation of certain intestinal bacteria, which are naturally occurring or applied as feed additives. Using differentiated porcine intestinal epithelial cells (IPEC-J2), we provide the first multi-parameter comparative cytotoxicity analysis of DON and DOM-1, based on the parallel evaluation of lysosomal activity, total protein content, membrane integrity, mitochondrial metabolism and ATP synthesis. The study investigated the ability of DON and-for the first time of its metabolite DOM-1-to induce apoptosis, mitogen-activated protein kinase (MAPK) signalling, oxidative events and alterations of mitochondrial structure in porcine intestinal epithelial cells (IECs). The degree of DON toxicity strongly varied, depending on the cytotoxicity parameter evaluated. DON compromised viability according to the parameters of lysosomal activity, total protein content and membrane integrity, but increased viability according to assays based on mitochondrial metabolism and ATP synthesis. DON induced expression of cleaved caspase-3 (maximum induction 3.9-fold) and MAPK p38 and p42/p44 (maximum induction 2.51- and 2.30-fold, respectively). DON altered mitochondrial morphology, but did not increase intracellular ROS. DOM-1-treated IPEC-J2 remained unaffected at equimolar concentrations in all assays, thereby confirming the safety of feed additives using DON- to DOM-1-transforming bacteria. The study additionally highlights that an extensive multi-parameter analysis significantly contributes to the quality of in vitro data.

  17. Semen molecular and cellular features: these parameters can reliably predict subsequent ART outcome in a goat model

    PubMed Central

    Berlinguer, Fiammetta; Madeddu, Manuela; Pasciu, Valeria; Succu, Sara; Spezzigu, Antonio; Satta, Valentina; Mereu, Paolo; Leoni, Giovanni G; Naitana, Salvatore

    2009-01-01

    Currently, the assessment of sperm function in a raw or processed semen sample is not able to reliably predict sperm ability to withstand freezing and thawing procedures and in vivo fertility and/or assisted reproductive biotechnologies (ART) outcome. The aim of the present study was to investigate which parameters among a battery of analyses could predict subsequent spermatozoa in vitro fertilization ability and hence blastocyst output in a goat model. Ejaculates were obtained by artificial vagina from 3 adult goats (Capra hircus) aged 2 years (A, B and C). In order to assess the predictive value of viability, computer assisted sperm analyzer (CASA) motility parameters and ATP intracellular concentration before and after thawing and of DNA integrity after thawing on subsequent embryo output after an in vitro fertility test, a logistic regression analysis was used. Individual differences in semen parameters were evident for semen viability after thawing and DNA integrity. Results of IVF test showed that spermatozoa collected from A and B lead to higher cleavage rates (0 < 0.01) and blastocysts output (p < 0.05) compared with C. Logistic regression analysis model explained a deviance of 72% (p < 0.0001), directly related with the mean percentage of rapid spermatozoa in fresh semen (p < 0.01), semen viability after thawing (p < 0.01), and with two of the three comet parameters considered, i.e tail DNA percentage and comet length (p < 0.0001). DNA integrity alone had a high predictive value on IVF outcome with frozen/thawed semen (deviance explained: 57%). The model proposed here represents one of the many possible ways to explain differences found in embryo output following IVF with different semen donors and may represent a useful tool to select the most suitable donors for semen cryopreservation. PMID:19900288

  18. Parameters for cellular viability and membrane function in chenopodium cells show a specific response of extracellular pH to heat shock with extreme Q10.

    PubMed

    Chaidee, A; Pfeiffer, W

    2006-01-01

    The effect of brief heat shock on Chenopodium cells was investigated by measuring biochemical parameters for cellular vitality, membrane function and integrity: extracellular pH, release of osmotic compounds, phosphatase, protein and betalain, and cellular reduction of DCPIP and MTT. A threshold temperature was found at 45 degrees C, where release of osmotic compounds, protein and betalain, and reduction of DCPIP and MTT indicate loss of vitality. Extracellular pH and an alkaline phosphatase responded 10-20 degrees C below this threshold, suggesting that extracellular alkalinization, and probably the release of a phosphatase, are part of a specific cellular response to abiotic stress induced by heat shock. The extracellular proton concentration did not increase above 45 degrees C: this may indicate equilibration of gradients driving this process or an inactivation of cellular mechanisms responsible for extracellular alkalinization. The response of extracellular pH to heat shock in Chenopodium cell suspensions was fast, i.e., up to +1 pH in 5 min. Addition of the K+/H+ antiporter nigericin to Chenopodium cells caused an extracellular alkalinization similar to heat shock. The heat shock-induced extracellular alkalinization was characterized by Q10 values for distinct ranges of temperature (Q10 of 56 for 24-31 degrees C, 2.3 for 31-42 degrees C, and 1.0 for 42-50 degrees C). To the author's knowledge, the Q10 of 56 is the highest found up to now. These results suggest that extracellular protons are involved in temperature sensing and signalling in plant cells, probably via a channel-mediated pathway.

  19. Interaction between cellular voltage-sensitive conductance and network parameters in a model of neocortex can generate epileptiform bursting.

    SciTech Connect

    van Drongelen, W.; Lee, H. C.; Koch, H.; Elsen, F.; Carroll, M. S.; Hereld, M.; Stevens, R. L.; Mathematics and Computer Science; Univ. of Chicago

    2004-01-01

    We examined the effects of both intrinsic neuronal membrane properties and network parameters on oscillatory activity in a model of neocortex. A scalable network model with six different cell types was built with the pGENESIS neural simulator. The neocortical network consisted of two types of pyramidal cells and four types of inhibitory interneurons. All cell types contained both fast sodium and delayed rectifier potassium channels for generation of action potentials. A subset of the pyramidal neurons contained an additional slow inactivating (persistent) sodium current (NaP). The neurons with the NaP current showed spontaneous bursting activity in the absence of external stimulation. The model also included a routine to calculate a simulated electroencephalogram (EEG) trace from the population activity. This revealed emergent network behavior which ranged from desynchronized activity to different types of seizure-like bursting patterns. At settings with weaker excitatory network effects, the propensity to generate seizure-like behavior increased. Strong excitatory network connectivity destroyed oscillatory behavior, whereas weak connectivity enhanced the relative importance of the spontaneously bursting cells. Our findings are in contradiction with the general opinion that strong excitatory synaptic and/or insufficient inhibition effects are associated with seizure initiation, but are in agreement with previously reported behavior in neocortex.

  20. Exposure of Daphnia magna to trichloroethylene (TCE) and vinyl chloride (VC): evaluation of gene transcription, cellular activity, and life-history parameters.

    PubMed

    Houde, Magali; Douville, Mélanie; Gagnon, Pierre; Sproull, Jim; Cloutier, François

    2015-06-01

    Trichloroethylene (TCE) is a ubiquitous contaminant classified as a human carcinogen. Vinyl chloride (VC) is primarily used to manufacture polyvinyl chloride and can also be a degradation product of TCE. Very few data exist on the toxicity of TCE and VC in aquatic organisms particularly at environmentally relevant concentrations. The aim of this study was to evaluate the sub-lethal effects (10 day exposure; 0.1; 1; 10 µg/L) of TCE and VC in Daphnia magna at the gene, cellular, and life-history levels. Results indicated impacts of VC on the regulation of genes related to glutathione-S-transferase (GST), juvenile hormone esterase (JHE), and the vitelline outer layer membrane protein (VMO1). On the cellular level, exposure to 0.1, 1, and 10 µg/L of VC significantly increased the activity of JHE in D. magna and TCE increased the activity of chitinase (at 1 and 10 µg/L). Results for life-history parameters indicated a possible tendency of TCE to affect the number of molts at the individual level in D. magna (p=0.051). Measurement of VG-like proteins using the alkali-labile phosphates (ALP) assay did not show differences between TCE treated organisms and controls. However, semi-quantitative measurement using gradient gel electrophoresis (213-218 kDa) indicated significant decrease in VG-like protein levels following exposure to TCE at all three concentrations. Overall, results indicate effects of TCE and VC on genes and proteins related to metabolism, reproduction, and growth in D. magna.

  1. Medium energy measurements of N-N parameters. Final technical report, April 1, 1994--September 30, 1996

    SciTech Connect

    Ambrose, D.; Betts, W.; Coffey, P.; Glass, G.; McDonough, J.; Riley, P.; Tang, J.L.

    1998-08-01

    This document is a final technical report describing the accomplishments of the medium/high energy nuclear physics research program at the University of Texas at Austin. The research program had four main thrusts, only one of which can be considered as measurements of N-N parameters: (1) finishing the data analyses associated with recent LAMPF and TRIUMPF N-N experiments, whose overall purpose has been the determination of the nucleon-nucleon amplitudes, both for isospin 0 and 1 at medium energies; (2) continuing work on BNL E871, a search for rare decay modes of the K{sub L}; (3) work on the RHIC-STAR project, an experiment to create and study a quark gluon plasma and nuclear matter at high energy density; (4) beginning a new AGS experiment (E896) which will search for the lowest mass state of the predicted strange di-baryons, the Ho, and other exotic states of nuclear matter through nucleus-nucleus collisions.

  2. Applying genetic algorithms in a parallel computing environment for optimising parameters of complex cellular automata models: the case of SCIDDICA S3hex

    NASA Astrophysics Data System (ADS)

    D'Ambrosio, D.; Iovine, G.

    2003-04-01

    Cellular Automata (CA) offer a valid alternative to the classic approach, based on partial differential equation, in order to simulate complex phenomena, when these latter can be described in terms of local interactions among their constituent parts. SCIDDICA S3hex is a two-dimensional hexagonal CA model developed for simulating debris flows: it has recently been applied to several real cases of landslides occurred in Campania (Southern Italy). The release S3hex has been derived by progressively improving an initial simplified CA model, originally derived for simulating simple cases of flow-type landslides. The model requires information related to topography, thickness of erodable regolith overlying the bedrock, and location and extension of landslide sources. Performances depend on a set of global parameters which are utilised in the transition function of the model: their value affect the elementary processes of the transition function and thus the overall results. A fine calibration is therefore an essential phase, in order to evaluate the reliability of the model for successive applications to debris-flow susceptibility zonation. The complexity of both the model and the phenomena to be simulated suggested to employ an automated technique of evaluation, for the determination of the best set of global parameters. Genetic Algorithms (GA) are a powerful optimization tool inspired to natural selection. In the last decades, in spite of their intrinsic simplicity, they have largely been successfully applied on a wide number of highly complex problems. The calibration of the model could therefore be performed through such technique of optimisation, by considering several real cases of study. Owing to the large number of simulations generally needed for performing GA experiments on complex phenomena, which imply long lasting tests on sequential computational architectures, the adoption of a parallel computational environment seemed appropriate: the original source code

  3. Investigation of the use of fly-ash based autoclaved cellular concrete blocks in coal mines for air duct work. Final report, January 25, 1993--December 31, 1994

    SciTech Connect

    Horvath, M.L.

    1995-06-19

    Coal mines are required to provide ventilation to occupied portions of underground mines. Concrete block is used in this process to construct air duct walls. However, normal concrete block is heavy and not easy to work with and eventually fails dramatically after being loaded due to mine ceiling convergence and/or floor heave. Autoclaved cellular concrete block made from (70{plus_minus}%) coal fly ash is lightweight and less rigid when loaded. It is lighter and easier to use than regular concrete block for underground mine applications. It has also been used in surface construction around the world for over 40 years. Ohio Edison along with eight other electric utility companies, the Electric Power Research Institute (EPRI), and North American Cellular Concrete constructed a mobile demonstration plant to produce autoclaved cellular concrete block from utility fly ash. To apply this research in Ohio, Ohio Edison also worked with the Ohio Coal Development Office and CONSOL Inc. to produce autoclaved cellular concrete block not only from coal ash but also from LIMB ash, SNRB ash, and PFBC ash from various clean coal technology projects sponsored by the Ohio Coal Development Office. The purpose of this project was to demonstrate the potential for beneficial use of fly ash and clean coal technology by-products in the production of lightweight block.

  4. High frequency 3-component waveform inversion for source and structural parameters. Final report, 31 December 1993--30 June 1998

    SciTech Connect

    Harvey, D.J.; Lavehio, A.L.

    1998-09-01

    The authors present the results of three studies to develop and verify techniques to classify weak seismic events. (1) The method and results of full waveform inversion for both detailed source parameters and structure parameters are described. Input data were seismograms from industrial explosions in Eastern Kazakhstan recorded by the NRDC seismic network in 1987. Very good fits were produced between the synthetic seismograms and the observed data on all three components simultaneously and for P-wave, Rayleigh wave, and Love wave. They interpreted some of the inverted source parameters as characteristic of several different types of industrial surface mining operations. (2) The same technique was used to determine detailed source and structure parameters using an event that is highly relevant to nuclear monitoring. They determined that a salt mine collapse near Solikamsk, the Ural Mountains on 5 January 1995 was most likely a mine collapse instead of an underground explosions. (3) This study was carried out jointly by the Seismology Group of the University of Colorado and the Russian team from the Int`l Institute of Earthquake Prediction Theory and Math. Geophysics. They developed a new technique to identify a seismic event based on simultaneous inversion of surface wave amplitude spectra and signs of first motions of body wave. They applied this technique to several events near the Chinese test site at Lop Nor and demonstrated significant differences in source parameters characterizing explosions and natural earthquakes in this region.

  5. Comparative study of effects of magnesium and taurine on electrical parameters of natural and artificial membranes. VII. Effects on cellular and paracellular ionic transfer through isolated human amnion.

    PubMed

    Bara, M; Guiet-Bara, A; Durlach, J

    1990-12-01

    The comparative effects of 2 mM magnesium and taurine on various components of the human transamniotic conductance, Gt, were observed. The use of both microelectrodes and metabolic inhibitors enables 10 components of Gt to be distinguished: six cellular components (Na-K ATPase, Na-H antiport, Na-K-2Cl cotransport and Na, K, Cl channels), one coupling component, and three paracellular components (Na, K, Cl). Mg increased all components of Gt while taurine only increased five of them (Na and K channels, coupling, Na and K paracellular conductance). A potentiometric effect of taurine on Mg2+ modified membrane, obtained on paracellular components, was not measured on cellular components. There was only a vicarious effect between Mg and taurine on the non-enzymatic cellular and paracellular transfer of Na and K.

  6. Geoelectrical Measurement of Multi-Scale Mass Transfer Parameters Final Report to the Subsurface Biogeochemical Research Program

    SciTech Connect

    Day-Lewis, Frederick; Singha, Kamini; Haggerty, Roy; Johnson, Timothy; Binley, Andrew; Lane, John

    2014-03-10

    . In this project, we sought to capitalize on the geophysical signatures of mass transfer. Previous numerical modeling and pilot-scale field experiments suggested that mass transfer produces a geoelectrical signature—a hysteretic relation between sampled (mobile-domain) fluid conductivity and bulk (mobile + immobile) conductivity—over a range of scales relevant to aquifer remediation. In this work, we investigated the geoelectrical signature of mass transfer during tracer transport in a series of controlled experiments to determine the operation of controlling parameters, and also investigated the use of complex-resistivity (CR) as a means of quantifying mass transfer parameters in situ without tracer experiments. In an add-on component to our grant, we additionally considered nuclear magnetic resonance (NMR) to help parse mobile from immobile porosities. Our study objectives were to: 1. Develop and demonstrate geophysical approaches to measure mass-transfer parameters spatially and over a range of scales, including the combination of electrical resistivity monitoring, tracer tests, complex resistivity, nuclear magnetic resonance, and materials characterization; and 2. Provide mass-transfer estimates for improved understanding of contaminant fate and transport at DOE sites, such as uranium transport at the Hanford 300 Area. To achieve our objectives, we implemented a 3-part research plan involving (1) development of computer codes and techniques to estimate mass-transfer parameters from time-lapse electrical data; (2) bench-scale experiments on synthetic materials and materials from cores from the Hanford 300 Area; and (3) field demonstration experiments at the DOE’s Hanford 300 Area.

  7. Maximum safe pulling lengths for solid dielectric insulated cables. Volume 1. Research data and cable-pulling parameters. Final report

    SciTech Connect

    Silver, D.A.; Seman, G.W.; Bush, R.A.; Matthews, G.H.

    1984-02-01

    This two-volume report presents the results of a recent program to investigate and update the parameters that affect the maximum safe pulling length for solid dielectric cables. In this program, 23 types of solid dielectric cables rated 600 V through 138 kV were studied. The cables had copper and aluminum conductors in sizes from 1/0 AWG (54 mm/sup 2/) to 2500 kcmil (1266 mm/sup 2/) and insulations of cross-linked polyethylene and ethylene propylene rubber.

  8. Current good tissue practice for human cell, tissue, and cellular and tissue-based product establishments; inspection and enforcement. Final rule.

    PubMed

    2004-11-24

    The Food and Drug Administration (FDA) is requiring human cell, tissue, and cellular and tissue-based product (HCT/P) establishments to follow current good tissue practice (CGTP), which governs the methods used in, and the facilities and controls used for, the manufacture of HCT/Ps; recordkeeping; and the establishment of a quality program. The agency is also issuing new regulations pertaining to labeling, reporting, inspections, and enforcement that will apply to manufacturers of those HCT/Ps regulated solely under the authority of the Public Health Service Act (PHS Act), and not as drugs, devices, and/or biological products. The agency's actions are intended to improve protection of the public health while keeping regulatory burden to a minimum, which in turn would encourage significant innovation.

  9. In-situ parameter estimation for solar domestic hot water heating systems components. Final report, June 1995--May 1996

    SciTech Connect

    Smith, T.R.

    1997-03-01

    Three different solar domestic hot water systems are being tested at the Colorado State University Solar Energy Applications Laboratory; an unpressurized drain-back system with a load side heat exchanger, an integral collector storage system, and an ultra low flow natural convection heat exchanger system. The systems are fully instrumented to yield data appropriate for in-depth analyses of performance. The level of detail allows the observation of the performance of the total system and the performance of the individual components. This report evaluates the systems based on in-situ experimental data and compares the performances with simulated performances. The verification of the simulations aids in the rating procedure. The whole system performance measurements are also used to analyze the performance of individual components of a solar hot water system and to develop improved component models. The data are analyzed extensively and the parameters needed to characterize the systems fully are developed. Also resulting from this indepth analysis are suggested design improvements wither to the systems or the system components.

  10. Final Report for NFE-07-00912: Development of Model Fuels Experimental Engine Data Base & Kinetic Modeling Parameter Sets

    SciTech Connect

    Bunting, Bruce G

    2012-10-01

    The automotive and engine industries are in a period of very rapid change being driven by new emission standards, new types of after treatment, new combustion strategies, the introduction of new fuels, and drive for increased fuel economy and efficiency. The rapid pace of these changes has put more pressure on the need for modeling of engine combustion and performance, in order to shorten product design and introduction cycles. New combustion strategies include homogeneous charge compression ignition (HCCI), partial-premixed combustion compression ignition (PCCI), and dilute low temperature combustion which are being developed for lower emissions and improved fuel economy. New fuels include bio-fuels such as ethanol or bio-diesel, drop-in bio-derived fuels and those derived from new crude oil sources such as gas-to-liquids, coal-to-liquids, oil sands, oil shale, and wet natural gas. Kinetic modeling of the combustion process for these new combustion regimes and fuels is necessary in order to allow modeling and performance assessment for engine design purposes. In this research covered by this CRADA, ORNL developed and supplied experimental data related to engine performance with new fuels and new combustion strategies along with interpretation and analysis of such data and consulting to Reaction Design, Inc. (RD). RD performed additional analysis of this data in order to extract important parameters and to confirm engine and kinetic models. The data generated was generally published to make it available to the engine and automotive design communities and also to the Reaction Design Model Fuels Consortium (MFC).

  11. Final Report for Grant No. DE-FG02-01ER63220 "The Dynamics of Cellular Stress Responses in Deinococcus radiodurans"

    SciTech Connect

    PI: Michael J. Daly, Ph.D., Uniformed Services University of the Health Sciences; Co-Investigators: James K. Fredrickson, Ph.D., Pacific Northwest National Laboratory; Richard D. Smith, Ph.D., Pacific Northwest National Laboratory; Eugene Koonin, Ph.D., National Center for Biotechnology Information; Jizhong Zhou, Ph.D. , Oak Ridge National Laboratory; Mary S. Lipton, Ph.D., Pacific Northwest National Laboratory

    2006-03-06

    Bacteria belonging to the family Deinococcaceae are some of the most ionizing radiation (IR) resistant organisms yet discovered. Deinococcus radiodurans is obligate aerobic, capable of growth under chronic IR (60 Gy/hour) and relatively resistant to many DNA damaging conditions including exposure to desiccation, ultraviolet radiation and hydrogen peroxide. The genes and cellular pathways underlying the survival strategies of D. radiodurans have been under investigation for fifty years. In the last decade, D. radiodurans was subjected to whole-genome sequencing, annotation and comparative analysis, whole-transcriptome and whole-proteome analyses, and numerous DNA repair studies. Collectively, published reports support that the key to survival of D. radiodurans resides in its ability to repair DNA, but the mechanisms responsible remain poorly defined. Unexpectedly, many novel genes implicated in recovery from IR by transcriptome and proteome profiling have had little effect on survival when disrupted, and there is reason to ask if something is missing from classical models of radiation resistance. The prevailing dogma of radiation toxicity has been that the cytotoxic and mutagenic effects of radiation are principally the result of DNA damage that occurs during IR. However, in light of available whole genome sequences, one broad observation that is difficult to reconcile with this view is that many organisms that encode a compliment of DNA repair and protection functions are killed at radiation doses that cause little DNA damage. This indicates that there are cellular targets involved in recovery that are more vulnerable to IR damage than DNA. It has been reported that D. radiodurans and other resistant organisms accumulate very high intracellular concentrations of Mn(II), and restricting the amount of Mn(II) during recovery from IR substantially reduced survival of D. radiodurans. At high intracellular concentrations, Mn(II) is known to act as a true catalyst of the

  12. Multifaceted interplay between lipophilicity, protein interaction and luminescence parameters of non-intercalative ruthenium(II) polypyridyl complexes controlling cellular imaging and cytotoxic properties.

    PubMed

    Mazuryk, Olga; Magiera, Katarzyna; Rys, Barbara; Suzenet, Franck; Kieda, Claudine; Brindell, Małgorzata

    2014-12-01

    Here, we examine the photophysical properties of five ruthenium(II) complexes comprising two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and functionalized bipyridine (R₁bpy-R₂, where R₁= H or CH3, R₂= H, CH₃, COO⁻,4-[3-(2-nitro-1H-imidazol-1-yl)propyl] or 1,3-dicyclohexyl-1-carbonyl-urea) towards development of luminescence probes for cellular imaging. These complexes have been shown to interact with albumin and the formed adducts exhibited up to eightfold increase in the luminescence quantum yield as well as the average lifetime of emission. It was demonstrated that they cannot bind to DNA through the intercalation mode and its luminescence in the presence of DNA is quenching. Cell viability experiments indicated that all complexes possess significant dose-dependent cytotoxicity (with IC₅₀ 5-19 μM) on 4T1 breast cancer cell line and their anti-proliferative activity correlates very well with their lipophilicity. Cellular uptake was studied by measuring the ruthenium content in cells using ICP-MS technique. As expected, the better uptake is directly related to higher lipophilicity of doubly charged ruthenium complexes while uptake of monocationic one is much lower in spite of the highest lipophilicity. Additionally staining properties were assessed using flow cytometry and fluorescence microscopy. These experiments showed that complex with 1,3-dicyclohexyl-1-carbonyl-urea substituent exhibits the best staining properties in spite of the lowest luminescence quantum yield in buffered solution (pH 7.4). Our results point out that both the imaging and cytotoxic properties of the studied ruthenium complexes are strongly influence by the level of internalization and protein interaction.

  13. SU-E-T-667: Radiosensitization Due to Gold Nanoparticles: A Monte Carlo Cellular Dosimetry Investigation of An Expansive Parameter Space

    SciTech Connect

    Martinov, M; Thomson, R

    2015-06-15

    Purpose: To investigate dose enhancement to cellular compartments following gold nanoparticle (GNP) uptake in tissue, varying cell and tissue morphology, intra and extracellular GNP distribution, and source energy using Monte Carlo (MC) simulations. Methods: Models of single and multiple cells are developed for normal and cancerous tissues; cells (outer radii 5–10 µm) are modeled as concentric spheres comprising the nucleus (radii 2.5–7.5 µm) and cytoplasm. GNP distributions modeled include homogeneous distributions throughout the cytoplasm, variable numbers of GNP-containing endosomes within the cytoplasm, or distributed in a spherical shell about the nucleus. Gold concentrations range from 1 to 30 mg/g. Dose to nucleus and to cytoplasm for simulations including GNPs are compared to simulations without GNPs to compute Nuclear and Cytoplasm Dose Enhancement Factors (NDEF, CDEF). Photon source energies are between 20 keV and 1.25 MeV. Results: DEFs are highly sensitive to GNP intracellular distribution; for a 2.5 µm radius nucleus irradiated by a 30 keV source, NDEF varies from 1.2 for a single endosome containing all GNPs to 8.2 for GNPs distributed about the nucleus (7 mg/g). DEFs vary with cell dimensions and source energy: NDEFs vary from 2.5 (90 keV) to 8.2 (30 keV) for a 2.5 µm radius nucleus and from 1.1 (90 keV) to 1.3 (30 keV) for a 7.5 µm radius nucleus, both with GNPs in a spherical shell about the nucleus (7 mg/g). NDEF and CDEF are generally different within a single cell. For multicell models, the presence of gold within intervening tissues between source and target perturbs the fluence reaching cellular targets, resulting in DEF inhomogeneities within a population of irradiated cells. Conclusion: DEFs vary by an order of magnitude for different cell models, GNP distributions, and source energies, demonstrating the importance of detailed modelling for advancing GNP development for radiotherapy. Funding provided by the Natural Sciences and

  14. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field

    PubMed Central

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; d’Angelo, Raffaele; Zeni, Olga

    2016-01-01

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components. PMID:26762783

  15. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field.

    PubMed

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; d'Angelo, Raffaele; Zeni, Olga

    2016-01-14

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components.

  16. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field

    NASA Astrophysics Data System (ADS)

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; D’Angelo, Raffaele; Zeni, Olga

    2016-01-01

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components.

  17. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    SciTech Connect

    Damodaran, T.V.; Attia, M.K.; Abou-Donia, M.B.

    2011-11-15

    analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: Black-Right-Pointing-Pointer Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. Black-Right-Pointing-Pointer Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. Black-Right-Pointing-Pointer Multiple anomalous cellular (neuronal and astroglial) features were recorded. Black-Right-Pointing-Pointer Anatomical specificity of the neurodegeneration was described.

  18. L-DOPA-induced dyskinesia in the intrastriatal 6-hydroxydopamine model of parkinson's disease: relation to motor and cellular parameters of nigrostriatal function.

    PubMed

    Winkler, Christian; Kirik, Deniz; Björklund, Anders; Cenci, M Angela

    2002-07-01

    In order to assess the role of striatal dopamine (DA) afferents in L-DOPA-induced dyskinesia, we have studied a large series of rats sustaining 2, 3, or 4 unilateral injections of 6-hydroxydopamine (6-OHDA) in the lateral striatum. This type of lesion produced a dose-dependent depletion of DA fibers in the caudate-putamen, which was most pronounced in the lateral aspects of this structure. An additional group of rats was injected with 6-OHDA in the medial forebrain bundle to obtain complete DA denervation on one side of the brain. During a course of chronic L-DOPA treatment, rats with intrastriatal 6-OHDA lesions developed abnormal involuntary movements (AIMs), which mapped onto striatal domains exhibiting at least approximately 90% denervation, as judged by DA transporter autoradiography. The denervated areas showed local upregulation of preproenkephalin and prodynorphin mRNA, and FosB-like immunoreactivity, which were highly correlated with the rats' AIM scores. When compared to completely DA-denervated animals, the rats with intrastriatal 6-OHDA lesions showed an overall lower incidence, lower severity and different topographic distribution of AIMs. The involvement of proximal limb and axial muscles in the abnormal movements was proportional to the spreading of the lesion from lateral towards medial aspects of the caudate-putamen. Locomotive AIMs were only seen in rats with complete lesions, but not in any of the animals with intrastriatal 6-OHDA (which showed > 5% DA fiber sparing in the medial striatum). Intrastriatally 6-OHDA-lesioned rats had a larger therapeutic window for L-DOPA than did rats with complete bundle lesions, since they exhibited an overall lower predisposition to dyskinesia but a similar degree of drug-induced motor improvement in a test of forelimb stepping. Our results are the first to demonstrate that selective and partial DA denervation in the sensorimotor part of the striatum can confer cellular and behavioral supersensitivity to L

  19. Critical modeling parameters identified for 3D CFD modeling of rectangular final settling tanks for New York City wastewater treatment plants.

    PubMed

    Ramalingam, K; Xanthos, S; Gong, M; Fillos, J; Beckmann, K; Deur, A; McCorquodale, J A

    2012-01-01

    New York City Environmental Protection is in the process of incorporating biological nitrogen removal (BNR) in its wastewater treatment plants (WWTPs) which entails operating the aeration tanks with higher levels of mixed liquor suspended solids (MLSS) than a conventional activated sludge process. The objective of this paper is to discuss two of the important parameters introduced in the 3D CFD model that has been developed by the City College of New York (CCNY) group: (a) the development of the 'discrete particle' measurement technique to carry out the fractionation of the solids in the final settling tank (FST) which has critical implications in the prediction of the effluent quality; and (b) the modification of the floc aggregation (K(A)) and floc break-up (K(B)) coefficients that are found in Parker's flocculation equation (Parker et al. 1970, 1971) used in the CFD model. The dependence of these parameters on the predictions of the CFD model will be illustrated with simulation results on one of the FSTs at the 26th Ward WWTP in Brooklyn, NY.

  20. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters

    PubMed Central

    Gahete, Manuel D.; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D.; Castaño, Justo P.; Marazuela, Mónica

    2015-01-01

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value. PMID:26124083

  1. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters.

    PubMed

    Luque, Raul M; Sampedro-Nuñez, Miguel; Gahete, Manuel D; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D; Castaño, Justo P; Marazuela, Mónica

    2015-08-14

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value.

  2. A two parameter family of travelling waves with a singular barrier arising from the modelling of extracellular matrix mediated cellular invasion

    NASA Astrophysics Data System (ADS)

    Perumpanani, Abbey J.; Sherratt, Jonathan A.; Norbury, John; Byrne, Helen M.

    1999-02-01

    Invasive cells variously show changes in adhesion, protease production and motility. In this paper the authors develop and analyse a model for malignant invasion, brought about by a combination of proteolysis and haptotaxis. A common feature of these two mechanisms is that they can be produced by contact with the extracellular matrix through the mediation of a class of surface receptors called integrins. An unusual feature of the model is the absence of cell diffusion. By seeking travelling wave solutions the model is reduced to a system of ordinary differential equations which can be studied using phase plane analysis. The authors demonstrate the presence of a singular barrier in the phase plane and a “hole” in this singular barrier which admits a phase trajectory. The model admits a family of travelling waves which depend on two parameters, i.e. the tissue concentration of connective tissue and the rate of decay of the initial spatial profile of the invading cells. The slowest member of this family corresponds to the phase trajectory which goes through the “hole” in the singular barrier. Using a power series method the authors derive an expression relating the minimum wavespeed to the tissue concentration of the extracellular matrix which is arbitrary. The model is applicable in a wide variety of biological settings which combine haptotaxis with proteolysis. By considering various functional forms the authors show that the key mathematical features of the particular model studied in the early parts of the paper are exhibited by a wider class of models which characterise the behaviour of invading cells.

  3. Approaches to Biosimulation of Cellular Processes

    PubMed Central

    Westerhoff, H. V.

    2006-01-01

    Modelling and simulation are at the heart of the rapidly developing field of systems biology. This paper reviews various types of models, simulation methods, and theoretical approaches that are presently being used in the quantitative description of cellular processes. We first describe how molecular interaction networks can be represented by means of stoichiometric, topological and kinetic models. We briefly discuss the formulation of kinetic models using mesoscopic (stochastic) or macroscopic (continuous) approaches, and we go on to describe how detailed models of molecular interaction networks (silicon cells) can be constructed on the basis of experimentally determined kinetic parameters for cellular processes. We show how theory can help in analyzing models by applying control analysis to a recently published silicon cell model. Finally, we review some of the theoretical approaches available to analyse kinetic models and experimental data, respectively. PMID:19669467

  4. Matrix and Backstage: Cellular Substrates for Viral Vaccines

    PubMed Central

    Jordan, Ingo; Sandig, Volker

    2014-01-01

    Vaccines are complex products that are manufactured in highly dynamic processes. Cellular substrates are one critical component that can have an enormous impact on reactogenicity of the final preparation, level of attenuation of a live virus, yield of infectious units or antigens, and cost per vaccine dose. Such parameters contribute to feasibility and affordability of vaccine programs both in industrialized countries and developing regions. This review summarizes the diversity of cellular substrates for propagation of viral vaccines from primary tissue explants and embryonated chicken eggs to designed continuous cell lines of human and avian origin. PMID:24732259

  5. Optimization of Fluorescence Assay of Cellular Manganese Status for High Throughput Screening

    PubMed Central

    Kumar, Kevin K.; Aboud, Asad A.; Patel, Devin K.; Aschner, Michael; Bowman, Aaron B.

    2013-01-01

    The advent of high throughput screening (HTS) technology permits identification of compounds that influence various cellular phenotypes. However, screening for small molecule chemical modifiers of neurotoxicants has been limited by the scalability of existing phenotyping assays. Furthermore, the adaptation of existing cellular assays to HTS format requires substantial modification of experimental parameters and analysis methodology to meet the necessary statistical requirements. Here we describe the successful optimization of the Cellular Fura-2 Manganese Extraction Assay (CFMEA) for HTS. By optimizing cellular density, manganese (Mn) exposure conditions, and extraction parameters, the sensitivity and dynamic range of the fura-2 Mn response was enhanced to permit detection of positive and negative modulators of cellular manganese status. Finally, we quantify and report strategies to control sources of intra-and inter-plate variability by batch level and plate-geometric level analysis. Our goal is to enable HTS with the CFMEA to identify novel modulators of Mn transport. PMID:23169769

  6. Fatigue of cellular materials

    SciTech Connect

    Huang, J.S.; Lin, J.Y.

    1996-01-01

    The fatigue of cellular materials is analyzed using dimensional arguments. When the first unbroken cell wall ahead of the macrocrack tip fails after some cycles of loading, the macrocrack advances one cell diameter, giving the macrocrack growth rate of cellular materials. Paris law for microcrack propagation, Basquin law for high cycle fatigue and Coffin-Manson law for low cycle fatigue are employed in calculating the number of cycles to failure of the first unbroken cell wall ahead of the macrocrack tip. It is found that fatigue of cellular materials depends on cyclic stress intensity range, cell size, relative density and the fatigue parameters of the solid from which they are made. Theoretical modelling of fatigue of foams is compared to data in polymer foams; agreement is good.

  7. Cellular recurrent deep network for image registration

    NASA Astrophysics Data System (ADS)

    Alam, M.; Vidyaratne, L.; Iftekharuddin, Khan M.

    2015-09-01

    Image registration using Artificial Neural Network (ANN) remains a challenging learning task. Registration can be posed as a two-step problem: parameter estimation and actual alignment/transformation using the estimated parameters. To date ANN based image registration techniques only perform the parameter estimation, while affine equations are used to perform the actual transformation. In this paper, we propose a novel deep ANN based image rigid registration that combines parameter estimation and transformation as a simultaneous learning task. Our previous work shows that a complex universal approximator known as Cellular Simultaneous Recurrent Network (CSRN) can successfully approximate affine transformations with known transformation parameters. This study introduces a deep ANN that combines a feed forward network with a CSRN to perform full rigid registration. Layer wise training is used to pre-train feed forward network for parameter estimation and followed by a CSRN for image transformation respectively. The deep network is then fine-tuned to perform the final registration task. Our result shows that the proposed deep ANN architecture achieves comparable registration accuracy to that of image affine transformation using CSRN with known parameters. We also demonstrate the efficacy of our novel deep architecture by a performance comparison with a deep clustered MLP.

  8. Cellular and Molecular Parameters of Mesothelioma

    PubMed Central

    Ramos-Nino, Maria E.; Testa, Joseph R.; Altomare, Deborah A.; Pass, Harvey I.; Carbone, Michele; Bocchetta, Maurizio; Mossman, Brooke T.

    2009-01-01

    Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high-throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin-related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors. PMID:16795078

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  11. Predictability in cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

  12. The Effect of the Number of Simulations on the Exponents Obtained by Finite-Size Scaling Relations of the Order Parameter and the Magnetic Susceptibility for the Four-Dimensional Ising Model on the Creutz Cellular Automaton

    NASA Astrophysics Data System (ADS)

    Merdan, Z.; Güzelsoy, E.

    2012-05-01

    The four-dimensional Ising model is simulated on the Creutz cellular automaton using finite-size lattices with linear dimension 4≤ L≤8. The exponents in the finite-size scaling relations for the order parameter and the magnetic susceptibility at the finite-lattice critical temperature are computed to be β=0.49(7), β=0.49(5), β=0.50(1) and γ=1.04(4), γ=1.03(4), γ=1.02(4) for 7, 14, and 21 independent simulations, respectively. As the number of independent simulations increases, the obtained results are consistent with the renormalization group predictions of β=0.5 and γ=1. The values for the critical temperature of the infinite lattice T c (∞)=6.6788(65), T c (∞)=6.6798(69), T c (∞)=6.6802(70) are obtained from the straight-line fit of the magnetic susceptibility maxima using 4≤ L≤8 for 7, 14, and 21 independent simulations, respectively. As the number of independent simulations increases, the obtained results are in very good agreement with the series expansion results of T c (∞)=6.6817(15), T c (∞)=6.6802(2), the dynamic Monte Carlo result of T c (∞)=6.6803(1), the cluster Monte Carlo result of T c (∞)=6.680(1) and the Monte Carlo using Metropolis and Wolff-cluster algorithm result of T c (∞)=6.6802632±5×10-5.

  13. Patient Protection and Affordable Care Act; HHS Notice of Benefit and Payment Parameters for 2018; Amendments to Special Enrollment Periods and the Consumer Operated and Oriented Plan Program. Final rule.

    PubMed

    2016-12-22

    This final rule sets forth payment parameters and provisions related to the risk adjustment program; cost-sharing parameters and cost-sharing reductions; and user fees for Federally-facilitated Exchanges and State-based Exchanges on the Federal platform. It also provides additional guidance relating to standardized options; qualified health plans; consumer assistance tools; network adequacy; the Small Business Health Options Programs; stand-alone dental plans; fair health insurance premiums; guaranteed availability and guaranteed renewability; the medical loss ratio program; eligibility and enrollment; appeals; consumer-operated and oriented plans; special enrollment periods; and other related topics.

  14. Microfluidic Electroporation for Cellular Analysis and Delivery

    PubMed Central

    Geng, Tao

    2013-01-01

    Electroporation is a simple yet powerful technique for breaching cell membrane barrier. The applications of electroporation can be generally divided into two categories: the release of intracellular proteins, nucleic acids and other metabolites for analysis and the delivery of exogenous reagents such as genes, drugs and nanoparticles with therapeutic purposes or for cellular manipulation. In this review, we go over the basic physics associated with cell electroporation and highlight recent technological advances on microfluidic platforms for conducting electroporation. Within the context of its working mechanism, we summarize the accumulated knowledge on how the parameters of electroporation affect its performance for various tasks. We discuss various strategies and designs for conducting electroporation at microscale and then focus on analysis of intracellular contents and delivery of exogenous agents as two major applications of the technique. Finally, an outlook for future applications of microfluidic electroporation in increasingly diverse utilities is presented. PMID:23917998

  15. Boron combustion model development with kinetic sensitivity analysis and measurement of key chemical-rate parameters. Final report, 1 Jan 88-31 Dec 90

    SciTech Connect

    Brown, R.C.; Kolb, C.E.; Cho, S.Y.; Yetter, R.A.; Rabitz, H.R.

    1991-01-01

    This report presents kinetics models for the chemically facilitated gasification of the ubiguitous boron oxide coating that inhibits particulate boron ignition and the second stage high temperature boron surface burning that occurs once the oxide coating has been removed. These models include a homogeneous gas phase oxidation mechanism consisting of 19 chemical species and 58 forward and reverse elementary reactions, multicomponent gas phase diffusion and heterogeneous reactions between gas phase oxidation products and the boron oxide/boron surface. Kinetic mechanisms are formulated to describe the heterogeneous surface reactions for both B2O3(1) and B(s) surfaces in terms of simple adsorption and desorption reaction steps. Thermochemical parameters for these reaction steps are estimated from the current heats of formation and gas phase bond energies for the major reactants. Reaction rate parameters are estimated from available experimental data or using elementary transition state theory arguments.

  16. Patient Protection and Affordable Care Act; program integrity: exchange, premium stabilization programs, and market standards; amendments to the HHS notice of benefit and payment parameters for 2014. Final rule.

    PubMed

    2013-10-30

    This final rule implements provisions of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010 (collectively referred to as the Affordable Care Act). Specifically, this final rule outlines financial integrity and oversight standards with respect to Affordable Insurance Exchanges, qualified health plan (QHP) issuers in Federally-facilitated Exchanges (FFEs), and States with regard to the operation of risk adjustment and reinsurance programs. It also establishes additional standards for special enrollment periods, survey vendors that may conduct enrollee satisfaction surveys on behalf of QHP issuers, and issuer participation in an FFE, and makes certain amendments to definitions and standards related to the market reform rules. These standards, which include financial integrity provisions and protections against fraud and abuse, are consistent with Title I of the Affordable Care Act. This final rule also amends and adopts as final interim provisions set forth in the Amendments to the HHS Notice of Benefit and Payment Parameters for 2014 interim final rule, published in the Federal Register on March 11, 2013, related to risk corridors and cost-sharing reduction reconciliation.

  17. Cellular automaton for chimera states

    NASA Astrophysics Data System (ADS)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  18. Final report on the study of the effect of primary and secondary plant parameters on light-water-reactor transient behavior. Progress report, July 1-December 31, 1982

    SciTech Connect

    Baratta, A.J.; Robinson, G.E.; Kim, D.; Brownson, D.A.; Morales, J.B.; Huegel, D.; Gul, M.; Macario, F.

    1983-04-01

    Since the Three Mile Island Accident of March 1979, various approaches have been undertaken to reduce the probability of such occurrences. In general, these involve the addition of more complex and sophisticated engineered safety systems and instrumentation and control systems. Such improvements will undoubtedly improve overall plant safety. This project explores an alternative approach - the optimization of the transient behavior of the reactor and associated systems. Specifically, the ability of B and W and Westinghouse reactor to withstand a turbine trip was investigated. The project examined whether the plant's transient behavior with respect to peak reactor coolant system (RCS) behavior could be optimized. Several key parameters including pressurizer size, surge line impedence, time to SCRAM, and fuel and moderator temperature coefficients were varied. It was found that increasing pressurizer size decreased peak RCS pressure.

  19. A Study of Relationships among Technical, Tactical, Physical Parameters and Final Outcomes in Elite Soccer Matches as Analyzed by a Semiautomatic Video Tracking System.

    PubMed

    Filetti, Cristoforo; Ruscello, Bruno; D'Ottavio, Stefano; Fanelli, Vito

    2017-06-01

    The performance of a soccer team depends on many factors such as decision-making, cognitive and physical skills, and dynamic ever-changing space-time interactions between teammate and opponents in relation to the ball. Seventy ( n = 70) matches of the Italian SERIE A season 2013-2014 were investigated to analyze the mean performance of 360 players in terms of physical (physical efficiency index; PEI) and technical-tactical (technical efficiency index; TEI) standpoints. Using a semiautomatic video analysis system that has incorporated new parameters able to measure technical-tactical and physical efficiency (Patent IB2010/002593, 2011-ISA), the correlation between these new variables and how much it relates to the likelihood of winning were verified. Correlations between TEI and PEI were significant ( n = 140, r = .60, p < .001), and TEI showed a higher likelihood of winning than PEI factors ( p < .0001 vs. .0001, CI 95% [1.64, 3.00] vs. [1.28, 2.07]). Higher TEI and TEI + PEI differences between the teams were associated with a greater likelihood of winning, but PEI differences were not. Key performance indicators and this performance assessment method might be useful to better understand what determines winning and to assist the overall training process and match management.

  20. Toxicity of carbon monoxide-hydrogen cyanide gas mixtures: Expose concentration, time-to-incapacitation, carboxyhemoglobin, and blood cyanide parameters. Final report

    SciTech Connect

    Sanders, D.C.; Chaturvedi, A.K.; Endecott, B.R.; Ritter, R.M.; Vu, N.

    1994-04-01

    During aircraft interior fires, carbon monoxide (CO) and hydrogen cyanide (HCN) are produced in sufficient amounts to cause incapacitation and death. Time-to-incapacitation (ti) is a practical parameter for estimating escape time in fire environments. Exposures to CO-HCN mixtures have demonstrated that these gases have additive effects (producing shorter times to incapacitation), but the resulting concentrations of carboxyhemoglobin (COHb) and blood cyanide (CN-) at incapacitation are not well defined. These undefined relationships between COHb and blood CN- levels and the onset of incapacitation make the interpretation of postmortem levels difficult for medical accident investigators. To explore these relationships, ti was determined in laboratory rats exposed to two CO-HCN mixtures consisting of CO and HCN concentrations that produce 5- and 35-min ti in individual gas exposures; COHb and blood CN- concentrations were determined at incapacitation. In the high concentration CO-HCN mixture, the resultant ti was shortened from 5 min to 2.6 min; COHb dropped from 81% to 55% and CN- from 2.3 microns/mL to 1.1 microns/mL. At the lower concentration COHCN mixture, where the resultant ti was reduced from 35 min to 11.1 min, COHb dropped from 71% to 61% and blood CN- decreased from 4.2 microns/mL to 1.1 microns/mL. Comparison of the COHb and blood CN- values with the values from our signal gas exposure studies indicated that any alteration of the uptake of either gas in blood by the presence of the other was minimal. These findings suggest that changes in COHb and blood CN- may not be directly correlated with the onset of incapacitation and that postmortem blood levels should be carefully evaluated, particularly when both gases are present.

  1. Continuum representations of cellular solids

    NASA Astrophysics Data System (ADS)

    Neilsen, M. K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics, and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  2. Continuum representations of cellular solids

    SciTech Connect

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  3. Cellular Phone Towers

    MedlinePlus

    ... the call. How are people exposed to the energy from cellular phone towers? As people use cell ... where people can be exposed to them. The energy from a cellular phone tower antenna, like that ...

  4. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-12-31

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young`s modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  5. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-01-01

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young's modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  6. Fibre based cellular transfection.

    PubMed

    Tsampoula, X; Taguchi, K; Cizmár, T; Garces-Chavez, V; Ma, N; Mohanty, S; Mohanty, K; Gunn-Moore, F; Dholakia, K

    2008-10-13

    Optically assisted transfection is emerging as a powerful and versatile method for the delivery of foreign therapeutic agents to cells at will. In particular the use of ultrashort pulse lasers has proved an important route to transiently permeating the cell membrane through a multiphoton process. Though optical transfection has been gaining wider usage to date, all incarnations of this technique have employed free space light beams. In this paper we demonstrate the first system to use fibre delivery for the optical transfection of cells. We engineer a standard optical fibre to generate an axicon tip with an enhanced intensity of the remote output field that delivers ultrashort (~ 800 fs) pulses without requiring the fibre to be placed in very close proximity to the cell sample. A theoretical model is also developed in order to predict the light propagation from axicon tipped and bare fibres, in both air and water environments. The model proves to be in good agreement with the experimental findings and can be used to establish the optimum fibre parameters for successful cellular transfection. We readily obtain efficiencies of up to 57 % which are comparable with free space transfection. This advance paves the way for optical transfection of tissue samples and endoscopic embodiments of this technique.

  7. Effects of electromagnetic field stimulation on cellular signal transduction mechanisms: Analyses of the effects of low frequency electromagnetic fields on calcium spiking in ROS 17/2.8 cells. Final report

    SciTech Connect

    Sisken, B.F.; Sisken, J.E.

    1997-12-01

    The general goals of this work were to determine whether resting levels of cellular second messengers, especially calcium, are affected by low-level electromagnetic fields and the mechanisms that could lead to such changes. The work performed was directed at (1) verifying the report of McLeod et al (1990) that low frequency sinusoidal EMF can alter basal calcium fluctuations in cultured ROS 17/2.8 osteoblast-like cells and (2) reproducing the findings of Luben et al (1982) that pulsed electromagnetic fields can affect PTH-stimulated adenylate cyclase activity in osteoblasts. Initially a system was constructed so that cells could be exposed to sinusoidal electric fields using platinum electrodes. In this system, the electrodes were separated from the cells and culture medium by agar barriers. A series of experiments indicated that this system was subject to a significant, though little-known artifact in which a not well understood interaction between the electrodes and sodium ions in the medium or in plain salt solutions led to frequency and amplitude dependent emission of photons that are recorded by the detection system. They therefore designed and constructed an air gap reactor system that utilizes a ferromagnetic core to direct the magnetic flux generated by a sinusoidal coil. Studies on the effects of a 15 Hz pulsed electromagnetic field (PEMF) on cyclic AMP metabolism were performed on ROS 17/2.8 and MC3T3 cells.

  8. A Cellular Biophysics Textbook

    NASA Astrophysics Data System (ADS)

    Wilder, Alan Joseph

    2011-12-01

    In the past two decades, great advances have been made in understanding of the biophysical mechanisms of the protein machines that carry out the fundamental processes of the cell. It is now known that all major eukaryotic cellular processes require a complicated assemblage of proteins acting via a series of concerted motions. In order to grasp current understanding of cellular mechanisms, the new generation of cell biologists needs to be trained in the general characteristics of these cellular properties and the methods with which to study them. This cellular biophysics textbook, to be used in conjunction with the cellular biophysics course (MCB143) at UC-Davis, provides a great tool in the instruction of the new generation of cellular biologists. It provides a hierarchical view of the cell, from atoms to protein machines and explains in depth the mechanisms of cytoskeletal force generators as an example of these principles.

  9. Modelling cellular behaviour

    NASA Astrophysics Data System (ADS)

    Endy, Drew; Brent, Roger

    2001-01-01

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

  10. Parametric study of double cellular detonation structure

    NASA Astrophysics Data System (ADS)

    Khasainov, B.; Virot, F.; Presles, H.-N.; Desbordes, D.

    2013-05-01

    A parametric numerical study is performed of a detonation cellular structure in a model gaseous explosive mixture whose decomposition occurs in two successive exothermic reaction steps with markedly different characteristic times. Kinetic and energetic parameters of both reactions are varied in a wide range in the case of one-dimensional steady and two-dimensional (2D) quasi-steady self-supported detonations. The range of governing parameters of both exothermic steps is defined where a "marked" double cellular structure exists. It is shown that the two-level cellular structure is completely governed by the kinetic parameters and the local overdrive ratio of the detonation front propagating inside large cells. Furthermore, since it is quite cumbersome to use detailed chemical kinetics in unsteady 2D case, the proposed work should help to identify the mixtures and the domain of their equivalence ratio where double detonation structure could be observed.

  11. Stochastic extension of cellular manufacturing systems: a queuing-based analysis

    NASA Astrophysics Data System (ADS)

    Fardis, Fatemeh; Zandi, Afagh; Ghezavati, Vahidreza

    2013-07-01

    Clustering parts and machines into part families and machine cells is a major decision in the design of cellular manufacturing systems which is defined as cell formation. This paper presents a non-linear mixed integer programming model to design cellular manufacturing systems which assumes that the arrival rate of parts into cells and machine service rate are stochastic parameters and described by exponential distribution. Uncertain situations may create a queue behind each machine; therefore, we will consider the average waiting time of parts behind each machine in order to have an efficient system. The objective function will minimize summation of idleness cost of machines, sub-contracting cost for exceptional parts, non-utilizing machine cost, and holding cost of parts in the cells. Finally, the linearized model will be solved by the Cplex solver of GAMS, and sensitivity analysis will be performed to illustrate the effectiveness of the parameters.

  12. Deleted in Breast Cancer 1 regulates cellular senescence during obesity.

    PubMed

    Escande, Carlos; Nin, Veronica; Pirtskhalava, Tamar; Chini, Claudia C; Thereza Barbosa, Maria; Mathison, Angela; Urrutia, Raul; Tchkonia, Tamar; Kirkland, James L; Chini, Eduardo N

    2014-10-01

    Chronic obesity leads to inflammation, tissue dysfunction, and cellular senescence. It was proposed that cellular senescence during obesity and aging drives inflammation and dysfunction. Consistent with this, clearance of senescent cells increases healthspan in progeroid mice. Here, we show that the protein Deleted in Breast Cancer-1 (DBC1) regulates cellular senescence during obesity. Deletion of DBC1 protects preadipocytes against cellular senescence and senescence-driven inflammation. Furthermore, we show protection against cellular senescence in DBC1 KO mice during obesity. Finally, we found that DBC1 participates in the onset of cellular senescence in response to cell damage by mechanism that involves binding and inhibition of HDAC3. We propose that by regulating HDAC3 activity during cellular damage, DBC1 participates in the fate decision that leads to the establishment of cellular senescence and consequently to inflammation and tissue dysfunction during obesity. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  13. Plasmonic Nanostructured Cellular Automata

    NASA Astrophysics Data System (ADS)

    Alkhazraji, Emad; Ghalib, A.; Manzoor, K.; Alsunaidi, M. A.

    2017-03-01

    In this work, we have investigated the scattering plasmonic resonance characteristics of silver nanospheres with a geometrical distribution that is modelled by Cellular Automata using time-domain numerical analysis. Cellular Automata are discrete mathematical structures that model different natural phenomena. Two binary one-dimensional Cellular Automata rules are considered to model the nanostructure, namely rule 30 and rule 33. The analysis produces three-dimensional scattering profiles of the entire plasmonic nanostructure. For the Cellular Automaton rule 33, the introduction of more Cellular Automata generations resulted only in slight red and blue shifts in the plasmonic modes with respect to the first generation. On the other hand, while rule 30 introduced significant red shifts in the resonance peaks at early generations, at later generations however, a peculiar effect is witnessed in the scattering profile as new peaks emerge as a feature of the overall Cellular Automata structure rather than the sum of the smaller parts that compose it. We strongly believe that these features that emerge as a result adopting the different 256 Cellular Automata rules as configuration models of nanostructures in different applications and systems might possess a great potential in enhancing their capability, sensitivity, efficiency, and power utilization.

  14. Cellular Reflectarray Antenna

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  15. Electromagnetic cellular interactions.

    PubMed

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating.

  16. Cellular aging and cancer

    PubMed Central

    Hornsby, Peter J.

    2010-01-01

    Aging is manifest in a variety of changes over time, including changes at the cellular level. Cellular aging acts primarily as a tumor suppressor mechanism, but also may enhance cancer development under certain circumstances. One important process of cellular aging is oncogene-induced senescence, which acts as an important anti-cancer mechanism. Cellular senescence resulting from damage caused by activated oncogenes prevents the growth or potentially neoplastic cells. Moreover, cells that have entered senescence appear to be targets for elimination by the innnate immune system. In another aspect of cellular aging, the absence of telomerase activity in normal tissues results in such cells lacking a telomere maintenance mechanism. One consequence is that in aging there is an increase in cells with shortened telomeres. In the presence of active oncogenes that cause expansion of a neoplastic clone, shortening of telomeres leading to telomere dysfunction prevents the indefinite expansion of the clone because the cells enter crisis. Crisis results from fusions and other defects caused by dysfunctional telomeres and is a terminal state of the neoplastic clone. In this way the absence of telomerase in human cells, while one cause of cellular aging, also acts as an anti-cancer mechanism. PMID:20705476

  17. Fitting Laguerre Tessellations to the Microstructure of Cellular Materials

    NASA Astrophysics Data System (ADS)

    Vecchio, Irene; Schladitz, Katja; Redenbach, Claudia

    Cellular materials are employed in many fields, ranging from medical technologies to aerospace industry. In applications, understanding the influence of the microstructures on the physical properties of materials is of crucial importance. Stochastic models are a powerful tool to investigate this link. In particular, random Laguerre tessellations (weighted generalizations of the well-known Voronoi model) generated by systems of non-overlapping balls have proven to be a promising model for rigid foams. Model fitting is based on geometric characteristics estimated from micro-computed tomographic images of the microstructures. More precisely, the model is chosen to minimize a distance measure composed of several geometric characteristics of the typical cell. However, with this approach, inference on the model parameters is time consuming and needs expert knowledge. In this talk, we investigate strategies leading to an automatic model fitting. Finally, this model fitting approach is applied to polymethacrylimide (PMI) foam samples.

  18. Passive drug permeation through membranes and cellular distribution.

    PubMed

    Scott, D O; Ghosh, A; Di, L; Maurer, T S

    2017-03-01

    Although often overlooked, passive mechanisms can lead to significant accumulation or restriction of drugs to intracellular sites of drug action. These mechanisms include lipoidal diffusion of ionized species and pH partitioning according to the electrochemical potential and to pH gradients that exist across subcellular compartments, respectively. These mechanisms are increasingly being exploited in the design of safe and effective drugs for the treatment of a wide variety of diseases. In this work, the authors review these efforts and the associated passive mechanisms of cellular drug permeation. A generic mathematical model of the cell is provided and used to illustrate concepts relevant to steady-state intracellular distribution. Finally, the authors review methods for estimating determinant parameters and measuring the net effect at the level of unbound intracellular drug concentrations.

  19. Cellular dynamics of RNA modification.

    PubMed

    Yi, Chengqi; Pan, Tao

    2011-12-20

    Five decades of research have identified more than 100 ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved throughout bacteria, archaea, and eukaryotes, while some are unique to each branch of life. However, the cellular and functional dynamics of RNA modification remain largely unexplored, mostly because of the lack of functional hypotheses and experimental methods for quantification and large-scale analysis. Many RNA modifications are not essential for life, which parallels the observation that many well-characterized protein and DNA modifications are not essential for life. Instead, increasing evidence indicates that RNA modifications can play regulatory roles in cells, especially in response to stress conditions. In this Account, we review some examples of RNA modification that are dynamically controlled in cells. We also discuss some recently developed methods that have enhanced the ability to study the cellular dynamics of RNA modification. We discuss four specific examples of RNA modification in detail here. We begin with 4-thio uridine (s(4)U), which can act as a cellular sensor of near-UV light. Then we consider queuosine (Q), which is a potential biomarker for malignancy. Next we examine N(6)-methyl adenine (m(6)A), which is the prevalent modification in eukaryotic messenger RNAs (mRNAs). Finally, we discuss pseudouridine (ψ), which is inducible by nutrient deprivation. We then consider two recent technical advances that have stimulated the study of the cellular dynamics in modified ribonucleosides. The first is a genome-wide method that combines primer extension with a microarray. It was used to study the N(1)-methyl adenine (m(1)A) hypomodification in human transfer RNA (tRNA). The second is a quantitative mass spectrometric method used to investigate dynamic changes in a wide range of tRNA modifications under stress conditions in yeast. In addition, we discuss potential mechanisms that control dynamic

  20. Cellular immune response experiment MA-031

    NASA Technical Reports Server (NTRS)

    Criswell, B. S.

    1976-01-01

    Significant changes in phytohemagglutinin (PHA) lymphocytic responsiveness occurred in the cellular immune response of three astronauts during the 9 day flight of the Apollo Soyuz Test Project. Parameters studied were white blood cell concentrations, lymphocyte numbers, B- and T-lymphocyte distributions in peripheral blood, and lymphocyte responsiveness to PHA, pokeweed mitogen, Concanavalin A, and influenza virus antigen.

  1. 77 FR 1889 - Drivers of CMVs: Restricting the Use of Cellular Phones; Technical Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-12

    ... Use of Cellular Phones; Technical Amendment AGENCY: Federal Motor Carrier Safety Administration (FMCSA... the Use of Cellular Phones final rule (76 FR 75470) had a clerical error in Sec. 391.15(f)(1)...

  2. Architected Cellular Materials

    NASA Astrophysics Data System (ADS)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  3. Irregular Cellular Learning Automata.

    PubMed

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

    Cellular learning automaton (CLA) is a recently introduced model that combines cellular automaton (CA) and learning automaton (LA). The basic idea of CLA is to use LA to adjust the state transition probability of stochastic CA. This model has been used to solve problems in areas such as channel assignment in cellular networks, call admission control, image processing, and very large scale integration placement. In this paper, an extension of CLA called irregular CLA (ICLA) is introduced. This extension is obtained by removing the structure regularity assumption in CLA. Irregularity in the structure of ICLA is needed in some applications, such as computer networks, web mining, and grid computing. The concept of expediency has been introduced for ICLA and then, conditions under which an ICLA becomes expedient are analytically found.

  4. Epigenetics and Cellular Metabolism

    PubMed Central

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  5. Cellular immunotherapies for cancer.

    PubMed

    Berraondo, Pedro; Labiano, Sara; Minute, Luna; Etxeberria, Iñaki; Vasquez, Marcos; Sanchez-Arraez, Alvaro; Teijeira, Alvaro; Melero, Ignacio

    2017-01-01

    Lessons learned over decades on the use of gene and cell therapies have found clinical applicability in the field of cancer immunotherapy. On December 16(th), 2016 a symposium was held in Pamplona (Spain) to analyze and discuss the critical points for the clinical success of adoptive cell transfer strategies in cancer immunotherapy. Cellular immunotherapy is being currently exploited for the development of new cancer vaccines using ex vivo manipulated dendritic cells or to enhance the number of effector cells, transferring reinvigorated NK cells or T cells. In this meeting report, we summarize the main topics covered and provide an overview of the field of cellular immunotherapy.

  6. Cellular structural biology.

    PubMed

    Ito, Yutaka; Selenko, Philipp

    2010-10-01

    While we appreciate the complexity of the intracellular environment as a general property of every living organism, we collectively lack the appropriate tools to analyze protein structures in a cellular context. In-cell NMR spectroscopy represents a novel biophysical tool to investigate the conformational and functional characteristics of biomolecules at the atomic level inside live cells. Here, we review recent in-cell NMR developments and provide an outlook towards future applications in prokaryotic and eukaryotic cells. We hope to thereby emphasize the usefulness of in-cell NMR techniques for cellular studies of complex biological processes and for structural analyses in native environments. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Measuring information flow in cellular networks by the systems biology method through microarray data

    PubMed Central

    Chen, Bor-Sen; Li, Cheng-Wei

    2015-01-01

    In general, it is very difficult to measure the information flow in a cellular network directly. In this study, based on an information flow model and microarray data, we measured the information flow in cellular networks indirectly by using a systems biology method. First, we used a recursive least square parameter estimation algorithm to identify the system parameters of coupling signal transduction pathways and the cellular gene regulatory network (GRN). Then, based on the identified parameters and systems theory, we estimated the signal transductivities of the coupling signal transduction pathways from the extracellular signals to each downstream protein and the information transductivities of the GRN between transcription factors in response to environmental events. According to the proposed method, the information flow, which is characterized by signal transductivity in coupling signaling pathways and information transductivity in the GRN, can be estimated by microarray temporal data or microarray sample data. It can also be estimated by other high-throughput data such as next-generation sequencing or proteomic data. Finally, the information flows of the signal transduction pathways and the GRN in leukemia cancer cells and non-leukemia normal cells were also measured to analyze the systematic dysfunction in this cancer from microarray sample data. The results show that the signal transductivities of signal transduction pathways change substantially from normal cells to leukemia cancer cells. PMID:26082788

  8. What determines organ size differences between species? A meta-analysis of the cellular basis.

    PubMed

    Gázquez, Ayelén; Beemster, Gerrit T S

    2017-07-01

    Little is known about how the characteristic differences in organ size between species are regulated. At the cellular level, the size of an organ is strictly regulated by cell division and expansion during its development. We performed a meta-analysis of the growth parameters of roots, and Graminae and eudicotyledonous leaves, to address the question of how quantitative variation in these two processes contributes to size differences across a range of species. We extracted or derived cellular parameters from published kinematic growth analyses. These data were subjected to linear regression analyses to identify the parameters that determine differences in organ growth. Our results demonstrate that, across all species and organs, similar conclusions can be made: cell number rather than cell size determines the final size of plant organs; cell number is determined by meristem size rather than the rate at which cells divide; cells that are small when leaving the meristem compensate by expanding for longer; mature cell size is primarily determined by the duration of cell expansion. These results identify the regulation of the transition from cell division to expansion as the key cellular mechanism targeted by the evolution of organ size. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. Measuring information flow in cellular networks by the systems biology method through microarray data.

    PubMed

    Chen, Bor-Sen; Li, Cheng-Wei

    2015-01-01

    In general, it is very difficult to measure the information flow in a cellular network directly. In this study, based on an information flow model and microarray data, we measured the information flow in cellular networks indirectly by using a systems biology method. First, we used a recursive least square parameter estimation algorithm to identify the system parameters of coupling signal transduction pathways and the cellular gene regulatory network (GRN). Then, based on the identified parameters and systems theory, we estimated the signal transductivities of the coupling signal transduction pathways from the extracellular signals to each downstream protein and the information transductivities of the GRN between transcription factors in response to environmental events. According to the proposed method, the information flow, which is characterized by signal transductivity in coupling signaling pathways and information transductivity in the GRN, can be estimated by microarray temporal data or microarray sample data. It can also be estimated by other high-throughput data such as next-generation sequencing or proteomic data. Finally, the information flows of the signal transduction pathways and the GRN in leukemia cancer cells and non-leukemia normal cells were also measured to analyze the systematic dysfunction in this cancer from microarray sample data. The results show that the signal transductivities of signal transduction pathways change substantially from normal cells to leukemia cancer cells.

  10. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  11. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  12. Cellular genetic therapy.

    PubMed

    Del Vecchio, F; Filareto, A; Spitalieri, P; Sangiuolo, F; Novelli, G

    2005-01-01

    Cellular genetic therapy is the ultimate frontier for those pathologies that are consequent to a specific nonfunctional cellular type. A viable cure for there kinds of diseases is the replacement of sick cells with healthy ones, which can be obtained from the same patient or a different donor. In fact, structures can be corrected and strengthened with the introduction of undifferentiated cells within specific target tissues, where they will specialize into the desired cellular types. Furthermore, consequent to the recent results obtained with the transdifferentiation experiments, a process that allows the in vitro differentiation of embryonic and adult stem cells, it has also became clear that many advantages may be obtained from the use of stem cells to produce drugs, vaccines, and therapeutic molecules. Since stem cells can sustain lineage potentials, the capacity for differentiation, and better tolerance for the introduction of exogenous genes, they are also considered as feasible therapeutic vehicles for gene therapy. In fact, it is strongly believed that the combination of cellular genetic and gene therapy approaches will definitely allow the development of new therapeutic strategies as well as the production of totipotent cell lines to be used as experimental models for the cure of genetic disorders.

  13. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  14. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  15. Cavity theory applications for kilovoltage cellular dosimetry

    NASA Astrophysics Data System (ADS)

    Oliver, P. A. K.; Thomson, Rowan M.

    2017-06-01

    Relationships between macroscopic (bulk tissue) and microscopic (cellular) dose descriptors are investigated using cavity theory and Monte Carlo (MC) simulations. Small, large, and multiple intermediate cavity theory (SCT, LCT, and ICT, respectively) approaches are considered for 20 to 370 keV incident photons; ICT is a sum of SCT and LCT contributions weighted by parameter d. Considering μm-sized cavities of water in bulk tissue phantoms, different cavity theory approaches are evaluated via comparison of Dw, m/Dm, m (where D w,m is dose-to-water-in-medium and D m,m is dose-to-medium-in-medium) with MC results. The best overall agreement is achieved with an ICT approach in which d=(1-e-β L)/(β L) , where L is the mean chord length of the cavity and β is given by e-β R_CSDA=0.04 (R CSDA is the continuous slowing down approximation range of an electron of energy equal to that of incident photons). Cell nucleus doses, D nuc, computed with this ICT approach are compared with those from MC simulations involving multicellular soft tissue models considering a representative range of cell/nucleus sizes and elemental compositions. In 91% of cases, ICT and MC predictions agree within 3% ; disagreement is at most 8.8%. These results suggest that cavity theory may be useful for linking doses from model-based dose calculation algorithms (MBDCAs) with energy deposition in cellular targets. Finally, based on the suggestion that clusters of water molecules associated with DNA are important radiobiological targets, two approaches for estimating dose-to-water by application of SCT to MC results for D m,m or D nuc are compared. Results for these two estimates differ by up to 35% , demonstrating the sensitivity of energy deposition within a small volume of water in nucleus to the geometry and composition of its surroundings. In terms of the debate over the dose specification medium for MBDCAs, these results do not support conversion of D m,m to D w,m using SCT.

  16. Final Report

    SciTech Connect

    Gurney, Kevin R.

    2015-01-12

    This document constitutes the final report under DOE grant DE-FG-08ER64649. The organization of this document is as follows: first, I will review the original scope of the proposed research. Second, I will present the current draft of a paper nearing submission to Nature Climate Change on the initial results of this funded effort. Finally, I will present the last phase of the research under this grant which has supported a Ph.D. student. To that end, I will present the graduate student’s proposed research, a portion of which is completed and reflected in the paper nearing submission. This final work phase will be completed in the next 12 months. This final workphase will likely result in 1-2 additional publications and we consider the results (as exemplified by the current paper) high quality. The continuing results will acknowledge the funding provided by DOE grant DE-FG-08ER64649.

  17. Final Report

    SciTech Connect

    DeTar, Carleton

    2012-12-10

    This document constitutes the Final Report for award DE-FC02-06ER41446 as required by the Office of Science. It summarizes accomplishments and provides copies of scientific publications with significant contribution from this award.

  18. Detonation cellular structure and image proces

    NASA Astrophysics Data System (ADS)

    Shepherd, J. E.; Tieszen, S. R.

    Gaseous detonations universally exhibit an instability that is manifested as cellular patterns on witness plates (sooted foils) or open shutter photographs. The characteristic dimension or cell width lambda of the periodic cellular pattern has previously been shown to correlate with failure diameter, critical diffraction aperture dimension and direct initiation energy requirements. Due to the importance of predicting these parameters in assessing detonability hazards, a quantitative method for cell size mesurement is urgently needed. We discuss a technique based on digital image processing of sooted foil records and illustrate the results with data from experiments performed in the Heated Detonation Tube facility at Sandia. We demonstrate that image processing can be used to eliminate some of the uncertainty now present in cell size measurements. The possibility of quantifying cellular irregularity is also explored.

  19. Probabilistic cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

  20. Cellular Communication through Light

    PubMed Central

    Fels, Daniel

    2009-01-01

    Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source) as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials) allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more) frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry. PMID:19340303

  1. Cellular automata model for citrus variegated chlorosis.

    PubMed

    Martins, M L; Ceotto, G; Alves, S G; Bufon, C C; Silva, J M; Laranjeira, F F

    2000-11-01

    A cellular automata model is proposed to analyze the progress of citrus variegated chlorosis epidemics in São Paulo orange plantations. In this model epidemiological and environmental features, such as motility of sharpshooter vectors that perform Lévy flights, level of plant hydric and nutritional stress, and seasonal climatic effects, are included. The observed epidemic data were quantitatively reproduced by the proposed model on varying the parameters controlling vector motility, plant stress, and initial population of diseased plants.

  2. Formin’ cellular structures

    PubMed Central

    Bogdan, Sven; Schultz, Jörg; Grosshans, Jörg

    2014-01-01

    Members of the Diaphanous (Dia) protein family are key regulators of fundamental actin driven cellular processes, which are conserved from yeast to humans. Researchers have uncovered diverse physiological roles in cell morphology, cell motility, cell polarity, and cell division, which are involved in shaping cells into tissues and organs. The identification of numerous binding partners led to substantial progress in our understanding of the differential functions of Dia proteins. Genetic approaches and new microscopy techniques allow important new insights into their localization, activity, and molecular principles of regulation. PMID:24719676

  3. Ultradiscrete Systems (Cellular Automata)

    NASA Astrophysics Data System (ADS)

    Tokihiro, Tetsuji

    Ultradiscretization is a limiting procedure which allows one to obtain a cellular automaton (CA) from continuous equations. Using this method, we can construct integrable CAs from integrable partial difference equations. In this course, we focus on a typical integrable CA, called a Box and Ball system (BBS), and review its peculiar features. Since a BBS is an ultradiscrete limit of the discrete KP equation and discrete Toda equation, we can obtain explicit solutions and conserved quantities for the BBS. Furthermore the BBS is also regarded as a limit (crystallization) of an integrable lattice model. Recent topics, and a periodic BBS in particular are also reviewed.

  4. Review of cellular mechanotransduction

    NASA Astrophysics Data System (ADS)

    Wang, Ning

    2017-06-01

    Living cells and tissues experience physical forces and chemical stimuli in the human body. The process of converting mechanical forces into biochemical activities and gene expression is mechanochemical transduction or mechanotransduction. Significant advances have been made in understanding mechanotransduction at the cellular and molecular levels over the last two decades. However, major challenges remain in elucidating how a living cell integrates signals from mechanotransduction with chemical signals to regulate gene expression and to generate coherent biological responses in living tissues in physiological conditions and diseases.

  5. Cellular mechanics and motility

    NASA Astrophysics Data System (ADS)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  6. Oral Cellular Neurothekeoma

    PubMed Central

    Emami, Nader; Zawawi, Faisal; Ywakim, Rania; Daniel, Sam J.

    2013-01-01

    Cellular neurothekeoma is known as a cutaneous tumor with uncertain histogenesis. Very little involvement of mucosal membrane has been reported in the literature so far. This is a case report of an intraoral lesion in a 15-years-old girl. Histopathologic evaluation showed a tumor-consists of spindle to epitheloid cells forming micronodules in a concentric whorled shape pattern. Tumor cells were positive for CD63, vimentin, and NKI-C3. Total excision was performed and no recurrence happened after 16-month followup. PMID:23691398

  7. To study the effects of gamma irradiation on single donor apheresis platelet units by measurement of cellular counts, functional indicators and a panel of biochemical parameters, in order to assess pre-transfusion platelet quantity and quality during the shelf life of the product

    PubMed Central

    Mallhi, R.S.; Biswas, A.K.; Philip, J.; Chatterjee, T.

    2016-01-01

    Background The occurrence of transfusion associated graft versus host disease can be prevented by gamma irradiation of blood components. This study was undertaken to assess the effects of gamma irradiation on single donor platelet (SDP) concentrate units. Method SDPs were collected by a continuous flow apheresis technique (n = 400). The SDPs from each donor were divided into two parts, one gamma-irradiated with 25 Gy and the other used as a non-irradiated control. Swirling and morphological features, cellular counts, biochemical parameters including blood gas analysis, and platelet activation levels (CD62P: p-selectin) by flow cytometry were analyzed on Day 1 and on Day 5. Results Swirling and morphology were maintained in all products, in both the groups throughout the shelf life. No significant change was seen in both groups, on the first and fifth day, as far as pO2, pCO2, Na+, K+, HCO3− & Ca2+ were concerned. However, lactate increased and glucose decreased significantly in irradiated products over 5-day storage period. A small but significant decrease in pH and platelet count was found in the irradiated PCs after 5-day storage. The mean proportion of platelets expressing CD62P over 5-day storage increased significantly. Conclusion After an overall assessment of all our in vitro parameter results and observations, a few of which were significant, while most were not significant, we concluded that a well-preserved quality of gamma irradiated apheresis platelets is maintained throughout the entire 5-day shelf life of the platelet product, with minimal difference compared to non-irradiated platelets. PMID:26900218

  8. MINOR PARAMETERS NEEDED FOR INDIVIDUAL-DOSE CALCULATIONS: Final Report for Tasks 7.1, 7.2, 8.1, 8.2, 9.1, 9.2, and 9.3

    SciTech Connect

    Anspaugh, L. R.; Napier, Bruce A.

    2009-10-23

    This brief report documents the selection of parameters needed to support individual-dose calculations from 131I released into the environment with gaseous effluents from the Mayak Production Association.

  9. Cellular Analogs of Operant Behavior

    DTIC Science & Technology

    1990-12-31

    activity rather than by a cellular reinforcement process. We have always required as critical evidence of cellular reinforcement that noncontingent or... reinforcement process. We have always required as critical evidence of cellular reinforcement that noncortingent or random presentations of the positive...the burst- ing of hippocampal pyramidal cells. One approach is to attempt to reinforce hippocamp- al bursting with a nonspecific depolarizing agent

  10. Solid films and transports in cellular foams

    NASA Astrophysics Data System (ADS)

    Tan Hoang, Minh; Perrot, Camille

    2012-09-01

    We show that critical path ideas lead to the identification of two local characteristic sizes for the long wavelength acoustic properties in cellular solids, the pore and throat sizes. Application of the model to real foam samples, which may contain solid films or membranes yields quantitative agreement between a finite-element numerical homogenization approach and experimental results. From three routinely available laboratory measurements: the open porosity ϕ, the static viscous permeability k0, and the average struts length Lm obtained from microscopy analysis; asymptotic transport parameters at high-frequencies and the normal incidence sound absorption coefficient are derived with no adjustable parameters.

  11. Final Report

    SciTech Connect

    Stinis, Panos

    2016-08-07

    This is the final report for the work conducted at the University of Minnesota (during the period 12/01/12-09/18/14) by PI Panos Stinis as part of the "Collaboratory on Mathematics for Mesoscopic Modeling of Materials" (CM4). CM4 is a multi-institution DOE-funded project whose aim is to conduct basic and applied research in the emerging field of mesoscopic modeling of materials.

  12. Final Report

    SciTech Connect

    Marchant, Gary E.

    2013-04-23

    This is the final report of a two year project entitled "Governing Nanotechnology Risks and Benefits in the Transition to Regulation: Innovative Public and Private Approaches." This project examined the role of new governance or "soft law" mechanisms such as codes of conduct, voluntary programs and partnership agreements to manage the risks of emerging technologies such as nanotechnology. A series of published or in publication papers and book chapters are attached.

  13. Final Report

    SciTech Connect

    R. Paul Drake

    2001-11-30

    This final report describes work involving 22 investigators from 11 institutions to explore the dynamics present in supernova explosions by means of experiments on the Omega laser. The specific experiments emphasized involved the unstable expansion of a spherical capsule and the coupling of perturbations at a first interface to a second interface by means of a strong shock. Both effects are present in supernovae. The experiments were performed at Omega and the computer simulations were undertaken at several institutions. B139

  14. Multifunctional periodic cellular metals.

    PubMed

    Wadley, Haydn N G

    2006-01-15

    Periodic cellular metals with honeycomb and corrugated topologies are widely used for the cores of light weight sandwich panel structures. Honeycombs have closed cell pores and are well suited for thermal protection while also providing efficient load support. Corrugated core structures provide less efficient and highly anisotropic load support, but enable cross flow heat exchange opportunities because their pores are continuous in one direction. Recent advances in topology design and fabrication have led to the emergence of lattice truss structures with open cell structures. These three classes of periodic cellular metals can now be fabricated from a wide variety of structural alloys. Many topologies are found to provide adequate stiffness and strength for structural load support when configured as the cores of sandwich panels. Sandwich panels with core relative densities of 2-10% and cell sizes in the millimetre range are being assessed for use as multifunctional structures. The open, three-dimensional interconnected pore networks of lattice truss topologies provide opportunities for simultaneously supporting high stresses while also enabling cross flow heat exchange. These highly compressible structures also provide opportunities for the mitigation of high intensity dynamic loads created by impacts and shock waves in air or water. By filling the voids with polymers and hard ceramics, these structures have also been found to offer significant resistance to penetration by projectiles.

  15. Cellular Array Processing Simulation

    NASA Astrophysics Data System (ADS)

    Lee, Harry C.; Preston, Earl W.

    1981-11-01

    The Cellular Array Processing Simulation (CAPS) system is a high-level image language that runs on a multiprocessor configuration. CAPS is interpretively decoded on a conventional minicomputer with all image operation instructions executed on an array processor. The synergistic environment that exists between the minicomputer and the array processor gives CAPS its high-speed throughput, while maintaining a convenient conversational user language. CAPS was designed to be both modular and table driven so that it can be easily maintained and modified. CAPS uses the image convolution operator as one of its primitives and performs this cellular operation by decomposing it into parallel image steps that are scheduled to be executed on the array processor. Among its features is the ability to observe the imagery in real time as a user's algorithm is executed. This feature reduces the need for image storage space, since it is feasible to retain only original images and produce resultant images when needed. CAPS also contains a language processor that permits users to develop re-entrant image processing subroutines or algorithms.

  16. Articulatory Parameters.

    ERIC Educational Resources Information Center

    Ladefoged, Peter

    1980-01-01

    Summarizes the 16 parameters hypothesized to be necessary and sufficient for linguistic phonetic specifications. Suggests seven parameters affecting tongue shapes, three determining the positions of the lips, one controlling the position of the velum, four varying laryngeal actions, and one controlling respiratory activity. (RL)

  17. Geolocation Technologies Final Report

    SciTech Connect

    Magnoli, D E

    2003-06-02

    This paper is the final report for LL998 In Situ Sensing Subtask 7 (Geo-location) undertaken for NNSA NA-22 enabling technologies R&D for Counterproliferation Detection. A few state-of-the-art resolution parameters are presented for accelerometers, indoor and outdoor GPS (Global Positioning Satellite) systems, and INSs (Inertial Navigation Systems). New technologies are described, including one which has demonstrated the ability to track within a building to a resolution of under a foot.

  18. Cellular inactivation by ultrasound.

    PubMed

    Li, G C; Hahn, G M; Tolmach, L J

    1977-05-12

    The lethal effect of ultrasound (US) on mammalian cells has received relatively little attention. Understandably, potential genetic aspects of US have been of prime concern to physicians who use US as a diagnostic tool; at the average power densities involved (<1 W cm(-2)) little, if any cell killing is to be expected. There have been sporadic attempts to use higher intensities ( approximately 1 W cm(-2)) as a treatment modality in cancer therapy, but those experiments seem to have been based on inadequate cellular studies. The effects of US usually were evaluated in terms of morphological criteria rather than on quantitative determination of the loss of viability as measured by colony formation. There are few reports of the effects of US on survival of mammalian cells, and none specifically examine hyperthermic interaction. With the increased interest in hyperthermia for tumour therapy, attention has been directed towards the use of ultrasound to achieve tumour heating. In preliminary experiments in which US was used to heat the EMT6 sarcoma and KHJJ carcinoma in mice, we found a high percentage of tumour cures with short (approximately 30 min) treatments at temperatures (43-44 degrees C) where in vitro results of hyperthermia-induced cell killing would not have led to a prediction of any cures. We therefore initiated an investigation of the effects of US on survival of Chinese hamster cells to see if direct cell killing by US could explain our in vivo results, or, as in the case of radiofrequency (RF) electromagnetic heating, we would be forced to invoke host response(8). In particular, we examined the thermal and non-thermal components of cellular inactivation by US. We report here that there is a definite non-thermal cytotoxic effect of US. Its relative contribution to cell killing is a highly nonlinear function of the temperature of the cellular milieu. The survival curves show clearly that, beyond an initial threshold, small changes in temperature and/or US

  19. Integrated cellular systems

    NASA Astrophysics Data System (ADS)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  20. Distinct cellular states determine calcium signaling response.

    PubMed

    Yao, Jason; Pilko, Anna; Wollman, Roy

    2016-12-15

    The heterogeneity in mammalian cells signaling response is largely a result of pre-existing cell-to-cell variability. It is unknown whether cell-to-cell variability rises from biochemical stochastic fluctuations or distinct cellular states. Here, we utilize calcium response to adenosine trisphosphate as a model for investigating the structure of heterogeneity within a population of cells and analyze whether distinct cellular response states coexist. We use a functional definition of cellular state that is based on a mechanistic dynamical systems model of calcium signaling. Using Bayesian parameter inference, we obtain high confidence parameter value distributions for several hundred cells, each fitted individually. Clustering the inferred parameter distributions revealed three major distinct cellular states within the population. The existence of distinct cellular states raises the possibility that the observed variability in response is a result of structured heterogeneity between cells. The inferred parameter distribution predicts, and experiments confirm that variability in IP3R response explains the majority of calcium heterogeneity. Our work shows how mechanistic models and single-cell parameter fitting can uncover hidden population structure and demonstrate the need for parameter inference at the single-cell level. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  1. Cellular basis of memory for addiction.

    PubMed

    Nestler, Eric J

    2013-12-01

    DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. Here, we review the types of molecular and cellular adaptations that occur in specific brain regions to mediate addiction-associated behavioral abnormalities. These include alterations in gene expression achieved in part via epigenetic mechanisms, plasticity in the neurophysiological functioning of neurons and synapses, and associated plasticity in neuronal and synaptic morphology mediated in part by altered neurotrophic factor signaling. Each of these types of drug-induced modifications can be viewed as a form of "cellular or molecular memory." Moreover, it is striking that most addiction-related forms of plasticity are very similar to the types of plasticity that have been associated with more classic forms of "behavioral memory," perhaps reflecting the finite repertoire of adaptive mechanisms available to neurons when faced with environmental challenges. Finally, addiction-related molecular and cellular adaptations involve most of the same brain regions that mediate more classic forms of memory, consistent with the view that abnormal memories are important drivers of addiction syndromes. The goal of these studies which aim to explicate the molecular and cellular basis of drug addiction is to eventually develop biologically based diagnostic tests, as well as more effective treatments for addiction disorders.

  2. Final Report

    SciTech Connect

    R Paul Drake

    2004-01-12

    OAK-B135 This is the final report from the project Hydrodynamics by High-Energy-Density Plasma Flow and Hydrodynamics and Radiation Hydrodynamics with Astrophysical Applications. This project supported a group at the University of Michigan in the invention, design, performance, and analysis of experiments using high-energy-density research facilities. The experiments explored compressible nonlinear hydrodynamics, in particular at decelerating interfaces, and the radiation hydrodynamics of strong shock waves. It has application to supernovae, astrophysical jets, shock-cloud interactions, and radiative shock waves.

  3. Cellular Morphogenesis In Silico

    PubMed Central

    Shinbrot, Troy; Chun, Young; Caicedo-Carvajal, Carlos; Foty, Ramsey

    2009-01-01

    Abstract We describe a model that simulates spherical cells of different types that can migrate and interact either attractively or repulsively. We find that both expected morphologies and previously unreported patterns spontaneously self-assemble. Among the newly discovered patterns are a segmented state of alternating discs, and a “shish-kebab” state, in which one cell type forms a ring around a second type. We show that these unique states result from cellular attraction that increases with distance (e.g., as membranes stretch viscoelastically), and would not be seen in traditional, e.g., molecular, potentials that diminish with distance. Most of the states found computationally have been observed in vitro, and it remains to be established what role these self-assembled states may play in in vivo morphogenesis. PMID:19686642

  4. [Senescence and cellular immortality].

    PubMed

    Trentesaux, C; Riou, J-F

    2010-11-01

    Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

  5. Active Degradation Explains the Distribution of Nuclear Proteins during Cellular Senescence

    PubMed Central

    Giampieri, Enrico; De Cecco, Marco; Remondini, Daniel; Sedivy, John; Castellani, Gastone

    2015-01-01

    The amount of cellular proteins is a crucial parameter that is known to vary between cells as a function of the replicative passages, and can be important during physiological aging. The process of protein degradation is known to be performed by a series of enzymatic reactions, ranging from an initial step of protein ubiquitination to their final fragmentation by the proteasome. In this paper we propose a stochastic dynamical model of nuclear proteins concentration resulting from a balance between a constant production of proteins and their degradation by a cooperative enzymatic reaction. The predictions of this model are compared with experimental data obtained by fluorescence measurements of the amount of nuclear proteins in murine tail fibroblast (MTF) undergoing cellular senescence. Our model provides a three-parameter stationary distribution that is in good agreement with the experimental data even during the transition to the senescent state, where the nuclear protein concentration changes abruptly. The estimation of three parameters (cooperativity, saturation threshold, and maximal velocity of the reaction), and their evolution during replicative passages shows that only the maximal velocity varies significantly. Based on our modeling we speculate the reduction of functionality of the protein degradation mechanism as a possible competitive inhibition of the proteasome. PMID:26115222

  6. Active Degradation Explains the Distribution of Nuclear Proteins during Cellular Senescence.

    PubMed

    Giampieri, Enrico; De Cecco, Marco; Remondini, Daniel; Sedivy, John; Castellani, Gastone

    2015-01-01

    The amount of cellular proteins is a crucial parameter that is known to vary between cells as a function of the replicative passages, and can be important during physiological aging. The process of protein degradation is known to be performed by a series of enzymatic reactions, ranging from an initial step of protein ubiquitination to their final fragmentation by the proteasome. In this paper we propose a stochastic dynamical model of nuclear proteins concentration resulting from a balance between a constant production of proteins and their degradation by a cooperative enzymatic reaction. The predictions of this model are compared with experimental data obtained by fluorescence measurements of the amount of nuclear proteins in murine tail fibroblast (MTF) undergoing cellular senescence. Our model provides a three-parameter stationary distribution that is in good agreement with the experimental data even during the transition to the senescent state, where the nuclear protein concentration changes abruptly. The estimation of three parameters (cooperativity, saturation threshold, and maximal velocity of the reaction), and their evolution during replicative passages shows that only the maximal velocity varies significantly. Based on our modeling we speculate the reduction of functionality of the protein degradation mechanism as a possible competitive inhibition of the proteasome.

  7. Cellular automaton for bacterial towers

    NASA Astrophysics Data System (ADS)

    Indekeu, J. O.; Giuraniuc, C. V.

    2004-05-01

    A simulation approach to the stochastic growth of bacterial towers is presented, in which a non-uniform and finite nutrient supply essentially determines the emerging structure through elementary chemotaxis. The method is based on cellular automata and we use simple, microscopic, local rules for bacterial division in nutrient-rich surroundings. Stochastic nutrient diffusion, while not crucial to the dynamics of the total population, is influential in determining the porosity of the bacterial tower and the roughness of its surface. As the bacteria run out of food, we observe an exponentially rapid saturation to a carrying capacity distribution, similar in many respects to that found in a recently proposed phenomenological hierarchical population model, which uses heuristic parameters and macroscopic rules. Complementary to that phenomenological model, the simulation aims at giving more microscopic insight into the possible mechanisms for one of the recently much studied bacterial morphotypes, known as “towering biofilm”, observed experimentally using confocal laser microscopy. A simulation suggesting a mechanism for biofilm resistance to antibiotics is also shown.

  8. SELF-ORGANIZED CRITICALITY AND CELLULAR AUTOMATA

    SciTech Connect

    CREUTZ,M.

    2007-01-01

    Cellular automata provide a fascinating class of dynamical systems based on very simple rules of evolution yet capable of displaying highly complex behavior. These include simplified models for many phenomena seen in nature. Among other things, they provide insight into self-organized criticality, wherein dissipative systems naturally drive themselves to a critical state with important phenomena occurring over a wide range of length and the scales. This article begins with an overview of self-organized criticality. This is followed by a discussion of a few examples of simple cellular automaton systems, some of which may exhibit critical behavior. Finally, some of the fascinating exact mathematical properties of the Bak-Tang-Wiesenfeld sand-pile model [1] are discussed.

  9. Extracting cellular automaton rules from physical Langevin equation models for single and collective cell migration.

    PubMed

    Nava-Sedeño, J M; Hatzikirou, H; Peruani, F; Deutsch, A

    2017-02-27

    Cellular automata (CA) are discrete time, space, and state models which are extensively used for modeling biological phenomena. CA are "on-lattice" models with low computational demands. In particular, lattice-gas cellular automata (LGCA) have been introduced as models of single and collective cell migration. The interaction rule dictates the behavior of a cellular automaton model and is critical to the model's biological relevance. The LGCA model's interaction rule has been typically chosen phenomenologically. In this paper, we introduce a method to obtain lattice-gas cellular automaton interaction rules from physically-motivated "off-lattice" Langevin equation models for migrating cells. In particular, we consider Langevin equations related to single cell movement (movement of cells independent of each other) and collective cell migration (movement influenced by cell-cell interactions). As examples of collective cell migration, two different alignment mechanisms are studied: polar and nematic alignment. Both kinds of alignment have been observed in biological systems such as swarms of amoebae and myxobacteria. Polar alignment causes cells to align their velocities parallel to each other, whereas nematic alignment drives cells to align either parallel or antiparallel to each other. Under appropriate assumptions, we have derived the LGCA transition probability rule from the steady-state distribution of the off-lattice Fokker-Planck equation. Comparing alignment order parameters between the original Langevin model and the derived LGCA for both mechanisms, we found different areas of agreement in the parameter space. Finally, we discuss potential reasons for model disagreement and propose extensions to the CA rule derivation methodology.

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

    PubMed Central

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

    2016-01-01

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

  11. Effect of canopy structure and open-top chamber techniques on micrometeorological parameters and the gradients and transport of water vapor, carbon dioxide and ozone in the canopies of plum trees (`prunus salicina`) in the San Joaquin valley. Final report

    SciTech Connect

    Grantz, D.A.; Vaughn, D.L.; Metheny, P.A.; Malkus, P.; Wosnik, K.

    1995-03-15

    Plum trees (Prunus salicina cv. Casselman) were exposed to ozone in open-top chambers (OTC) or chamberless plots, and trace gas concentrations and microenvironmental conditions were monitored within tree canopies inside the outside the OTC. Concentrations of ozone, carbon dioxide and water vapor, leaf and air temperature, light intensity, and wind speed were measured at nine positions in the tree canopies. The objectives were to: (1) map the distribution of microenvironmental parameters within the canopies inside and outside the OTC; (2) determine transport parameters for gas exchange, and (3) calculate ozone flux. Significant vertical and horizontal gradients were observed; gradients were diminished and often inverted inside relative to outside the OTC due to air distribution at the bottom of the OCT. Ozone flux was readily modeled from measures of stomatal conductance, nonstomatal conductance and ozone concentration at the leaf surface.

  12. Final Report

    SciTech Connect

    David A. Benson

    2012-09-24

    This project combines outcrop-scale heterogeneity characterization, laboratory experiments, and numerical simulations. The study is designed to test whether established dispersion theory accurately predicts the behavior of solute transport through heterogeneous media and to investigate the relationship between heterogeneity and the parameters that populate these models. The dispersion theory tested by this work is based upon the fractional advection-dispersion equation (fADE) model. Unlike most dispersion studies that develop a solute transport model by fitting the solute transport breakthrough curve, this project will explore the nature of the heterogeneous media to better understand the connection between the model parameters and the aquifer heterogeneity. Our work at the Colorado School of Mines was focused on the following questions: 1) What are the effects of multi-scale geologic variability on transport of conservative and reactive solutes? 2) Can those transport effects be accounted for by classical methods, and if not, can the nonlocal fractional-order equations provide better predictions? 3) Can the fractional-order equations be parameterized through a link to some simple observable geologic features? 4) Are the classical equations of transport and reaction sufficient? 5) What is the effect of anomalous transport on chemical reaction in groundwater systems? The work is predicated on the observation that upscaled transport is defined by loss of information, or spatio-temporal averaging. This averaging tends to make the transport laws such as Fick's 2nd-order diffusion equation similar to central limit theory. The fractional-order advection-dispersion equations rely on limit theory for heavy-tailed random motion that has some diverging moments. The equations predict larger tails of a plume in space and/or time than those predicted by the classical 2nd-order advection-dispersion equation. The heavy tails are often seen in plumes at field sites.

  13. Cellular energy metabolism

    SciTech Connect

    Glaser, M.

    1991-06-01

    Studies have been carried out on adenylate kinase which is an important enzyme in determining the concentrations of the adenine nucleotides. An efficient method has been developed to clone mutant adenylate kinase genes in E. coli. Site-specific mutagenesis of the wild type gene also has been used to obtain forms of adenylate kinase with altered amino acids. The wild type and mutant forms of adenylate kinase have been overexpressed and large quantities were readily isolated. The kinetic and fluorescence properties of the different forms of adenylate kinase were characterized. This has led to a new model for the location of the AMP and ATP bindings sites on the enzyme and a proposal for the mechanism of substrate inhibition. Crystals of the wild type enzyme were obtained that diffract to at least 2.3 {angstrom} resolution. Experiments were also initiated to determine the function of adenylate kinase in vivo. In one set of experiments, E. coli strains with mutations in adenylate kinase showed large changes in cellular nucleotides after reaching the stationary phase in a low phosphate medium. This was caused by selective proteolytic degradation of the mutant adenylate kinase caused by phosphate starvation.

  14. Final Report

    SciTech Connect

    Webb, Robert C.; Kamon, Teruki; Toback, David; Safonov, Alexei; Dutta, Bhaskar; Dimitri, Nanopoulos; Pope, Christopher; White, James

    2013-11-18

    Overview The High Energy Physics Group at Texas A&M University is submitting this final report for our grant number DE-FG02-95ER40917. This grant has supported our wide range of research activities for over a decade. The reports contained here summarize the latest work done by our research team. Task A (Collider Physics Program): CMS & CDF Profs. T. Kamon, A. Safonov, and D. Toback co-lead the Texas A&M (TAMU) collider program focusing on CDF and CMS experiments. Task D: Particle Physics Theory Our particle physics theory task is the combined effort of Profs. B. Dutta, D. Nanopoulos, and C. Pope. Task E (Underground Physics): LUX & NEXT Profs. R. Webb and J. White(deceased) lead the Xenon-based underground research program consisting of two main thrusts: the first, participation in the LUX two-phase xenon dark matter search experiment and the second, detector R&D primarily aimed at developing future detectors for underground physics (e.g. NEXT and LZ).

  15. Cavity theory applications for kilovoltage cellular dosimetry.

    PubMed

    Oliver, Patricia A K; Thomson, Rowan

    2017-03-30

    Relationships between macroscopic (bulk tissue) and microscopic (cellular) dose 
descriptors are investigated using cavity theory and Monte Carlo (MC) simulations. 
Small, large, and multiple intermediate cavity theory (SCT, LCT, and ICT, respectively) approaches are considered for 20 to 370 keV incident photons; ICT is a sum 
of SCT and LCT contributions weighted by parameter d. Considering μm-sized cavities of water in bulk tissue phantoms, different cavity theory approaches are evaluated 
via comparison of Dw,m/Dm,m (where Dw,m is dose-to-water-in-medium and Dm,m is 
dose-to-medium-in-medium) with MC results. The best overall agreement is achieved 
with an ICT approach in which d=(1-e-βL)/(βL), where L is the mean chord length 
of the cavity and β is given by e-βRCSDA=0.04 (RCSDA is the continuous slowing 
down approximation range of an electron of energy equal to that of incident photons). 
Cell nucleus doses, Dnuc, computed with this ICT approach are compared with those 
from MC simulations involving multicellular soft tissue models considering a representative range of cell/nucleus sizes and elemental compositions. In 91% of cases, ICT and 
MC predictions agree within 3%; disagreement is at most 8.8%. These results suggest 
that cavity theory may be useful for linking doses from model-based dose calculation 
algorithms (MBDCAs) with energy deposition in cellular targets. Finally, based on 
the suggestion that clusters of water molecules associated with DNA are important 
radiobiological targets, two approaches for estimating dose-to-water by application of 
SCT to MC results for Dm,m or Dnuc are compared. Results for these two estimates 
differ by up to 35%, demonstrating the sensitivity of energy

  16. Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices.

    PubMed

    Lo, Justin H; Bassett, Erik K; Penson, Elliot J N; Hoganson, David M; Vacanti, Joseph P

    2015-08-01

    Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.

  17. Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices

    PubMed Central

    Lo, Justin H.; Bassett, Erik K.; Penson, Elliot J. N.; Hoganson, David M.

    2015-01-01

    Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m2 of oxygen and ∼685 mL/min/m2 of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions. PMID:26020102

  18. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  19. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  20. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  1. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  2. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  3. Integrated segmentation of cellular structures

    NASA Astrophysics Data System (ADS)

    Ajemba, Peter; Al-Kofahi, Yousef; Scott, Richard; Donovan, Michael; Fernandez, Gerardo

    2011-03-01

    Automatic segmentation of cellular structures is an essential step in image cytology and histology. Despite substantial progress, better automation and improvements in accuracy and adaptability to novel applications are needed. In applications utilizing multi-channel immuno-fluorescence images, challenges include misclassification of epithelial and stromal nuclei, irregular nuclei and cytoplasm boundaries, and over and under-segmentation of clustered nuclei. Variations in image acquisition conditions and artifacts from nuclei and cytoplasm images often confound existing algorithms in practice. In this paper, we present a robust and accurate algorithm for jointly segmenting cell nuclei and cytoplasm using a combination of ideas to reduce the aforementioned problems. First, an adaptive process that includes top-hat filtering, Eigenvalues-of-Hessian blob detection and distance transforms is used to estimate the inverse illumination field and correct for intensity non-uniformity in the nuclei channel. Next, a minimum-error-thresholding based binarization process and seed-detection combining Laplacian-of-Gaussian filtering constrained by a distance-map-based scale selection is used to identify candidate seeds for nuclei segmentation. The initial segmentation using a local maximum clustering algorithm is refined using a minimum-error-thresholding technique. Final refinements include an artifact removal process specifically targeted at lumens and other problematic structures and a systemic decision process to reclassify nuclei objects near the cytoplasm boundary as epithelial or stromal. Segmentation results were evaluated using 48 realistic phantom images with known ground-truth. The overall segmentation accuracy exceeds 94%. The algorithm was further tested on 981 images of actual prostate cancer tissue. The artifact removal process worked in 90% of cases. The algorithm has now been deployed in a high-volume histology analysis application.

  4. Astrobiological complexity with probabilistic cellular automata.

    PubMed

    Vukotić, Branislav; Ćirković, Milan M

    2012-08-01

    The search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling the astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous space of the input parameters. We perform a simple clustering analysis of typical astrobiological histories with "Copernican" choice of input parameters and discuss the relevant boundary conditions of practical importance for planning and guiding empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.

  5. Astrobiological Complexity with Probabilistic Cellular Automata

    NASA Astrophysics Data System (ADS)

    Vukotić, Branislav; Ćirković, Milan M.

    2012-08-01

    The search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling the astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous space of the input parameters. We perform a simple clustering analysis of typical astrobiological histories with "Copernican" choice of input parameters and discuss the relevant boundary conditions of practical importance for planning and guiding empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.

  6. Final Report

    SciTech Connect

    Taylor, Philip L.

    2012-11-11

    Our research program was aimed at elucidating the nature of proton transport in ionomer membranes by means of a combination of analytical theory and molecular modeling. There were two broad thrusts. The first of these was directed towards understanding the equilibrium structure of Nafion and related polymers at various levels of hydration. The second thrust was concerned with the transport of protons through a membrane of this type. The research on structure proceeded by building on existing work, but with the introduction of some novel techniques, among which is a hybrid Molecular Dynamics--Monte Carlo approach. This method permits rapid computations by temporarily decoupling the motion of the polar side chains from that of the perfluorinated backbone, while still retaining the essential aspects of the constraint that phase separation can only continue to a very limited degree. Competition between an elastic energy due to this constraint and the tendency to phase separation lead to the equilibrium structure, which turns out to be qualitatively different at different levels of hydration. The use of a carefully formulated dielectric function was necessary to achieve accurate results. The work on transport of protons in Nafion-like membranes also involved a combination of theory and simulation. Atomistic molecular-dynamics simulations were employed to determine some of the characteristic parameters for the diffusion of hydronium in hydrated membranes. These results were used in a theoretical model of non-linear diffusion to predict transport coefficients. Among our results was the discovery that treatment with strong electric fields may enhance the properties of the polymer membranes. Our computer simulations showed that the vigorous application of a stretching force or an electric field can modify the structure of the ionomer that lies at the heart of a polymer-electrolyte-membrane fuel cell. If these predictions are verified experimentally, then it should be

  7. MSAT and cellular hybrid networking

    NASA Technical Reports Server (NTRS)

    Baranowsky, Patrick W., II

    1993-01-01

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  8. Final Report

    SciTech Connect

    Wessels, B. W.

    2002-08-02

    Final report for program on the study of structure and properties of epitaxial oxide films. The defect structure of epitaxial oxide thin films was investigated. Both binary and complex oxides were studied. Epitaxial oxides were synthesized by organometallic chemical vapor deposition (OMCVD). This technique has been found to be highly versatile for the synthesis of a wide range of epitaxial oxide including dielectrics, ferroelectrics and high T{sub c} superconductors. Systems investigated include the binary oxides ZnO and TiO{sub 2} and ferroelectric oxides BaTiO{sub 3}, BaSrTiO{sub 3} and KNbO{sub 3}. Techniques used to evaluate the defect structure included deep level transient spectroscopy (DLTS), photocapacitance spectroscopy, and photoluminescence (PL) spectroscopy. High purity, stoichiometric oxide films were deposited and their defect structure evaluated. Epitaxial ZnO was deposited at temperatures as low as 250 C. PL indicated only near band edge ultraviolet emission showing that both extrinsic and intrinsic point defects could be significantly lowered in OMCVD derived thin films compared to that of the bulk. This presumably was a result of low deposition temperatures and high purity starting materials. Ferroelectric oxides epitaxial thin films of BaTiO{sub 3} and the solid solution BaSrTiO{sub 3} were synthesized and the defect structure determined. Photocapacitance spectroscopy was developed to quantify electrically active defects in the oxides. Defects with concentrations as low as 10{sup 14} cm{sup -3} were observed and their properties determined. A new model was developed for the electronic transport properties of intrinsic and extrinsic BaTiO{sub 3}. A transport model was proposed whereby conduction in La doped films occurs via hopping in localized states within a pseudogap formed between a lower Hubbard band and the conduction band edge. The influence of the size effect on the ferroelectric phase transition in the thin films was investigated. The

  9. [Aging and neurodegeneration: molecular and cellular bases].

    PubMed

    Peinado, M A; del Moral, M L; Esteban, F J; Martínez-Lara, E; Siles, E; Jiménez, A; Hernández-Cobo, R; Blanco, S; Rodrigo, J; Pedrosa, J A

    A review about the possible cellular and molecular mechanisms of aging and related neurodegenerative diseases. The mechanisms involved in neuronal decrease, connectivity losses and glial reactivity, detected both in neurodegenerative (Alzheimer's disease) and physiological aging, are analyzed from the morphological and histological point of view to provide the morphofunctional base of the cognitive and intellectual alterations characterizing the senescence process. Taken together, these data are correlated to the possible genetical aspects implied in this process, reviewing the most relevant results on senescence and cellular death obtained from yeast, fruit fly and nematodes; besides this, a brief review of the molecular biology of gerontogenes was carried out, and the possible mechanisms inducing aging and neurodegenerative processes are analyzed according to the state-of-the-art related theories. Finally, cellular, biochemical and genetical data are correlated in the signal transduction way implied in the increase of the intracellular calcium level as the starting point of cell death. The main process implied in the neuronal cell death responsible for aging and the related neurodegenerative diseases are started by different agents such as the lacking of neurotrophic factors, hypoxia, hypoglycemia, excitotoxicity, and oxygen and nitrogen free radicals.

  10. Final Report

    NASA Technical Reports Server (NTRS)

    Linsky, Jeffrey L.

    1998-01-01

    This grant was made to fund two accepted proposals to observe with the ASCA satellite: (1) Debunking the myth of two-temperature coronae of active stars, and (2) Dynamic coronae of dMe stars. We obtained the requested observations and have now completed two papers that will be published in the Astrophysical Journal. The RS CVn binary star UX Ari was observed for 14 hours with all four detectors onboard the ASCA satellite. The X-ray emission was at a constant, quiescent level during the first 12 hours, after which time a powerful flare with a peak luminosity of 1.4 x 10(exp 32) ergs/s started. The flare was observed until shortly after its peak. We present a spectral and temporal analysis of the UX Ari observations and analyze the data with a two-ribbon flare model including estimates for cooling losses. A time-dependent reconstruction of the emission measure (EM) distribution shows that two separate plasma components evolve during the flare (one being identified with the quiescent EM). Most of the flare EM reaches temperatures between 50 MK and 100 MK or more. Magnetic confinement requires the loop arcade to be geometrically large, with length scales on the order of one stellar radius. The electron densities inferred from the model decrease from initial values around 10(exp 12)/cc early in the flare to about 10(exp 11)/cc at the flare peak. The best-fit models require surface magnetic field strengths of a few hundred G, compatible with the maximum photospheric fields expected from equipartition. The flare parameters imply a (conductive and radiative) cooling loss time of less than one hour at flare peak. The elemental abundances increase significantly during the flare rise, with the abundances of the low-FIP elements Fe, Mg, Si, and Ni typically increasing to higher levels than the high-FIP elements such as S or Ne. The Fe abundance increases from (17 +/- 4)% of the solar photospheric value during quiescence up to (89 +/- 18)% at flare peak. A fractionation process

  11. Final Report

    NASA Technical Reports Server (NTRS)

    Linsky, Jeffrey L.

    1998-01-01

    This grant was made to fund two accepted proposals to observe with the ASCA satellite: (1) Debunking the myth of two-temperature coronae of active stars, and (2) Dynamic coronae of dMe stars. We obtained the requested observations and have now completed two papers that will be published in the Astrophysical Journal. The RS CVn binary star UX Ari was observed for 14 hours with all four detectors onboard the ASCA satellite. The X-ray emission was at a constant, quiescent level during the first 12 hours, after which time a powerful flare with a peak luminosity of 1.4 x 10(exp 32) ergs/s started. The flare was observed until shortly after its peak. We present a spectral and temporal analysis of the UX Ari observations and analyze the data with a two-ribbon flare model including estimates for cooling losses. A time-dependent reconstruction of the emission measure (EM) distribution shows that two separate plasma components evolve during the flare (one being identified with the quiescent EM). Most of the flare EM reaches temperatures between 50 MK and 100 MK or more. Magnetic confinement requires the loop arcade to be geometrically large, with length scales on the order of one stellar radius. The electron densities inferred from the model decrease from initial values around 10(exp 12)/cc early in the flare to about 10(exp 11)/cc at the flare peak. The best-fit models require surface magnetic field strengths of a few hundred G, compatible with the maximum photospheric fields expected from equipartition. The flare parameters imply a (conductive and radiative) cooling loss time of less than one hour at flare peak. The elemental abundances increase significantly during the flare rise, with the abundances of the low-FIP elements Fe, Mg, Si, and Ni typically increasing to higher levels than the high-FIP elements such as S or Ne. The Fe abundance increases from (17 +/- 4)% of the solar photospheric value during quiescence up to (89 +/- 18)% at flare peak. A fractionation process

  12. FINAL REPORT

    SciTech Connect

    PETER, GARY F.

    2014-07-16

    of biomass samples imaged with all three methods, and using common analytical software to quantify parameters from the three dimensional images. In addition to the proposed experiments, we conducted imaging studies with a novel TOF-SIMS instrument available through collaborations with the AMOLF goup led by Ron Heeren at the FOM Institute in Amersterdam, Netherlands. ToF-SIMS was used to image intact cross sections of Populus stems with high spatial resolution, chemically selectivity. ToF-SIMS images were correlated with fluorescence microscopy which allowed for more positive ion identification.

  13. Target parameter estimation

    NASA Technical Reports Server (NTRS)

    Hocking, W. K.

    1989-01-01

    The objective of any radar experiment is to determine as much as possible about the entities which scatter the radiation. This review discusses many of the various parameters which can be deduced in a radar experiment, and also critically examines the procedures used to deduce them. Methods for determining the mean wind velocity, the RMS fluctuating velocities, turbulence parameters, and the shapes of the scatterers are considered. Complications with these determinations are discussed. It is seen throughout that a detailed understanding of the shape and cause of the scatterers is important in order to make better determinations of these various quantities. Finally, some other parameters, which are less easily acquired, are considered. For example, it is noted that momentum fluxes due to buoyancy waves and turbulence can be determined, and on occasions radars can be used to determine stratospheric diffusion coefficients and even temperature profiles in the atmosphere.

  14. Aircraft parameter estimation

    NASA Technical Reports Server (NTRS)

    Iliff, Kenneth W.

    1987-01-01

    The aircraft parameter estimation problem is used to illustrate the utility of parameter estimation, which applies to many engineering and scientific fields. Maximum likelihood estimation has been used to extract stability and control derivatives from flight data for many years. This paper presents some of the basic concepts of aircraft parameter estimation and briefly surveys the literature in the field. The maximum likelihood estimator is discussed, and the basic concepts of minimization and estimation are examined for a simple simulated aircraft example. The cost functions that are to be minimized during estimation are defined and discussed. Graphic representations of the cost functions are given to illustrate the minimization process. Finally, the basic concepts are generalized, and estimation from flight data is discussed. Some of the major conclusions for the simulated example are also developed for the analysis of flight data from the F-14, highly maneuverable aircraft technology (HiMAT), and space shuttle vehicles.

  15. STS 65 Final Report

    NASA Technical Reports Server (NTRS)

    Rice, James E.

    1996-01-01

    The report is organized into sections representing the phases of work performed in analyzing the STS 65 results and preparing the instrument for STS 73. Section 1 briefly outlines the Orbital Acceleration Research Experiment (OARE) system features, coordinates, and measurement parameters. Section 2 describes the results from STS 65. The mission description, data calibration, and representative data obtained on STS 65 are presented. Also, the anomalous performance of OARE on STS 65 is discussed. Finally, Section 3 presents a discussion of accuracy achieved and achievable with OARE.

  16. Final report

    SciTech Connect

    Dobbs, Fred C.

    2003-01-15

    species of flagellates, Spumella sp. and Bodo sp. (identifications are tentative) were isolated from South Oyster sediments by repetitive serial dilution/extinction method. Protistan cells were cultured with Cereal leaf Prescott medium and pelleted by centrifugation. Protistan DNAs were extracted with a DNA extraction kit (Sigma Co.) and the sequencing of their SSrDNA is underway. Finally, to follow up on our collaboration of Dr. Bill Johnson (Univ. of Utah), one of the co-PIs under the same NABIR umbrella, we are pleased to report we have successfully tested antibody-ferrographic capture of protists (See previous year's report for more background). Polyclonal FITC-conjugated antibody specific for a flagellate, Spumella sp., was produced by Rockland Inc., and we now are able to enumerate that species using ferrographic capture. There are, however, some issues of non-specific staining that remain to be resolved.

  17. A cellular automaton nanoflare model of coronal loops

    NASA Astrophysics Data System (ADS)

    Lopez Fuentes, Marcelo; Klimchuk, James

    In Lopez-Fuentes, Klimchuk and Mandrini (2007) we found that the evolution of soft X-ray loops can be separated into three main phases that suggest the development, maintainance, and decay of a self-organized system. Here, we present a cellular automaton model that reproduces the main features of the observed evolution. The model is based on the idea that loops are made of multiple unresolved strands which have footpoints that are displaced by random photospheric motions (Parker 1988). In this scenario, there is a continuous increase of the magnetic stress between neighboring strands until a critical stress is reached and the accumulated energy is suddenly released by reconnection. Each of these reconnection "events" is associated with a nanoflare. Using the EBTEL hydrodynamic code (Klimchuk, Patsourakos and Cargill 2008) to model the plasma response we construct synthetic light curves that we compare with the observations. We also study how the properties of the light curves scale with the different parameters of the model. Finally, we discuss how the present model can be used to explain loop observations in different wavelengths.

  18. Final Report

    SciTech Connect

    Robert D. Cess

    2008-12-05

    Paper number 1 addresses the fact that the procedure used in the Earth Radiation Budget Experiment for identifying the presence of clouds over snow/ice surfaces is known to have shortcomings, and this is corroborated through use of surface insolation measurements at the South Pole as an independent means of identifying clouds. These surface insolation measurements are then used to validate the more detailed cloud identification scheme used in the follow-up Clouds and the Earth's Radiant Energy System (CERES), and this validation is extended to the polar night through use of CERES measurements of the outgoing longwave radiation. General circulation models (GCMs) are highly sophisticated computer tools for modeling climate change, and they incorporate a large number of physical processes and variables. One of the most important challenges is to properly account for water vapor (clouds and humidity) in climate warming. In this Perspective, Cess discusses results reported in the same issue by Soden et al. in which water vapor feedback effects are tested by studying moistening trends in the upper troposphere. Satellite observations of atmospheric water vapor are found to agree well with moisture predictions generated by one of the key GCMs, showing that these feedback effects are being properly handled in the model, which eliminates a major potential source of uncertainty. Zhou and Cess [2001] developed an algorithm for retrieving surface downwelling longwave radiation (SDLW) based upon detailed studies using radiative transfer model calculations and surface radiometric measurements. Their algorithm linked clear sky SDLW with surface upwelling longwave flux and column precipitable water vapor. For cloudy sky cases, they used cloud liquid water path as an additional parameter to account for the effects of clouds. Despite the simplicity of their algorithm, it performed very well for most geographical regions except for those regions where the atmospheric conditions near

  19. Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

    NASA Astrophysics Data System (ADS)

    Gao, Ziyang

    Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

  20. Top-down cellular pyramids

    SciTech Connect

    Wu, A.Y.; Rosenfeld, A.

    1982-07-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors ('cells'), where each cell is connected to its neighbors ('siblings') on its own level, to a 'parent' on the level above, and to its 'children' on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case.

  1. Four faces of cellular senescence

    PubMed Central

    Rodier, Francis

    2011-01-01

    Cellular senescence is an important mechanism for preventing the proliferation of potential cancer cells. Recently, however, it has become apparent that this process entails more than a simple cessation of cell growth. In addition to suppressing tumorigenesis, cellular senescence might also promote tissue repair and fuel inflammation associated with aging and cancer progression. Thus, cellular senescence might participate in four complex biological processes (tumor suppression, tumor promotion, aging, and tissue repair), some of which have apparently opposing effects. The challenge now is to understand the senescence response well enough to harness its benefits while suppressing its drawbacks. PMID:21321098

  2. A magnetically actuated cellular strain assessment tool for quantitative analysis of strain induced cellular reorientation and actin alignment

    NASA Astrophysics Data System (ADS)

    Khademolhosseini, F.; Liu, C.-C.; Lim, C. J.; Chiao, M.

    2016-08-01

    Commercially available cell strain tools, such as pneumatically actuated elastomer substrates, require special culture plates, pumps, and incubator setups. In this work, we present a magnetically actuated cellular strain assessment tool (MACSAT) that can be implemented using off-the-shelf components and conventional incubators. We determine the strain field on the MACSAT elastomer substrate using numerical models and experimental measurements and show that a specific region of the elastomer substrate undergoes a quasi-uniaxial 2D stretch, and that cells confined to this region of the MACSAT elastomer substrate undergo tensile, compressive, or zero axial strain depending on their angle of orientation. Using the MACSAT to apply cyclic strain on endothelial cells, we demonstrate that actin filaments within the cells reorient away from the stretching direction, towards the directions of minimum axial strain. We show that the final actin orientation angles in strained cells are spread over a region of compressive axial strain, confirming previous findings on the existence of a varied pre-tension in the actin filaments of the cytoskeleton. We also demonstrate that strained cells exhibit distinctly different values of actin alignment coherency compared to unstrained cells and therefore propose that this parameter, i.e., the coherency of actin alignment, can be used as a new readout to determine the occurrence/extent of actin alignment in cell strain experiments. The tools and methods demonstrated in this study are simple and accessible and can be easily replicated by other researchers to study the strain response of other adherent cells.

  3. Superconducting quadrupoles for the SLC final focus

    SciTech Connect

    Erickson, R.; Fieguth, T.; Murray, J.J.

    1987-01-01

    The final focus system of the SLC will be upgraded by replacing the final quadrupoles with higher gradient superconducting magnets positioned closer to the interaction point. The parameters of the new system have been chosen to be compatible with the experimental detectors with a minimum of changes to other final focus components. These parameter choices are discussed along with the expected improvement in SLC performance.

  4. A Course in Cellular Bioengineering.

    ERIC Educational Resources Information Center

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  5. The cellular microscopy phenotype ontology.

    PubMed

    Jupp, Simon; Malone, James; Burdett, Tony; Heriche, Jean-Karim; Williams, Eleanor; Ellenberg, Jan; Parkinson, Helen; Rustici, Gabriella

    2016-01-01

    Phenotypic data derived from high content screening is currently annotated using free-text, thus preventing the integration of independent datasets, including those generated in different biological domains, such as cell lines, mouse and human tissues. We present the Cellular Microscopy Phenotype Ontology (CMPO), a species neutral ontology for describing phenotypic observations relating to the whole cell, cellular components, cellular processes and cell populations. CMPO is compatible with related ontology efforts, allowing for future cross-species integration of phenotypic data. CMPO was developed following a curator-driven approach where phenotype data were annotated by expert biologists following the Entity-Quality (EQ) pattern. These EQs were subsequently transformed into new CMPO terms following an established post composition process. CMPO is currently being utilized to annotate phenotypes associated with high content screening datasets stored in several image repositories including the Image Data Repository (IDR), MitoSys project database and the Cellular Phenotype Database to facilitate data browsing and discoverability.

  6. Origami interleaved tube cellular materials

    NASA Astrophysics Data System (ADS)

    Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

    2014-09-01

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

  7. A Course in Cellular Bioengineering.

    ERIC Educational Resources Information Center

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  8. Supergranular Parameters

    NASA Astrophysics Data System (ADS)

    Udayashankar, Paniveni

    2016-07-01

    I study the complexity of supergranular cells using intensity patterns from Kodaikanal solar observatory. The chaotic and turbulent aspect of the solar supergranulation can be studied by examining the interrelationships amongst the parameters characterizing supergranular cells namely size, horizontal flow field, lifetime and physical dimensions of the cells and the fractal dimension deduced from the size data. The findings are supportive of Kolmogorov's theory of turbulence. The Data consists of visually identified supergranular cells, from which a fractal dimension 'D' for supergranulation is obtained according to the relation P α AD/2 where 'A' is the area and 'P' is the perimeter of the supergranular cells. I find a fractal dimension close to about 1.3 which is consistent with that for isobars and suggests a possible turbulent origin. The cell circularity shows a dependence on the perimeter with a peak around (1.1-1.2) x 105 m. The findings are supportive of Kolmogorov's theory of turbulence.

  9. Mathematical Modeling of Cellular Metabolism.

    PubMed

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

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

  10. Membrane potential mediates the cellular binding of nanoparticles

    NASA Astrophysics Data System (ADS)

    Shin, Edwin H.; Li, Ye; Kumar, Umesh; Sureka, Hursh V.; Zhang, Xianren; Payne, Christine K.

    2013-06-01

    The use of nanoparticles for cellular therapeutic or sensing applications requires nanoparticles to bind, or adhere, to the cell surface. While nanoparticle parameters such as size, shape, charge, and composition are important factors in cellular binding, the cell itself must also be considered. All cells have an electrical potential across the plasma membrane driven by an ion gradient. Under standard conditions the ion gradient will result in a -10 to -100 mV potential across the membrane with a net negative charge on the cytosolic face. Using a combination of flow cytometry and fluorescence microscopy experiments and dissipative particle dynamics simulations, we have found that a decrease in membrane potential leads to decreased cellular binding of anionic nanoparticles. The decreased cellular binding of anionic nanoparticles is a general phenomenon, independent of depolarization method, nanoparticle composition, and cell type. Increased membrane potential reverses this trend resulting in increased binding of anionic nanoparticles. The cellular binding of cationic nanoparticles is minimally affected by membrane potential due to the interaction of cationic nanoparticles with cell surface proteins. The influence of membrane potential on the cellular binding of nanoparticles is especially important when considering the use of nanoparticles in the treatment or detection of diseases, such as cancer, in which the membrane potential is decreased.The use of nanoparticles for cellular therapeutic or sensing applications requires nanoparticles to bind, or adhere, to the cell surface. While nanoparticle parameters such as size, shape, charge, and composition are important factors in cellular binding, the cell itself must also be considered. All cells have an electrical potential across the plasma membrane driven by an ion gradient. Under standard conditions the ion gradient will result in a -10 to -100 mV potential across the membrane with a net negative charge on the

  11. Shock enhancement of cellular materials subjected to intensive pulse loading

    NASA Astrophysics Data System (ADS)

    Zhang, J.; Fan, J.; Wang, Z.; Zhao, L.; Li, Z.

    2017-06-01

    Cellular materials can dissipate a large amount of energy due to their considerable stress plateau, which contributes to their extensive applications in structural design for crashworthiness. However, in some experiments with specimens subjected to intense impact loads, transmitted stress enhancement has been observed, leading to severe damage to the objects protected. Transmitted stress through two-dimensional Voronoi cellular materials as a protective device is qualitatively studied in this paper. Dimensionless parameters of material properties and loading parameters are defined to give critical conditions for shock enhancement and clarify the correlation between the deformations and stress enhancement. The effect of relative density on this amplifying phenomenon is investigated as well. In addition, local strain fields are calculated by using the optimal local deformation gradient, which gives a clear presentation of deformations and possible local non-uniformity in the crushing process. This research provides valuable insight into the reliability of cellular materials as protective structures.

  12. Sound attenuation characteristics of cellular metamaterials

    NASA Astrophysics Data System (ADS)

    Varanasi, Satya Surya Srinivas

    could be mitigated by the addition of appropriate treatments such as a lightweight grid that modified the incident sound field to be normally directed. Although the performance of the metamaterial-based barrier solutions was better compared to the conventional ones, the performance can be poor at the system eigenfrequencies. The possibility of shifting energy from the deficit bands to other regions where the barriers are more efficient was numerically explored for embodiments of segmented cellular materials having non-linear stiffness characteristics. The acoustical behavior of such materials was probed through representative two-dimensional models of a segmented plate with a contact interface. Super-harmonic response peaks were observed for pure harmonic excitations, the strength of which were found to strongly depend on the degree of non-linearity or bilinear stiffness ratio. The closer an excitation frequency was to the characteristic eigenfrequencies of the structure, the stronger was the super-harmonic response, which supported the idea of transferring energy from problematic frequency bands to higher frequencies. Finally, the possibility of a spatial-shift of energy from longitudinal to lateral direction was explored with the idea of eliminating the design constraints associated with conventional absorbing materials, and with the hope of realizing a compact sound absorber. The embodiment was a two-phase chiral composite made using a Topologically Interlocked Material (TIM) with its unit cell being a tetrahedron consisting of two helicoid dissections. A comparative study was conducted with standard microstructures inspired by the Voigt and Reuss models. The twist mode of the chiral composites was found to be excited by an incident sound field normal to the plane of the TIM assembly. Although this behavior is not unique to a chiral microstructure, many other microstructures do not exhibit this behavior. The excitation of the twist mode by the incident sound field

  13. Multiple cellular cascades participate in long-term potentiation and in hippocampus-dependent learning

    PubMed Central

    Baudry, Michel; Zhu, Guoqi; Liu, Yan; Wang, Yubin; Briz, Victor; Bi, Xiaoning

    2015-01-01

    Since its discovery by Bliss and Lomo, the phenomenon of long-term potentiation (LTP) has been extensively studied, as it was viewed as a potential cellular mechanism of learning and memory. Over the years, many signaling cascades have been implicated in its induction, consolidation and maintenance, raising questions regarding its real significance. Here, we review several of the most commonly studies signaling cascades and discuss how they converge on a common set of mechanisms likely to be involved in the maintenance of LTP. We further argue that the existence of cross-talks between these different signaling cascades can not only account for several discrepancies in the literature, but also account for the existence of different forms of LTP, which can be engaged by different types of stimulus parameters under different experimental conditions. Finally, we discuss how the understanding of the diversity of LTP mechanisms can help us understand the diversity of the types of learning and memory. PMID:25482663

  14. Geoengineering design parameters workshop

    SciTech Connect

    St. John, C.M. and Associates, Grand Junction, CO ); Kim, Kunsoo . Rockwell Hanford Operations)

    1985-12-12

    A one-day workshop on the subject of the geotechnical design parameters, in situ stress and rock mass strength, for a nuclear waste repository in basalt was held in Rapid City, South Dakota, on June 25, 1989. A panel comprised of five widely recognized experts in the field of rock mechanics, met to discuss the state of stress at the Hanford Site and the strength of a basalt rock mass. This report summarizes the discussions that took place and presents a set of final position statements developed collaboratively by the panel and the workshop moderator. The report concludes with a set of specific recommendations for future actions considered necessary to adequately define the in situ stress and the rock mass strength at the Hanford Site and to document the position of the Basalt Waste Isolation Project in respect to these two critical design parameters.

  15. The origins of cellular life.

    PubMed

    Koonin, Eugene V

    2014-07-01

    All life on earth can be naturally classified into cellular life forms and virus-like selfish elements, the latter being fully dependent on the former for their reproduction. Cells are reproducers that not only replicate their genome but also reproduce the cellular organization that depends on semipermeable, energy-transforming membranes and cannot be recovered from the genome alone, under the famous dictum of Rudolf Virchow, Omnis cellula e cellula. In contrast, simple selfish elements are replicators that can complete their life cycles within the host cell starting from genomic RNA or DNA alone. The origin of the cellular organization is the central and perhaps the hardest problem of evolutionary biology. I argue that the origin of cells can be understood only in conjunction with the origin and evolution of selfish genetic elements. A scenario of precellular evolution is presented that involves cohesion of the genomes of the emerging cellular life forms from primordial pools of small genetic elements that eventually segregated into hosts and parasites. I further present a model of the coevolution of primordial membranes and membrane proteins, discuss protocellular and non-cellular models of early evolution, and examine the habitats on the primordial earth that could have been conducive to precellular evolution and the origin of cells.

  16. Classifying cellular automata using grossone

    NASA Astrophysics Data System (ADS)

    D'Alotto, Louis

    2016-10-01

    This paper proposes an application of the Infinite Unit Axiom and grossone, introduced by Yaroslav Sergeyev (see [7] - [12]), to the development and classification of one and two-dimensional cellular automata. By the application of grossone, new and more precise nonarchimedean metrics on the space of definition for one and two-dimensional cellular automata are established. These new metrics allow us to do computations with infinitesimals. Hence configurations in the domain space of cellular automata can be infinitesimally close (but not equal). That is, they can agree at infinitely many places. Using the new metrics, open disks are defined and the number of points in each disk computed. The forward dynamics of a cellular automaton map are also studied by defined sets. It is also shown that using the Infinite Unit Axiom, the number of configurations that follow a given configuration, under the forward iterations of cellular automaton maps, can now be computed and hence a classification scheme developed based on this computation.

  17. YAP/TEAD-mediated transcription controls cellular senescence.

    PubMed

    Xie, Qi; Chen, Jing; Feng, Han; Peng, Shengyi; Adams, Ursula; Bai, Yujie; Huang, Li; Li, Ji; Huang, Junjian; Meng, Songshu; Yuan, Zengqiang

    2013-06-15

    Transcription coactivator Yes-associated protein (YAP) plays an important role in the regulation of cell proliferation and apoptosis. Here, we identify a new role of YAP in the regulation of cellular senescence. We find that the expression levels of YAP proteins decrease following the replication-induced cellular senescence in IMR90 cells. Silencing of YAP inhibits cell proliferation and induces premature senescence. In additional experiments, we observe that cellular senescence induced by YAP deficiency is TEAD- and Rb/p16/p53-dependent. Furthermore, we show that Cdk6 is a direct downstream target gene of YAP in the regulation of cellular senescence, and the expression of Cdk6 is through the YAP-TEAD complex. Ectopic expression of Cdk6 rescued YAP knockdown-induced senescence. Finally, we find that downregulation of YAP in tumor cells increases senescence in response to chemotherapeutic agents, and YAP or Cdk6 expression rescues cellular senescence. Taken together, our findings define the critical role of YAP in the regulation of cellular senescence and provide a novel insight into a potential chemotherapeutic avenue for tumor suppression. ©2013 AACR.

  18. Roles of Apoptosis and Cellular Senescence in Cancer and Aging.

    PubMed

    Cerella, Claudia; Grandjenette, Cindy; Dicato, Mario; Diederich, Marc

    2016-01-01

    Cancer and aging are two similar processes representing the final outcome of timedependent accumulation of various irreversible dysfunctions, mainly caused by stress-induced DNA and cellular damages. Apoptosis and senescence are two types of cellular response to damages that are altered in both cancer and aging, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the ability of the cells to trigger apoptosis and senescence. In contrast, in aging tissues, there is an increased accumulation of senescent cells, and the nature of apoptosis deregulation varies depending on the tissue. Thus, the prevailing model suggests that apoptosis and cellular senescence function as two essential tumor-suppressor mechanisms, ensuring the health of the individual during early and reproductive stages of life, but become detrimental and promote aging later in life. The recent discovery that various anticancer agents, including canonical inducers of apoptosis, act also as inducers of cellular senescence indicates that pro-senescence strategies may have applications in cancer prevention therapy. Therefore, dissection of the mechanisms mediating the delicate balance between apoptosis and cellular senescence will be beneficial in the therapeutic exploitation of both processes in the development of future anticancer and anti-aging strategies, including minimizing the side effects of such strategies. Here, we provide an overview of the roles of apoptosis and cellular senescence in cancer and aging.

  19. Aging, Cellular Senescence, and Cancer

    PubMed Central

    Campisi, Judith

    2014-01-01

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

  20. Viral Activation of Cellular Metabolism

    PubMed Central

    Sanchez, Erica L.; Lagunoff, Michael

    2015-01-01

    To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways. PMID:25812764

  1. Fracture mechanics of cellular glass

    NASA Technical Reports Server (NTRS)

    Zwissler, J. G.; Adams, M. A.

    1981-01-01

    The fracture mechanics of cellular glasses (for the structural substrate of mirrored glass for solr concentrator reflecting panels) are discussed. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials were developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region 1 may be slower, by orders of magnitude, than that found in dense glasses.

  2. Cellular-based preemption system

    NASA Technical Reports Server (NTRS)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  3. Aging, cellular senescence, and cancer.

    PubMed

    Campisi, Judith

    2013-01-01

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

  4. A Nucleator Arms Race: Cellular Control of Actin Assembly

    PubMed Central

    Campellone, Kenneth G.; Welch, Matthew D.

    2010-01-01

    For more than a decade the Arp2/3 complex, a handful of nucleation-promoting factors, and formins were the only molecules known to directly nucleate actin filament formation de novo. However, the past several years have brought a surge in the discovery of mammalian proteins with roles in actin nucleation and dynamics. Newly recognized nucleation-promoting factors, such as WASH, WHAMM, and JMY stimulate Arp2/3 complex activity at distinct cellular locations. Formin nucleators with additional biochemical and cellular activities have also been uncovered. Finally, the Spire, Cordon-bleu, and Leiomodin nucleators have revealed new ways of overcoming the kinetic barriers to actin polymerization. PMID:20237478

  5. Cellular models for Parkinson's disease.

    PubMed

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

    2016-10-01

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

  6. Genetic Algorithm Calibration of Probabilistic Cellular Automata for Modeling Mining Permit Activity

    USGS Publications Warehouse

    Louis, S.J.; Raines, G.L.

    2003-01-01

    We use a genetic algorithm to calibrate a spatially and temporally resolved cellular automata to model mining activity on public land in Idaho and western Montana. The genetic algorithm searches through a space of transition rule parameters of a two dimensional cellular automata model to find rule parameters that fit observed mining activity data. Previous work by one of the authors in calibrating the cellular automaton took weeks - the genetic algorithm takes a day and produces rules leading to about the same (or better) fit to observed data. These preliminary results indicate that genetic algorithms are a viable tool in calibrating cellular automata for this application. Experience gained during the calibration of this cellular automata suggests that mineral resource information is a critical factor in the quality of the results. With automated calibration, further refinements of how the mineral-resource information is provided to the cellular automaton will probably improve our model.

  7. Cellular automata for traffic simulations

    NASA Astrophysics Data System (ADS)

    Wolf, Dietrich E.

    1999-02-01

    Traffic phenomena such as the transition from free to congested flow, lane inversion and platoon formation can be accurately reproduced using cellular automata. Being computationally extremely efficient, they simulate large traffic systems many times faster than real time so that predictions become feasible. A riview of recent results is given. The presence of metastable states at the jamming transition is discussed in detail. A simple new cellular automation is introduced, in which the interaction between cars is Galilei-invariant. It is shown that this type of interaction accounts for metastable states in a very natural way.

  8. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  9. Cellular basis of Alzheimer's disease.

    PubMed

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  10. Regulation of Cellular Tension in Adherent Cells

    NASA Astrophysics Data System (ADS)

    Oakes, Patrick

    2013-03-01

    Cells generate stress on their surrounding extracellular matrix (ECM) via myosin II motor generated forces which are transmitted through the actin cytoskeleton. The mechanisms in the cell which regulate the magnitude and spatial distribution of these stresses, however, remain unknown. Consistent with previous reports, we find that the total magnitude of traction force exerted on the ECM scales with cell size. Such scaling is observed across numerous cell types and reflects an inherent cellular tension determined by the level of myosin II activity. Surprisingly, while stiffness modulates the cellular spread area, we find this scaling relationship to be independent of ECM stiffness. To identify the biophysical mechanisms regulating the generation of tension, we utilize micro-patterning to isolate cell spread area from cell geometry and to spatially control the distribution of stress on the ECM. We find that traction stress magnitude is dependent on the local curvature of the cell. Changes in cell geometry result in a redistribution of local stresses, but little change in the total stress applied to the ECM. Finally, for a constant geometry, we find that both the total stress and the average stress exerted on the ECM increase with cell area. Together these data suggest that the cell can be modeled as a uniformly contracting mesh, where the magnitude of tension is regulated by the cell spread area, and the distribution of tension is regulated by local geometry.

  11. Single-Molecule Imaging of Cellular Signaling

    NASA Astrophysics Data System (ADS)

    De Keijzer, Sandra; Snaar-Jagalska, B. Ewa; Spaink, Herman P.; Schmidt, Thomas

    Single-molecule microscopy is an emerging technique to understand the function of a protein in the context of its natural environment. In our laboratory this technique has been used to study the dynamics of signal transduction in vivo. A multitude of signal transduction cascades are initiated by interactions between proteins in the plasma membrane. These cascades start by binding a ligand to its receptor, thereby activating downstream signaling pathways which finally result in complex cellular responses. To fully understand these processes it is important to study the initial steps of the signaling cascades. Standard biological assays mostly call for overexpression of the proteins and high concentrations of ligand. This sets severe limits to the interpretation of, for instance, the time-course of the observations, given the large temporal spread caused by the diffusion-limited binding processes. Methods and limitations of single-molecule microscopy for the study of cell signaling are discussed on the example of the chemotactic signaling of the slime-mold Dictyostelium discoideum. Single-molecule studies, as reviewed in this chapter, appear to be one of the essential methodologies for the full spatiotemporal clarification of cellular signaling, one of the ultimate goals in cell biology.

  12. Cellular commitment in the developing cerebellum

    PubMed Central

    Marzban, Hassan; Del Bigio, Marc R.; Alizadeh, Javad; Ghavami, Saeid; Zachariah, Robby M.; Rastegar, Mojgan

    2014-01-01

    The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum. PMID:25628535

  13. Particles and Patterns in Cellular Automata

    SciTech Connect

    Jen, E.; Das, R.; Beasley, C.E.

    1999-06-03

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Our objective has been to develop tools for studying particle interactions in a class of dynamical systems characterized by discreteness, determinism, local interaction, and an inherently parallel form of evolution. These systems can be described by cellular automata (CA) and the behavior we studied has improved our understanding of the nature of patterns generated by CAs, their ability to perform global computations, and their relationship to continuous dynamical systems. We have also developed a rule-table mathematics that enables one to custom-design CA rule tables to generate patterns of specified types, or to perform specified computational tasks.

  14. Retrodifferentiation--a mechanism for cellular regeneration?

    PubMed

    Hass, Ralf

    2009-01-01

    Cellular differentiation can be characterized by the acquisition of specified properties during several steps of development whereby the original stem- or precursor-like populations can finally obtain a certain phenotype with highly specific cell functions. The continuing maturation process can be paralleled by progressively reduced proliferative capacity in various cell types functioning as postmitotic tissues. Conversely, other cell populations (e.g., distinct immune cells) may carry out their specific function upon stimulation of proliferation. While these differentiated phenotypes perform their appropriate specific duties throughout the functioning organism, nature may provide an interesting alternative within this concept of life: sometimes, differentiation steps appear to be reversible. Thus, retrograde differentiation--also termed retrodifferentiation--and accordingly rejuvenation may occur when differentiated cells lose their specific properties acquired during previous steps of maturation. Consequently, retrodifferentiation and rejuvenation could provide enormous potential for tissue repair and cell renewal; however, regulatory dysfunctions within these retrograde developments may also involve the risk of tumor promotion.

  15. Spatial Dynamics of Multilayer Cellular Neural Networks

    NASA Astrophysics Data System (ADS)

    Wu, Shi-Liang; Hsu, Cheng-Hsiung

    2017-06-01

    The purpose of this work is to study the spatial dynamics of one-dimensional multilayer cellular neural networks. We first establish the existence of rightward and leftward spreading speeds of the model. Then we show that the spreading speeds coincide with the minimum wave speeds of the traveling wave fronts in the right and left directions. Moreover, we obtain the asymptotic behavior of the traveling wave fronts when the wave speeds are positive and greater than the spreading speeds. According to the asymptotic behavior and using various kinds of comparison theorems, some front-like entire solutions are constructed by combining the rightward and leftward traveling wave fronts with different speeds and a spatially homogeneous solution of the model. Finally, various qualitative features of such entire solutions are investigated.

  16. Microsystems for cellular force measurement: a review

    NASA Astrophysics Data System (ADS)

    Rayne Zheng, Xiaoyu; Zhang, Xin

    2011-05-01

    Microsystems are providing key advances in studying single cell mechanical behavior. The mechanical interaction of cells with their extracellular matrix is fundamentally important for cell migration, division, phagocytosis and aptoptosis. This review reports the development of microsystems on studying cell forces. Microsystems provide advantages of studying single cells since the scale of cells is on the micron level. The components of microsystems provide culture, loading, guiding, trapping and on chip analysis of cellular mechanical forces. This paper gives overviews on how MEMS are advancing in the field of cell biomechno sensory systems. It presents different materials, and mode of studying cell mechanics. Finally, we comment on the future directions and challenges on the state of art techniques.

  17. Threshold effects and cellular recognition. Progress report

    SciTech Connect

    Rando, R R

    1980-01-01

    In the first year we focused on developing the techniques required for the successful incorporation of synthetic glycolipids into cells. To these ends a new water-soluble spacer group (8-amino-3-6-dioxaoctanoic acid) was developed and incorporated into the cholesterol based synthetic glycolipids. These glycolipids could be incorporated into liposomes, rendering them susceptible to aggregation by the appropriate lectin. They also allowed us to define the minimal distance between the sugar moiety and membrane required for agglutination. Finally and most importantly, we were able to functionally incorporate these new glycolipids in cells and render them agglutinable with the appropriate lectins. Functional incorporation does not occur with glycolipids bearing hydropholic spacer groups. We are now in a position to begin using the new glycolipids to answer questions about the roles of cell surface sugars in cellular recognition, which is the subject of this renewal proposal.

  18. Identifying Cellular and Molecular Mechanisms for Magnetosensation

    PubMed Central

    Clites, Benjamin L.; Pierce, Jonathan T.

    2017-01-01

    Diverse animals ranging from worms and insects to birds and turtles perf orm impressive journeys using the magnetic field of the earth as a cue. Although major cellular and molecular mechanisms for sensing mechanical and chemical cues have been elucidated over the past three decades, the mechanisms that animals use to sense magnetic fields remain largely mysterious. Here we survey progress on the search for magnetosensory neurons and magnetosensitive molecules important for animal behaviors. Emphasis is placed on magnetosensation in insects and birds, as well as on the magnetosensitive neuron pair AFD in the nematode Caenorhabditis elegans. We also review conventional criteria used to define animal magnetoreceptors and suggest how approaches used to identify receptors for other sensory modalities may be adapted for magnetoreceptors. Finally, we discuss prospects for under-utilized and novel approaches to identify the elusive magnetoreceptors in animals. PMID:28772099

  19. Cellular Instabilities and Self-Acceleration of Expanding Spherical Flames

    NASA Technical Reports Server (NTRS)

    Law, C. K.; Kwon, O. C.

    2003-01-01

    In the present investigation we aim to provide experimental information on and thereby understanding of the generation and propagation of spark-ignited, outwardly propagating cellular flames, with three major focuses. The first is to unambiguously demonstrate the influence of the four most important parameters in inducing hydrodynamic and diffusional-thermal cellularities, namely thermal expansion, flame thickness, non-unity Lewis number, and global activation energy. The second is to investigate the critical state for the onset of cellularity for the stretch-affected, expanding flame. The third is to identify and consequently quantify the phenomena of self-acceleration and possibly auto-turbulization of cellular flames. Due to space limitation the effects of activation energy and the critical state for the onset of cellularity will not be discussed herein. Experiments were conducted using C3H8-air and H2-O2-N2 mixtures for their opposite influences of non-equidiffusivity. The additional system parameters varied were the chamber pressure (p) and the mixture composition including the equivalence ratio (phi). From a sequence of the flame images we can assess the propensity of cell formation, and determine the instantaneous flame radius (R), the flame propagation rate, the global stretch rate experienced by the flame, the critical flame radius at which cells start to grow, and the average cell size.

  20. Cellular basis for QT dispersion.

    PubMed

    Antzelevitch, C; Shimizu, W; Yan, G X; Sicouri, S

    1998-01-01

    The cellular basis for the dispersion of the QT interval recorded at the body surface is incompletely understood. Contributing to QT dispersion are heterogeneities of repolarization time in the three-dimensional structure of the ventricular myocardium, which are secondary to regional differences in action potential duration (APD) and activation time. While differences in APD occur along the apicobasal and anteroposterior axes in both epicardium and endocardium of many species, transitions are usually gradual. Recent studies have also demonstrated important APD gradients along the transmural axis. Because transmural heterogeneities in repolarization time are more abrupt than those recorded along the surfaces of the heart, they may represent a more onerous substrate for the development of arrhythmias, and their quantitation may provide a valuable tool for evaluation of arrhythmia risk. Our data, derived from the arterially perfused canine left ventricular wedge preparation, suggest that transmural gradients of voltage during repolarization contribute importantly to the inscription of the T wave. The start of the T wave is caused by a more rapid decline of the plateau, or phase 2 of the epicardial action potential, creating a voltage gradient across the wall. The gradient increases as the epicardial action potential continues to repolarize, reaching a maximum with full repolarization of epicardium; this juncture marks the peak of the T wave. The next region to repolarize is endocardium, giving rise to the initial descending limb of the upright T wave. The last region to repolarize is the M region, contributing to the final segment of the T wave. Full repolarization of the M region marks the end of the T wave. The time interval between the peak and the end of the T wave therefore represents the transmural dispersion of repolarization. Conditions known to augment QTc dispersion, including acquired long QT syndrome (class IA or III antiarrhythmics) lead to augmentation

  1. A CRITERION PAPER ON PARAMETERS OF EDUCATION. FINAL REVISION.

    ERIC Educational Resources Information Center

    MEIERHENRY, W. C.

    THIS POSITION PAPER DEFINES ASPECTS OF INNOVATION IN EDUCATION. THE APPROPRIATENESS OF PLANNED CHANGE AND THE LEGITIMACY OF FUNCTION OF PLANNED CHANGE ARE DISCUSSED. PRIMARY ELEMENTS OF INNOVATION INCLUDE THE SUBSTITUTION OF ONE MATERIAL OR PROCESS FOR ANOTHER, THE RESTRUCTURING OF TEACHER ASSIGNMENTS, VALUE CHANGES WITH RESPECT TO TEACHING…

  2. Evaluation of fluid bed heat exchanger optimization parameters. Final report

    SciTech Connect

    Not Available

    1980-03-01

    Uncertainty in the relationship of specific bed material properties to gas-side heat transfer in fluidized beds has inhibited the search for optimum bed materials and has led to over-conservative assumptions in the design of fluid bed heat exchangers. An experimental program was carried out to isolate the effects of particle density, thermal conductivity, and heat capacitance upon fluid bed heat transfer. A total of 31 tests were run with 18 different bed material loads on 12 material types; particle size variations were tested on several material types. The conceptual design of a fluidized bed evaporator unit was completed for a diesel exhaust heat recovery system. The evaporator heat transfer surface area was substantially reduced while the physical dimensions of the unit increased. Despite the overall increase in unit size, the overall cost was reduced. A study of relative economics associated with bed material selection was conducted. For the fluidized bed evaporator, it was found that zircon sand was the best choice among materials tested in this program, and that the selection of bed material substantially influences the overall system costs. The optimized fluid bed heat exchanger has an estimated cost 19% below a fin augmented tubular heat exchanger; 31% below a commercial design fluid bed heat exchanger; and 50% below a conventional plain tube heat exchanger. The comparisons being made for a 9.6 x 10/sup 6/ Btu/h waste heat boiler. The fluidized bed approach potentially has other advantages such as resistance to fouling. It is recommended that a study be conducted to develop a systematic selection of bed materials for fluidized bed heat exchanger applications, based upon findings of the study reported herein.

  3. 3D surface reconstruction and visualization of the Drosophila wing imaginal disc at cellular resolution

    NASA Astrophysics Data System (ADS)

    Bai, Linge; Widmann, Thomas; Jülicher, Frank; Dahmann, Christian; Breen, David

    2013-01-01

    Quantifying and visualizing the shape of developing biological tissues provide information about the morphogenetic processes in multicellular organisms. The size and shape of biological tissues depend on the number, size, shape, and arrangement of the constituting cells. To better understand the mechanisms that guide tissues into their final shape, it is important to investigate the cellular arrangement within tissues. Here we present a data processing pipeline to generate 3D volumetric surface models of epithelial tissues, as well as geometric descriptions of the tissues' apical cell cross-sections. The data processing pipeline includes image acquisition, editing, processing and analysis, 2D cell mesh generation, 3D contourbased surface reconstruction, cell mesh projection, followed by geometric calculations and color-based visualization of morphological parameters. In their first utilization we have applied these procedures to construct a 3D volumetric surface model at cellular resolution of the wing imaginal disc of Drosophila melanogaster. The ultimate goal of the reported effort is to produce tools for the creation of detailed 3D geometric models of the individual cells in epithelial tissues. To date, 3D volumetric surface models of the whole wing imaginal disc have been created, and the apicolateral cell boundaries have been identified, allowing for the calculation and visualization of cell parameters, e.g. apical cross-sectional area of cells. The calculation and visualization of morphological parameters show position-dependent patterns of cell shape in the wing imaginal disc. Our procedures should offer a general data processing pipeline for the construction of 3D volumetric surface models of a wide variety of epithelial tissues.

  4. Symmetry of integrable cellular automaton

    NASA Astrophysics Data System (ADS)

    Hikami, Kazuhiro; Inoue, Rei

    2001-03-01

    We study an integrable cellular automaton which is called the box-ball system (BBS). The BBS can be derived directly from the integrable differential-difference equation by either ultradiscretization or crystallization. We clarify the integrable structure and the hidden symmetry of the BBS.

  5. Fracture mechanics of cellular glass

    SciTech Connect

    Zwissler, J.G.; Adams, M.A.

    1981-02-01

    Cellular glasses are prime candidate materials for the structural substrate of mirrored glass for solar concentrator reflecting panels. These materials are brittle, however, and susceptible to mechanical failure from slow crack growth caused by a stress corrosion mechanism. The results are detailed of one part of a program established to develop improved cellular glasses and to characterize the behavior of these and commercially available materials. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials are developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region I may be slower, by orders of magnitude, than that found in dense glasses.

  6. Cellular Automata and the Humanities.

    ERIC Educational Resources Information Center

    Gallo, Ernest

    1994-01-01

    The use of cellular automata to analyze several pre-Socratic hypotheses about the evolution of the physical world is discussed. These hypotheses combine characteristics of both rigorous and metaphoric language. Since the computer demands explicit instructions for each step in the evolution of the automaton, such models can reveal conceptual…

  7. Engineering Cellular Photocomposite Materials Using Convective Assembly

    PubMed Central

    Jenkins, Jessica S.; Flickinger, Michael C.; Velev, Orlin D.

    2013-01-01

    Fabricating industrial-scale photoreactive composite materials containing living cells, requires a deposition strategy that unifies colloid science and cell biology. Convective assembly can rapidly deposit suspended particles, including whole cells and waterborne latex polymer particles into thin (<10 µm thick), organized films with engineered adhesion, composition, thickness, and particle packing. These highly ordered composites can stabilize the diverse functions of photosynthetic cells for use as biophotoabsorbers, as artificial leaves for hydrogen or oxygen evolution, carbon dioxide assimilation, and add self-cleaning capabilities for releasing or digesting surface contaminants. This paper reviews the non-biological convective assembly literature, with an emphasis on how the method can be modified to deposit living cells starting from a batch process to its current state as a continuous process capable of fabricating larger multi-layer biocomposite coatings from diverse particle suspensions. Further development of this method will help solve the challenges of engineering multi-layered cellular photocomposite materials with high reactivity, stability, and robustness by clarifying how process, substrate, and particle parameters affect coating microstructure. We also describe how these methods can be used to selectively immobilize photosynthetic cells to create biomimetic leaves and compare these biocomposite coatings to other cellular encapsulation systems. PMID:28809244

  8. Information theory based approaches to cellular signaling.

    PubMed

    Waltermann, Christian; Klipp, Edda

    2011-10-01

    Cells interact with their environment and they have to react adequately to internal and external changes such changes in nutrient composition, physical properties like temperature or osmolarity and other stresses. More specifically, they must be able to evaluate whether the external change is significant or just in the range of noise. Based on multiple external parameters they have to compute an optimal response. Cellular signaling pathways are considered as the major means of information perception and transmission in cells. Here, we review different attempts to quantify information processing on the level of individual cells. We refer to Shannon entropy, mutual information, and informal measures of signaling pathway cross-talk and specificity. Information theory in systems biology has been successfully applied to identification of optimal pathway structures, mutual information and entropy as system response in sensitivity analysis, and quantification of input and output information. While the study of information transmission within the framework of information theory in technical systems is an advanced field with high impact in engineering and telecommunication, its application to biological objects and processes is still restricted to specific fields such as neuroscience, structural and molecular biology. However, in systems biology dealing with a holistic understanding of biochemical systems and cellular signaling only recently a number of examples for the application of information theory have emerged. This article is part of a Special Issue entitled Systems Biology of Microorganisms. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Light Weight Biomorphous Cellular Ceramics from Cellulose Templates

    NASA Technical Reports Server (NTRS)

    Singh, Mrityunjay; Yee, Bo-Moon; Gray, Hugh R. (Technical Monitor)

    2003-01-01

    Bimorphous ceramics are a new class of materials that can be fabricated from the cellulose templates derived from natural biopolymers. These biopolymers are abundantly available in nature and are produced by the photosynthesis process. The wood cellulose derived carbon templates have three- dimensional interconnectivity. A wide variety of non-oxide and oxide based ceramics have been fabricated by template conversion using infiltration and reaction-based processes. The cellular anatomy of the cellulose templates plays a key role in determining the processing parameters (pyrolysis, infiltration conditions, etc.) and resulting ceramic materials. The processing approach, microstructure, and mechanical properties of the biomorphous cellular ceramics (silicon carbide and oxide based) have been discussed.

  10. Nonsynchronous updating in the multiverse of cellular automata

    NASA Astrophysics Data System (ADS)

    Reia, Sandro M.; Kinouchi, Osame

    2015-04-01

    In this paper we study updating effects on cellular automata rule space. We consider a subset of 6144 order-3 automata from the space of 262144 bidimensional outer-totalistic rules. We compare synchronous to asynchronous and sequential updatings. Focusing on two automata, we discuss how update changes destroy typical structures of these rules. Besides, we show that the first-order phase transition in the multiverse of synchronous cellular automata, revealed with the use of a recently introduced control parameter, seems to be robust not only to changes in update schema but also to different initial densities.

  11. The 3-dimensional cellular automata for HIV infection

    NASA Astrophysics Data System (ADS)

    Mo, Youbin; Ren, Bin; Yang, Wencao; Shuai, Jianwei

    2014-04-01

    The HIV infection dynamics is discussed in detail with a 3-dimensional cellular automata model in this paper. The model can reproduce the three-phase development, i.e., the acute period, the asymptotic period and the AIDS period, observed in the HIV-infected patients in a clinic. We show that the 3D HIV model performs a better robustness on the model parameters than the 2D cellular automata. Furthermore, we reveal that the occurrence of a perpetual source to successively generate infectious waves to spread to the whole system drives the model from the asymptotic state to the AIDS state.

  12. Nonsynchronous updating in the multiverse of cellular automata.

    PubMed

    Reia, Sandro M; Kinouchi, Osame

    2015-04-01

    In this paper we study updating effects on cellular automata rule space. We consider a subset of 6144 order-3 automata from the space of 262144 bidimensional outer-totalistic rules. We compare synchronous to asynchronous and sequential updatings. Focusing on two automata, we discuss how update changes destroy typical structures of these rules. Besides, we show that the first-order phase transition in the multiverse of synchronous cellular automata, revealed with the use of a recently introduced control parameter, seems to be robust not only to changes in update schema but also to different initial densities.

  13. Cellular immunity and lymphokine production during spaceflights

    NASA Technical Reports Server (NTRS)

    Konstantinova, I. V.; Sonnenfeld, G.; Lesniak, A. T.; Shaffar, L.; Mandel, A.; Rykova, M. P.; Antropova, E. N.; Ferrua, B.

    1991-01-01

    Results are presented on changes in cellular immunity and in the production of lymphokine in spacecrews during spaceflights. Measurements were carried out on blood samples collected from 50 cosmonauts before and after spaceflights of different duration, on board Salyut-6, Salyut-7, or Mir. Additional data were obtained from rats flown on board the Cosmos-1667 and Cosmos-1887 biosatellites. The parameters measured included the PHA responsiveness of T lymphocytes, the activity of T-helper cells and of nonspecific T suppressors, the activity of the so-called natural killer lymphocytes, the production of gamma-interferon, and the cell-surface markers. Results showed that the frequency and the extent of changes in the immunologic resistance of subjects depended on the duration of the flight. However, even after the most prolonged (365 days) spaceflight, the changes observed were mostly of a functional character with subsequent rapid return to normal.

  14. Cellular immunity and lymphokine production during spaceflights

    NASA Technical Reports Server (NTRS)

    Konstantinova, I. V.; Sonnenfeld, G.; Lesniak, A. T.; Shaffar, L.; Mandel, A.; Rykova, M. P.; Antropova, E. N.; Ferrua, B.

    1991-01-01

    Results are presented on changes in cellular immunity and in the production of lymphokine in spacecrews during spaceflights. Measurements were carried out on blood samples collected from 50 cosmonauts before and after spaceflights of different duration, on board Salyut-6, Salyut-7, or Mir. Additional data were obtained from rats flown on board the Cosmos-1667 and Cosmos-1887 biosatellites. The parameters measured included the PHA responsiveness of T lymphocytes, the activity of T-helper cells and of nonspecific T suppressors, the activity of the so-called natural killer lymphocytes, the production of gamma-interferon, and the cell-surface markers. Results showed that the frequency and the extent of changes in the immunologic resistance of subjects depended on the duration of the flight. However, even after the most prolonged (365 days) spaceflight, the changes observed were mostly of a functional character with subsequent rapid return to normal.

  15. Lightweight 3D cellular composites inspired by balsa.

    PubMed

    Malek, Sardar; Raney, Jordan R; Lewis, Jennifer A; Gibson, Lorna J

    2017-03-17

    Additive manufacturing technologies offer new ways to fabricate cellular materials with composite cell walls, mimicking the structure and mechanical properties of woods. However, materials limitations and a lack of design tools have confined the usefulness of 3D printed cellular materials. We develop new carbon fiber reinforced, epoxy inks for 3D printing which result in printed materials with longitudinal Young's modulus up to 57 GPa (exceeding the longitudinal modulus of wood cell wall material). To guide the design of hierarchical cellular materials, we developed a parameterized, multi-scale, finite element model. Computational homogenization based on finite element simulations at multiple length scales is employed to obtain the elastic properties of the material at multiple length scales. Parameters affecting the elastic response of cellular composites, such as the volume fraction, orientation distribution, and aspect ratio of fibers within the cell walls as well as the cell geometry and relative density are included in the model. To validate the model, experiments are conducted on both solid carbon fiber/epoxy composites and cellular structures made from them, showing excellent agreement with computational multi-scale model predictions, both at the cell-wall and at the cellular-structure levels. Using the model, cellular structures are designed and experimentally shown to achieve a specific stiffness nearly as high as that observed in balsa wood. The good agreement between the multi-scale model predictions and experimental data provides confidence in the practical utility of this model as a tool for designing novel 3D cellular composites with unprecedented specific elastic properties.

  16. Isolation and analysis of linker histones across cellular compartments

    PubMed Central

    Harshman, Sean W.; Chen, Michael M.; Branson, Owen E.; Jacob, Naduparambil K.; Johnson, Amy J.; Byrd, John C.; Freitas, Michael A.

    2013-01-01

    Analysis of histones, especially histone H1, is severely limited by immunological reagent availability. This paper describes the application of cellular fractionation with LC-MS for profiling histones in the cytosol and upon chromatin. First, we show that linker histones enriched by cellular fractionation gives less nuclear contamination and higher histone content than when prepared by nuclei isolation. Second, we profiled the soluble linker histones throughout the cell cycle revealing phosphorylation increases as cells reach mitosis. Finally, we monitored histone H1.2–H1.5 translocation to the cytosol in response to the CDK inhibitor flavopiridol in primary CLL cells treated ex vivo. Data shows all H1 variants translocate in response to drug treatment with no specific order to their cytosolic appearance. The results illustrate the utility of cellular fractionation in conjunction with LC-MS for the analysis of histone H1 throughout the cell. PMID:24013129

  17. Cellular therapy in bone-tendon interface regeneration

    PubMed Central

    Rothrauff, Benjamin B; Tuan, Rocky S

    2014-01-01

    The intrasynovial bone-tendon interface is a gradual transition from soft tissue to bone, with two intervening zones of uncalcified and calcified fibrocartilage. Following injury, the native anatomy is not restored, resulting in inferior mechanical properties and an increased risk of re-injury. Recent in vivo studies provide evidence of improved healing when surgical repair of the bone-tendon interface is augmented with cells capable of undergoing chondrogenesis. In particular, cellular therapy in bone-tendon healing can promote fibrocartilage formation and associated improvements in mechanical properties. Despite these promising results in animal models, cellular therapy in human patients remains largely unexplored. This review highlights the development and structure-function relationship of normal bone-tendon insertions. The natural healing response to injury is discussed, with subsequent review of recent research on cellular approaches for improved healing. Finally, opportunities for translating in vivo findings into clinical practice are identified. PMID:24326955

  18. Cellular phones and their hazards: the current evidence.

    PubMed

    Munshi, Anusheel; Jalali, Rakesh

    2002-01-01

    The past decade has seen an exponential increase globally in the use of cellular phones (popularly known as mobile or cell phones). These phones are convenient and trendy. Discarding the wire means that the communication is through electromagnetic waves, which could have potential hazards. Alarmist reports in the lay press and high profile lawsuits, particularly in the West, have attracted attention to the possible harmful effects of cellular phones. Adverse effects investigated by various clinical trials include the possible link to increased risk of vehicular accidents, leukaemias, sleep disturbances and the more serious brain tumours. Available level II evidence suggests that the only proven side-effect is an increased risk of vehicular accidents. So far, all studies have consistently negated any association between cellular phones and brain tumours. Yet, the final word remains to be said.

  19. Cellular electrical impedance spectroscopy: an emerging technology of microscale biosensors.

    PubMed

    Gu, Wenwen; Zhao, Yi

    2010-11-01

    Electrical impedance spectroscopy, owing to its label-free, noninvasive and easy miniaturization nature, has shown great potential in cellular biochemical sensing and cell-based diagnostics. In this article, cutting-edge technologies of electrical impedance spectroscopy are reviewed according to different sensing mechanisms, including monitoring of ion release from live cells, utilization of nonconductive cellular membranes, and detection of the spatial distribution of cells. The most successful applications where the electrical impedance sensors have been proven effective are introduced, including investigation of anticancer drug therapies, wound healing, cytotoxicity evaluation and measurement of blood rheological behavior. Furthermore, the research advances that yield enhanced sensitivities and functionalities are introduced. Finally, the commercialization challenges and the critical barriers that hinder the sustaining development of cellular electrical impedance spectroscopy are discussed.

  20. Cellular cardiomyoplasty: routes of cell delivery and retention.

    PubMed

    Al Kindi, Adil; Ge, Yin; Shum-Tim, Dominique; Chiu, Ray C-J

    2008-01-01

    Experimental and clinical studies have proven the feasibility of cellular cardiomyoplasty in treating the damaged myocardium following ischemic injury. Over the years, this field has exploded with different investigators trying different routes of cell delivery ranging from direct cell injection into the heart to peripheral intravenous delivery utilizing the various signaling mechanisms known. These different routes have resulted in a wide range of retention and engraftment of cells in the target tissues. In this review, we will explore the different modalities of cell delivery, the pros and cons of each route and the cellular retention and therapeutic efficacy of these routes. We will then look into the different theories that try to explain the observed retention and engraftment of cells in the target tissues. Finally, we will discuss various methods that can improve cellular retention and engraftment and hence better improvement in myocardial function.

  1. Comparison of the effects of metals on cellular injury and lipid peroxidation in isolated rat hepatocytes

    SciTech Connect

    Stacey, N.H.; Klaassen, C.D.

    1981-01-01

    Various mechanisms, including increases in lipid peroxidation, have been proposed to account for metal-induced cellular injury. By comparing several metals in the same cell population, it is possible to determine whether a correlation exists between ability to produce cell injury and ability to alter parameters pertaining to a particular mechanism. Of particular interest in this study was the relation between metal-induced cytotoxicity and increases in lipid peroxidation. The effects of Cr, Mn, Zn, Ni, Pb, Se, V, Fe, Cd, Hg, and Cu, at final concentrations of 1 to 1000 ..mu..M, on the viability of isolated hepatocytes were therefore examined by assessing the loss of intracellular K/sup +/ and aspartate aminotransferase (AST). Simultaneously, the ability of the metals to induce lipid peroxidation, as measured by an increase in thiobarbituric acid (TBA) reactants, was assessed. Hg and Cu required the lowest concentration to produce cellular injury, while Cd produced less dramatic changes in cell viability and Fe at 1000 ..mu..M produced only a small decrease in intracellular K/sup +/. The largest absolute increases in lipid peroxidation were found in the presence of V, followed by Fe and Hg, with Cd and Se causing the smallest increase in TBA reactants. These observations suggest that the lipid peroxidation associated with Cd and Hg is not necessarily responsible for the loss of cell viability induced by these two metals.

  2. EBNA1 regulates cellular gene expression by binding cellular promoters.

    PubMed

    Canaan, Allon; Haviv, Izhak; Urban, Alexander E; Schulz, Vincent P; Hartman, Steve; Zhang, Zhengdong; Palejev, Dean; Deisseroth, Albert B; Lacy, Jill; Snyder, Michael; Gerstein, Mark; Weissman, Sherman M

    2009-12-29

    Epstein-Barr virus (EBV) is associated with several types of lymphomas and epithelial tumors including Burkitt's lymphoma (BL), HIV-associated lymphoma, posttransplant lymphoproliferative disorder, and nasopharyngeal carcinoma. EBV nuclear antigen 1 (EBNA1) is expressed in all EBV associated tumors and is required for latency and transformation. EBNA1 initiates latent viral replication in B cells, maintains the viral genome copy number, and regulates transcription of other EBV-encoded latent genes. These activities are mediated through the ability of EBNA1 to bind viral-DNA. To further elucidate the role of EBNA1 in the host cell, we have examined the effect of EBNA1 on cellular gene expression by microarray analysis using the B cell BJAB and the epithelial 293 cell lines transfected with EBNA1. Analysis of the data revealed distinct profiles of cellular gene changes in BJAB and 293 cell lines. Subsequently, chromatin immune-precipitation revealed a direct binding of EBNA1 to cellular promoters. We have correlated EBNA1 bound promoters with changes in gene expression. Sequence analysis of the 100 promoters most enriched revealed a DNA motif that differs from the EBNA1 binding site in the EBV genome.

  3. Peroxisome Metabolism and Cellular Aging

    PubMed Central

    Titorenko, Vladimir I.; Terlecky, Stanley R.

    2010-01-01

    The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest these and other related biochemical processes governed by the organelle may also play a critical role in regulating cellular aging. The goal of this review is to summarize and integrate into a model, the evidence that peroxisome metabolism actually helps define the replicative and chronological age of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS) are seen as altering organelle biogenesis and function, and eliciting changes in the dynamic communication networks that exist between peroxisomes and other cellular compartments. At low levels, peroxisomal ROS activate an anti-aging program in the cell; at concentrations beyond a specific threshold, a pro-aging course is triggered. PMID:21083858

  4. Cellular solidification of transparent monotectics

    NASA Technical Reports Server (NTRS)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  5. Energetic costs of cellular computation.

    PubMed

    Mehta, Pankaj; Schwab, David J

    2012-10-30

    Cells often perform computations in order to respond to environmental cues. A simple example is the classic problem, first considered by Berg and Purcell, of determining the concentration of a chemical ligand in the surrounding media. On general theoretical grounds, it is expected that such computations require cells to consume energy. In particular, Landauer's principle states that energy must be consumed in order to erase the memory of past observations. Here, we explicitly calculate the energetic cost of steady-state computation of ligand concentration for a simple two-component cellular network that implements a noisy version of the Berg-Purcell strategy. We show that learning about external concentrations necessitates the breaking of detailed balance and consumption of energy, with greater learning requiring more energy. Our calculations suggest that the energetic costs of cellular computation may be an important constraint on networks designed to function in resource poor environments, such as the spore germination networks of bacteria.

  6. Energetic costs of cellular computation

    PubMed Central

    Mehta, Pankaj; Schwab, David J.

    2012-01-01

    Cells often perform computations in order to respond to environmental cues. A simple example is the classic problem, first considered by Berg and Purcell, of determining the concentration of a chemical ligand in the surrounding media. On general theoretical grounds, it is expected that such computations require cells to consume energy. In particular, Landauer’s principle states that energy must be consumed in order to erase the memory of past observations. Here, we explicitly calculate the energetic cost of steady-state computation of ligand concentration for a simple two-component cellular network that implements a noisy version of the Berg–Purcell strategy. We show that learning about external concentrations necessitates the breaking of detailed balance and consumption of energy, with greater learning requiring more energy. Our calculations suggest that the energetic costs of cellular computation may be an important constraint on networks designed to function in resource poor environments, such as the spore germination networks of bacteria. PMID:23045633

  7. Optofluidic Detection for Cellular Phenotyping

    PubMed Central

    Tung, Yi-Chung; Huang, Nien-Tsu; Oh, Bo-Ram; Patra, Bishnubrata; Pan, Chi-Chun; Qiu, Teng; Paul, K. Chu; Zhang, Wenjun; Kurabayashi, Katsuo

    2012-01-01

    Quantitative analysis of the output of processes and molecular interactions within a single cell is highly critical to the advancement of accurate disease screening and personalized medicine. Optical detection is one of the most broadly adapted measurement methods in biological and clinical assays and serves cellular phenotyping. Recently, microfluidics has obtained increasing attention due to several advantages, such as small sample and reagent volumes, very high throughput, and accurate flow control in the spatial and temporal domains. Optofluidics, which is the attempt to integrate optics with microfluidic, shows great promise to enable on-chip phenotypic measurements with high precision, sensitivity, specificity, and simplicity. This paper reviews the most recent developments of optofluidic technologies for cellular phenotyping optical detection. PMID:22854915

  8. Hox Targets and Cellular Functions

    PubMed Central

    Sánchez-Herrero, Ernesto

    2013-01-01

    Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function. PMID:24490109

  9. Modal equations for cellular convection

    NASA Technical Reports Server (NTRS)

    Gough, D. O.; Spiegel, E. A.; Toomre, J.

    1975-01-01

    We expand the fluctuating flow variables of Boussinesq convection in the planform functions of linear theory. Our proposal is to consider a drastic truncation of this expansion as a possible useful approximation scheme for studying cellular convection. With just one term included, we obtain a fairly simple set of equations which reproduces some of the qualitative properties of cellular convection and whose steady-state form has already been derived by Roberts (1966). This set of 'modal equations' is analyzed at slightly supercritical and at very high Rayleigh numbers. In the latter regime the Nusselt number varies with Rayleigh number just as in the mean-field approximation with one horizontal scale when the boundaries are rigid. However, the Nusselt number now depends also on the Prandtl number in a way that seems compatible with experiment. The chief difficulty with the approach is the absence of a deductive scheme for deciding which planforms should be retained in the truncated expansion.

  10. Glycosylation regulates prestin cellular activity.

    PubMed

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  11. Cellular Analogs of Operant Behavior.

    DTIC Science & Technology

    1992-07-31

    selective PI antagonist SCH23390, blocks CAI cellular operant FIG. 4. Chlorpromazine blocks dopamine-reintorced operant conditioning conditioning in...hand. when I mM REINF). When I rn’M chlorpromazine was added to the dopamine solution SCH23390 i I mM) was added to the dopamine solution (DA + SCH...rate was suppressed below the saline control. Neurons that had treatment gro’- !icated in parentheses. *Differs from SALINE, received chlorpromazine

  12. Cellular Detection of Infrared Sources

    DTIC Science & Technology

    1990-02-27

    depending on wavelength) is 2 to 10 Urn. Phototaxis is measured by the quantitation of the locomotion of the cells in tlic vicinity of the beam. PROGRESS...Northwestern University Medical School, Chicago CONTRACT TITLE: Cellular Detection of Infrared Sources RESEARCH OBJECTIVE: a. Test for phototaxis of...passes. The wavelength of the beam is variable and its diameter (depending on wavelength) is 2 to 10 am. Phototaxis is measured by the quantitation of the

  13. Xtoys: Cellular automata on xwindows

    SciTech Connect

    Creutz, M.

    1995-08-15

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  14. Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant.

    PubMed

    Ivey, Jill W; Latouche, Eduardo L; Richards, Megan L; Lesser, Glenn J; Debinski, Waldemar; Davalos, Rafael V; Verbridge, Scott S

    2017-07-25

    Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  15. Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms

    PubMed Central

    Subramanya, Sandeep B.; Subramanian, Veedamali S.; Kumar, Jeyan S.; Hoiness, Robert

    2011-01-01

    The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5′-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5′-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding. PMID:21148397

  16. Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms.

    PubMed

    Subramanya, Sandeep B; Subramanian, Veedamali S; Kumar, Jeyan S; Hoiness, Robert; Said, Hamid M

    2011-03-01

    The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5'-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5'-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding.

  17. Innate cellular immunity and xenotransplantation

    PubMed Central

    Wang, Hui; Yang, Yong-Guang

    2012-01-01

    Purpose of review This review assesses the recent progress in xenograft rejection by innate immune responses, with a focus on innate cellular xenoreactivity. Recent findings Current literature was reviewed for new insights into the role of innate cellular immunity in xenograft rejection. Increasing evidence confirms that vigorous innate immune cell activation is accounted for by a combination of xenoantigen recognition by activating receptors, and incompatibility in inhibitory receptor-ligand interactions. Although both innate humoral and cellular xenoimmune responses are predominantly elicited by preformed and induced xenoreactive antibodies in nonhuman primates following porcine xenotransplantation, innate immune cells can also be activated by xenografts in the absence of antibodies. The latter antibody-independent response will likely persist in recipients even when adaptive xenoimmune responses are suppressed. In addition to xenograft rejection by recipient innate immune cells, phagocytic cells within liver xenografts are also deleterious to recipients by causing thrombocytopenia. Summary Strategies of overcoming innate immune responses are required for successful clinical xenotransplantation. In addition to developing better immunosuppressive and tolerance induction protocols, endeavors towards further genetic modifications of porcine source animals are ultimately important for successful clinical xenotransplantation. PMID:22262106

  18. Cellular Functions of Tissue Transglutaminase

    PubMed Central

    Nurminskaya, Maria V.; Belkin, Alexey M.

    2013-01-01

    Transglutaminase 2 (TG2 or tissue transglutaminase) is a highly complex multifunctional protein that acts as transglutaminase, GTPase/ATPase, protein disulfide isomerase, and protein kinase. Moreover, TG2 has many well-documented nonenzymatic functions that are based on its noncovalent interactions with multiple cellular proteins. A vast array of biochemical activities of TG2 accounts for its involvement in a variety of cellular processes, including adhesion, migration, growth, survival, apoptosis, differentiation, and extracellular matrix organization. In turn, the impact of TG2 on these processes implicates this protein in various physiological responses and pathological states, contributing to wound healing, inflammation, autoimmunity, neurodegeneration, vascular remodeling, tumor growth and metastasis, and tissue fibrosis. TG2 is ubiquitously expressed and is particularly abundant in endothelial cells, fibroblasts, osteoblasts, monocytes/macrophages, and smooth muscle cells. The protein is localized in multiple cellular compartments, including the nucleus, cytosol, mitochondria, endolysosomes, plasma membrane, and cell surface and extracellular matrix, where Ca2+, nucleotides, nitric oxide, reactive oxygen species, membrane lipids, and distinct protein–protein interactions in the local microenvironment jointly regulate its activities. In this review, we discuss the complex biochemical activities and molecular interactions of TG2 in the context of diverse subcellular compartments and evaluate its wide ranging and cell type-specific biological functions and their regulation. PMID:22364871

  19. [Cellular phones and public health].

    PubMed

    Leventhal, Alex; Karsenty, Eric; Sadetzki, Siegal

    2004-08-01

    The increased use of mobile cellular phone by the public is associated with a wave of contradictory reports about the possible health effects, due to the exposure of the users to electromagnetic non-ionizing radiation. This article reviews the state of the art of the present knowledge concerning the biological and medical effects of exposure to cellular phones, with an emphasis on its possible carcinogenic effect. Health conditions, which have been ascribed to the use of mobile phones mainly include some types of cancer and changes of brain activity. However, the balance of evidence from available studies has not yet supported these claims. Following the recommendation of special international expert committees, the IARC (International Association for Research on Cancer) is conducting a multi-center study to determine the possible effect of cellular phone use on brain and salivary gland tumors. Israel is one of the participants of this study. The only established health effect associated with the use of such technology is an increased risk for road accidents, unrelated to the amount of radiation emitted by phone. The challenge posed by this new technology to health authorities all over the world has lead to the definition of a new principle, the so-called "prudent avoidance", used as guidelines for the definition of an adequate public health policy. The public policy in Israel has used the prudent avoidance principles, while awaiting the results of the multi-national epidemiological studies.

  20. Viral activation of cellular metabolism.

    PubMed

    Sanchez, Erica L; Lagunoff, Michael

    2015-05-01

    To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for the replication of each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Passive cellular microrheology in developing fruit fly embryos

    NASA Astrophysics Data System (ADS)

    Crews, Sarah; Ma, Xiaoyan; Lawrence, Stacey; Hutson, M. Shane

    2012-02-01

    The development of fruit fly (Drosophila) embryos involves spatial and temporal regulation of cellular mechanical properties. These properties can be probed in vivo using laser hole drilling experiments; however, this technique only infers relative forces. Conversion to absolute forces requires measurement of cellular viscoelastic properties. Here, we use passive microrheology of fluorescently labeled cell membranes to measure the viscoelastic properties of amnioserosa cells. These dynamic epithelial cells play an important mechanical role during two developmental stages: germ band retraction and dorsal closure. Passive microrheology in this system is confounded by active contractions in the cytoskeleton. Thus, the fruit fly embryos are transiently anesthetized with CO2, halting active cellular movements, leaving only passive Brownian motion. The power spectra of these fluctuations are well fit by a Lorentzian -- as expected for Brownian motion -- and allow us to extract cellular viscoelastic parameters at different developmental stages. These measured parameters inform previous hole-drilling experiments and provide inputs for quantitative computational models of fruit fly embryonic development.

  2. Verb-Final Typology

    ERIC Educational Resources Information Center

    Ogihara, Saeko

    2010-01-01

    This dissertation is a typological study of verb-final languages, the purpose of which is to examine various grammatical phenomena in verb-final languages to discover whether there are correlations between the final position of the verb and other aspects of grammar. It examines how finality of the verb interacts with argument coding in simple…

  3. Arrayed cellular environments for stem cells and regenerative medicine.

    PubMed

    Titmarsh, Drew M; Chen, Huaying; Wolvetang, Ernst J; Cooper-White, Justin J

    2013-02-01

    The behavior and composition of both multipotent and pluripotent stem cell populations are exquisitely controlled by a complex, spatiotemporally variable interplay of physico-chemical, extracellular matrix, cell-cell interaction, and soluble factor cues that collectively define the stem cell niche. The push for stem cell-based regenerative medicine models and therapies has fuelled demands for increasingly accurate cellular environmental control and enhanced experimental throughput, driving an evolution of cell culture platforms away from conventional culture formats toward integrated systems. Arrayed cellular environments typically provide a set of discrete experimental elements with variation of one or several classes of stimuli across elements of the array. These are based on high-content/high-throughput detection, small sample volumes, and multiplexing of environments to increase experimental parameter space, and can be used to address a range of biological processes at the cell population, single-cell, or subcellular level. Arrayed cellular environments have the capability to provide an unprecedented understanding of the molecular and cellular events that underlie expansion and specification of stem cell and therapeutic cell populations, and thus generate successful regenerative medicine outcomes. This review focuses on recent key developments of arrayed cellular environments and their contribution and potential in stem cells and regenerative medicine.

  4. Statistical physical models of cellular motility

    NASA Astrophysics Data System (ADS)

    Banigan, Edward J.

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

  5. Fluorescent Sensing of Fluoride in Cellular System

    PubMed Central

    Jiao, Yang; Zhu, Baocun; Chen, Jihua; Duan, Xiaohong

    2015-01-01

    Fluoride ions have the important roles in a lot of physiological activities related with biological and medical system, such as water fluoridation, caries treatment, and bone disease treatment. Great efforts have been made to develop new methods and strategies for F- detection in the past decades. Traditional methods for the detection of F- including ion chromatography, ion-selective electrodes, and spectroscopic techniques have the limitations in the biomedicine research. The fluorescent probes for F- are very promising that overcome some drawbacks of traditional fluoride detection methods. These probes exhibit high selectivity, high sensitivity as well as quick response to the detection of fluoride anions. The review commences with a brief description of photophysical mechanisms for fluorescent probes for fluoride, including photo induced electron transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), and excited-state intramolecular proton transfer (ESIPT). Followed by a discussion about common dyes for fluorescent fluoride probes, such as anthracene, naphalimide, pyrene, BODIPY, fluorescein, rhodamine, resorufin, coumarin, cyanine, and near-infrared (NIR) dyes. We divide the fluorescent probes for fluoride in cellular application systems into nine groups, for example, type of hydrogen bonds, type of cleavage of Si-O bonds, type of Si-O bond cleavage and cylization reactions, etc. We also review the recent reported carriers in the delivery of fluorescent fluoride probes. Seventy-four typical fluorescent fluoride probes are listed and compared in detail, including quantum yield, reaction medium, excitation and emission wavelengths, linear detection range, selectivity for F-, mechanism, and analytical applications. Finally, we discuss the future challenges of the application of fluorescent fluoride probes in cellular system and in vivo. We wish that more and more excellent fluorescent fluoride probes will be developed

  6. Fluorescent sensing of fluoride in cellular system.

    PubMed

    Jiao, Yang; Zhu, Baocun; Chen, Jihua; Duan, Xiaohong

    2015-01-01

    Fluoride ions have the important roles in a lot of physiological activities related with biological and medical system, such as water fluoridation, caries treatment, and bone disease treatment. Great efforts have been made to develop new methods and strategies for F(-) detection in the past decades. Traditional methods for the detection of F(-) including ion chromatography, ion-selective electrodes, and spectroscopic techniques have the limitations in the biomedicine research. The fluorescent probes for F(-) are very promising that overcome some drawbacks of traditional fluoride detection methods. These probes exhibit high selectivity, high sensitivity as well as quick response to the detection of fluoride anions. The review commences with a brief description of photophysical mechanisms for fluorescent probes for fluoride, including photo induced electron transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), and excited-state intramolecular proton transfer (ESIPT). Followed by a discussion about common dyes for fluorescent fluoride probes, such as anthracene, naphalimide, pyrene, BODIPY, fluorescein, rhodamine, resorufin, coumarin, cyanine, and near-infrared (NIR) dyes. We divide the fluorescent probes for fluoride in cellular application systems into nine groups, for example, type of hydrogen bonds, type of cleavage of Si-O bonds, type of Si-O bond cleavage and cylization reactions, etc. We also review the recent reported carriers in the delivery of fluorescent fluoride probes. Seventy-four typical fluorescent fluoride probes are listed and compared in detail, including quantum yield, reaction medium, excitation and emission wavelengths, linear detection range, selectivity for F(-), mechanism, and analytical applications. Finally, we discuss the future challenges of the application of fluorescent fluoride probes in cellular system and in vivo. We wish that more and more excellent fluorescent fluoride probes will be

  7. 47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition... the 800 MHz band from cellular radiotelephone or part 90-800 MHz cellular systems will be deemed to...

  8. A quantum relativistic battle of the sexes cellular automaton

    NASA Astrophysics Data System (ADS)

    Alonso-Sanz, Ramón; Situ, Haozhen

    2017-02-01

    The effect of variable entangling on the dynamics of a spatial quantum relativistic formulation of the iterated battle of the sexes game is studied in this work. The game is played in the cellular automata manner, i.e., with local and synchronous interaction. The game is assessed in fair and unfair contests. Despite the full range of quantum parameters initially accessible, they promptly converge into fairly stable configurations, that often show rich spatial structures in simulations with no negligible entanglement.

  9. Variable entangling in a quantum prisoner's dilemma cellular automaton

    NASA Astrophysics Data System (ADS)

    Alonso-Sanz, Ramón

    2015-01-01

    The effect of variable entangling on the dynamics of a spatial quantum formulation of the iterated prisoner's dilemma game is studied in this work. The game is played in the cellular automata manner, i.e., with local and synchronous interaction. The effect of spatial structure is assessed when allowing the players to adopt quantum and classical strategies, both in the two- and three-parameter strategy spaces.

  10. Primitive control of cellular metabolism

    NASA Technical Reports Server (NTRS)

    Mitz, M. A.

    1974-01-01

    It is pointed out that control substances must have existed from the earliest times in the evolution of life and that the same control mechanisms must exist today. The investigation reported is concerned with the concept that carbon dioxide is a primitive regulator of cell function. The effects of carbon dioxide on cellular materials are examined, taking into account questions of solubilization, dissociation, changes of charge, stabilization, structural changes, wettability, the exclusion of other gases, the activation of compounds, changes in plasticity, and changes in membrane permeability.

  11. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  12. Primitive control of cellular metabolism

    NASA Technical Reports Server (NTRS)

    Mitz, M. A.

    1974-01-01

    It is pointed out that control substances must have existed from the earliest times in the evolution of life and that the same control mechanisms must exist today. The investigation reported is concerned with the concept that carbon dioxide is a primitive regulator of cell function. The effects of carbon dioxide on cellular materials are examined, taking into account questions of solubilization, dissociation, changes of charge, stabilization, structural changes, wettability, the exclusion of other gases, the activation of compounds, changes in plasticity, and changes in membrane permeability.

  13. Symmetry analysis of cellular automata

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2013-01-01

    By means of B-calculus [V. García-Morales, Phys. Lett. A 376 (2012) 2645] a universal map for deterministic cellular automata (CAs) has been derived. The latter is shown here to be invariant upon certain transformations (global complementation, reflection and shift). When constructing CA rules in terms of rules of lower range a new symmetry, “invariance under construction” is uncovered. Modular arithmetic is also reformulated within B-calculus and a new symmetry of certain totalistic CA rules, which calculate the Pascal simplices modulo an integer number p, is then also uncovered.

  14. Therapeutic cloning and cellular reprogramming.

    PubMed

    Rodriguez, Ramon M; Ross, Pablo J; Cibelli, Jose B

    2012-01-01

    Embryonic stem cells are capable of differentiating into any cell-type present in an adult organism, and constitute a renewable source of tissue for regenerative therapies. The transplant of allogenic stem cells is challenging due to the risk of immune rejection. Nevertheless, somatic cell reprogramming techniques allow the generation of isogenic embryonic stem cells, genetically identical to the patient. In this chapter we will discuss the cellular reprogramming techniques in the context of regenerative therapy and the biological and technical barriers that they will need to overcome before clinical use.

  15. Reversibility of a Symmetric Linear Cellular Automata

    NASA Astrophysics Data System (ADS)

    Del Rey, A. Martín; Sánchez, G. Rodríguez

    The characterization of the size of the cellular space of a particular type of reversible symmetric linear cellular automata is introduced in this paper. Specifically, it is shown that those symmetric linear cellular with 2k + 1 cells, and whose transition matrix is a k-diagonal square band matrix with nonzero entries equal to 1 are reversible. Furthermore, in this case the inverse cellular automata are explicitly computed. Moreover, the reversibility condition is also studied for a general number of cells.

  16. Final Technical Report

    SciTech Connect

    Alexander Pigarov

    2012-06-05

    This is the final report for the Research Grant DE-FG02-08ER54989 'Edge Plasma Simulations in NSTX and CTF: Synergy of Lithium Coating, Non-Diffusive Anomalous Transport and Drifts'. The UCSD group including: A.Yu. Pigarov (PI), S.I. Krasheninnikov and R.D. Smirnov, was working on modeling of the impact of lithium coatings on edge plasma parameters in NSTX with the multi-species multi-fluid code UEDGE. The work was conducted in the following main areas: (i) improvements of UEDGE model for plasma-lithium interactions, (ii) understanding the physics of low-recycling divertor regime in NSTX caused by lithium pumping, (iii) study of synergistic effects with lithium coatings and non-diffusive ballooning-like cross-field transport, (iv) simulation of experimental multi-diagnostic data on edge plasma with lithium pumping in NSTX via self-consistent modeling of D-Li-C plasma with UEDGE, and (v) working-gas balance analysis. The accomplishments in these areas are given in the corresponding subsections in Section 2. Publications and presentations made under the Grant are listed in Section 3.

  17. Final Report to DOE

    SciTech Connect

    Ismail Gultepe

    2012-05-15

    This final report summarizes the accomplished goals and provide a list of the publications and presentations made during the project. The goals of the project were accomplished through the various publications submitted to Journals and presentations done at the DOE and international meetings and conferences. The 8 journal articles related to the goals of this project were accepted or submitted. The 23 presentations related to goals of the project were presented at the meetings. There were some minor changes regarding to project goals because of issues encountered during the analysis of the data. For example, a total water probe sensor mounted on the Convair-580 that can be used for defining mixed phase conditions and parameterization, had some problems to estimate magnitude of total water mass, and this resulted in issues providing an accurate parameterization for cloud fraction. Variability related aerosol number concentrations and their composition for direct and indirect effects were studied and published. Results were given to explain aerosol and ice microphysical effects on climate change studies. It is suggested that developed parameterizations should consider the variability in aerosol and ice parameters over the Arctic regions.

  18. Protein accounting in the cellular economy.

    PubMed

    Vázquez-Laslop, Nora; Mankin, Alexander S

    2014-04-24

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the functional needs.

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

    PubMed

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

    2007-11-01

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

  20. Micromechanics of cellularized biopolymer networks

    PubMed Central

    Jones, Christopher A. R.; Cibula, Matthew; Feng, Jingchen; Krnacik, Emma A.; McIntyre, David H.; Levine, Herbert; Sun, Bo

    2015-01-01

    Collagen gels are widely used in experiments on cell mechanics because they mimic the extracellular matrix in physiological conditions. Collagen gels are often characterized by their bulk rheology; however, variations in the collagen fiber microstructure and cell adhesion forces cause the mechanical properties to be inhomogeneous at the cellular scale. We study the mechanics of type I collagen on the scale of tens to hundreds of microns by using holographic optical tweezers to apply pN forces to microparticles embedded in the collagen fiber network. We find that in response to optical forces, particle displacements are inhomogeneous, anisotropic, and asymmetric. Gels prepared at 21 °C and 37 °C show qualitative difference in their micromechanical characteristics. We also demonstrate that contracting cells remodel the micromechanics of their surrounding extracellular matrix in a strain- and distance-dependent manner. To further understand the micromechanics of cellularized extracellular matrix, we have constructed a computational model which reproduces the main experiment findings. PMID:26324923

  1. Cellular dynamics and embryonic morphogenesis

    NASA Astrophysics Data System (ADS)

    Zallen, Jennifer

    2007-11-01

    The elongated body axis is a characteristic feature of many multicellular animals. Axis elongation occurs largely through cell rearrangements that are coordinated across a large cell population and driven by an asymmetric distribution of cytoskeletal and junctional proteins [1]. To visualize cellular dynamics during this process, we performed time-lapse confocal imaging of cell behavior in the Drosophila embryo. These studies revealed that rearranging cells display a steady increase in topological disorder that is accompanied by the formation of transient structures where 5-11 cells meet [2,3]. These multicellular rosettes form and resolve in a directional fashion to produce a local change in the aspect ratio of the cellular assembly, contributing to an overall change in tissue structure. We propose that higher-order rosette structures link local cell interactions to global tissue reorganization during morphogenesis. [1] J. Zallen and E. Wieschaus, Developmental Cell 6, 343 (2004). [2] J. Zallen and R. Zallen, J. Phys.: Condens. Matter 16, S5073 (2004). [3] J. Blankenship et al., Developmental Cell 11, 459 (2006).

  2. Cellular uptake of metallated cobalamins.

    PubMed

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry; Gammelgaard, Bente; Furger, Evelyne; Alberto, Roger

    2016-03-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities of the charged B12 derivatives to the B12 transporters HC, IF and TC were similar to that of native vitamin B12.

  3. Cellular Biology of Prion Diseases

    PubMed Central

    Harris, David A.

    1999-01-01

    Prion diseases are fatal neurodegenerative disorders of humans and animals that are important because of their impact on public health and because they exemplify a novel mechanism of infectivity and biological information transfer. These diseases are caused by conformational conversion of a normal host glycoprotein (PrPC) into an infectious isoform (PrPSc) that is devoid of nucleic acid. This review focuses on the current understanding of prion diseases at the cell biological level. The characteristics of the diseases are introduced, and a brief history and description of the prion hypothesis are given. Information is then presented about the structure, expression, biosynthesis, and possible function of PrPC, as well as its posttranslational processing, cellular localization, and trafficking. The latest findings concerning PrPSc are then discussed, including cell culture systems used to generate this pathogenic isoform, the subcellular distribution of the protein, its membrane attachment, proteolytic processing, and its kinetics and sites of synthesis. Information is also provided on molecular models of the PrPC→PrPSc conversion reaction and the possible role of cellular chaperones. The review concludes with suggestions of several important avenues for future investigation. PMID:10398674

  4. Cellular senescence and protein degradation

    PubMed Central

    Deschênes-Simard, Xavier; Lessard, Frédéric; Gaumont-Leclerc, Marie-France; Bardeesy, Nabeel; Ferbeyre, Gerardo

    2014-01-01

    Autophagy and the ubiquitin–proteasome pathway (UPP) are the major protein degradation systems in eukaryotic cells. Whereas the former mediate a bulk nonspecific degradation, the UPP allows a rapid degradation of specific proteins. Both systems have been shown to play a role in tumorigenesis, and the interest in developing therapeutic agents inhibiting protein degradation is steadily growing. However, emerging data point to a critical role for autophagy in cellular senescence, an established tumor suppressor mechanism. Recently, a selective protein degradation process mediated by the UPP was also shown to contribute to the senescence phenotype. This process is tightly regulated by E3 ubiquitin ligases, deubiquitinases, and several post-translational modifications of target proteins. Illustrating the complexity of UPP, more than 600 human genes have been shown to encode E3 ubiquitin ligases, a number which exceeds that of the protein kinases. Nevertheless, our knowledge of proteasome-dependent protein degradation as a regulated process in cellular contexts such as cancer and senescence remains very limited. Here we discuss the implications of protein degradation in senescence and attempt to relate this function to the protein degradation pattern observed in cancer cells. PMID:24866342

  5. Cellular functions of the microprocessor.

    PubMed

    Macias, Sara; Cordiner, Ross A; Cáceres, Javier F

    2013-08-01

    The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.

  6. Cellular monosaccharide patterns of Neisseriaceae.

    PubMed

    Jantzen, E; Bryn, K; Bovre, K

    1976-08-01

    Sixty-four strains of Neisseria, Moraxella, and Acinetobacter were screened for cellular monosaccharides by gas-liquid chromatography and other chromatographic techniques. The four sugars ribose, glucose, glucosamine, and 2-keto-3-deoxyoctonate (KDO) were detected in all strains. Heptose was detected only in "true neisseriae" (Neisseria gonorrhoeae, N. meningitidis, N. sicca, N. cinerea, N. flavescens, and N. elongata) and in the tentaively named species Moraxella urethralis. Some marked interspecies dissimilarities within groups were revealed. Thus, N. ovis and M. atlantae were characterized by the presence of mannose. Intraspecies differences were also encountered. N. meningitidis strains of serogroups B and C were distinguished from strains of serogroup A by their sialic acid content. This sugar was also detected in two out of three examined strains of M. nonliquefaciens. In Acinetobacter, heterogeneity of monosaccharide patterns was rather pronounced. The results show the applicability of gas chromatographic "monosaccharide" profiles fo whole cells or extracted carbohydrate in bacterial classification and identification, including differentiation at the subspecies level. In addition, such profiles may be useful for monitoring during purification of cellular polysaccharides.

  7. Melanoma screening with cellular phones.

    PubMed

    Massone, Cesare; Hofmann-Wellenhof, Rainer; Ahlgrimm-Siess, Verena; Gabler, Gerald; Ebner, Christoph; Soyer, H Peter

    2007-05-30

    Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria). Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp) where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  8. Melanoma Screening with Cellular Phones

    PubMed Central

    Massone, Cesare; Hofmann-Wellenhof, Rainer; Ahlgrimm-Siess, Verena; Gabler, Gerald; Ebner, Christoph; Peter Soyer, H.

    2007-01-01

    Background Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. Methodology/Principal Findings In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria). Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp) where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. Conclusions/Significance The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media. PMID:17534433

  9. CELLULAR PATHOGENESIS OF DIABETIC GASTROENTEROPATHY

    PubMed Central

    Ördög, Tamás; Hayashi, Yujiro; Gibbons, Simon J.

    2010-01-01

    SUMMARY Gastroenteropathy manifesting in upper gastrointestinal symptoms, delayed gastric emptying, constipation, diarrhea and fecal incontinence occurs frequently in patients with diabetes mellitus and represents a significant health care burden. Current treatments are largely symptomatic and ineffective. Better understanding of the cellular and molecular pathogenesis of these disorders is required for the development of more effective therapies. Recent advances in our understanding of the inherent, high-level complexities of the control systems that execute and regulate gastrointestinal motility, together with the utilization of new experimental models and sophisticated physiological, morphological and molecular techniques have lead to the realization that diabetic gastroenteropathies cannot be ascribed to any singular defect or dysfunction. In fact, these disorders are multifactorial and involve a spectrum of metabolic and dystrophic changes that can potentially affect all key components of motor control including the systemic autonomic and enteric nervous systems, interstitial cells of Cajal and smooth muscle cells. Candidate pathomechanisms are also varied and include imbalance between pro- and anti-oxidative factors, altered trophic stimuli to mature cells and their progenitors, and, possibly, autoimmune factors. The goal of this paper is to review the cellular changes underlying diabetic gastroenteropathies and their potential causes, with particular focus on functional interactions between various cell types. It is proposed that diabetic gastroenteropathies should be considered a form of gastrointestinal neuromuscular dystrophy rather than a “functional” disorder. Future research should identify ways to block cytotoxic factors, support the regeneration of damaged cells and translate the experimental findings into new treatment modalities. PMID:19829287

  10. Influence parameters of impact grinding mills

    NASA Technical Reports Server (NTRS)

    Hoeffl, K.; Husemann, K.; Goldacker, H.

    1984-01-01

    Significant parameters for impact grinding mills were investigated. Final particle size was used to evaluate grinding results. Adjustment of the parameters toward increased charge load results in improved efficiency; however, it was not possible to define a single, unified set to optimum grinding conditions.

  11. Cellular Therapies Clinical Research Roadmap: lessons learned on how to move a cellular therapy into a clinical trial.

    PubMed

    Ouseph, Stacy; Tappitake, Darah; Armant, Myriam; Wesselschmidt, Robin; Derecho, Ivy; Draxler, Rebecca; Wood, Deborah; Centanni, John M

    2015-04-01

    A clinical research roadmap has been developed as a resource for researchers to identify critical areas and potential pitfalls when transitioning a cellular therapy product from the research laboratory, by means of an Investigational New Drug (IND) application, into early-phase clinical trials. The roadmap describes four key areas: basic and preclinical research, resource development, translational research and Good Manufacturing Practice (GMP) and IND assembly and submission. Basic and preclinical research identifies a new therapeutic concept and demonstrates its potential value with the use of a model of the relevant disease. During resource development, the appropriate specialists and the required expertise to bring this product into the clinic are identified (eg, researchers, regulatory specialists, GMP manufacturing staff, clinicians and clinical trials staff, etc). Additionally, the funds required to achieve this goal (or a plan to procure them) are identified. In the next phase, the plan to translate the research product into a clinical-grade therapeutic is developed. Finally regulatory approval to start the trial must be obtained. In the United States, this is done by filing an IND application with the Food and Drug Administration. The National Heart, Lung and Blood Institute-funded Production Assistance for Cellular Therapies program has facilitated the transition of a variety of cellular therapy products from the laboratory into Phase1/2 trials. The five Production Assistance for Cellular Therapies facilities have assisted investigators by performing translational studies and GMP manufacturing to ensure that cellular products met release specifications and were manufactured safely, reproducibly and at the appropriate scale. The roadmap resulting from this experience is the focus of this article. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. A Cellular GWAS Approach to Define Human Variation in Cellular Pathways Important to Inflammation.

    PubMed

    Miller, Samuel I; Chaudhary, Anu

    2016-04-26

    An understanding of common human diversity in innate immune pathways should be beneficial in understanding autoimmune diseases, susceptibility to infection, and choices of anti-inflammatory treatment. Such understanding could also result in definition of currently unknown components of human inflammation pathways. A cellular genome-wide association studies (GWAS) platform, termed Hi-HOST (High-throughput human in vitro susceptibility testing), was developed to assay in vitro cellular phenotypes of infection in genotyped lymphoblastoid cells from genetically diverse human populations. Hi-HOST allows for measurement of multiple host and pathogen parameters of infection/inflammation including: bacterial invasion and intracellular replication, host cell death, and cytokine production. Hi-HOST has been used to successfully define a significant portion of the heritable human diversity in inflammatory cell death in response to Salmonella typhimurium. It also led to the discovery of genetic variants important to protection against systemic inflammatory response syndrome (SIRS) and protection against death and bacteremia in individuals with SIRS. Our laboratory is currently using this platform to define human diversity in autophagy and the NLPR3 inflammasome pathways, and to define new components that can impact the expression of phenotypes related to these pathways.

  13. Cellular immune reactions in the lung.

    PubMed

    Hasenberg, Mike; Stegemann-Koniszewski, Sabine; Gunzer, Matthias

    2013-01-01

    The lung constantly interacts with the environment through thousands of liters of air that are inhaled daily. This continually transports toxic chemicals and particles or pathogenic microorganisms deep into the respiratory system, posing a challenge to physicochemical barriers and the local immune system. Thus, complex structures and mechanisms have evolved to recognize and fend off environmental dangers while at the same time allowing efficient gas exchange. Here we review our current knowledge regarding cellular mechanisms of the immune system in context with the highly specialized anatomical features of the airways and especially the alveolar compartment. The focus is on fungal and viral infections, merging anatomical aspects well known to pulmonologists with fundamental immunological concepts. We discuss the specialized morphological constraints of immune cells compressed under a continuous layer of the surfactant lining within alveoli as well as the importance of functional polarization of respiratory tract epithelia. Furthermore, we summarize the different types of innate and adaptive immune cells and their relative contribution to lung homeostasis with respect to localization. Finally, we provide a list of currently unresolved questions with high relevance for the field that might serve as food for thought regarding future research directions.

  14. Wireless Fractal Ultra-Dense Cellular Networks.

    PubMed

    Hao, Yixue; Chen, Min; Hu, Long; Song, Jeungeun; Volk, Mojca; Humar, Iztok

    2017-04-12

    With the ever-growing number of mobile devices, there is an explosive expansion in mobile data services. This represents a challenge for the traditional cellular network architecture to cope with the massive wireless traffic generated by mobile media applications. To meet this challenge, research is currently focused on the introduction of a small cell base station (BS) due to its low transmit power consumption and flexibility of deployment. However, due to a complex deployment environment and low transmit power of small cell BSs, the coverage boundary of small cell BSs will not have a traditional regular shape. Therefore, in this paper, we discuss the coverage boundary of an ultra-dense small cell network and give its main features: aeolotropy of path loss fading and fractal coverage boundary. Simple performance analysis is given, including coverage probability and transmission rate, etc., based on stochastic geometry theory and fractal theory. Finally, we present an application scene and discuss challenges in the ultra-dense small cell network.

  15. Optimal flux patterns in cellular metabolic networks.

    PubMed

    Almaas, Eivind

    2007-06-01

    The availability of whole-cell-level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate the metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations has relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reactions are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central carbon metabolic pathways for the sample of random environments.

  16. Life and Times of a Cellular Bleb☆

    PubMed Central

    Charras, Guillaume T.; Coughlin, Margaret; Mitchison, Timothy J.; Mahadevan, L.

    2008-01-01

    Blebs are spherical cellular protrusions that occur in many physiological situations. Two distinct phases make up the life of a bleb, each of which have their own biology and physics: expansion, which lasts ∼30 s, and retraction, which lasts ∼2 min. We investigate these phases using optical microscopy and simple theoretical concepts, seeking information on blebbing itself, and on cytomechanics in general. We show that bleb nucleation depends on pressure, membrane-cortex adhesion energy, and membrane tension, and test this experimentally. Bleb growth occurs through a combination of bulk flow of lipids and delamination from the cell cortex via the formation and propagation of tears. In extreme cases, this can give rise to a traveling wave around the cell periphery, known as “circus movement.” When growth stalls, an actin cortex reforms under the bleb membrane, and retraction starts, driven by myosin-II. Using flicker spectroscopy, we find that retracting blebs are fivefold more rigid than expanding blebs, an increase entirely explained by the properties of the newly formed cortical actin mesh. Finally, using artificially nucleated blebs as pressure sensors, we show that cells rounded up in mitosis possess a substantial intracellular pressure. PMID:17921219

  17. Optimal flux patterns in cellular metabolic networks

    SciTech Connect

    Almaas, E

    2007-01-20

    The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.

  18. Optimal flux patterns in cellular metabolic networks

    NASA Astrophysics Data System (ADS)

    Almaas, Eivind

    2007-06-01

    The availability of whole-cell-level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate the metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30 000 random cellular environments. The distribution of reaction fluxes is heavy tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations has relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reactions are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central carbon metabolic pathways for the sample of random environments.

  19. Final Technical Report

    SciTech Connect

    Schuur, Edward; Luo, Yiqi

    2016-12-01

    This final grant report is a continuation of the final grant report submitted for DE-SC0006982 as the Principle Investigator (Schuur) relocated from the University of Florida to Northern Arizona University. This report summarizes the original project goals, as well as includes new project activities that were completed in the final period of the project.

  20. The Dynamics of Cellular Flames.

    NASA Astrophysics Data System (ADS)

    Palacios, Jose Antonio

    1995-01-01

    A quantitative description of the dynamics of two-dimensional cellular flames, produced in a laboratory experiment, is presented. The cell boundaries are extracted from a sequence of video images, in which the motion of the flames is recorded, using a computational procedure. A data structure is then created to encapsulate the motion of the cell boundaries into one-dimensional complex vectors. Four regimes are analyzed using the Karhunen-Loeve decomposition as a tool: a rotating state with alternating speeds, a fast rigid rotation, a ratcheting state described by the locking-unlocking mechanism of two rotating rings of cells, and an intermittent state with two ordered patterns. It is demonstrated that most of these cases are examples of low-dimensional spatio-temporal complexity.

  1. Regulation of cellular chromatin state

    PubMed Central

    Mishra, Rakesh K; Dhawan, Jyotsna

    2010-01-01

    The identity and functionality of eukaryotic cells is defined not just by their genomic sequence which remains constant between cell types, but by their gene expression profiles governed by epigenetic mechanisms. Epigenetic controls maintain and change the chromatin state throughout development, as exemplified by the setting up of cellular memory for the regulation and maintenance of homeotic genes in proliferating progenitors during embryonic development. Higher order chromatin structure in reversibly arrested adult stem cells also involves epigenetic regulation and in this review we highlight common trends governing chromatin states, focusing on quiescence and differentiation during myogenesis. Together, these diverse developmental modules reveal the dynamic nature of chromatin regulation providing fresh insights into the role of epigenetic mechanisms in potentiating development and differentiation. PMID:20592864

  2. Cellular compartmentalization of secondary metabolism

    PubMed Central

    Kistler, H. Corby; Broz, Karen

    2015-01-01

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

  3. REGULATORY MECHANISMS OF CELLULAR RESPIRATION

    PubMed Central

    Barron, E. S. Guzman; Nelson, Leonard; Ardao, Maria Isabel

    1948-01-01

    Oxidizing agents of sulfhydryl groups such as iodosobenzoate, alkylating agents such as iodoacetamide, and mercaptide-forming agents such as cadmium chloride, mercuric chloride, p-chloromercuribenzoate, sodium arsenite, and p-carboxyphenylarsine oxide, added in small concentrations to a suspension of sea urchin sperm produced an increase in respiration. When the concentration was increased there was an inhibition. These effects are explained by postulating the presence in the cells of two kinds of sulfhydryl groups: soluble sulfhydryl groups, which regulate cellular respiration, and fixed sulfhydryl groups, present in the protein moiety of enzymes. Small concentrations of sulfhydryl reagents combine only with the first, thus producing an increase in respiration; when the concentration is increased, the fixed sulfhydryl groups are also attacked and inhibition of respiration is the consequence. Other inhibitors of cell respiration, such as cyanide and urethanes, which do not combine with —SH groups, did not stimulate respiration in small concentration. PMID:18891144

  4. Cellular immune mechanisms in myocarditis.

    PubMed

    Noutsias, M; Patil, V J; Maisch, B

    2012-12-01

    The introduction of immunohistological techniques enabled a substantially more reliable diagnosis of inflammatory cardiomyopathy (DCMi) in endomyocardial biopsies (EMB) compared to the histological Dallas criteria. Decisive progress has been made in the understanding of cellular immune mechanisms in DCMi using immunohistological techniques, which apart from the field of diagnosis refinement have had prognostic implications and an influence on the selection criteria of DCMi patients who will likely benefit from immunosuppressive treatment. Digital image analysis systems have been employed to standardize quantification of immunohistological EMB stainings. Quantification of T cell-related genes by a methodologically validated preamplified real-time RT-PCR revealed that the T cells are characterized by differential expression of Th1-, Treg-, and CTL-related markers, while no major role could be confirmed for Th17 cells. The reported virus-associated differential T cell receptor Vbeta dominance suggests an antiviral specificity of virus-induced T cell responses in human DCMi.

  5. Thermomechanical characterisation of cellular rubber

    NASA Astrophysics Data System (ADS)

    Seibert, H.; Scheffer, T.; Diebels, S.

    2016-09-01

    This contribution discusses an experimental possibility to characterise a cellular rubber in terms of the influence of multiaxiality, rate dependency under environmental temperature and its behaviour under hydrostatic pressure. In this context, a mixed open and closed cell rubber based on an ethylene propylene diene monomer is investigated exemplarily. The present article intends to give a general idea of the characterisation method and the considerable effects of this special type of material. The main focus lies on the experimental procedure and the used testing devices in combination with the analysis methods such as true three-dimensional digital image correlation. The structural compressibility is taken into account by an approach for a material model using the Theory of Porous Media with additional temperature dependence.

  6. Pressure-actuated cellular structures.

    PubMed

    Pagitz, M; Lamacchia, E; Hol, J M A M

    2012-03-01

    Shape changing structures will play an important role in future engineering designs since rigid structures are usually only optimal for a small range of service conditions. Hence, a concept for reliable and energy-efficient morphing structures that possess a large strength to self-weight ratio would be widely applicable. We propose a novel concept for morphing structures that is inspired by the nastic movement of plants. The idea is to connect prismatic cells with tailored pentagonal and/or hexagonal cross sections such that the resulting cellular structure morphs into given target shapes for certain cell pressures. An efficient algorithm for computing equilibrium shapes as well as cross-sectional geometries is presented. The potential of this novel concept is demonstrated by several examples that range from a flagellum like propulsion device to a morphing aircraft wing.

  7. Sensing phosphatidylserine in cellular membranes.

    PubMed

    Kay, Jason G; Grinstein, Sergio

    2011-01-01

    Phosphatidylserine, a phospholipid with a negatively charged head-group, is an important constituent of eukaryotic cellular membranes. On the plasma membrane, rather than being evenly distributed, phosphatidylserine is found preferentially in the inner leaflet. Disruption of this asymmetry, leading to the appearance of phosphatidylserine on the surface of the cell, is known to play a central role in both apoptosis and blood clotting. Despite its importance, comparatively little is known about phosphatidylserine in cells: its precise subcellular localization, transmembrane topology and intracellular dynamics are poorly characterized. The recent development of new, genetically-encoded probes able to detect phosphatidylserine within live cells, however, is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of the current methods for phosphatidylserine detection within cells, and some of the recent realizations derived from their use.

  8. Zika Virus Induced Cellular Remodeling.

    PubMed

    Rossignol, Evan D; Peters, Kristen N; Connor, John H; Bullitt, Esther

    2017-03-20

    Zika virus (ZIKV) has been associated with morbidities such as Guillain-Barré, infant microcephaly, and ocular disease. The spread of this positive-sense, single-stranded RNA virus and its growing public health threat underscore gaps in our understanding of basic ZIKV virology. To advance knowledge of the virus replication cycle within mammalian cells, we use serial section three-dimensional electron tomography to demonstrate the widespread remodeling of intracellular membranes upon infection with ZIKV. We report extensive structural rearrangements of the endoplasmic reticulum and reveal stages of the ZIKV viral replication cycle. Structures associated with RNA genome replication and virus assembly are observed integrated within the endoplasmic reticulum, and we show viruses in transit through the Golgi apparatus for viral maturation, and subsequent cellular egress. This study characterizes in detail the three-dimensional ultrastructural organization of the ZIKV replication cycle stages. Our results show close adherence of the ZIKV replication cycle to the existing flavivirus replication paradigm.

  9. Cellular ageing mechanisms in osteoarthritis.

    PubMed

    Sacitharan, P K; Vincent, T L

    2016-08-01

    Age is the strongest independent risk factor for the development of osteoarthritis (OA) and for many years this was assumed to be due to repetitive microtrauma of the joint surface over time, the so-called 'wear and tear' arthritis. As our understanding of OA pathogenesis has become more refined, it has changed our appreciation of the role of ageing on disease. Cartilage breakdown in disease is not a passive process but one involving induction and activation of specific matrix-degrading enzymes; chondrocytes are exquisitely sensitive to changes in the mechanical, inflammatory and metabolic environment of the joint; cartilage is continuously adapting to these changes by altering its matrix. Ageing influences all of these processes. In this review, we will discuss how ageing affects tissue structure, joint use and the cellular metabolism. We describe what is known about pathways implicated in ageing in other model systems and discuss the potential value of targeting these pathways in OA.

  10. Cellular stress and RNA splicing.

    PubMed

    Biamonti, Giuseppe; Caceres, Javier F

    2009-03-01

    In response to physical and chemical stresses that affect protein folding and, thus, the execution of normal metabolic processes, cells activate gene-expression strategies aimed at increasing their chance of survival. One target of several stressing agents is pre-mRNA splicing, which is inhibited upon heat shock. Recently, the molecular basis of this splicing inhibition has begun to emerge. Interestingly, different mechanisms seem to be in place to block constitutive pre-mRNA splicing and to affect alternative splicing regulation. This could be important to modulate gene expression during recovery from stress. Thus, pre-mRNA splicing emerges as a central mechanism to integrate cellular and metabolic stresses into gene-expression profiles.

  11. Fundamental Limits to Cellular Sensing

    NASA Astrophysics Data System (ADS)

    ten Wolde, Pieter Rein; Becker, Nils B.; Ouldridge, Thomas E.; Mugler, Andrew

    2016-03-01

    In recent years experiments have demonstrated that living cells can measure low chemical concentrations with high precision, and much progress has been made in understanding what sets the fundamental limit to the precision of chemical sensing. Chemical concentration measurements start with the binding of ligand molecules to receptor proteins, which is an inherently noisy process, especially at low concentrations. The signaling networks that transmit the information on the ligand concentration from the receptors into the cell have to filter this receptor input noise as much as possible. These networks, however, are also intrinsically stochastic in nature, which means that they will also add noise to the transmitted signal. In this review, we will first discuss how the diffusive transport and binding of ligand to the receptor sets the receptor correlation time, which is the timescale over which fluctuations in the state of the receptor, arising from the stochastic receptor-ligand binding, decay. We then describe how downstream signaling pathways integrate these receptor-state fluctuations, and how the number of receptors, the receptor correlation time, and the effective integration time set by the downstream network, together impose a fundamental limit on the precision of sensing. We then discuss how cells can remove the receptor input noise while simultaneously suppressing the intrinsic noise in the signaling network. We describe why this mechanism of time integration requires three classes (groups) of resources—receptors and their integration time, readout molecules, energy—and how each resource class sets a fundamental sensing limit. We also briefly discuss the scheme of maximum-likelihood estimation, the role of receptor cooperativity, and how cellular copy protocols differ from canonical copy protocols typically considered in the computational literature, explaining why cellular sensing systems can never reach the Landauer limit on the optimal trade

  12. Role of cellular communication in the pathways of radiation-induced biological damage

    NASA Astrophysics Data System (ADS)

    Ballarini, Francesca; Facoetti, Angelica; Mariotti, Luca; Nano, Rosanna; Ottolenghi, Andrea

    During the last decade, a large number of experimental studies on the so-called "non-targeted effects", in particular bystander effects, outlined that cellular communication plays a signifi- cant role in the pathways leading to radiation-induced biological damage. This might imply a paradigm shift in (low-dose) radiobiology, according to which one has to consider the response of groups of cells behaving like a population rather than single cells behaving as individuals. Furthermore, bystander effects, which are observed both for lethal endpoints (e.g. clonogenic inactivation and apoptosis) and for non-lethal ones (e.g. mutations and neoplastic transformation), tend to show non-linear dose responses characterized by a sharp increase followed by a plateau. This might have significant consequences in terms of low-dose risk, which is generally calculated on the basis of the "Linear No Threshold" hypothesis. Although it is known that two types of cellular communication (i.e. via gap junctions and/or molecular messengers diffusing in the extra-cellular environment, such as cytokines) play a major role, it is of utmost importance to better understand the underlying mechanisms, and how such mechanisms can be modulated by ionizing radiation. Though the "final" goal is to elucidate the in vivo scenario, in the meanwhile also in vitro studies can provide useful insights. In the present paper we will discuss key issues on the mechanisms underlying non-targeted effects and, more generally, cell communication, with focus on candidate molecular signals. Theoretical models and simulation codes can be of help in elucidating such mechanisms. In this framework, we will present a model and Monte Carlo code, under development at the University of Pavia, simulating the release, diffusion and internalization of candidate signals (typically cytokines) travelling in the extra-cellular environment, both by unirradiated (i.e., control) cells and by irradiated cells. The focus will be on the

  13. Optical information storage in cellular mobile terminals

    NASA Astrophysics Data System (ADS)

    Makela, Jakke S.; Aikio, Janne K.; Vadde, Venkatesh; Kolehmainen, Timo T.; Karioja, Pentti

    2001-11-01

    The trend towards so-called digital convergence (multiple functionality within a single terminal) is opening up a need for high-capacity storage within the cellular mobile terminals (CMT). Solid-state memories and magnetic microdrives are the most commercially mature options. Optical disk technology in this size range is immature, but has a unique potential: no other medium at present has the capability to be simultaneously low-cost, high-capacity, and exchangeable. In this paper, we explore the requirements for the implementation of optical disk storage in a CMT environment. From the technical point of view, these requirements include small form factor, high-enough data density and throughput, low power consumption, robustness, low cost, mass productability, and modularity. Although current technologies may satisfy some of these requirements individually, there is a need for combined optimization of all of these parameters. From the commercial point of view, the most crucial requirement is global standardization. Such standardization is crucial if wide interoperability is wanted (between CMT manufacturers, and even more crucially between CMTs and other appliances). Current optical storage standards are industry-driven and tend to be proprietary and/or incompatible. Even if the technical challenges can be met, optical data storage is not likely to be accepted in CMT applications unless global standardization proceeds more quickly than it is doing at present.

  14. Final Technical Report

    SciTech Connect

    Aristos Aristidou Natureworks); Robert Kean; Tom Schechinger; Stuart Birrell; Jill Euken

    2007-10-01

    /storage/transportation equipment and the processor would build and operate the plant. Pilot fermentation studies demonstrated dramatic improvements in yields and rates with optimization of batch fermentor parameters. Demonstrated yields and rates are approaching those necessary for profitable commercial operation for production of ethanol or lactic acid. The ability of the biocatalyst to adapt to biomass hydrolysate (both biomass sugars and toxins in the hydrolysate) was demonstrated and points towards ultimate successful commercialization of the technology. However, some of this work will need to be repeated and possibly extended to adapt the final selected biocatalyst for the specific commercial hydrolysate composition. The path from corn stover in the farm field to final products, involves a number of steps. Each of these steps has options, problems, and uncertainties; thus creating a very complex multidimensional obstacle to successful commercial development. Through the tasks of this project, the technical and commercial uncertainties of many of these steps have been addressed; thus providing for a clearer understanding of paths forward and commercial viability of a corn stover-based biorefinery.

  15. Photovoltaic module parameters acquisition model

    NASA Astrophysics Data System (ADS)

    Cibira, Gabriel; Koščová, Marcela

    2014-09-01

    This paper presents basic procedures for photovoltaic (PV) module parameters acquisition using MATLAB and Simulink modelling. In first step, MATLAB and Simulink theoretical model are set to calculate I-V and P-V characteristics for PV module based on equivalent electrical circuit. Then, limited I-V data string is obtained from examined PV module using standard measurement equipment at standard irradiation and temperature conditions and stated into MATLAB data matrix as a reference model. Next, the theoretical model is optimized to keep-up with the reference model and to learn its basic parameters relations, over sparse data matrix. Finally, PV module parameters are deliverable for acquisition at different realistic irradiation, temperature conditions as well as series resistance. Besides of output power characteristics and efficiency calculation for PV module or system, proposed model validates computing statistical deviation compared to reference model.

  16. Cellular models to study schizophrenia: A systematic review.

    PubMed

    Seshadri, Manasa; Banerjee, Debanjan; Viswanath, Biju; Ramakrishnan, K; Purushottam, Meera; Venkatasubramanian, Ganesan; Jain, Sanjeev

    2017-02-01

    Advancements in cellular reprogramming techniques have made it possible to directly study brain cells from patients with neuropsychiatric disorders. We have systematically reviewed the applications of induced pluripotent stem cells (IPSCs) and their neural derivatives in understanding the biological basis of schizophrenia. We searched the scientific literature published in MEDLINE with the following search strategy: (Pluripotent) AND (Schizophrenia OR Antipsychotic OR Psychosis). Studies written in English that used IPSCs derived from patients with schizophrenia were included. Out of 23 articles, which had used IPSCs from patients with schizophrenia, neurons or neural stem cells had been derived from them in a majority. Several parameters had been studied; the key cellular phenotypes identified included those of synaptic pathology, neural migration/proliferation deficits, and abnormal oxidative phosphorylation. Cellular modelling using IPSCs could improve the biological understanding of schizophrenia. Emerging findings are consistent with those of other study designs (post-mortem brain expression, animal studies, genome-wide association, brain imaging). Future studies should focus on refined study designs (family-based, pharmacogenomics, gene editing) and a combination of cellular studies with deep clinical phenotyping. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Cell dipole behaviour revealed by ECM sub-cellular geometry

    NASA Astrophysics Data System (ADS)

    Mandal, Kalpana; Wang, Irène; Vitiello, Elisa; Orellana, Laura Andreina Chacòn; Balland, Martial

    2014-12-01

    Cells sense and respond to their mechanical environment by exerting forces on their surroundings. The way forces are modulated by extra-cellular matrix (ECM) properties plays a key role in tissue homoeostasis. Using highly resolved micropatterns that constrain cells into the same square envelope but vary the adhesive geometry, here we investigate how the adhesive micro-environment affects the architecture of actin cytoskeleton and the orientation of traction forces. Our data demonstrate that local adhesive changes can trigger orientational ordering of stress fibres throughout the cell, suggesting that cells are capable of integrating information on ECM geometry at the whole-cell level. Finally, we show that cells tend to generate highly polarized force pattern, that is, unidirectional pinching, in response to adequate adhesive conditions. Hence, the geometry of adhesive environment can induce cellular orientation, a process which may have significant implications for the formation and mechanical properties of tissues.

  18. A palette of fluorescent proteins optimized for diverse cellular environments

    PubMed Central

    Costantini, Lindsey M.; Baloban, Mikhail; Markwardt, Michele L.; Rizzo, Mark; Guo, Feng; Verkhusha, Vladislav V.; Snapp, Erik L.

    2015-01-01

    To perform quantitative live cell imaging, investigators require fluorescent reporters that accurately report protein localization and levels, while minimally perturbing the cell. Yet, within the biochemically distinct environments of cellular organelles, popular fluorescent proteins (FPs), including EGFP, can be unreliable for quantitative imaging, resulting in underestimation of protein levels and incorrect localization. Specifically, within the secretory pathway, significant populations of FPs misfold and fail to fluoresce due to non-native disulphide bond formation. Furthermore, transmembrane FP fusion constructs can disrupt organelle architecture due to oligomerizing tendencies of numerous common FPs. Here, we describe a powerful set of bright and inert FPs optimized for use in multiple cellular compartments, especially oxidizing environments and biological membranes. Also, we provide new insights into use of red FPs in the secretory pathway. Our monomeric "oxFPs" finally resolve long standing, underappreciated, and important problems of cell biology and should be useful for a number of applications. PMID:26158227

  19. Molecular and cellular aspects of protein misfolding and disease.

    PubMed

    Herczenik, Eszter; Gebbink, Martijn F B G

    2008-07-01

    Proteins are essential elements for life. They are building blocks of all organisms and the operators of cellular functions. Humans produce a repertoire of at least 30,000 different proteins, each with a different role. Each protein has its own unique sequence and shape (native conformation) to fulfill its specific function. The appearance of incorrectly shaped (misfolded) proteins occurs on exposure to environmental changes. Protein misfolding and the subsequent aggregation is associated with various, often highly debilitating, diseases for which no sufficient cure is available yet. In the first part of this review we summarize the structural composition of proteins and the current knowledge of underlying forces that lead proteins to lose their native structure. In the second and third parts we describe the molecular and cellular mechanisms that are associated with protein misfolding in disease. Finally, in the last part we portray recent efforts to develop treatments for protein misfolding diseases.

  20. Mechanistic effects of protein palmitoylation and the cellular consequences thereof.

    PubMed

    Blaskovic, Sanja; Adibekian, Alexander; Blanc, Mathieu; van der Goot, Gisou F

    2014-05-01

    S-palmitoylation involves the attachment of a 16-carbon long fatty acid chain to the cysteine residues of proteins. The process is enzymatic and dynamic with DHHC enzymes mediating palmitoylation and acyl-protein thioesterases reverting the reaction. Proteins that undergo this modification span almost all cellular functions. While the increase in hydrophobicity generated by palmitoylation has the obvious consequence of triggering membrane association, the effects on transmembrane proteins are less intuitive and span a vast range. We review here the current knowledge on palmitoylating and depalmitoylating enzymes, the methods that allow the study of this lipid modification and which drugs can affect it, and finally we focus on four cellular processes for which recent studies reveal an involvement of palmitoylation: endocytosis, reproduction and cell growth, fat and sugar homeostasis and signal transduction at the synapse. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Surface chemistry governs cellular tropism of nanoparticles in the brain

    NASA Astrophysics Data System (ADS)

    Song, Eric; Gaudin, Alice; King, Amanda R.; Seo, Young-Eun; Suh, Hee-Won; Deng, Yang; Cui, Jiajia; Tietjen, Gregory T.; Huttner, Anita; Saltzman, W. Mark

    2017-05-01

    Nanoparticles are of long-standing interest for the treatment of neurological diseases such as glioblastoma. Most past work focused on methods to introduce nanoparticles into the brain, suggesting that reaching the brain interstitium will be sufficient to ensure therapeutic efficacy. However, optimized nanoparticle design for drug delivery to the central nervous system is limited by our understanding of their cellular deposition in the brain. Here, we investigated the cellular fate of poly(lactic acid) nanoparticles presenting different surface chemistries, after administration by convection-enhanced delivery. We demonstrate that nanoparticles with `stealth' properties mostly avoid internalization by all cell types, but internalization can be enhanced by functionalization with bio-adhesive end-groups. We also show that association rates measured in cultured cells predict the extent of internalization of nanoparticles in cell populations. Finally, evaluating therapeutic efficacy in an orthotopic model of glioblastoma highlights the need to balance significant uptake without inducing adverse toxicity.

  2. Protein Targeting and Transport as a Necessary Consequence of Increased Cellular Complexity

    PubMed Central

    Sommer, Maik S.; Schleiff, Enrico

    2014-01-01

    With increasing intracellular complexity, a new cell-biological problem that is the allocation of cytoplasmically synthesized proteins to their final destinations within the cell emerged. A special challenge is thereby the translocation of proteins into or across cellular membranes. The underlying mechanisms are only in parts well understood, but it can be assumed that the course of cellular evolution had a deep impact on the design of the required molecular machines. In this article, we aim to summarize the current knowledge and concepts of the evolutionary development of protein trafficking as a necessary premise and consequence of increased cellular complexity. PMID:25085907

  3. Cellular basis of gravity resistance in plants

    NASA Astrophysics Data System (ADS)

    Hoson, Takayuki; Matsumoto, Shouhei; Inui, Kenichi; Zhang, Yan; Soga, Kouichi; Wakabayashi, Kazuyuki; Hashimoto, Takashi

    Mechanical resistance to the gravitational force is a principal gravity response in plants distinct from gravitropism. In the final step of gravity resistance, plants increase the rigidity of their cell walls via modifications to the cell wall metabolism and apoplastic environment. We studied cellular events that are related to the cell wall changes under hypergravity conditions produced by centrifugation. Hypergravity induced reorientation of cortical microtubules from transverse to longitudinal directions in epidermal cells of stem organs. In Arabidopsis tubulin mutants, the percentage of cells with longitudinal microtubules was high even at 1 g, and it was further increased by hypergravity. Hypocotyls of tubulin mutants also showed either left-handed or right-handed helical growth at 1 g, and the degree of twisting phenotype was intensified under hypergravity conditions. The left-handed helical growth mutants had right-handed microtubule arrays, whereas the right-handed mutant had left-handed arrays. There was a close correlation between the alignment angle of epidermal cell files and the alignment of cortical microtubules. Gadolinium ions suppressed both the twisting phenotype and reorientation of microtubules in tubulin mutants. These results support the hypothesis that cortical microtubules play an es-sential role in maintenance of normal growth phenotype against the gravitational force, and suggest that mechanoreceptors are involved in modifications to morphology and orientation of microtubule arrays by hypergravity. Actin microfilaments, in addition to microtubules, may be involved in gravity resistance. The nucleus of epidermal cells of azuki bean epicotyls, which is present almost in the center of the cell at 1 g, was displaced to the cell bottom by increasing the magnitude of gravity. Cytochalasin D stimulated the sedimentation by hypergravity of the nu-cleus, suggesting that the positioning of the nucleus is regulated by actin microfilaments, which is

  4. Cellular phones: are they detrimental?

    PubMed

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

    The issue of possible health effects of cellular phones is very much alive in the public's mind where the rapid increase in the number of the users of cell phones in the last decade has increased the exposure of people to the electromagnetic fields (EMFs). Health consequences of long term use of mobile phones are not known in detail but available data indicates the development of non specific annoying symptoms on acute exposure to mobile phone radiations. In an attempt to determine the prevalence of such cell phones associated health manifestations and the factors affecting their occurrence, a cross sectional study was conducted in five randomly selected faculties of Alexandria University. Where, 300 individuals including teaching staff, students and literate employee were equally allocated and randomly selected among the five faculties. Data about mobile phone's users and their medical history, their pattern of mobile usage and the possible deleterious health manifestations associated with cellular phone use was collected. The results revealed 68% prevalence of mobile phone usage, nearly three quarters of them (72.5%) were complainers of the health manifestations. They suffered from headache (43%), earache (38.3%), sense of fatigue (31.6%), sleep disturbance (29.5%), concentration difficulty (28.5%) and face burning sensation (19.2%). Both univariate and multivariate analysis were consistent in their findings. Symptomatic users were found to have significantly higher frequency of calls/day, longer call duration and longer total duration of mobile phone usage/day than non symptomatic users. For headache both call duration and frequency of calls/day were the significant predicting factors for its occurrence (chi2 = 18.208, p = 0.0001). For earache, in addition to call duration, the longer period of owning the mobile phone were significant predictors (chi2 = 16.996, p = 0.0002). Sense of fatigue was significantly affected by both call duration and age of the user

  5. Marine molluscs in environmental monitoring. I. Cellular and molecular responses

    NASA Astrophysics Data System (ADS)

    Bresler, Vladimir; Abelson, Avigdor; Fishelson, Lev; Feldstein, Tamar; Rosenfeld, Michael; Mokady, Ofer

    2003-10-01

    The study reported here is part of an ongoing effort to establish sensitive and reliable biomonitoring markers for probing the coastal marine environment. Here, we report comparative measurements of a range of histological, cellular and sub-cellular parameters in molluscs sampled in polluted and reference sites along the Mediterranean coast of Israel and in the northern tip of the Gulf of Aqaba, Red Sea. Available species enabled an examination of conditions in two environmental 'compartments': benthic (Donax trunculus) and intertidal (Brachidontes pharaonis, Patella caerulea) in the Mediterranean; pelagic (Pteria aegyptia) and intertidal (Cellana rota) in the Red Sea. The methodology used provides rapid results by combining specialized fluorescent probes and contact microscopy, by which all parameters are measured in unprocessed animal tissue. The research focused on three interconnected levels. First, antixenobiotic defence mechanisms aimed at keeping hazardous agents outside the cell. Paracellular permeability was 70-100% higher in polluted sites, and membrane pumps (MXRtr and SATOA) activity was up to 65% higher in polluted compared to reference sites. Second, intracellular defence mechanisms that act to minimize potential damage by agents having penetrated the first line of defence. Metallothionein expression and EROD activity were 160-520% higher in polluted sites, and lysosomal functional activity (as measured by neutral red accumulation) was 25-50% lower. Third, damage caused by agents not sufficiently eliminated by the above mechanisms (e.g. single-stranded DNA breaks, chromosome damage and other pathological alterations). At this level, the most striking differences were observed in the rate of micronuclei formation and DNA breaks (up to 150% and 400% higher in polluted sites, respectively). The different mollusc species used feature very similar trends between polluted and reference sites in all measured parameters. Concentrating on relatively basic

  6. Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells.

    PubMed

    Domura, Ryota; Sasaki, Rie; Ishikawa, Yuma; Okamoto, Masami

    2017-06-06

    The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

  7. Cellular neuron and large wireless neural network

    NASA Astrophysics Data System (ADS)

    Jannson, Tomasz; Forrester, Thomas; Ambrose, Barry; Kazantzidis, Matheos; Lin, Freddie

    2006-05-01

    A new approach to neural networks is proposed, based on wireless interconnects (synapses) and cellular neurons, both software and hardware; with the capacity of 10 10 neurons, almost fully connected. The core of the system is Spatio-Temporal-Variant (STV) kernel and cellular axon with synaptic plasticity variable in time and space. The novel large neural network hardware is based on two established wireless technologies: RF-cellular and IR-wireless.

  8. The origins of cellular life.

    PubMed

    Schrum, Jason P; Zhu, Ting F; Szostak, Jack W

    2010-09-01

    Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of functional information. Recent studies of vesicles composed of fatty-acid membranes have shed considerable light on pathways for protocell growth and division, as well as means by which protocells could take up nutrients from their environment. Additional work with genetic polymers has provided insight into the potential for chemical genome replication and compatibility with membrane encapsulation. The integration of a dynamic fatty-acid compartment with robust, generalized genetic polymer replication would yield a laboratory model of a protocell with the potential for classical Darwinian biological evolution, and may help to evaluate potential pathways for the emergence of life on the early Earth. Here we discuss efforts to devise such an integrated protocell model.

  9. Efficiency of cellular information processing

    NASA Astrophysics Data System (ADS)

    Barato, Andre C.; Hartich, David; Seifert, Udo

    2014-10-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the Escherichia coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium in an environment that changes at a very slow time-scale is quite inefficient, dissipating much more than it learns. Using the concept of a coarse-grained learning rate, we show for the model with adaptation that while the activity learns about the external signal the option of changing the methylation level increases the concentration range for which the learning rate is substantial.

  10. Electrostatic Tuning of Cellular Excitability

    PubMed Central

    Börjesson, Sara I.; Parkkari, Teija; Hammarström, Sven; Elinder, Fredrik

    2010-01-01

    Abstract Voltage-gated ion channels regulate the electric activity of excitable tissues, such as the heart and brain. Therefore, treatment for conditions of disturbed excitability is often based on drugs that target ion channels. In this study of a voltage-gated K channel, we propose what we believe to be a novel pharmacological mechanism for how to regulate channel activity. Charged lipophilic substances can tune channel opening, and consequently excitability, by an electrostatic interaction with the channel's voltage sensors. The direction of the effect depends on the charge of the substance. This was shown by three compounds sharing an arachidonyl backbone but bearing different charge: arachidonic acid, methyl arachidonate, and arachidonyl amine. Computer simulations of membrane excitability showed that small changes in the voltage dependence of Na and K channels have prominent impact on excitability and the tendency for repetitive firing. For instance, a shift in the voltage dependence of a K channel with −5 or +5 mV corresponds to a threefold increase or decrease in K channel density, respectively. We suggest that electrostatic tuning of ion channel activity constitutes a novel and powerful pharmacological approach with which to affect cellular excitability. PMID:20141752

  11. Cellular neuropathology of tuberous sclerosis.

    PubMed

    Huttenlocher, P R; Wollmann, R L

    1991-01-01

    The study of cerebral lesions of TSC by special histologic methods suggests that two populations of neurons and glia occur in TSC brains. One is a population of normally differentiated cells that form a normally constituted cortical plate. The other is a group of cells that are poorly differentiated, fail to organize into a normal cortical architecture, and form a variety of abnormal cellular aggregates in cortex and in subcortical locations. The proportion of these abnormal cells varies greatly from patient to patient. In some the central nervous system appears to be entirely spared. In others, only one or a few islands of dysplastic cells occur, whereas in still others a large number, perhaps even a majority, of neuroectodermal cells in the forebrain may be affected. The proportion of total cells that undergo abnormal differentiation apparently is an important factor relative to cortical function in TSC. At present we have no explanation for this marked heterogeneity in expression of the TSC gene or genes, and it remains one of the many unsolved mysteries of this illness.

  12. Reference materials for cellular therapeutics.

    PubMed

    Bravery, Christopher A; French, Anna

    2014-09-01

    The development of cellular therapeutics (CTP) takes place over many years, and, where successful, the developer will anticipate the product to be in clinical use for decades. Successful demonstration of manufacturing and quality consistency is dependent on the use of complex analytical methods; thus, the risk of process and method drift over time is high. The use of reference materials (RM) is an established scientific principle and as such also a regulatory requirement. The various uses of RM in the context of CTP manufacturing and quality are discussed, along with why they are needed for living cell products and the analytical methods applied to them. Relatively few consensus RM exist that are suitable for even common methods used by CTP developers, such as flow cytometry. Others have also identified this need and made proposals; however, great care will be needed to ensure any consensus RM that result are fit for purpose. Such consensus RM probably will need to be applied to specific standardized methods, and the idea that a single RM can have wide applicability is challenged. Written standards, including standardized methods, together with appropriate measurement RM are probably the most appropriate way to define specific starting cell types. The characteristics of a specific CTP will to some degree deviate from those of the starting cells; consequently, a product RM remains the best solution where feasible. Each CTP developer must consider how and what types of RM should be used to ensure the reliability of their own analytical measurements.

  13. Respiring cellular nano-magnets.

    PubMed

    Talib, Ayesha; Khan, Zanib; Bokhari, Habib; Hidayathula, Syed; Jilani, Ghulam; Khan, Abid Ali

    2017-11-01

    Magnetotactic bacteria provide an interesting example for the biosynthesis of magnetic (Fe3O4 or Fe3S4) nanoparticles, synthesized through a process known as biologically controlled mineralization, resulting in complex monodispersed, and nanostructures with unique magnetic properties. In this work, we report a novel aerobic bacterial strain isolated from sludge of an oil refinery. Microscopic and staining analysis revealed that it was a gram positive rod with the capability to thrive in a medium (9K) supplemented, with Fe(2+) ions at an acidic pH (~3.2). The magnetic behaviour of these cells was tested by their alignment towards a permanent magnet, and later on confirmed by magnetometry analysis. The X-ray diffraction studies proved the cellular biosynthesis of magnetite nanoparticles inside the bacteria. This novel, bio-nano-magnet, could pave the way for green synthesis of magnetic nanoparticles to be used in industrial and medical applications such as MRI, magnetic hyperthermia and ferrofluids. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Cellular telephone interference with medical equipment.

    PubMed

    Tri, Jeffrey L; Severson, Rodney P; Firl, Allen R; Hayes, David L; Abenstein, John P

    2005-10-01

    To assess the potential electromagnetic interference (EMI) effects that new or current-generation cellular telephones have on medical devices. For this study, performed at the Mayo Clinic in Rochester, Minn, between March 9, 2004, and April 24, 2004, we tested 16 different medical devices with 6 cellular telephones to assess the potential for EMI. Two of the medical devices were tested with both new and old interface modules. The 6 cellular telephones chosen represent the different cellular technology protocols in use: Code Division Multiple Access (2 models), Global System for Mobile communications, Integrated Digital Enhanced Network, Time Division Multiple Access, and analog. The cellular telephones were tested when operating at or near their maximum power output. The medical devices, connected to clinical simulators during testing, were monitored by observing the device displays and alarms. Of 510 tests performed, the incidence of clinically important interference was 1.2%; EMI was Induced in 108 tests (21.2%). Interference occurred in 7 (44%) of the 16 devices tested. Cellular telephones can interfere with medical equipment. Technology changes in both cellular telephones and medical equipment may continue to mitigate or may worsen clinically relevant interference. Compared with cellular telephones tested in previous studies, those currently in use must be closer to medical devices before any interference is noticed. However, periodic testing of cellular telephones to determine their effects on medical equipment will be required.

  15. The cellular memory disc of reprogrammed cells.

    PubMed

    Anjamrooz, Seyed Hadi

    2013-04-01

    The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

  16. Integration of mobile satellite and cellular systems

    NASA Technical Reports Server (NTRS)

    Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

    1993-01-01

    By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

  17. Are aberrant phase transitions a driver of cellular aging?

    PubMed Central

    2016-01-01

    Why do cells age? Recent advances show that the cytoplasm is organized into many membrane‐less compartments via a process known as phase separation, which ensures spatiotemporal control over diffusion‐limited biochemical reactions. Although phase separation is a powerful mechanism to organize biochemical reactions, it comes with the trade‐off that it is extremely sensitive to changes in physical‐chemical parameters, such as protein concentration, pH, or cellular energy levels. Here, we highlight recent findings showing that age‐related neurodegenerative diseases are linked to aberrant phase transitions in neurons. We discuss how these aberrant phase transitions could be tied to a failure to maintain physiological physical‐chemical conditions. We generalize this idea to suggest that the process of cellular aging involves a progressive loss of the organization of phase‐separated compartments in the cytoplasm. PMID:27554449

  18. Cellular copper distribution: a mechanistic systems biology approach.

    PubMed

    Banci, Lucia; Bertini, Ivano; Cantini, Francesca; Ciofi-Baffoni, Simone

    2010-08-01

    Copper is an essential but potentially harmful trace element required in many enzymatic processes involving redox chemistry. Cellular copper homeostasis in mammals is predominantly maintained by regulating copper transport through the copper import CTR proteins and the copper exporters ATP7A and ATP7B. Once copper is imported into the cell, several pathways involving a number of copper proteins are responsible for trafficking it specifically where it is required for cellular life, thus avoiding the release of harmful free copper ions. In this study we review recent progress made in understanding the molecular mechanisms of copper transport in cells by analyzing structural features of copper proteins, their mode of interaction, and their thermodynamic and kinetic parameters, thus contributing to systems biology of copper within the cell.

  19. Vet Centers. Final rule.

    PubMed

    2016-03-02

    The Department of Veterans Affairs (VA) adopts as final an interim final rule that amends its medical regulation that governs Vet Center services. The National Defense Authorization Act for Fiscal Year 2013 (the 2013 Act) requires Vet Centers to provide readjustment counseling services to broader groups of veterans, members of the Armed Forces, including a member of a reserve component of the Armed Forces, and family members of such veterans and members. This final rule adopts as final the regulatory criteria to conform to the 2013 Act, to include new and revised definitions.

  20. Controlling Cellular Endocytosis at the Nanoscale

    NASA Astrophysics Data System (ADS)

    Battaglia, Giuseppe

    2011-03-01

    , amphiphilic molecules, and hydrophilic molecules without affecting the viability of cells or even triggering inflammatory pathways. Finally we show how size, surface chemistry and surface topology of the vesicles affect their interaction with the cell membrane and hence their cellular uptake. References: C. Lo Presti, M. Massignani, T. Smart, H. Lomas, and G. Battaglia J. Mater. Chem. (2009) 19, 3576-3590 H. Lomas, I. Canton, S. MacNeil, J. Du, S.P. Armes, A.J. Ryan, A.L. Lewis and G. Battaglia Adv. Mater. (2007). 19, 4238-4243 M. Massignani, I. Canton, N. Patikarnmonthon, N. J. Warren, S. P. Armes, A. L. Lewis and G. Battaglia, Nature Prec., 2010, http://hdl.handle.net/10101/npre.2010.4427.1 M. Massignani, C. LoPresti, A. Blanazs, J. Madsen, S. P. Armes, A. L. Lewis and G. Battaglia Small, 2009, 5, 2424-2432. M. Massignani, T. Sun, A. Blanazs, V. Hearnden, I. Canton, P. Desphande, S. Armes, S. MacNeil, A. Lewis and G. Battaglia PLoS One, 2010, 5, e10459.

  1. Wearable vital parameters monitoring system

    NASA Astrophysics Data System (ADS)

    Caramaliu, Radu Vadim; Vasile, Alexandru; Bacis, Irina

    2015-02-01

    The system we propose monitors body temperature, heart rate and beside this, it tracks if the person who wears it suffers a faint. It uses a digital temperature sensor, a pulse sensor and a gravitational acceleration sensor to monitor the eventual faint or small heights free falls. The system continuously tracks the GPS position when available and stores the last valid data. So, when measuring abnormal vital parameters the module will send an SMS, using the GSM cellular network , with the person's social security number, the last valid GPS position for that person, the heart rate, the body temperature and, where applicable, a valid fall alert or non-valid fall alert. Even though such systems exist, they contain only faint detection or heart rate detection. Usually there is a strong correlation between low/high heart rate and an eventual faint. Combining both features into one system results in a more reliable detection device.

  2. GENERAL: A modified weighted probabilistic cellular automaton traffic flow model

    NASA Astrophysics Data System (ADS)

    Zhuang, Qian; Jia, Bin; Li, Xin-Gang

    2009-08-01

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

  3. Molecular and Cellular Mechanics (Part I): A moderated discussion

    NASA Astrophysics Data System (ADS)

    Corey, David P.; Martin, Pascal

    2015-12-01

    The following is an edited transcript of a recorded discussion session on the topic of "Molecular and Cellular Mechanics". The discussion, moderated by the authors, took place at the 12th International Workshop on the Mechanics of Hearing held at Cape Sounio, Greece, in June 2014. All participants knew that the session was being recorded. In view of both the spontaneous nature of the discussion and the editing, however, this transcript may not represent the considered or final views of the participants, and may not represent a consensus of experts in the field. The reader is advised to consult additional independent publications.

  4. Molecular and Cellular Mechanics (Part II): A moderated discussion

    NASA Astrophysics Data System (ADS)

    Santos-Sacchi, Joseph

    2015-12-01

    The following is an edited transcript of a recorded discussion session on the topic of "Molecular and Cellular Mechanics". The discussion, moderated by the author, took place at the 12th International Workshop on the Mechanics of Hearing held at Cape Sounio, Greece, in June 2014. All participants knew that the session was being recorded. In view of both the spontaneous nature of the discussion and the editing, however, this transcript may not represent the considered or final views of the participants, and may not represent a consensus of experts in the field. The reader is advised to consult additional independent publications.

  5. Interplay of drug metabolizing enzymes with cellular transporters.

    PubMed

    Böhmdorfer, Michaela; Maier-Salamon, Alexandra; Riha, Juliane; Brenner, Stefan; Höferl, Martina; Jäger, Walter

    2014-11-01

    Many endogenous and xenobiotic substances and their metabolites are substrates for drug metabolizing enzymes and cellular transporters. These proteins may not only contribute to bioavailability of molecules but also to uptake into organs and, consequently, to overall elimination. The coordinated action of uptake transporters, metabolizing enzymes, and efflux pumps, therefore, is a precondition for detoxification and elimination of drugs. As the understanding of the underlying mechanisms is important to predict alterations in drug disposal, adverse drug reactions and, finally, drug-drug interactions, this review illustrates the interplay between selected uptake/efflux transporters and phase I/II metabolizing enzymes.

  6. "Biomoléculas": cellular metabolism didactic software

    NASA Astrophysics Data System (ADS)

    Menghi, M. L.; Novella, L. P.; Siebenlist, M. R.

    2007-11-01

    "Biomoléculas" is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingeniería - Universidad Nacional de Entre Ríos.

  7. Cellular models to study bipolar disorder: A systematic review.

    PubMed

    Viswanath, Biju; Jose, Sam P; Squassina, Alessio; Thirthalli, Jagadisha; Purushottam, Meera; Mukherjee, Odity; Vladimirov, Vladimir; Patrinos, George P; Del Zompo, Maria; Jain, Sanjeev

    2015-09-15

    There is an emerging interest in the use of cellular models to study psychiatric disorders. We have systematically reviewed the application of cellular models to understand the biological basis of bipolar disorder (BD). Published scientific literature in MEDLINE, PsychINFO and SCOPUS databases were identified with the following search strategy: [(Lymphoblastoid OR Lymphoblast OR Fibroblast OR Pluripotent OR Olfactory epithelium OR Olfactory mucosa) AND (Bipolar disorder OR Lithium OR Valproate OR Mania)]. Studies were included if they had used cell cultures derived from BD patients. There were 65 articles on lymphoblastoid cell lines, 14 articles on fibroblasts, 4 articles on olfactory neuronal epithelium (ONE) and 2 articles on neurons reprogrammed from induced pluripotent stem cell lines (IPSC). Several parameters have been studied, and the most replicated findings are abnormalities in calcium signaling, endoplasmic reticulum (ER) stress response, mitochondrial oxidative pathway, membrane ion channels, circadian system and apoptosis related genes. These, although present in basal state, seem to be accentuated in the presence of cellular stressors (e.g. oxidative stress--rotenone; ER stress--thapsigargin), and are often reversed with in-vitro lithium. Cellular modeling has proven useful in BD, and potential pathways, especially in cellular resilience related mechanisms have been identified. These findings show consistency with other study designs (genome-wide association, brain-imaging, and post-mortem brain expression). ONE cells and IPSC reprogrammed neurons represent the next generation of cell models in BD. Future studies should focus on family-based study designs and combine cell models with deep sequencing and genetic manipulations. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2013-01-01

    The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM) that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them using such more

  9. Modeling integrated cellular machinery using hybrid Petri-Boolean networks.

    PubMed

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

    2013-01-01

    The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM) that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them using such more

  10. Phononic Band Gaps in 2D Quadratic and 3D Cubic Cellular Structures

    PubMed Central

    Warmuth, Franziska; Körner, Carolin

    2015-01-01

    The static and dynamic mechanical behaviour of cellular materials can be designed by the architecture of the underlying unit cell. In this paper, the phononic band structure of 2D and 3D cellular structures is investigated. It is shown how the geometry of the unit cell influences the band structure and eventually leads to full band gaps. The mechanism leading to full band gaps is elucidated. Based on this knowledge, a 3D cellular structure with a broad full band gap is identified. Furthermore, the dependence of the width of the gap on the geometry parameters of the unit cell is presented. PMID:28793713

  11. A Cellular Automata Based Model for Simulating Surface Hydrological Processes in Catchments

    NASA Astrophysics Data System (ADS)

    Shao, Qi; Baumgartl, Thomas; Huang, Longbin; Weatherley, Dion

    2014-05-01

    The Runoff Model Based on Cellular Automata (RunCA) has been developed to simulate the surface hydrological processes at the catchment scale by integrating basic cellular automata (CA) rules with fundamental measureable hydraulic properties. In this model, a two-dimensional lattice composed of a series of rectangular cells was employed to cover the study area. Runoff production within each cell was simulated by determining its water depth based on the rainfall, interception, infiltration and the balance between inflows and outflows. Particularly different infiltration equations were incorporated to make the model applicable for both single rainfall event (short term simulation) and multiple rainfall events (long term simulation). The distribution of water flow among cells was determined by applying CA transition rules based on the improved minimization-of-difference algorithm and the calculated spatially and temporally varied flow velocities according to the Manning's equation. RunCA was tested and validated at two catchments (Pine Glen Basin and Snow Shoe Basin, USA) with data taken from literature. The predicted hydrographs agreed well with the measured results. Simulated flow maps also demonstrated the model capability in capturing both the spatial and temporal variations in the runoff process. Model sensitivity analysis results showed that the simulated hydrographs were mostly influenced by the input parameters that represent the final steady infiltration rate, as well as the model settings of time step and cell size. Compared to some conventional distributed hydrologic models that calculate the runoff routing process by solving complex continuity equations, this model integrates a novel method and is expected to be more computationally efficient as it is based on simple CA transition rules when determining the flow distribution.

  12. Modeling approaches for qualitative and semi-quantitative analysis of cellular signaling networks

    PubMed Central

    2013-01-01

    A central goal of systems biology is the construction of predictive models of bio-molecular networks. Cellular networks of moderate size have been modeled successfully in a quantitative way based on differential equations. However, in large-scale networks, knowledge of mechanistic details and kinetic parameters is often too limited to allow for the set-up of predictive quantitative models. Here, we review methodologies for qualitative and semi-quantitative modeling of cellular signal transduction networks. In particular, we focus on three different but related formalisms facilitating modeling of signaling processes with different levels of detail: interaction graphs, logical/Boolean networks, and logic-based ordinary differential equations (ODEs). Albeit the simplest models possible, interaction graphs allow the identification of important network properties such as signaling paths, feedback loops, or global interdependencies. Logical or Boolean models can be derived from interaction graphs by constraining the logical combination of edges. Logical models can be used to study the basic input–output behavior of the system under investigation and to analyze its qualitative dynamic properties by discrete simulations. They also provide a suitable framework to identify proper intervention strategies enforcing or repressing certain behaviors. Finally, as a third formalism, Boolean networks can be transformed into logic-based ODEs enabling studies on essential quantitative and dynamic features of a signaling network, where time and states are continuous. We describe and illustrate key methods and applications of the different modeling formalisms and discuss their relationships. In particular, as one important aspect for model reuse, we will show how these three modeling approaches can be combined to a modeling pipeline (or model hierarchy) allowing one to start with the simplest representation of a signaling network (interaction graph), which can later be refined to

  13. Cassini's Grand Finale: The Final Orbits

    NASA Astrophysics Data System (ADS)

    Spilker, Linda; Edgington, Scott

    2016-04-01

    The Cassini-Huygens mission, a joint collaboration between NASA, ESA and the Italian Space Agency, is approaching its last year of operations after nearly 12 years in orbit around Saturn. Cassini will send back its final bits of unique data on September 15th, 2017 as it plunges into Saturn's atmosphere, vaporizing and satisfying planetary protection requirements. Before that time Cassini will continue its legacy of exploration and discovery with 12 close flybys of Titan in 2016 and 2017 that will return new science data as well as sculpt the inclinations and periods of the final orbits. Even though all of our close icy satellite flybys, including those of Enceladus, are now completed, numerous Voyager-class flybys (<100,000 km) of Mimas and Enceladus remain as well as some of our best flybys of the tiny ring moons. Cassini will also continue to study seasonal and temporal changes in the system as northern summer solstice approaches. In November 2016 Cassini will transition to a series of orbits with peripases just outside Saturn's F ring. These 20 orbits will include close flybys of some tiny ring moons and excellent views of the F ring and outer A ring. The 126th and final close flyby of Titan will propel Cassini across Saturn's main rings and into its final orbits. Cassini's Grand Finale, starting in April 2017, is comprised of 22 orbits at an inclination of 63 degrees. Cassini will repeatedly dive between the innermost rings and the upper atmosphere of the planet providing insights into fundamental questions unattainable during the rest of the mission. Cassini will be the first spacecraft to explore this region. These close orbits provide the highest resolution observations of both the rings and Saturn, and direct in situ sampling of the ring particles, composition, plasma, Saturn's exosphere and the innermost radiation belts. Saturn's gravitational field will be measured to unprecedented accuracy, providing information on the interior structure of the planet

  14. Quantum-Dot Cellular Automata

    NASA Astrophysics Data System (ADS)

    Snider, Gregory

    2000-03-01

    Quantum-dot Cellular Automata (QCA) [1] is a promising architecture which employs quantum dots for digital computation. It is a revolutionary approach that holds the promise of high device density and low power dissipation. A basic QCA cell consists of four quantum dots coupled capacitively and by tunnel barriers. The cell is biased to contain two excess electrons within the four dots, which are forced to opposite "corners" of the four-dot cell by mutual Coulomb repulsion. These two possible polarization states of the cell will represent logic "0" and "1". Properly arranged, arrays of these basic cells can implement Boolean logic functions. Experimental results from functional QCA devices built of nanoscale metal dots defined by tunnel barriers will be presented. The experimental devices to be presented consist of Al islands, which we will call quantum dots, interconnected by tunnel junctions and lithographically defined capacitors. Aluminum/ aluminum-oxide/aluminum tunnel junctions were fabricated using a standard e-beam lithography and shadow evaporation technique. The experiments were performed in a dilution refrigerator at a temperature of 70 mK. The operation of a cell is evaluated by direct measurements of the charge state of dots within a cell as the input voltage is changed. The experimental demonstration of a functioning cell will be presented. A line of three cells demonstrates that there are no metastable switching states in a line of cells. A QCA majority gate will also be presented, which is a programmable AND/OR gate and represents the basic building block of QCA systems. The results of recent experiments will be presented. 1. C.S. Lent, P.D. Tougaw, W. Porod, and G.H. Bernstein, Nanotechnology, 4, 49 (1993).

  15. Cellular toxicity of nicotinamide metabolites.

    PubMed

    Rutkowski, Bolesław; Rutkowski, Przemysław; Słomińska, Ewa; Smolenski, Ryszard T; Swierczyński, Julian

    2012-01-01

    There are almost 100 different substances called uremic toxins. Nicotinamide derivatives are known as new family of uremic toxins. These uremic compounds play a role in an increased oxidative stress and disturbances in cellular repair processes by inhibiting poly (ADP-ribose) polymerase activity. New members of this family were discovered and described. Their toxic properties were a subject of recent studies. This study evaluated the concentration of 4-pyridone-3-carboxamid-1-β-ribonucleoside-triphosphate (4PYTP) and 4-pyridone-3-carboxamid-1-β-ribonucleoside-monophosphate (4PYMP) in erythrocytes of patients with chronic renal failure. Serum and red blood cells were collected from chronic renal failure patients on conservative treatment, those treated with hemodialysis, and at different times from those who underwent kidney transplantation. Healthy volunteers served as a control group. Nicotinamide metabolites were determined using liquid chromatography with mass spectrometry based on originally discovered and described method. Three novel compounds were described: 4-pyridone-3-carboxamid-1-β-ribonucleoside (4PYR), 4PYMP, and 4PYTP. 4PYR concentration was elevated in the serum, whereas 4PYMP and 4PYTP concentrations were augmented in erythrocytes of dialysis patients. Interestingly, concentrations of these compounds were less elevated during the treatment with erythropoietin-stimulating agents (ESAs). After successful kidney transplantation, concentrations of 4PYR and 4PYMP normalized according to the graft function, whereas that of 4PYTP was still elevated. During the incubation of erythrocytes in the presence of 4PYR, concentration of 4PYMP rose very rapidly while that of 4PYTP increased slowly. Therefore, we hypothesized that 4PYR, as a toxic compound, was actively absorbed by erythrocytes and metabolized to the 4PYMP and 4PYTP, which may interfere with function and life span of these cells.

  16. [Genetic safety of cellular therapy].

    PubMed

    Bochkov, N P; Voronina, E S; Katosova, L D; Kuleshov, N P; Nikitina, V A; Chausheva, A I

    2011-01-01

    This paper presents the main results of the study on chromosome and genome variability of mesenchymal stem cell cultures from bone marrow and adipose tissue carried out in the Laboratory of Mutagenesis, Research Centre for Medical Genetics, over the last three years. Genome stability was assessed from DNA damage using the DNA comet assay, karyotyping and registration of aneuploidy by the FISH method. We found that DNA damage rate in MSC cultures from bone marrow was 3.9% and 3.8% at the early (2-5) passages and the late (10-15) passages respectively. The cultures were characterized by high dispersion of individual values. Karyotyping showed mosaicism in both types of MSC cultures at the early and late stages of cultivation. The fraction of abnormal cells in some cultures amounted to 80-90%. Evaluation of aneuploidy in interphase cells revealed 1.34% of aneuploid cells (on the average) per one "conventional" chromosome; their overall frequency in the genome amounted to 20-40%. The frequency of aneuploid cells was similar at the early and late passages. Cultures with clones of trisomic and monosomic cells were revealed. The probability of occurrence of abnormal cells may increase by virtue of de novo mutations in the culture and as a result of positive selection of the cells existing in the organism that exhibit a higher reproduction rate in culture. Based on the experimental data on mutational process, selection of mutant cells and clone formation, it is concluded that cytogenetic control of stem cells is necessary to ensure the safety of cellular therapy.

  17. Molecular and cellular limits to somatosensory specificity

    PubMed Central

    Belmonte, Carlos; Viana, Félix

    2008-01-01

    impulse generation can also influence the gating of transducing channels, dramatically modifying their activation profile. Thus, we propose that the capacity exhibited by the different functional types of somatosensory receptor neurons to preferentially detect and encode specific stimuli into a discharge of nerve impulses, appears to result of a characteristic combinatorial expression of different ion channels in each neuronal type that finally determines their transduction and impulse firing properties. Transduction channels don't operate in isolation and their cellular context should also be taken into consideration to fully understand their function. Moreover, the inhomogeneous distribution of transduction and voltage-gated channels at soma, axonal branches and peripheral endings of primary sensory neurons influences the characteristics of the propagated impulse discharge that encodes the properties of the stimulus. Alteration of this concerted operation of ion channels in pathological conditions may underlie the changes in excitability accompanying peripheral sensory neuron injuries. PMID:18419827

  18. Oscillatory cellular patterns in three-dimensional directional solidification

    DOE PAGES

    Tourret, D.; Debierre, J. -M.; Song, Y.; ...

    2015-09-11

    We present a phase-field study of oscillatory breathing modes observed during the solidification of three-dimensional cellular arrays in micro-gravity. Directional solidification experiments conducted onboard the International Space Station have allowed for the first time to observe spatially extended homogeneous arrays of cells and dendrites while minimizing the amount of gravity-induced convection in the liquid. In situ observations of transparent alloys have revealed the existence, over a narrow range of control parameters, of oscillations in cellular arrays with a period ranging from about 25 to 125 minutes. Cellular patterns are spatially disordered, and the oscillations of individual cells are spatiotemporally uncorrelatedmore » at long distance. However, in regions displaying short-range spatial ordering, groups of cells can synchronize into oscillatory breathing modes. Quantitative phase-field simulations show that the oscillatory behavior of cells in this regime is linked to a stability limit of the spacing in hexagonal cellular array structures. For relatively high cellular front undercooling (\\ie low growth velocity or high thermal gradient), a gap appears in the otherwise continuous range of stable array spacings. Close to this gap, a sustained oscillatory regime appears with a period that compares quantitatively well with experiment. For control parameters where this gap exist, oscillations typically occur for spacings at the edge of the gap. However, after a change of growth conditions, oscillations can also occur for nearby values of control parameters where this gap just closes and a continuous range of spacings exists. In addition, sustained oscillations at to the opening of this stable gap exhibit a slow periodic modulation of the phase-shift among cells with a slower period of several hours. While long-range coherence of breathing modes can be achieved in simulations for a perfect spatial arrangement of cells as initial condition, global

  19. Oscillatory cellular patterns in three-dimensional directional solidification

    SciTech Connect

    Tourret, D.; Debierre, J. -M.; Song, Y.; Mota, F. L.; Bergeon, N.; Guerin, R.; Trivedi, R.; Billia, B.; Karma, A.

    2015-09-11

    We present a phase-field study of oscillatory breathing modes observed during the solidification of three-dimensional cellular arrays in micro-gravity. Directional solidification experiments conducted onboard the International Space Station have allowed for the first time to observe spatially extended homogeneous arrays of cells and dendrites while minimizing the amount of gravity-induced convection in the liquid. In situ observations of transparent alloys have revealed the existence, over a narrow range of control parameters, of oscillations in cellular arrays with a period ranging from about 25 to 125 minutes. Cellular patterns are spatially disordered, and the oscillations of individual cells are spatiotemporally uncorrelated at long distance. However, in regions displaying short-range spatial ordering, groups of cells can synchronize into oscillatory breathing modes. Quantitative phase-field simulations show that the oscillatory behavior of cells in this regime is linked to a stability limit of the spacing in hexagonal cellular array structures. For relatively high cellular front undercooling (\\ie low growth velocity or high thermal gradient), a gap appears in the otherwise continuous range of stable array spacings. Close to this gap, a sustained oscillatory regime appears with a period that compares quantitatively well with experiment. For control parameters where this gap exist, oscillations typically occur for spacings at the edge of the gap. However, after a change of growth conditions, oscillations can also occur for nearby values of control parameters where this gap just closes and a continuous range of spacings exists. In addition, sustained oscillations at to the opening of this stable gap exhibit a slow periodic modulation of the phase-shift among cells with a slower period of several hours. While long-range coherence of breathing modes can be achieved in simulations for a perfect spatial arrangement of cells as initial condition, global disorder is

  20. Oscillatory cellular patterns in three-dimensional directional solidification

    NASA Astrophysics Data System (ADS)

    Tourret, D.; Debierre, J.-M.; Song, Y.; Mota, F. L.; Bergeon, N.; Guérin, R.; Trivedi, R.; Billia, B.; Karma, A.

    2015-10-01

    We present a phase-field study of oscillatory breathing modes observed during the solidification of three-dimensional cellular arrays in microgravity. Directional solidification experiments conducted onboard the International Space Station have allowed us to observe spatially extended homogeneous arrays of cells and dendrites while minimizing the amount of gravity-induced convection in the liquid. In situ observations of transparent alloys have revealed the existence, over a narrow range of control parameters, of oscillations in cellular arrays with a period ranging from about 25 to 125 min. Cellular patterns are spatially disordered, and the oscillations of individual cells are spatiotemporally uncorrelated at long distance. However, in regions displaying short-range spatial ordering, groups of cells can synchronize into oscillatory breathing modes. Quantitative phase-field simulations show that the oscillatory behavior of cells in this regime is linked to a stability limit of the spacing in hexagonal cellular array structures. For relatively high cellular front undercooling (i.e., low growth velocity or high thermal gradient), a gap appears in the otherwise continuous range of stable array spacings. Close to this gap, a sustained oscillatory regime appears with a period that compares quantitatively well with experiment. For control parameters where this gap exists, oscillations typically occur for spacings at the edge of the gap. However, after a change of growth conditions, oscillations can also occur for nearby values of control parameters where this gap just closes and a continuous range of spacings exists. In addition, sustained oscillations at to the opening of this stable gap exhibit a slow periodic modulation of the phase-shift among cells with a slower period of several hours. While long-range coherence of breathing modes can be achieved in simulations for a perfect spatial arrangement of cells as initial condition, global disorder is observed in both

  1. Cellular Manufacturing Internet Performance Support System

    SciTech Connect

    Bohley, M.C.; Schwartz, M.E.

    1998-03-04

    The objective of this project was to develop an Internet-based electronic performance support system (EPSS) for cellular manufacturing providing hardware/software specifications, process descriptions, estimated cost savings, manufacturing simulations, training information, and service resources for government and industry users of Cincinnati Milacron machine tools and products. AlliedSignal Federal Manufacturing and Technologies (ASFM and T) used expertise in the areas of Internet design and multimedia creation to develop a performance support system (PSS) for the Internet with assistance from CM's subject matter experts from engineering, manufacturing, and technical support. Reference information was both created and re-purposed from other existing formats, then made available on the Internet. On-line references on cellular manufacturing operations include: definitions of cells and cellular manufacturing; illustrations on how cellular manufacturing improves part throughput, resource utilization, part quality, and manufacturing flexibility; illustrations on how cellular manufacturing reduces labor and overhead costs; identification of critical factors driving decisions toward cellular manufacturing; a method for identifying process improvement areas using cellular manufacturing; a method for customizing the size of cells for a specific site; a simulation for making a part using cellular manufacturing technology; and a glossary of terms and concepts.

  2. Transition from a planar interface to cellular and dendritic structures during rapid solidification processing

    NASA Technical Reports Server (NTRS)

    Laxmanan, V.

    1986-01-01

    The development of theoretical models which characterize the planar-cellular and cell-dendrite transitions is described. The transitions are analyzed in terms of the Chalmers number, the solute Peclet number, and the tip stability parameter, which correlate microstructural features and processing conditions. The planar-cellular transition is examined using the constitutional supercooling theory of Chalmers et al., (1953) and it is observed that the Chalmers number is between 0 and 1 during dendritic and cellular growth. Analysis of cell-dendrite transition data reveal that the transition occurs when the solute Peclet number goes through a minimum, the primary arm spacings go through a maximum, and the Chalmers number is equal to 1/2. The relation between the tip stability parameter and the solute Peclet number is investigated and it is noted that the tip stability parameter is useful for studying dendritic growth in alloys.

  3. Transition from a planar interface to cellular and dendritic structures during rapid solidification processing

    NASA Technical Reports Server (NTRS)

    Laxmanan, V.

    1986-01-01

    The development of theoretical models which characterize the planar-cellular and cell-dendrite transitions is described. The transitions are analyzed in terms of the Chalmers number, the solute Peclet number, and the tip stability parameter, which correlate microstructural features and processing conditions. The planar-cellular transition is examined using the constitutional supercooling theory of Chalmers et al., (1953) and it is observed that the Chalmers number is between 0 and 1 during dendritic and cellular growth. Analysis of cell-dendrite transition data reveal that the transition occurs when the solute Peclet number goes through a minimum, the primary arm spacings go through a maximum, and the Chalmers number is equal to 1/2. The relation between the tip stability parameter and the solute Peclet number is investigated and it is noted that the tip stability parameter is useful for studying dendritic growth in alloys.

  4. Redefining solubility parameters: the partial solvation parameters.

    PubMed

    Panayiotou, Costas

    2012-03-21

    The present work reconsiders a classical and universally accepted concept of physical chemistry, the solubility parameter. Based on the insight derived from modern quantum chemical calculations, a new definition of solubility parameter is proposed, which overcomes some of the inherent restrictions of the original definition and expands its range of applications. The original single solubility parameter is replaced by four partial solvation parameters reflecting the dispersion, the polar, the acidic and the basic character of the chemical compounds as expressed either in their pure state or in mixtures. Simple rules are adopted for the definition and calculation of these four parameters and their values are tabulated for a variety of common substances. In contrast, however, to the well known Hansen solubility parameters, their design and evaluation does not rely exclusively on the basic rule of "similarity matching" for solubility but it makes also use of the other basic rule of compatibility, namely, the rule of "complementarity matching". This complementarity matching becomes particularly operational with the sound definition of the acidic and basic components of the solvation parameter based on the third σ-moments of the screening charge distributions of the quantum mechanics-based COSMO-RS theory. The new definitions are made in a simple and straightforward manner, thus, preserving the strength and appeal of solubility parameter stemming from its simplicity. The new predictive method has been applied to a variety of solubility data for systems of pharmaceuticals and polymers. The results from quantum mechanics calculations are critically compared with the results from Abraham's acid/base descriptors.

  5. The mammary cellular hierarchy and breast cancer.

    PubMed

    Oakes, Samantha R; Gallego-Ortega, David; Ormandy, Christopher J

    2014-11-01

    Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

  6. Cellular stress response mechanisms as therapeutic targets of ginsenosides.

    PubMed

    Qi, Hong-Yi; Li, Li; Ma, Hui

    2017-06-06

    Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure-activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as "the King of all herbs" could be regarded as a well-characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective. © 2017 Wiley Periodicals, Inc.

  7. New Insights Into Cellular Stress Responses to Environmental Metal Toxicants.

    PubMed

    Park, H-R; Oh, R; Wagner, P; Panganiban, R; Lu, Q

    2017-01-01

    Exposures to metal toxicants in the environment disrupt normal physiological functions and have been linked to the development of a myriad of human diseases. While the molecular and cellular mechanisms underlying metal toxicities remain to be fully understood, it is well appreciated that metal toxicants induce cellular stresses and that how cells respond to the stresses plays an important role in metal toxicity. In this review, we focus on how metal exposures induce stresses in the endoplasmic reticulum (ER) to elicit the unfolded protein response (UPR). We document the emerging evidence that induction of ER stress and UPR in the development of human diseases is associated with metal exposures. We also discuss the role of the interplay between ER stress and oxidative stress in metal toxicity. Finally, we review recent advances in functional genomics approaches and discuss how applications of these new tools could help elucidate the molecular mechanisms underlying cellular stresses induced by environmental metal toxicants. © 2017 Elsevier Inc. All rights reserved.

  8. Automated parameter estimation of the Hodgkin-Huxley model using the differential evolution algorithm: application to neuromimetic analog integrated circuits.

    PubMed

    Buhry, Laure; Grassia, Filippo; Giremus, Audrey; Grivel, Eric; Renaud, Sylvie; Saïghi, Sylvain

    2011-10-01

    We propose a new estimation method for the characterization of the Hodgkin-Huxley formalism. This method is an alternative technique to the classical estimation methods associated with voltage clamp measurements. It uses voltage clamp type recordings, but is based on the differential evolution algorithm. The parameters of an ionic channel are estimated simultaneously, such that the usual approximations of classical methods are avoided and all the parameters of the model, including the time constant, can be correctly optimized. In a second step, this new estimation technique is applied to the automated tuning of neuromimetic analog integrated circuits designed by our research group. We present a tuning example of a fast spiking neuron, which reproduces the frequency-current characteristics of the reference data, as well as the membrane voltage behavior. The final goal of this tuning is to interconnect neuromimetic chips as neural networks, with specific cellular properties, for future theoretical studies in neuroscience.

  9. Cellular track model for study of heavy ion beams

    NASA Technical Reports Server (NTRS)

    Shinn, Judy L.; Katz, Robert; Cucinotta, Francis A.; Wilson, John W.; Ngo, Duc M.

    1993-01-01

    Track theory is combined with a realistic model of a heavy ion beam to study the effects of nuclear fragmentation on cell survival and biological effectiveness. The effects of secondary reaction products are studied as a function of depth in a water column. Good agreement is found with experimental results for the survival of human T-l cells exposed to monoenergetic carbon, neon, and argon beams under aerobic and hypoxia conditions. The present calculation, which includes the effect of target fragmentation, is a significant improvement over an earlier calculation because of the use of a vastly improved beam model with no change in the track theory or cellular response parameters.

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

    PubMed

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

    2013-02-28

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

  11. Convergence Time and Phase Transition in a Non-monotonic Family of Probabilistic Cellular Automata

    NASA Astrophysics Data System (ADS)

    Ramos, A. D.; Leite, A.

    2017-08-01

    In dynamical systems, some of the most important questions are related to phase transitions and convergence time. We consider a one-dimensional probabilistic cellular automaton where their components assume two possible states, zero and one, and interact with their two nearest neighbors at each time step. Under the local interaction, if the component is in the same state as its two neighbors, it does not change its state. In the other cases, a component in state zero turns into a one with probability α , and a component in state one turns into a zero with probability 1-β . For certain values of α and β , we show that the process will always converge weakly to δ 0, the measure concentrated on the configuration where all the components are zeros. Moreover, the mean time of this convergence is finite, and we describe an upper bound in this case, which is a linear function of the initial distribution. We also demonstrate an application of our results to the percolation PCA. Finally, we use mean-field approximation and Monte Carlo simulations to show coexistence of three distinct behaviours for some values of parameters α and β.

  12. Cell-to-cell communication in guided bone regeneration: molecular and cellular mechanisms.

    PubMed

    Gruber, Reinhard; Stadlinger, Bernd; Terheyden, Hendrik

    2016-08-23

    This overview provides insights into the molecular and cellular mechanisms involved in guided bone regeneration, in particular focusing on aspects presented in the 3D movie, Cell-To-Cell Communication in Guided Bone Regeneration. The information presented here is based almost exclusively on genetic mouse models in which single genes can be deleted or overexpressed, even in a specific cell type. This information needs to be extrapolated to humans and related to aspects relevant to graft consolidation under the clinical parameters of guided bone regeneration. The overview follows the ground tenor of the Cell-To-Cell Communication series and focuses on aspects of cell-to-cell communication in bone regeneration and guided bone regeneration. Here, we discuss (1) the role of inflammation during bone regeneration, including (2) the importance of the fibrin matrix, and (3) the pleiotropic functions of macrophages. We highlight (4) the origin of bone-forming osteoblasts and bone-resorbing osteoclasts as well as (5) what causes a progenitor cell to mature into an effector cell. (6) We touch on the complex bone adaptation and maintenance after graft consolidation and (7) how osteocytes control this process. Finally, we speculate on (8) how barrier membranes and the augmentation material can modulate graft consolidation.

  13. Periodic forcing in a three-level cellular automata model for a vector-transmitted disease

    NASA Astrophysics Data System (ADS)

    Santos, L. B. L.; Costa, M. C.; Pinho, S. T. R.; Andrade, R. F. S.; Barreto, F. R.; Teixeira, M. G.; Barreto, M. L.

    2009-07-01

    A periodically forced two-dimensional cellular automata model is used to reproduce and analyze the complex spatiotemporal patterns observed in the transmission of vector infectious diseases. The system, which comprises three population levels, is introduced to describe complex features of the dynamics of the vector-transmitted dengue epidemics, known to be very sensitive to seasonal variables. The three coupled levels represent the human, the adult, and immature vector populations. The dynamics includes external seasonality forcing, human and mosquito mobility, and vector control effects. The model parameters, even if bounded to well-defined intervals obtained from reported data, can be selected to reproduce specific epidemic outbursts. In the current study, explicit results are obtained by comparison with actual data retrieved from the time series of dengue epidemics in two cities in Brazil. The results show fluctuations that are not captured by mean-field models. It also reveals the qualitative behavior of the spatiotemporal patterns of the epidemics. In the extreme situation of the absence of external periodic drive, the model predicts a completely distinct long-time evolution. The model is robust in the sense that it is able to reproduce the time series of dengue epidemics of different cities, provided that the forcing term takes into account the local rainfall modulation. Finally, an analysis is provided of the effect of the dependence between epidemics threshold and vector control actions, both in the presence and absence of human mobility factor.

  14. Open boundaries in a cellular automaton model for traffic flow with metastable states.

    PubMed

    Barlovic, Robert; Huisinga, Torsten; Schadschneider, Andreas; Schreckenberg, Michael

    2002-10-01

    The effects of open boundaries in the velocity-dependent randomization (VDR) model, a modified version of the well-known Nagel-Schreckenberg (NaSch) cellular automaton model for traffic flow, are investigated. In contrast to the NaSch model, the VDR model exhibits metastable states and phase separation in a certain density regime. A proper insertion strategy allows us to investigate the whole spectrum of possible system states and the structure of the phase diagram by Monte Carlo simulations. We observe an interesting microscopic structure of the jammed phases, which is different from the one of the NaSch model. For finite systems, the existence of high flow states in a certain parameter regime leads to a special structure of the fundamental diagram measured in the open system. Apart from that, the results are in agreement with an extremal principle for the flow, which has been introduced for models with a unique flow-density relation. Finally, we discuss the application of our findings for a systematic flow optimization. Here some surprising results are obtained, e.g., a restriction of the inflow can lead to an improvement of the total flow through a bottleneck.

  15. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence

    PubMed Central

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID:26805432

  16. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence.

    PubMed

    Bernadotte, Alexandra; Mikhelson, Victor M; Spivak, Irina M

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data.

  17. Leaf development: a cellular perspective

    PubMed Central

    Kalve, Shweta; De Vos, Dirk; Beemster, Gerrit T. S.

    2014-01-01

    Through its photosynthetic capacity the leaf provides the basis for growth of the whole plant. In order to improve crops for higher productivity and resistance for future climate scenarios, it is important to obtain a mechanistic understanding of leaf growth and development and the effect of genetic and environmental factors on the process. Cells are both the basic building blocks of the leaf and the regulatory units that integrate genetic and environmental information into the developmental program. Therefore, to fundamentally understand leaf development, one needs to be able to reconstruct the developmental pathway of individual cells (and their progeny) from the stem cell niche to their final position in the mature leaf. To build the basis for such understanding, we review current knowledge on the spatial and temporal regulation mechanisms operating on cells, contributing to the formation of a leaf. We focus on the molecular networks that control exit from stem cell fate, leaf initiation, polarity, cytoplasmic growth, cell division, endoreduplication, transition between division and expansion, expansion and differentiation and their regulation by intercellular signaling molecules, including plant hormones, sugars, peptides, proteins, and microRNAs. We discuss to what extent the knowledge available in the literature is suitable to be applied in systems biology approaches to model the process of leaf growth, in order to better understand and predict leaf growth starting with the model species Arabidopsis thaliana. PMID:25132838

  18. Cellular and molecular neuronal plasticity.

    PubMed

    Griesbach, Grace S; Hovda, David A

    2015-01-01

    The brain has the capability to adapt to function when tissue is compromised. This capability of adaptation paves the road to recovery and allows for rehabilitation after a traumatic brain injury (TBI). This chapter addresses neuroplasticity within the context of TBI. Here neuroplasticity is defined as changes in neuronal structure and function, including synaptic changes as well as modifications in neural pathways. First, the influence of TBI pathology on neuroplasticity is addressed. Here, proteins that are important in neuroplasticity are introduced and a description given of how these are affected in a temporal and severity-dependent manner. Secondly, given that we are becoming increasingly aware that the brain's response to injury is highly influenced by the environmental milieu, the manner in which behavioral manipulations have an effect on TBI-associated neuroplasticity is addressed. A description is given of how specific environmental qualities may facilitate or hinder neuroplasticity. Finally, the long-term effects of neuroplasticity and the relevance it has to rehabilitation are described.

  19. World Cup Final

    NASA Image and Video Library

    2006-07-05

    On July 9, hundreds of millions of fans worldwide were glued to their television sets watching the final match of the 2006 FIFA World Cup, played in Berlin Olympic stadium Olympiastadion. This image was acquired by NASA Terra spacecraft.

  20. Cassini's Grand Finale

    NASA Astrophysics Data System (ADS)

    Edgington, Scott G.; Spilker, Linda J.

    2016-07-01

    After more than a decade exploring Saturn and its moons, the Cassini mission is in its closing act. Cassini's last year is an encore performance stuffed with science, including a final plunge into Saturn's atmosphere.

  1. Endeavour's Final Voyage

    NASA Image and Video Library

    After nearly two decades of achievements in space, Endeavour makes one last reach for the stars on its 25th and final mission, STS-134. This webcast examines the mission to come and explores the st...

  2. Final focus test beam

    SciTech Connect

    Not Available

    1991-03-01

    This report discusses the following: the Final Focus Test Beam Project; optical design; magnets; instrumentation; magnetic measurement and BPM calibration; mechanical alignment and stabilization; vacuum system; power supplies; control system; radiation shielding and personnel protection; infrastructure; and administration.

  3. Expedition 34 Final Training

    NASA Image and Video Library

    The Expedition 34 crew members conduct final training at the Gagarin Cosmonaut Training Center before their Dec. 19 launch to the International Space Station. Flight Engineers Chris Hadfield, Roman...

  4. Final focus nomenclature

    SciTech Connect

    Erickson, R.

    1986-08-08

    The formal names and common names for all devices in the final focus system of the SLC are listed. The formal names consist of a device type designator, microprocessor designator, and a four-digit unit number. (LEW)

  5. New NLC Final Focus

    SciTech Connect

    Raimondi, P.

    2004-10-11

    A novel design of the Final Focus has recently been proposed [1] and has been adopted now for the Next Linear Collider [2]. This new design has fewer optical elements and is much shorter, nonetheless achieving better chromatic properties. In this paper, the new final focus system is briefly discussed stressing one particular characteristic of the new design--its multi TeV energy reach.

  6. Data breaches. Final rule.

    PubMed

    2008-04-11

    This document adopts, without change, the interim final rule that was published in the Federal Register on June 22, 2007, addressing data breaches of sensitive personal information that is processed or maintained by the Department of Veterans Affairs (VA). This final rule implements certain provisions of the Veterans Benefits, Health Care, and Information Technology Act of 2006. The regulations prescribe the mechanisms for taking action in response to a data breach of sensitive personal information.

  7. Prenatal diazepam induced persisting depression of cellular immune responses.

    PubMed

    Schlumpf, M; Ramseier, H; Lichtensteiger, W

    1989-01-01

    Treatment of pregnant Long Evans rats with a low dose of diazepam (1.25 mg/kg per day s.c.) from gestational day (GD) 14 to 20 resulted in severe and long lasting depression of cellular immune responses in male and female offspring. T lymphocyte proliferation, induced by allogeneic stimulation in mixed lymphocyte culture (MLC) or geneic stimulation in mixed lymphocyte culture (MLC) or mitogenic stimulation (concanavalin A), decreased by 50 % or more over a postnatal period of about 2 months. Treatment of the pregnant dam during the early fetal period, from GD 12 to GD 16, did not significantly affect these immune parameters, whereas treatment during later gestation, from GD 16 to 20, significantly affected T lymphocyte function. Clonazepam, a benzodiazepine with high affinity for the central type benzodiazepine site, also affected cellular immune response in offspring. Our data indicate that benzodiazepine treatment during the fetal period may result in persistent postnatal deficiency of cellular immune responses. The relative role of central and peripheral type benzodiazepine receptor and possible interactions with maternal and fetal pituitary - adrenocortical systems are discussed.

  8. The effect of particle shape and size on cellular uptake.

    PubMed

    Zheng, M; Yu, J

    2016-02-01

    Particle shape and size have been well-recognized to exhibit important effect on drug delivery and as an excellent candidate for drug delivery applications. The recent advances in the "top-down" and "bottom-up" approaches make it possible to develop different shaped and sized polymeric nanostructures, which provide a chance to tailor the shape of the nanostructures as a drug carrier. Presently, a large amount of cellular uptake data is available for particle shape and size effect on drug delivery. However, the effect has not been well formulated or described quantitatively. In the present paper, the dynamic process of the effects of particle shape and size on cellular uptake is analyzed, quantitative expression for the influence of particle shape and size on cellular uptake is proposed on the basis of local geometric feature of particle shape and diffusion approach of a particle in a medium rationally, and the relevant parameters in the formulation are determined by the available test data. The results indicate the validity of the present formulations.

  9. Cellular solidification in a monotectic system

    NASA Technical Reports Server (NTRS)

    Kaukler, W. F.; Curreri, P. A.

    1987-01-01

    Succinonitrile-glycerol, SN-G, transparent organic monotectic alloy is studied with particular attention to cellular growth. The phase diagram is determined, near the monotectic composition, with greater accuracy than previous studies. A solidification interface stability diagram is determined for planar growth. The planar-to-cellular transition is compared to predictions from the Burton, Primm, Schlichter theory. A new technique to determine the solute segregation by Fourier transform infrared spectroscopy is developed. Proposed models that involve the cellular interface for alignment of monotectic second-phase spheres or rods are compared with observations.

  10. Cellular and molecular mechanisms in kidney fibrosis

    PubMed Central

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution. PMID:24892703

  11. Regulation of cellular identity in cancer

    PubMed Central

    Roy, Nilotpal; Hebrok, Matthias

    2015-01-01

    Summary Neoplastic transformation requires changes in cellular identity. Emerging evidence increasingly points to cellular reprogramming, a process during which fully differentiated and functional cells lose aspects of their identity while gaining progenitor characteristics, as a critical early step during cancer initiation. This cell identity crisis persists even at the malignant stage in certain cancers, suggesting that reactivation of progenitor functions supports tumorigenicity. Here, we review recent findings that establish the essential role of cellular reprogramming during neoplastic transformation and the major players involved in it with a special emphasis on pancreatic cancer. PMID:26702828

  12. Passive Noise Filtering by Cellular Compartmentalization.

    PubMed

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity.

  13. Exploring the Cellular Accumulation of Metal Complexes

    PubMed Central

    Puckett, Cindy A.; Ernst, Russell J.; Barton, Jacqueline K.

    2010-01-01

    Transition metal complexes offer great potential as diagnostic and therapeutic agents, and a growing number of biological applications have been explored. To be effective, these complexes must reach their intended target inside the cell. Here we review the cellular accumulation of metal complexes, including their uptake, localization, and efflux. Metal complexes are taken up inside cells through various mechanisms, including passive diffusion and entry through organic and metal transporters. Emphasis is placed on the methods used to examine cellular accumulation, to identify the mechanism(s) of uptake, and to monitor possible efflux. Conjugation strategies that have been employed to improve the cellular uptake characteristics of metal complexes are also described. PMID:20104335

  14. GFP as potential cellular viscosimeter

    NASA Astrophysics Data System (ADS)

    Visser, Antonie J. W. G.; Westphal, Adrie H.; Skakun, Victor V.; Borst, Jan Willem

    2016-09-01

    The molecular dimensions of proteins such as green fluorescent protein (GFP) are large as compared to the ones of solvents like water or glycerol. The microscopic viscosity, which determines the resistance to diffusion of, e.g. GFP, is then the same as that determined from the resistance of the solvent to flow, which is known as macroscopic viscosity. GFP in water/glycerol mixtures senses this macroscopic viscosity, because the translational and rotational diffusion coefficients are proportional to the reciprocal value of the viscosity as predicted by the Stokes-Einstein equations. To test this hypothesis, we have performed time-resolved fluorescence anisotropy (reporting on rotational diffusion) and fluorescence correlation spectroscopy (reporting on translational diffusion) experiments of GFP in water/glycerol mixtures. When the solvent also contains macromolecules of similar or larger dimensions as GFP, the microscopic and macroscopic viscosities can be markedly different and the Stokes-Einstein relations must be adapted. It was established from previous dynamic fluorescence spectroscopy observations of diffusing proteins with dextran polysaccharides as co-solvents (Lavalette et al 2006 Eur. Biophys. J. 35 517-22), that rotation and translation sense a different microscopic viscosity, in which the one arising from rotation is always less than that from translation. A microscopic viscosity parameter is defined that depends on scaling factors between GFP and its immediate environment. The direct consequence is discussed for two reported diffusion coefficients of GFP in living cells.

  15. Short Communication: High Cellular Iron Levels Are Associated with Increased HIV Infection and Replication

    PubMed Central

    Chang, Hsiang-Chun; Bayeva, Marina; Taiwo, Babafemi; Palella, Frank J.; Hope, Thomas J.

    2015-01-01

    Abstract HIV is a pandemic disease, and many cellular and systemic factors are known to alter its infectivity and replication. Earlier studies had suggested that anemia is common in HIV-infected patients; however, higher iron was also observed in AIDS patients prior to the introduction of antiretroviral therapy (ART). Therefore, the relationship between iron and viral infection is not well delineated. To address this issue, we altered the levels of cellular iron in primary CD4+ T cells and showed that higher iron is associated with increased HIV infection and replication. In addition, HIV infection alone leads to increased cellular iron, and several ART drugs increase cellular iron independent of HIV infection. Finally, HIV infection is associated with increased serum iron in HIV-positive patients regardless of treatment with ART. These results establish a relationship between iron and HIV infection and suggest that iron homeostasis may be a viable therapeutic target for HIV. PMID:25291189

  16. Short communication: high cellular iron levels are associated with increased HIV infection and replication.

    PubMed

    Chang, Hsiang-Chun; Bayeva, Marina; Taiwo, Babafemi; Palella, Frank J; Hope, Thomas J; Ardehali, Hossein

    2015-03-01

    HIV is a pandemic disease, and many cellular and systemic factors are known to alter its infectivity and replication. Earlier studies had suggested that anemia is common in HIV-infected patients; however, higher iron was also observed in AIDS patients prior to the introduction of antiretroviral therapy (ART). Therefore, the relationship between iron and viral infection is not well delineated. To address this issue, we altered the levels of cellular iron in primary CD4(+) T cells and showed that higher iron is associated with increased HIV infection and replication. In addition, HIV infection alone leads to increased cellular iron, and several ART drugs increase cellular iron independent of HIV infection. Finally, HIV infection is associated with increased serum iron in HIV-positive patients regardless of treatment with ART. These results establish a relationship between iron and HIV infection and suggest that iron homeostasis may be a viable therapeutic target for HIV.

  17. Novel local rules of cellular automata applied to topology and size optimization

    NASA Astrophysics Data System (ADS)

    Bochenek, Bogdan; Tajs-Zielińska, Katarzyna

    2012-01-01

    Cellular automata are mathematical idealization of physical systems in which the design domains are divided into lattices of cells, states of which are updated synchronously in discrete time steps according to some local rules. The principle of the cellular automata is that global behaviour of the system is governed by cells that only interact with their neighbours. Because of its simplicity and versatility the method has been found as useful tool for structural design, especially that cellular automata methodology can be adopted for both optimal sizing and topology optimization. This article presents the application of the cellular automata concept to topology optimization of plane elastic structures. As to the optimal sizing, the design of columns exposed to loss of stability is also discussed. A new local update rule is proposed, selected optimal design problems are formulated, and finally the article is illustrated by results of numerical optimization.

  18. 76 FR 82179 - Drivers of CMVs: Restricting the Use of Cellular Phones

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration 49 CFR Part 390 Drivers of CMVs: Restricting the Use of Cellular Phones AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Final...

  19. Complex I Disorders: Causes, Mechanisms, and Development of Treatment Strategies at the Cellular Level

    ERIC Educational Resources Information Center

    Valsecchi, Federica; Koopman, Werner J. H.; Manjeri, Ganesh R.; Rodenburg, Richard J.; Smeitink, Jan A. M.; Willems, Peter H. G. M.

    2010-01-01

    Mitochondrial oxidative phosphorylation (OXPHOS) represents the final step in the conversion of nutrients into cellular energy. Genetic defects in the OXPHOS system have an incidence between 1:5,000 and 1:10,000 live births. Inherited isolated deficiency of the first complex (CI) of this system, a multisubunit assembly of 45 different proteins,…

  20. Complex I Disorders: Causes, Mechanisms, and Development of Treatment Strategies at the Cellular Level

    ERIC Educational Resources Information Center

    Valsecchi, Federica; Koopman, Werner J. H.; Manjeri, Ganesh R.; Rodenburg, Richard J.; Smeitink, Jan A. M.; Willems, Peter H. G. M.

    2010-01-01

    Mitochondrial oxidative phosphorylation (OXPHOS) represents the final step in the conversion of nutrients into cellular energy. Genetic defects in the OXPHOS system have an incidence between 1:5,000 and 1:10,000 live births. Inherited isolated deficiency of the first complex (CI) of this system, a multisubunit assembly of 45 different proteins,…

  1. Game level layout generation using evolved cellular automata

    NASA Astrophysics Data System (ADS)

    Pech, Andrew; Masek, Martin; Lam, Chiou-Peng; Hingston, Philip

    2016-01-01

    Design of level layouts typically involves the production of a set of levels which are different, yet display a consistent style based on the purpose of a particular level. In this paper, a new approach to the generation of unique level layouts, based on a target set of attributes, is presented. These attributes, which are learned automatically from an example layout, are used for the off-line evolution of a set of cellular automata rules. These rules can then be used for the real-time generation of level layouts that meet the target parameters. The approach is demonstrated on a set of maze-like level layouts. Results are presented to show the effect of various CA parameters and rule representation.

  2. Cassini's Grand Finale

    NASA Astrophysics Data System (ADS)

    Spilker, L. J.; Edgington, S. G.; Altobelli, N.

    2016-12-01

    After more than 12 years in Saturn orbit, the Cassini-Huygens mission has entered its final year of data collection. Cassini will return its final bits of unique data on 15 September 2017 as it plunges into Saturn's atmosphere, vaporizing and satisfying planetary protection requirements. Since early 2016 Cassini's orbital inclination was slowly increased towards its final inclination. In November Cassini transitioned to a series of 20 orbits with peripases just outside Saturn's F ring that include some of the closest flybys of the tiny ring moons and excellent views of the F ring and outer A ring. Cassini's final close flyby of Titan will propel it across Saturn's main rings and into its final orbits. Cassini's Grand Finale begins in April 2017 and is comprised of 22 orbits at an inclination of 63 degrees. Cassini will repeatedly dive between the innermost ring and Saturn's upper atmosphere providing insights into fundamental questions unattainable during the rest of the mission. It will be the first spacecraft to explore this region. These close orbits provide the highest resolution observations of both the rings and Saturn, and direct in situ sampling of the ring particles' composition, plasma, Saturn's exosphere and the innermost radiation belts. Saturn's gravitational field will be measured to unprecedented accuracy, providing information on Saturn's interior structure and mass distribution in the rings. Probing the magnetic field will give insight into the nature of the magnetic dynamo and the true rotation rate of Saturn's interior. The ion and neutral mass spectrometer will sniff the exosphere and upper atmosphere and examine water-based molecules originating from the rings. The cosmic dust analyzer will sample particle composition from different parts of the main rings. Recent science highlights and science objectives from Cassini's final orbits will be discussed. This work was carried out in part at the Jet Propulsion Laboratory, California Institute of

  3. Cellular heredity in haploid cultures of somatic cells, March 1968-April 1981. Final report

    SciTech Connect

    Freed, J.J.

    1982-03-01

    An account is given of the development and application to cell-culture genetics of unique haploid cell lines from frog embryo developed in this laboratory. Since 1968, the main aim of this project has been to develop the haploid cell system for studies of mutagenesis in culture, particularly by ultraviolet radiation. In the course of this work we isolated chromosomally stable cell lines, derived and characterized a number of variants, and adapted cell hybridization and other methods to this material. Particular emphasis was placed on ultraviolet photobiology, including studies of cell survival, mutagenesis, and pathways of repair of uv-damaged DNA. Although at present less widely used for genetic experiments than mammalian cell lines, the frog cells offer the advantages of authentic haploidy and a favorable repertory of DNA repair pathways for study of uv mutagenesis.

  4. Final Report on the Freeze-Drying of Cellular Materials: Cryopharm Research Report

    DTIC Science & Technology

    1993-09-14

    Buffer Water (msec) III Carbohydrate (sac) Cell Shrinks 1. Freeze 2. Dry • Water (insec) Store Dry Rehydrate Cell f l ; • • • • Swells H-b leaks...With drying , water is removed from the ice phase during primary drying and then is sublimed from thp glassy phase during secondary drying. Normally

  5. Cellular systems for toxicity testing. Final report 1 Sep 82-31 Aug 83

    SciTech Connect

    Williams, G.M.; Dunkel, V.C.; Ray, V.A.

    1983-06-01

    Metabolism and End Points of In Vitro Systems, Cytotoxicity, DNA Damage, Chromosome Effects, Mutagenicity Systems, Mammalian Mutagenesis, Transformation Systems, Effects of Tumor Promoters, Mechanistic Significance and Relevance of Short-Term Tests, Application of Short-Term Tests to Chemical Safety Evaluation, and Poster Papers.

  6. Cellular Therapies Clinical Research Roadmap: Lessons learned on how to move a cellular therapy into a clinical trial

    PubMed Central

    Ouseph, Stacy; Tappitake, Darah; Armant, Myriam; Wesselschmidt, Robin; Derecho, Ivy; Draxler, Rebecca; Wood, Deborah; Centanni, John M.

    2014-01-01

    A clinical research roadmap has been developed as a resource for researchers to identify critical areas and potential pitfalls when transitioning a cellular therapy product from the research laboratory, via and Investigational New Drug (IND) application, into early phase clinical trials. The roadmap describes four key areas; basic and preclinical research, resource development, translational research and good manufacturing practice (GMP), and IND assembly and submission. Basic and preclinical research identifies a new therapeutic concept and demonstrates its potential value using a model of the relevant disease. During resource development the appropriate specialists and the required expertise to bring this product into the clinic are identified (e.g., researchers, regulatory specialists, GMP manufacturing staff, clinicians, and clinical trials staff, etc.). Additionally, the funds required to achieve this goal (or a plan to procure them) are identified. In the next phase the plan to translate the research product into a clinical grade therapeutic is developed. Finally regulatory approval to start the trial must be obtained. In the United States this is done by filing an IND application with the Food and Drug Administration. The NHLBI-funded Production Assistance for Cellular Therapies (PACT) program has facilitated the transition of a variety of cellular therapy products from the laboratory into Phase1/2 trials. The five PACT facilities have assisted investigators by performing translational studies and GMP manufacturing to ensure that cellular products met release specifications and were manufactured safely, reproducibly, and at the appropriate scale. The roadmap resulting from this experience is the focus of this article. PMID:25484311

  7. Cellular interactions with tissue-engineered microenvironments and nanoparticles

    NASA Astrophysics Data System (ADS)

    Pan, Zhi

    Tissue-engineered hydrogels composed of intermolecularlly crosslinked hyaluronan (HA-DTPH) and fibronectin functional domains (FNfds) were applied as a physiological relevant ECM mimic with controlled mechanical and biochemical properties. Cellular interactions with this tissue-engineered environment, especially physical interactions (cellular traction forces), were quantitatively measured by using the digital image speckle correlation (DISC) technique and finite element method (FEM). By correlating with other cell functions such as cell morphology and migration, a comprehensive structure-function relationship between cells and their environments was identified. Furthermore, spatiotemporal redistribution of cellular traction stresses was time-lapse measured during cell migration to better understand the dynamics of cell mobility. The results suggest that the reinforcement of the traction stresses around the nucleus, as well as the relaxation of nuclear deformation, are critical steps during cell migration, serving as a speed regulator, which must be considered in any dynamic molecular reconstruction model of tissue cell migration. Besides single cell migration, en masse cell migration was studied by using agarose droplet migration assay. Cell density was demonstrated to be another important parameter to influence cell behaviors besides substrate properties. Findings from these studies will provide fundamental design criteria to develop novel and effective tissue-engineered constructs. Cellular interactions with rutile and anatase TiO2 nanoparticles were also studied. These particles can penetrate easily through the cell membrane and impair cell function, with the latter being more damaging. The exposure to nanoparticles was found to decrease cell area, cell proliferation, motility, and contractility. To prevent this, a dense grafted polymer brush coating was applied onto the nanoparticle surface. These modified nanoparticles failed to adhere to and penetrate

  8. Transcutical imaging with cellular and subcellular resolution.

    PubMed

    Tao, Xiaodong; Lin, Hui-Hao; Lam, Tuwin; Rodriguez, Ramiro; Wang, Jing W; Kubby, Joel

    2017-03-01

    We demonstrate transcutical structural and functional imaging of neurons labeled with genetically encoded red fluorescent proteins and calcium indicators in the living Drosophila brain with cellular and subcellular resolution.

  9. Transcutical imaging with cellular and subcellular resolution

    PubMed Central

    Tao, Xiaodong; Lin, Hui-Hao; Lam, Tuwin; Rodriguez, Ramiro; Wang, Jing W.; Kubby, Joel

    2017-01-01

    We demonstrate transcutical structural and functional imaging of neurons labeled with genetically encoded red fluorescent proteins and calcium indicators in the living Drosophila brain with cellular and subcellular resolution. PMID:28663828

  10. Expression of Cellular Oncogenes in Human Malignancies

    NASA Astrophysics Data System (ADS)

    Slamon, Dennis J.; Dekernion, Jean B.; Verma, Inder M.; Cline, Martin J.

    1984-04-01

    Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.

  11. Measurement Techniques for Cellular Biomechanics In Vitro

    PubMed Central

    Addae-Mensah, Kweku A; Wikswo, John P

    2014-01-01

    Living cells and tissues experience mechanical forces in their physiological environments that are known to affect many cellular processes. Also of importance are the mechanical properties of cells, as well as the microforces generated by cellular processes themselves in their microenvironments. The difficulty associated with studying these phenomena in vivo has led to alternatives such as using in vitro models. The need for experimental techniques for investigating cellular biomechanics and mechanobiology in vitro has fueled an evolution in the technology used in these studies. Particularly noteworthy are some of the new biomicroelectromechanical systems (BioMEMs) devices and techniques that have been introduced to the field. We describe some of the cellular micromechanical techniques and methods that have been developed for in vitro studies, and provide summaries of the ranges of measured values of various biomechanical quantities. We also briefly address some of our experiences in using these methods and include modifications we have introduced in order to improve them. PMID:18445766

  12. The Roles of Cellular Nanomechanics in Cancer

    PubMed Central

    Yallapu, Murali M.; Katti, Kalpana S.; Katti, Dinesh R.; Mishra, Sanjay R.; Khan, Sheema; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    The biomechanical properties of cells and tissues may be instrumental in increasing our understanding of cellular behavior and cellular manifestations of diseases such as cancer. Nanomechanical properties can offer clinical translation of therapies beyond what are currently employed. Nanomechanical properties, often measured by nanoindentation methods using atomic force microscopy, may identify morphological variations, cellular binding forces, and surface adhesion behaviors that efficiently differentiate normal cells and cancer cells. The aim of this review is to examine current research involving the general use of atomic force microscopy/nanoindentation in measuring cellular nanomechanics; various factors and instrumental conditions that influence the nanomechanical properties of cells; and implementation of nanoindentation methods to distinguish cancer cells from normal cells or tissues. Applying these fundamental nanomechanical properties to current discoveries in clinical treatment may result in greater efficiency in diagnosis, treatment, and prevention of cancer, which ultimately can change the lives of patients. PMID:25137233

  13. Cellular senescence in aging and osteoarthritis.

    PubMed

    Toh, Wei Seong; Brittberg, Mats; Farr, Jack; Foldager, Casper Bindzus; Gomoll, Andreas H; Hui, James Hoi Po; Richardson, James B; Roberts, Sally; Spector, Myron

    2016-12-01

    - It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population.

  14. Exercise: the Cellular 'Fountain of Youth'

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164328.html Exercise: The Cellular 'Fountain of Youth' Intense interval training ... TUESDAY, March 28, 2017 (HealthDay News) -- High-intensity exercise may help older adults reverse certain aspects of ...

  15. Cellular Effects of Perfluorinated Fatty Acids.

    DTIC Science & Technology

    1985-01-01

    TCDD appeared to interfere with fatty acid metabolism leading to an increase in unsaturation. Furthermore, Andersen et al. (2) proposed that such an...increase in cellular unsaturated fatty acids may lead-to excessive membrane fluidity (as indicated by induced changes in red blood cell fragility) and...TASK WORK UNITELEMENT NO. NO. NO. NO. 11. TITLE (include Security Claificati on) ~/~. Cellular Effects of Perfluorinated Fatty Ac ds 12. PERSONAL

  16. Gravimelt Process development. Final report

    SciTech Connect

    Not Available

    1983-06-01

    This final report contains the results of a bench-scale program to continue the development of the TRW proprietary Gravimelt Process for chemically cleaning coal. This project consisted of two major efforts, a laboratory study aimed at identifying parameters which would influence the operation of a bench unit for desulfurization and demineralization of coal and the design, construction and operation of two types of continuous plug-flow type bench-scale fused caustic leachers. This present bench scale project has demonstrated modes for the continuous operation of fused caustic leaching of coal at coal throughputs of 1 to 5 pounds per hour. The remaining process unit operations of leach solutions regeneration and coal washing and filtration should be tested at bench scale together with fused caustic leaching of coal to demonstrate the complete Gravimelt Process. 22 figures, 11 tables.

  17. Myokit: A simple interface to cardiac cellular electrophysiology.

    PubMed

    Clerx, Michael; Collins, Pieter; de Lange, Enno; Volders, Paul G A

    2016-01-01

    Myokit is a new powerful and versatile software tool for modeling and simulation of cardiac cellular electrophysiology. Myokit consists of an easy-to-read modeling language, a graphical user interface, single and multi-cell simulation engines and a library of advanced analysis tools accessible through a Python interface. Models can be loaded from Myokit's native file format or imported from CellML. Model export is provided to C, MATLAB, CellML, CUDA and OpenCL. Patch-clamp data can be imported and used to estimate model parameters. In this paper, we review existing tools to simulate the cardiac cellular action potential to find that current tools do not cater specifically to model development and that there is a gap between easy-to-use but limited software and powerful tools that require strong programming skills from their users. We then describe Myokit's capabilities, focusing on its model description language, simulation engines and import/export facilities in detail. Using three examples, we show how Myokit can be used for clinically relevant investigations, multi-model testing and parameter estimation in Markov models, all with minimal programming effort from the user. This way, Myokit bridges a gap between performance, versatility and user-friendliness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Dirac Cellular Automaton from Split-step Quantum Walk.

    PubMed

    Mallick, Arindam; Chandrashekar, C M

    2016-05-17

    Simulations of one quantum system by an other has an implication in realization of quantum machine that can imitate any quantum system and solve problems that are not accessible to classical computers. One of the approach to engineer quantum simulations is to discretize the space-time degree of freedom in quantum dynamics and define the quantum cellular automata (QCA), a local unitary update rule on a lattice. Different models of QCA are constructed using set of conditions which are not unique and are not always in implementable configuration on any other system. Dirac Cellular Automata (DCA) is one such model constructed for Dirac Hamiltonian (DH) in free quantum field theory. Here, starting from a split-step discrete-time quantum walk (QW) which is uniquely defined for experimental implementation, we recover the DCA along with all the fine oscillations in position space and bridge the missing connection between DH-DCA-QW. We will present the contribution of the parameters resulting in the fine oscillations on the Zitterbewegung frequency and entanglement. The tuneability of the evolution parameters demonstrated in experimental implementation of QW will establish it as an efficient tool to design quantum simulator and approach quantum field theory from principles of quantum information theory.

  19. Dirac Cellular Automaton from Split-step Quantum Walk

    NASA Astrophysics Data System (ADS)

    Mallick, Arindam; Chandrashekar, C. M.

    2016-05-01

    Simulations of one quantum system by an other has an implication in realization of quantum machine that can imitate any quantum system and solve problems that are not accessible to classical computers. One of the approach to engineer quantum simulations is to discretize the space-time degree of freedom in quantum dynamics and define the quantum cellular automata (QCA), a local unitary update rule on a lattice. Different models of QCA are constructed using set of conditions which are not unique and are not always in implementable configuration on any other system. Dirac Cellular Automata (DCA) is one such model constructed for Dirac Hamiltonian (DH) in free quantum field theory. Here, starting from a split-step discrete-time quantum walk (QW) which is uniquely defined for experimental implementation, we recover the DCA along with all the fine oscillations in position space and bridge the missing connection between DH-DCA-QW. We will present the contribution of the parameters resulting in the fine oscillations on the Zitterbewegung frequency and entanglement. The tuneability of the evolution parameters demonstrated in experimental implementation of QW will establish it as an efficient tool to design quantum simulator and approach quantum field theory from principles of quantum information theory.

  20. Dirac Cellular Automaton from Split-step Quantum Walk

    PubMed Central

    Mallick, Arindam; Chandrashekar, C. M.

    2016-01-01

    Simulations of one quantum system by an other has an implication in realization of quantum machine that can imitate any quantum system and solve problems that are not accessible to classical computers. One of the approach to engineer quantum simulations is to discretize the space-time degree of freedom in quantum dynamics and define the quantum cellular automata (QCA), a local unitary update rule on a lattice. Different models of QCA are constructed using set of conditions which are not unique and are not always in implementable configuration on any other system. Dirac Cellular Automata (DCA) is one such model constructed for Dirac Hamiltonian (DH) in free quantum field theory. Here, starting from a split-step discrete-time quantum walk (QW) which is uniquely defined for experimental implementation, we recover the DCA along with all the fine oscillations in position space and bridge the missing connection between DH-DCA-QW. We will present the contribution of the parameters resulting in the fine oscillations on the Zitterbewegung frequency and entanglement. The tuneability of the evolution parameters demonstrated in experimental implementation of QW will establish it as an efficient tool to design quantum simulator and approach quantum field theory from principles of quantum information theory. PMID:27184159

  1. Contaminant effect on cellular metabolic differential pressure curves.

    PubMed

    Milani, Marziale; Ballerini, Monica; Ferraro, L; Zabeo, M; Barberis, M; Cannone, M; Faraone, V

    2004-01-01

    The possibility of a pressure monitoring system by differential pressure sensors to detect contaminant effects on cellular cultures metabolic activity is discussed using Saccharomyces cerevisiae, lymphocyte, and AHH1 cell cultures. Metabolic (aerobic and anaerobic) processes in cells are accompanied by CO(2) production that induces changes in pressure values when cells are cultured in sealed vessels. These values are subsequently converted in voltage units and plotted pressure dynamics versus time. This procedure leads to a standard curve, typical of the cellular line, which characterizes cellular metabolism when all parameters are controlled, such as temperature and nutrients. Different phases appear in the S. cerevisiae differential pressure curve: an initial growth up to a maximum, followed by a decrement that leads to a typical "depression" (pressure values inside the test-tubes are lower than the initial one) after about 35 h from the beginning. The S. cerevisiae differential pressure curve is successfully used to test the effects of chemical (Amuchina, trieline) and physical (UV radiation, blue light, magnetic fields) contaminants. The same technique is applied to lymphocytes and AHH1 cultures to investigate the effects generated by a 72-h exposure to a 50-Hz, 60-microT electromagnetic field. Lymphocyte samples, cultured in a PHA medium, grow less than control ones, but exhibit a greater metabolic activity: changes in the exposure system configuration influence neither sample growth differences nor metabolic response variations between control and irradiated samples, while all the other irradiation parameters remain constant. Control and irradiated lymphocyte samples, without PHA in culture medium, show the same behavior both during irradiation and metabolic test. AHH1 control and irradiated samples show no difference both in growth percentage during irradiation and in metabolic activity. Different cell cultures respond to the same stimulus in different

  2. Transient inter-cellular polymeric linker.

    PubMed

    Ong, Siew-Min; He, Lijuan; Thuy Linh, Nguyen Thi; Tee, Yee-Han; Arooz, Talha; Tang, Guping; Tan, Choon-Hong; Yu, Hanry

    2007-09-01

    Three-dimensional (3D) tissue-engineered constructs with bio-mimicry cell-cell and cell-matrix interactions are useful in regenerative medicine. In cell-dense and matrix-poor tissues of the internal organs, cells support one another via cell-cell interactions, supplemented by small amount of the extra-cellular matrices (ECM) secreted by the cells. Here we connect HepG2 cells directly but transiently with inter-cellular polymeric linker to facilitate cell-cell interaction and aggregation. The linker consists of a non-toxic low molecular-weight polyethyleneimine (PEI) backbone conjugated with multiple hydrazide groups that can aggregate cells within 30 min by reacting with the aldehyde handles on the chemically modified cell-surface glycoproteins. The cells in the cellular aggregates proliferated; and maintained the cortical actin distribution of the 3D cell morphology while non-aggregated cells died over 7 days of suspension culture. The aggregates lost distinguishable cell-cell boundaries within 3 days; and the ECM fibers became visible around cells from day 3 onwards while the inter-cellular polymeric linker disappeared from the cell surfaces over time. The transient inter-cellular polymeric linker can be useful for forming 3D cellular and tissue constructs without bulk biomaterials or extensive network of engineered ECM for various applications.

  3. Recent Advances in Cellular Glycomic Analyses

    PubMed Central

    Furukawa, Jun-ichi; Fujitani, Naoki; Shinohara, Yasuro

    2013-01-01

    A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that control cell-cell adhesion, immune response, microbial pathogenesis and other cellular events. The glycomic profile also reflects cellular alterations, such as development, differentiation and cancerous change. A glycoconjugate-based approach would therefore be expected to streamline discovery of novel cellular biomarkers. Development of such an approach has proven challenging, due to the technical difficulties associated with the analysis of various types of cellular glycomes; however, recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various classes of glycoconjugates. This review focuses on recent advances in the technical aspects of cellular glycomic analyses of major classes of glycoconjugates, including N- and O-linked glycans, derived from glycoproteins, proteoglycans and glycosphingolipids. Articles that unveil the glycomics of various biologically important cells, including embryonic and somatic stem cells, induced pluripotent stem (iPS) cells and cancer cells, are discussed. PMID:24970165

  4. Sub-cellular proteomics of Medicago truncatula

    PubMed Central

    Lee, Jeonghoon; Lei, Zhentian; Watson, Bonnie S.; Sumner, Lloyd W.

    2013-01-01

    Medicago truncatula is a leading model species and substantial molecular, genetic, genomics, proteomics, and metabolomics resources have been developed for this species to facilitate the study of legume biology. Currently, over 60 proteomics studies of M. truncatula have been published. Many of these have focused upon the unique symbiosis formed between legumes and nitrogen fixing rhizobia bacteria, while others have focused on seed development and the specialized proteomes of distinct tissues/organs. These include the characterization of sub-cellular organelle proteomes such as nuclei and mitochondria, as well as proteins distributed in plasma or microsomal membranes from various tissues. The isolation of sub-cellular proteins typically requires a series of steps that are labor-intensive. Thus, efficient protocols for sub-cellular fractionation, purification, and enrichment are necessary for each cellular compartment. In addition, protein extraction, solubilization, separation, and digestion prior to mass spectral identification are important to enhance the detection of low abundance proteins and to increase the overall detectable proportion of the sub-cellular proteome. This review summarizes the sub-cellular proteomics studies in M. truncatula. PMID:23641248

  5. Self-organisation in Cellular Automata with Coalescent Particles: Qualitative and Quantitative Approaches

    NASA Astrophysics Data System (ADS)

    Hellouin de Menibus, Benjamin; Sablik, Mathieu

    2017-06-01

    This article introduces new tools to study self-organisation in a family of simple cellular automata which contain some particle-like objects with good collision properties (coalescence) in their time evolution. We draw an initial configuration at random according to some initial shift-ergodic measure, and use the limit measure to describe the asymptotic behaviour of the automata. We first take a qualitative approach, i.e. we obtain information on the limit measure(s). We prove that only particles moving in one particular direction can persist asymptotically. This provides some previously unknown information on the limit measures of various deterministic and probabilistic cellular automata: 3 and 4-cyclic cellular automata [introduced by Fisch (J Theor Probab 3(2):311-338, 1990; Phys D 45(1-3):19-25, 1990)], one-sided captive cellular automata [introduced by Theyssier (Captive Cellular Automata, 2004)], the majority-traffic cellular automaton, a self stabilisation process towards a discrete line [introduced by Regnault and Rémila (in: Mathematical Foundations of Computer Science 2015—40th International Symposium, MFCS 2015, Milan, Italy, Proceedings, Part I, 2015)]. In a second time we restrict our study to a subclass, the gliders cellular automata. For this class we show quantitative results, consisting in the asymptotic law of some parameters: the entry times [generalising K ůrka et al. (in: Proceedings of AUTOMATA, 2011)], the density of particles and the rate of convergence to the limit measure.

  6. Cellular immune responses to methylcholanthrene-induced fibrosarcoma in BALB/c mice

    PubMed Central

    1975-01-01

    Several in vitro parameters of cellular immunity were examined in BALB/c mice with an experimentally induced fibrosarcoma tumor. The results of capillary migration of spleen cells in high tumor cell dose inoculated mice show appearance of cellular immune response in the early stages of the tumor growth. As the tumor progresses, the cellular response declines and rapidly disappears, culminating in stimulation values near the time of the death of these mice. The blastogenic studies also show early cellular recognition of tumor antigen by mouse spleen cells and whole blood (Z24 h). After the 2nd day following tumor injection, no blast transformation is noted. However, the results obtained with a lower inoculating tumor cell dose demonstrate an initial cellular recognition on the 7th day. This response gradually disappears by the 19th day and remains negative up to the time of the death of these mice. This cellular immunity was confirmed by the cytotoxic experiments showing that the primary cells responsible for this cellular reactivity were the immune cells. An interesting finding was the presence of a factor(s) capable of blocking the cytotoxic effect. The nature and mechanism of this blocking factor(s) is now under investigation. PMID:1185107

  7. GALAPAGOS: from pixels to parameters

    NASA Astrophysics Data System (ADS)

    Barden, Marco; Häußler, Boris; Peng, Chien Y.; McIntosh, Daniel H.; Guo, Yicheng

    2012-05-01

    To automate source detection, two-dimensional light profile Sérsic modelling and catalogue compilation in large survey applications, we introduce a new code Galaxy Analysis over Large Areas: Parameter Assessment by GALFITting Objects from SEXTRACTOR (GALAPAGOS). Based on a single set-up, GALAPAGOS can process a complete set of survey images. It detects sources in the data, estimates a local sky background, cuts postage stamp images for all sources, prepares object masks, performs Sérsic fitting including neighbours and compiles all objects in a final output catalogue. For the initial source detection, GALAPAGOS applies SEXTRACTOR, while GALFIT is incorporated for modelling Sérsic profiles. It measures the background sky involved in the Sérsic fitting by means of a flux growth curve. GALAPAGOS determines postage stamp sizes based on SEXTRACTOR shape parameters. In order to obtain precise model parameters, GALAPAGOS incorporates a complex sorting mechanism and makes use of modern CPU's multiplexing capabilities. It combines SEXTRACTOR and GALFIT data in a single output table. When incorporating information from overlapping tiles, GALAPAGOS automatically removes multiple entries from identical sources. GALAPAGOS is programmed in the Interactive Data Language (IDL). We test the stability and the ability to properly recover structural parameters extensively with artificial image simulations. Moreover, we apply GALAPAGOS successfully to the STAGES data set. For one-orbit Hubble Space Telescope data, a single 2.2-GHz CPU processes about 1000 primary sources per 24 h. Note that GALAPAGOS results depend critically on the user-defined parameter set-up. This paper provides useful guidelines to help the user make sensible choices.

  8. 10 CFR 950.37 - Final agreement or final decision.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Final agreement or final decision. 950.37 Section 950.37 Energy DEPARTMENT OF ENERGY STANDBY SUPPORT FOR CERTAIN NUCLEAR PLANT DELAYS Dispute Resolution Process § 950.37 Final agreement or final decision. (a) If the parties reach a Final Agreement on a contract...

  9. 10 CFR 950.37 - Final agreement or final decision.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Final agreement or final decision. 950.37 Section 950.37 Energy DEPARTMENT OF ENERGY STANDBY SUPPORT FOR CERTAIN NUCLEAR PLANT DELAYS Dispute Resolution Process § 950.37 Final agreement or final decision. (a) If the parties reach a Final Agreement on a contract...

  10. RASSP Final Technical Report.

    DTIC Science & Technology

    1992-10-21

    AD-A258 56211t Ul!Il Hili11111 IMIl Uli GE Aerospace Advanced Technology Laboratories RASSP Final Technical Report DTIC CLIN 0002AB S /= 2 C U...2. REPORT DATE 4 REPORT TYPE AND DATES COVERED October 21, 1992 - Technical Report 5/18/92 - 10/21/92 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Rapid...Prototyping of Application Specific Signal CMDA972-92-R-O017 Processors (RASSP) Program - Stuay Phase Final Technical Report 6. AUTHOR(S) John 6delsh

  11. Parameter Identifiability of Fundamental Pharmacodynamic Models

    PubMed Central

    Janzén, David L. I.; Bergenholm, Linnéa; Jirstrand, Mats; Parkinson, Joanna; Yates, James; Evans, Neil D.; Chappell, Michael J.

    2016-01-01

    Issues of parameter identifiability of routinely used pharmacodynamics models are considered in this paper. The structural identifiability of 16 commonly applied pharmacodynamic model structures was analyzed analytically, using the input-output approach. Both fixed-effects versions (non-population, no between-subject variability) and mixed-effects versions (population, including between-subject variability) of each model structure were analyzed. All models were found to be structurally globally identifiable under conditions of fixing either one of two particular parameters. Furthermore, an example was constructed to illustrate the importance of sufficient data quality and show that structural identifiability is a prerequisite, but not a guarantee, for successful parameter estimation and practical parameter identifiability. This analysis was performed by generating artificial data of varying quality to a structurally identifiable model with known true parameter values, followed by re-estimation of the parameter values. In addition, to show the benefit of including structural identifiability as part of model development, a case study was performed applying an unidentifiable model to real experimental data. This case study shows how performing such an analysis prior to parameter estimation can improve the parameter estimation process and model performance. Finally, an unidentifiable model was fitted to simulated data using multiple initial parameter values, resulting in highly different estimated uncertainties. This example shows that although the standard errors of the parameter estimates often indicate a structural identifiability issue, reasonably “good” standard errors may sometimes mask unidentifiability issues. PMID:27994553

  12. Pseudo-epidermis: A model system for investigating molecular and cellular pathways of cutaneous epidermal toxicity from sulfur mustard

    SciTech Connect

    Bernstein, I.A.; Bernstam, L.I.; Yang, Y.H.; Lin, P.P.; Vaughan, F.L.

    1993-05-13

    Damage to DNA, Inhibition of DNA replication and mitosis, appearance of abnormal keratin peptide and large differentiated cells and, finally, death of cells occur dose- and time-responsively in submerged cultures of keratinocytes exposed to bis-(b-chloroethyl)sulfide (BCES). However, the relevance of these parameters to vesication in human skin exposed to mustard in vivo has yet to be established. The pseudo-epidermis cultured from human cutaneous keratinocytes offers a system in which the pathogenic importance of each of these parameters can be evaluated. To establish the validity of the system, it is necessary to show that the pseudo-epidermis undergoes similar dose- and time-dependent cytotoxicity from BCES as is observed in the human skin after topical exposure to the mustard. This report includes data which demonstrate a dose- and time-dependent destruction of the germinative layer in human pseudo-epidermis after topical application of BCES. In addition, data are included to show that DNA is a primary target for BCES in pseudo-epidermis as it is in vivo. Also included in this report is a proposed sequence of molecular and cellular events to account for cytotoxicity in the germinative population of the pseudo-epidermis after exposure to BCES.

  13. HYDROGEN ATOM THERMAL PARAMETERS.

    PubMed

    JENSEN, L H; SUNDARALINGAM, M

    1964-09-11

    Isotropic hydrogen atom thermal parameters for N,N'- hexamethylenebispropionamide have been determined. They show a definite trend and vary from approximately the same as the mean thermal parameters for atoms other than hydrogen near the center of the molecule to appreciably greater for atoms near the end. The indicated trend for this compound, along with other results, provides the basis for a possible explanation of the anomolous values that have been obtained for hydrogen atom thermal parameters.

  14. Parameter Plane Design Method

    DTIC Science & Technology

    1989-03-01

    Th usr a toente aninteer a thca sms b esta 1 Fp-ocsing 2. Enter P1 values, lwgt, ldig - > 9 Table I give us proper values. Table 1. PARAMETER TABLE...necessary and identify by block number) In this thesis a control systems analysis package is developed using parameter plane methods. It is an interactive...designer is able to choose values of the parameters which provide a good compromise between cost and dynamic behavior. 20 Distribution Availability of

  15. FINAL SCIENTIFIC/TECHNICAL REPORT

    SciTech Connect

    Satish Mohapatra

    2011-12-21

    Dynalene Inc has developed and patented a fuel cell coolant with the help of DOE SBIR Phase I and Phase II funding (Project DE-FG02-04ER83884). However, this coolant could only be produced in lab scale (500 ml to 2 L) due to problems in the optimization and scale-up of a nanoparticle ingredient. This project optimized the nanoparticle production process in 10 L and 100 L reactors (which translates to about 5000 gallons of coolant), optimized the filtration process for the nanoparticles, and develop a high throughput production as well as quality control method for the final coolant formulation. Scale-up of nanoparticle synthesis (using emulsion polymerization) is an extremely challenging task. Dynalene researchers, in collaboration with a university partner, identified all the parameters affecting the size, charge density and coagulation characteristics of the nanoparticles and then optimized these parameters to achieve the goals and the objectives of this project. Nanoparticle synthesis was demonstrated to be reproducible in the 10 L and 100 L scales.

  16. Project Adobe. Final Report.

    ERIC Educational Resources Information Center

    Van Curen, Sallie A.

    This final report describes activities and accomplishments of Project Adobe, the New Mexico Parent Training and Information Center, which provides information, support, education and training to families with school-aged children with disabilities in their local communities. Achievements include: (1) completion and printing of a booklet on the…

  17. Final Technical Report

    SciTech Connect

    Gilbert, Chris

    2014-11-13

    The project, Capital Investment to Fund Equipment Purchases and Facility Modifications to Create a Sustainable Future for EnergyXchange served to replace landfill gas energy with alternative energy resources, primarily solar and wood waste. This is the final project closeout report.

  18. Final FDA inspection manual.

    PubMed

    Donawa, M

    2001-04-01

    For some time now, the only publicly available compliance programme guidance manual on medical device inspections and administrative and enforcement activities has been a draft document. On 7 February 2001, a final guidance document was issued. This article discusses this document and its importance to non-US medical device manufacturers preparing for FDA facility inspections.

  19. Final Prep on SSME

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Alvin Pittman Sr., lead electronics technician with Pratt & Whitney Rocketdyne, and Janine Cuevas, a mechanical technician with PWR, perform final preparations on the space shuttle main engine tested Oct. 25, 2005, at NASA's Stennis Space Center. It was the first main engine test since Hurricane Katrina hit the Gulf Coast on Aug. 29.

  20. GENIE final state interactions

    SciTech Connect

    Dytman, Steven

    2015-10-15

    Final state interactions are an important component of any neutrino-nucleus Monte Carlo program. GENIE has 2 FSI programs which serve different purposes. Each has fair-good agreement with a wide range of hadron-nucleus data. Recent improvements and planned advancements are described.

  1. Rosetta: The Final Furlong

    NASA Astrophysics Data System (ADS)

    Wright, I. P.; Andrews, D. J.; Barber, S. J.; Sheridan, S.; Morgan, G. H.; Morse, A. D.

    2014-09-01

    By the time of the meeting, the Rosetta spacecraft will have formally arrived at its target comet, and final landing site selection will be in progress. One of the instruments that will be sent down to the surface of the comet is Ptolemy (a GC-MS).

  2. Final Prep on SSME

    NASA Image and Video Library

    2005-10-25

    Alvin Pittman Sr., lead electronics technician with Pratt & Whitney Rocketdyne, and Janine Cuevas, a mechanical technician with PWR, perform final preparations on the space shuttle main engine tested Oct. 25, 2005, at NASA's Stennis Space Center. It was the first main engine test since Hurricane Katrina hit the Gulf Coast on Aug. 29.

  3. GRCop-84 Rolling Parameter Study

    NASA Technical Reports Server (NTRS)

    Loewenthal, William S.; Ellis, David L.

    2008-01-01

    This report is a section of the final report on the GRCop-84 task of the Constellation Program and incorporates the results obtained between October 2000 and September 2005, when the program ended. NASA Glenn Research Center (GRC) has developed a new copper alloy, GRCop-84 (Cu-8 at.% Cr-4 at.% Nb), for rocket engine main combustion chamber components that will improve rocket engine life and performance. This work examines the sensitivity of GRCop-84 mechanical properties to rolling parameters as a means to better define rolling parameters for commercial warm rolling. Experiment variables studied were total reduction, rolling temperature, rolling speed, and post rolling annealing heat treatment. The responses were tensile properties measured at 23 and 500 C, hardness, and creep at three stress-temperature combinations. Understanding these relationships will better define boundaries for a robust commercial warm rolling process. The four processing parameters were varied within limits consistent with typical commercial production processes. Testing revealed that the rolling-related variables selected have a minimal influence on tensile, hardness, and creep properties over the range of values tested. Annealing had the expected result of lowering room temperature hardness and strength while increasing room temperature elongations with 600 C (1112 F) having the most effect. These results indicate that the process conditions to warm roll plate and sheet for these variables can range over wide levels without negatively impacting mechanical properties. Incorporating broader process ranges in future rolling campaigns should lower commercial rolling costs through increased productivity.

  4. Studies on the control of plant cell enlargement by cellular parameters

    SciTech Connect

    Cleland, R.E.

    1991-12-06

    The overall goal of this grant was to conduct research that would illuminate the mechanisms by which the plant hormone auxin induces plant cells to enlarge. A large body of knowledge already existed concerning this process. To begin with, it had been demonstrated, primarily by this laboratory during previous grant periods, that the effect of auxin is to cause a loosening of the cell wall, which is followed by turgor-driven wall expansion and water uptake. The wall contains a series of load-bearing wall bonds which must be cleaved in order to loosen the wall. The identification of these load-bearing bonds is one goal of this research. We proposed that an initial action of auxin is to cause cells to excrete protons, and that the resulting acidification of the apoplast activated enzymes responsible for wall loosening. Evidence has been obtained that indicates that the proton excretion is due to an enhanced activity of the plasma membrane H{sup +} {minus}ATPase. A critical question is how auxin activates this enzyme. The third project concerned the role of wall calcium as part of load-bearing wall bonds. It has long been thought that apoplastic calcium crosslinks carboxyl groups in the wall pectic substances and stiffens the walls. We examined the role of calcium-bridges as load-bearing bonds in soybean hypocotyl cell walls in two ways. The first was to measure the viscoelastic extensibility of walls after addition of exogenous calcium or removal of endogenous calcium. The second approach was to determine if removal of wall calcium from walls while under tension resulted in wall extension, as predicted if the calcium-bridges were load-bearing bonds.

  5. Identification of optimal parameter combinations for the emergence of bistability.

    PubMed

    Májer, Imre; Hajihosseini, Amirhossein; Becskei, Attila

    2015-11-24

    Bistability underlies cellular memory and maintains alternative differentiation states. Bistability can emerge only if its parameter range is either physically realizable or can be enlarged to become realizable. We derived a general rule and showed that the bistable range of a reaction parameter is maximized by a pair of other parameters in any gene regulatory network provided they satisfy a general condition. The resulting analytical expressions revealed whether or not such reaction pairs are present in prototypical positive feedback loops. They are absent from the feedback loop enclosed by protein dimers but present in both the toggle-switch and the feedback circuit inhibited by sequestration. Sequestration can generate bistability even at narrow feedback expression range at which cooperative binding fails to do so, provided inhibition is set to an optimal value. These results help to design bistable circuits and cellular reprogramming and reveal whether bistability is possible in gene networks in the range of realistic parameter values.

  6. Final Technical Report

    SciTech Connect

    W. C. Griffith

    2007-01-01

    In this project we provide an example of how to develop multi-tiered models to go across levels of biological organization to provide a framework for relating results of studies of low doses of ionizing radiation. This framework allows us to better understand how to extrapolate laboratory results to policy decisions, and to identify future studies that will increase confidence in policy decisions. In our application of the conceptual Model we were able to move across multiple levels of biological assessment for rodents going from molecular to organism level for in vitro and in vivo endpoints and to relate these to human in vivo organism level effects. We used the rich literature on the effects of ionizing radiation on the developing brain in our models. The focus of this report is on disrupted neuronal migration due to radiation exposure and the structural and functional implications of these early biological effects. The cellular mechanisms resulting in pathogenesis are most likely due to a combination of the three mechanisms mentioned. For the purposes of a computational model, quantitative studies of low dose radiation effects on migration of neuronal progenitor cells in the cerebral mantle of experimental animals were used. In this project we were able to show now results from studies of low doses of radiation can be used in a multidimensional framework to construct linked models of neurodevelopment using molecular, cellular, tissue, and organ level studies conducted both in vitro and in vivo in rodents. These models could also be linked to behavioral endpoints in rodents which can be compared to available results in humans. The available data supported modeling to 10 cGy with limited data available at 5 cGy. We observed gradual but non-linear changes as the doses decreased. For neurodevelopment it appears that the slope of the dose response decreases from 25 cGy to 10 cGy. Future studies of neurodevelopment should be able to better define the dose response in

  7. Tsonis final project report

    SciTech Connect

    Duane, Greg; Tsonis, Anastasios; Kocarev, Ljupco; Tribbia, Joseph

    2014-11-20

    This collaborative reserach has several components but the main idea is that when imperfect copies of a given nonlinear dynamical system are coupled, they may synchronize for some set of coupling parameters. This idea is to be tested for several IPCC-like models each one with its own formulation and representing an “imperfect” copy of the true climate system. By computing the coupling parameters, which will lead the models to a synchronized state, a consensus on climate change simulations may be achieved.

  8. Progressive utterance-final lengthening in syllables with final fricatives.

    PubMed

    Berkovits, R

    1993-01-01

    The generality of the pattern of progressively greater lengthening within the utterance-final syllable, previously found with respect to final stops, is shown to extend to syllables in Hebrew with final fricatives. Seven native speakers of Hebrew read matched sentence pairs in which bisyllabic key words appeared in non-final and sentence-final position. Final fricatives showed almost four times as much utterance-final lengthening as the preceding stressed vowel. Final lengthening affected the duration of each segment of the final syllable, and also extended to the initial unstressed syllable of the final word. Though final fricatives showed more lengthening in sentence-final position than final-stop closures, no difference was found in the lengthening of the vowels preceding these consonants. The greater lengthening of the final fricative relative to the preceding vowel resulted in C/V ratios which failed to distinguish between the voiceless fricative in non-final position and the voiced fricative in utterance-final position. These results suggest that sentence position is taken into account in the perception of voicing, such that the C/V ratio applicable in non-final position is increased by a factor of two in final position.

  9. Relations between demographic parameters.

    PubMed

    Demetrius, L

    1979-05-01

    The mean life-expectancy e describes the average prospective life-time of an individual aged zero. This parameter can be explicitly described in terms of the survivorship distribution of the population. The Malthusian parameter r represents the asymptotic growth rate of a population. This parameter can be implicitly expressed in terms of the net-maternity distribution. The parameters e and r incompletely incorporate the age-specific fertility and mortality pattern of a population; distinct populations may have the same growth rate but different net-maternity functions; distinct populations may be characterized by the same mean life expectation but may have different survivorship distributions. This article analyzes a class of parameters called the entropy of a population (Demetrius, 1974a) which distinguishes between net-maternity functions with the same growth rate and also mortality distributions with the same mean life expectation. This class of parameters measures the convexity of the fertility and mortality distributions. This paper analyzes the relations between the entropy parameter and the standard demographic parameters.

  10. Complexity, dynamic cellular network, and tumorigenesis.

    PubMed

    Waliszewski, P

    1997-01-01

    A holistic approach to tumorigenesis is proposed. The main element of the model is the existence of dynamic cellular network. This network comprises a molecular and an energetistic structure of a cell connected through the multidirectional flow of information. The interactions within dynamic cellular network are complex, stochastic, nonlinear, and also involve quantum effects. From this non-reductionist perspective, neither tumorigenesis can be limited to the genetic aspect, nor the initial event must be of molecular nature, nor mutations and epigenetic factors are mutually exclusive, nor a link between cause and effect can be established. Due to complexity, an unstable stationary state of dynamic cellular network rather than a group of unrelated genes determines the phenotype of normal and transformed cells. This implies relativity of tumor suppressor genes and oncogenes. A bifurcation point is defined as an unstable state of dynamic cellular network leading to the other phenotype-stationary state. In particular, the bifurcation point may be determined by a change of expression of a single gene. Then, the gene is called bifurcation point gene. The unstable stationary state facilitates the chaotic dynamics. This may result in a fractal dimension of both normal and tumor tissues. The co-existence of chaotic dynamics and complexity is the essence of cellular processes and shapes differentiation, morphogenesis, and tumorigenesis. In consequence, tumorigenesis is a complex, unpredictable process driven by the interplay between self-organisation and selection.

  11. At a glance: cellular biology for engineers.

    PubMed

    Khoshmanesh, K; Kouzani, A Z; Nahavandi, S; Baratchi, S; Kanwar, J R

    2008-10-01

    Engineering contributions have played an important role in the rise and evolution of cellular biology. Engineering technologies have helped biologists to explore the living organisms at cellular and molecular levels, and have created new opportunities to tackle the unsolved biological problems. There is now a growing demand to further expand the role of engineering in cellular biology research. For an engineer to play an effective role in cellular biology, the first essential step is to understand the cells and their components. However, the stumbling block of this step is to comprehend the information given in the cellular biology literature because it best suits the readers with a biological background. This paper aims to overcome this bottleneck by describing the human cell components as micro-plants that form cells as micro-bio-factories. This concept can accelerate the engineers' comprehension of the subject. In this paper, first the structure and function of different cell components are described. In addition, the engineering attempts to mimic various cell components through numerical modelling or physical implementation are highlighted. Next, the interaction of different cell components that facilitate complicated chemical processes, such as energy generation and protein synthesis, are described. These complex interactions are translated into simple flow diagrams, generally used by engineers to represent multi-component processes.

  12. Magnetic fields, radicals and cellular activity.

    PubMed

    Montoya, Ryan D

    2017-01-01

    Some effects of low-intensity magnetic fields on the concentration of radicals and their influence on cellular functions are reviewed. These fields have been implicated as a potential modulator of radical recombination rates. Experimental evidence has revealed a tight coupling between cellular function and radical pair chemistry from signaling pathways to damaging oxidative processes. The effects of externally applied magnetic fields on biological systems have been extensively studied, and the observed effects lack sufficient mechanistic understanding. Radical pair chemistry offers a reasonable explanation for some of the molecular effects of low-intensity magnetic fields, and changes in radical concentrations have been observed to modulate specific cellular functions. Applied external magnetic fields have been shown to induce observable cellular changes such as both inhibiting and accelerating cell growth. These and other mechanisms, such as cell membrane potential modulation, are of great interest in cancer research due to the variations between healthy and deleterious cells. Radical concentrations demonstrate similar variations and are indicative of a possible causal relationship. Radicals, therefore, present a possible mechanism for the modulation of cellular functions such as growth or regression by means of applied external magnetic fields.

  13. Force field parameters for S-nitrosocysteine and molecular dynamics simulations of S-nitrosated thioredoxin

    SciTech Connect

    Han, Sanghwa

    2008-12-12

    Estimation of structural perturbation induced by S-nitrosation is important to understand the mode of cellular signal transduction mediated by nitric oxide. Crystal structures of S-nitrosated proteins have been solved only for a few cases, however, so that molecular dynamics simulation may provide an alternative tool for probing structural perturbation. In this study AMBER-99 force field parameters for S-nitrosocysteine were developed and applied to molecular dynamics simulations of S-nitrosated thioredoxin. Geometry optimization at the level of HF/6-31G* was followed by a restrained electrostatic potential charge-fitting to obtain the atomic charges of S-nitrosocysteine. Force constants for bonds and angles were obtained from generalized AMBER force field. Torsional force constants for CC-SN and CS-NO were determined by fitting the torsional profiles obtained from geometry optimization with those from molecular mechanical energy minimization. Finally molecular dynamics simulations were performed with theses parameters on oxidized and reduced thioredoxin with and without S-nitrosocysteine. In all cases the root-mean-square deviations of {alpha}-carbons yielded well-behaved trajectories. The CC-SH dihedral angle which fluctuated severely during the simulation became quiet upon S-nitrosation. In conclusion the force field parameters developed in this study for S-nitrosocysteine appear to be suitable for molecular dynamics simulations of S-nitrosated proteins.

  14. Force field parameters for S-nitrosocysteine and molecular dynamics simulations of S-nitrosated thioredoxin.

    PubMed

    Han, Sanghwa

    2008-12-12

    Estimation of structural perturbation induced by S-nitrosation is important to understand the mode of cellular signal transduction mediated by nitric oxide. Crystal structures of S-nitrosated proteins have been solved only for a few cases, however, so that molecular dynamics simulation may provide an alternative tool for probing structural perturbation. In this study AMBER-99 force field parameters for S-nitrosocysteine were developed and applied to molecular dynamics simulations of S-nitrosated thioredoxin. Geometry optimization at the level of HF/6-31G * was followed by a restrained electrostatic potential charge-fitting to obtain the atomic charges of S-nitrosocysteine. Force constants for bonds and angles were obtained from generalized AMBER force field. Torsional force constants for CC-SN and CS-NO were determined by fitting the torsional profiles obtained from geometry optimization with those from molecular mechanical energy minimization. Finally molecular dynamics simulations were performed with theses parameters on oxidized and reduced thioredoxin with and without S-nitrosocysteine. In all cases the root-mean-square deviations of alpha-carbons yielded well-behaved trajectories. The CC-SH dihedral angle which fluctuated severely during the simulation became quiet upon S-nitrosation. In conclusion the force field parameters developed in this study for S-nitrosocysteine appear to be suitable for molecular dynamics simulations of S-nitrosated proteins.

  15. Design of a bistable switch to control cellular uptake.

    PubMed

    Oyarzún, Diego A; Chaves, Madalena

    2015-12-06

    Bistable switches are widely used in synthetic biology to trigger cellular functions in response to environmental signals. All bistable switches developed so far, however, control the expression of target genes without access to other layers of the cellular machinery. Here, we propose a bistable switch to control the rate at which cells take up a metabolite from the environment. An uptake switch provides a new interface to command metabolic activity from the extracellular space and has great potential as a building block in more complex circuits that coordinate pathway activity across cell cultures, allocate metabolic tasks among different strains or require cell-to-cell communication with metabolic signals. Inspired by uptake systems found in nature, we propose to couple metabolite import and utilization with a genetic circuit under feedback regulation. Using mathematical models and analysis, we determined the circuit architectures that produce bistability and obtained their design space for bistability in terms of experimentally tuneable parameters. We found an activation-repression architecture to be the most robust switch because it displays bistability for the largest range of design parameters and requires little fine-tuning of the promoters' response curves. Our analytic results are based on on-off approximations of promoter activity and are in excellent qualitative agreement with simulations of more realistic models. With further analysis and simulation, we established conditions to maximize the parameter design space and to produce bimodal phenotypes via hysteresis and cell-to-cell variability. Our results highlight how mathematical analysis can drive the discovery of new circuits for synthetic biology, as the proposed circuit has all the hallmarks of a toggle switch and stands as a promising design to control metabolic phenotypes across cell cultures. © 2015 The Author(s).

  16. Design of a bistable switch to control cellular uptake

    PubMed Central

    Oyarzún, Diego A.; Chaves, Madalena

    2015-01-01

    Bistable switches are widely used in synthetic biology to trigger cellular functions in response to environmental signals. All bistable switches developed so far, however, control the expression of target genes without access to other layers of the cellular machinery. Here, we propose a bistable switch to control the rate at which cells take up a metabolite from the environment. An uptake switch provides a new interface to command metabolic activity from the extracellular space and has great potential as a building block in more complex circuits that coordinate pathway activity across cell cultures, allocate metabolic tasks among different strains or require cell-to-cell communication with metabolic signals. Inspired by uptake systems found in nature, we propose to couple metabolite import and utilization with a genetic circuit under feedback regulation. Using mathematical models and analysis, we determined the circuit architectures that produce bistability and obtained their design space for bistability in terms of experimentally tuneable parameters. We found an activation–repression architecture to be the most robust switch because it displays bistability for the largest range of design parameters and requires little fine-tuning of the promoters' response curves. Our analytic results are based on on–off approximations of promoter activity and are in excellent qualitative agreement with simulations of more realistic models. With further analysis and simulation, we established conditions to maximize the parameter design space and to produce bimodal phenotypes via hysteresis and cell-to-cell variability. Our results highlight how mathematical analysis can drive the discovery of new circuits for synthetic biology, as the proposed circuit has all the hallmarks of a toggle switch and stands as a promising design to control metabolic phenotypes across cell cultures. PMID:26674196

  17. LTFT Operating Parameters

    SciTech Connect

    Brown, Donald W.; Albright, James N.

    1989-04-18

    In order to finalize planning, the following specifications are recommended for the operation of the LTFT. Although operation of the reservoir under the specified conditions provides for a comprehensive evaluation of the Phase II reservoir.

  18. Failure probability under parameter uncertainty.

    PubMed

    Gerrard, R; Tsanakas, A

    2011-05-01

    In many problems of risk analysis, failure is equivalent to the event of a random risk factor exceeding a given threshold. Failure probabilities can be controlled if a decisionmaker is able to set the threshold at an appropriate level. This abstract situation applies, for example, to environmental risks with infrastructure controls; to supply chain risks with inventory controls; and to insurance solvency risks with capital controls. However, uncertainty around the distribution of the risk factor implies that parameter error will be present and the measures taken to control failure probabilities may not be effective. We show that parameter uncertainty increases the probability (understood as expected frequency) of failures. For a large class of loss distributions, arising from increasing transformations of location-scale families (including the log-normal, Weibull, and Pareto distributions), the article shows that failure probabilities can be exactly calculated, as they are independent of the true (but unknown) parameters. Hence it is possible to obtain an explicit measure of the effect of parameter uncertainty on failure probability. Failure probability can be controlled in two different ways: (1) by reducing the nominal required failure probability, depending on the size of the available data set, and (2) by modifying of the distribution itself that is used to calculate the risk control. Approach (1) corresponds to a frequentist/regulatory view of probability, while approach (2) is consistent with a Bayesian/personalistic view. We furthermore show that the two approaches are consistent in achieving the required failure probability. Finally, we briefly discuss the effects of data pooling and its systemic risk implications.

  19. Final Technical Report

    SciTech Connect

    Maxwell, Mike, J., P.E.

    2012-08-30

    The STI product is the Final Technical Report from ReliOn, Inc. for contract award DE-EE0000487: Recovery Act PEM Fuel Cell Systems Providing Emergency Reserve and Backup Power. The program covered the turnkey deployment of 431 ReliOn fuel cell systems at 189 individual sites for AT&T and PG&E with ReliOn functioning as the primary equipment supplier and the project manager. The Final Technical Report provides an executive level summary, a comparison of the actual accomplishments vs. the goals and objectives of the project, as well as a summary of the project activity from the contract award date of August 1, 2009 through the contract expiration date of December 31, 2011. Two photos are included in the body of the report which show hydrogen storage and bulk hydrogen refueling technologies developed as a result of this program.

  20. Development and Evaluation of a Cellular Automata Model for Simulating Tillage Erosion in the Presence of Obstacles

    NASA Astrophysics Data System (ADS)

    Vanwalleghem, T.; Jiménez-Hornero, F. J.; Giráldez, J. V.; Laguna, A.

    2009-04-01

    The process of tillage translocation is well studied and can be described adequately by different existing models. Nevertheless, in complex environments such as olive orchards, characterized by numerous obstacles, application of such conventional tillage erosion models is not straightforward. However, these obstacles have important effects on the spatial pattern of soil redistribution and on resulting soil properties. In this kind of environment, cellular automata could provide a valuable alternative. This study aims at developing a cellular automata model for tillage translocation (CATT) that can take into account such obstacles and at exploring its possibilities and limitations. A simple model was developed, which main parameters are tillage direction, speed and depth. Firstly, the modeĺs outcome was tested against existing 137Cs inventories for a study site in the Belgian loam belt. The observed spatial soil redistribution patterns could be adequately represented by the CATT model. Secondly, a sensitivity analysis was performed to explore the effect of input uncertainty on several selected model outputs. The variance-based extended FAST method was used to determine first and total order sensitivity indices. Tillage depth was identified as the input parameter that determined most of the output variance, followed respectively by tillage direction and speed. The difference between the total and first-order sensitivity indices, between 0.8 and 2, indicated that, in spite of the simple model structure, the model behaves non-linearly with respect to some of the model output variables. Higher-order interactions were especially important for determining the proportion of eroding and deposition cells. Finally, simulations were performed to analyse the model behaviour in complex landscapes, applying it to a field with protruding obstacles (e.g. olive trees). The model adequately represented some morphological features observed in the olive orchards, such as mounds around

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

    PubMed

    Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

    2011-01-01

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

  2. Kinetic Theory Approach to Modeling of Cellular Repair Mechanisms under Genome Stress

    PubMed Central

    Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

    2011-01-01

    Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances. PMID:21857915

  3. Sirtuin 2 regulates cellular iron homeostasis via deacetylation of transcription factor NRF2.

    PubMed

    Yang, Xiaoyan; Park, Seong-Hoon; Chang, Hsiang-Chun; Shapiro, Jason S; Vassilopoulos, Athanassios; Sawicki, Konrad T; Chen, Chunlei; Shang, Meng; Burridge, Paul W; Epting, Conrad L; Wilsbacher, Lisa D; Jenkitkasemwong, Supak; Knutson, Mitchell; Gius, David; Ardehali, Hossein

    2017-03-13

    SIRT2 is a cytoplasmic sirtuin that plays a role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized that SIRT2 directly regulates cellular iron homeostasis. Here, we have demonstrated that SIRT2 depletion results in a decrease in cellular iron levels both in vitro and in vivo. Mechanistically, we determined that SIRT2 maintains cellular iron levels by binding to and deacetylating nuclear factor erythroid-derived 2-related factor 2 (NRF2) on lysines 506 and 508, leading to a reduction in total and nuclear NRF2 levels. The reduction in nuclear NRF2 leads to reduced ferroportin 1 (FPN1) expression, which in turn results in decreased cellular iron export. Finally, we observed that Sirt2 deletion reduced cell viability in response to iron deficiency. Moreover, livers from Sirt2-/- mice had decreased iron levels, while this effect was reversed in Sirt2-/- Nrf2-/- double-KO mice. Taken together, our results uncover a link between sirtuin proteins and direct control over cellular iron homeostasis via regulation of NRF2 deacetylation and stability.

  4. Aldose reductase in keratinocytes attenuates cellular apoptosis and senescence induced by UV radiation.

    PubMed

    Kang, Eun Sil; Iwata, Kazumi; Ikami, Kanako; Ham, Sun Ah; Kim, Hye Jung; Chang, Ki Churl; Lee, Jae Heun; Kim, Jae-Hwan; Park, Soo-Bong; Kim, Jin-Hoi; Yabe-Nishimura, Chihiro; Seo, Han Geuk

    2011-03-15

    Although aldose reductase (AR) has been implicated in the cellular response to oxidative stress, the role of AR in ultraviolet-B (UVB)-induced cellular injury has not been investigated. Here, we show that an increased expression of AR in human keratinocytes modulates UVB-induced apoptotic cell death and senescence. Overexpression of AR in HaCaT cells significantly attenuated UVB-induced cellular damage and apoptosis, with a decreased generation of reactive oxygen species (ROS) and aldehydes. Ablation of AR with small interfering RNA or inhibition of AR activity abolished these effects. We also show that increased AR activity suppressed UVB-induced activation of the p38 and c-Jun N-terminal kinases, but did not affect the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase pathways. Similarly, UVB-induced translocation of Bax and Bcl-2 to mitochondria and cytosol, respectively, was markedly attenuated in cells overexpressing AR. Knockdown or inhibition of AR activity in primary cultured keratinocytes enhanced UVB-induced cellular senescence and increased the level of a cell-cycle regulatory protein, p53. Finally, cellular apoptosis induced by UVB radiation was significantly reduced in the epidermis of transgenic mice overexpressing human AR. These findings suggest that AR plays an important role in the cellular response to oxidative stress by sequestering ROS and reactive aldehydes generated in keratinocytes. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Crack Propagation in Bamboo's Hierarchical Cellular Structure

    PubMed Central

    Habibi, Meisam K.; Lu, Yang

    2014-01-01

    Bamboo, as a natural hierarchical cellular material, exhibits remarkable mechanical properties including excellent flexibility and fracture toughness. As far as bamboo as a functionally graded bio-composite is concerned, the interactions of different constituents (bamboo fibers; parenchyma cells; and vessels.) alongside their corresponding interfacial areas with a developed crack should be of high significance. Here, by using multi-scale mechanical characterizations coupled with advanced environmental electron microscopy (ESEM), we unambiguously show that fibers' interfacial areas along with parenchyma cells' boundaries were preferred routes for crack growth in both radial and longitudinal directions. Irrespective of the honeycomb structure of fibers along with cellular configuration of parenchyma ground, the hollow vessels within bamboo culm affected the crack propagation too, by crack deflection or crack-tip energy dissipation. It is expected that the tortuous crack propagation mode exhibited in the present study could be applicable to other cellular natural materials as well. PMID:24998298

  6. Cellular Models for the Study of Prions.

    PubMed

    Holmes, Brandon B; Diamond, Marc I

    2017-02-01

    It is now established that numerous amyloid proteins associated with neurodegenerative diseases, including tau and α-synuclein, have essential characteristics of prions, including the ability to create transmissible cellular pathology in vivo. We have developed cellular bioassays that report on the various features of prion activity using genetic engineering and quantitative fluorescence-based detection systems. We have exploited these biosensors to measure the binding and uptake of tau seeds into cells in culture and to quantify seeding activity in brain samples. These cell models have also been used to propagate tau prion strains indefinitely in culture. In this review, we illustrate the utility of cellular biosensors to gain mechanistic insight into prion transmission and to study neurodegenerative diseases in a reductionist fashion.

  7. Comparative Cellular Biogerontology: Primer and Prospectus

    PubMed Central

    Miller, Richard A.; Williams, Joseph B.; Kiklevich, J. Veronika; Austad, Steve; Harper, James M.

    2010-01-01

    Most prior work on the biological basis of aging has focused on describing differences between young and old individuals but provided only limited insight into the mechanisms controlling the rate of aging. Natural selection has produced a goldmine of experimental material, in the form of species of differing aging rate, whose longevity can vary by 10-fold or more within mammalian orders, but these resources remain largely unexplored at the cellular level. In this review article we focus on one approach to comparative biogerontology: the strategy of evaluating the properties of cultured cells from organisms of varying lifespan and aging rate. In addition, we discuss problems associated with the analysis and interpretations of interspecific variation of cellular trait data among species with disparate longevity. Given the impressive array of ‘natural experiments’ in aging rate, overcoming the technical and conceptual obstacles confronting research in comparative cellular gerontology will be well worth the effort. PMID:20109583

  8. Comparative cellular biogerontology: primer and prospectus.

    PubMed

    Miller, Richard A; Williams, Joseph B; Kiklevich, J Veronika; Austad, Steve; Harper, James M

    2011-04-01

    Most prior work on the biological basis of aging has focused on describing differences between young and old individuals but provided only limited insight into the mechanisms controlling the rate of aging. Natural selection has produced a goldmine of experimental material, in the form of species of differing aging rate, whose longevity can vary by 10-fold or more within mammalian orders, but these resources remain largely unexplored at the cellular level. In this review article we focus on one approach to comparative biogerontology: the strategy of evaluating the properties of cultured cells from organisms of varying lifespan and aging rate. In addition, we discuss problems associated with the analysis and interpretations of interspecific variation of cellular trait data among species with disparate longevity. Given the impressive array of 'natural experiments' in aging rate, overcoming the technical and conceptual obstacles confronting research in comparative cellular gerontology will be well worth the effort. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Geroconversion: irreversible step to cellular senescence

    PubMed Central

    Blagosklonny, Mikhail V

    2014-01-01

    Cellular senescence happens in 2 steps: cell cycle arrest followed, or sometimes preceded, by gerogenic conversion (geroconversion). Geroconvesrion is a form of growth, a futile growth during cell cycle arrest. It converts reversible arrest to irreversible senescence. Geroconversion is driven by growth-promoting, mitogen-/nutrient-sensing pathways such as mTOR. Geroconversion leads to hyper-secretory, hypertrophic and pro-inflammatory cellular phenotypes, hyperfunctions and malfunctions. On organismal level, geroconversion leads to age-related diseases and death. Rapamycin, a gerosuppressant, extends life span in diverse species from yeast to mammals. Stress–and oncogene-induced accelerated senescence, replicative senescence in vitro and life-long cellular aging in vivo all can be described by 2-step model. PMID:25483060

  10. Cellular automatons applied to gas dynamic problems

    NASA Technical Reports Server (NTRS)

    Long, Lyle N.; Coopersmith, Robert M.; Mclachlan, B. G.

    1987-01-01

    This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

  11. Mesoporous silica nanoparticles inhibit cellular respiration.

    PubMed

    Tao, Zhimin; Morrow, Matthew P; Asefa, Tewodros; Sharma, Krishna K; Duncan, Cole; Anan, Abhishek; Penefsky, Harvey S; Goodisman, Jerry; Souid, Abdul-Kader

    2008-05-01

    We studied the effect of two types of mesoporous silica nanoparticles, MCM-41 and SBA-15, on mitochondrial O 2 consumption (respiration) in HL-60 (myeloid) cells, Jurkat (lymphoid) cells, and isolated mitochondria. SBA-15 inhibited cellular respiration at 25-500 microg/mL; the inhibition was concentration-dependent and time-dependent. The cellular ATP profile paralleled that of respiration. MCM-41 had no noticeable effect on respiration rate. In cells depleted of metabolic fuels, 50 microg/mL SBA-15 delayed the onset of glucose-supported respiration by 12 min and 200 microg/mL SBA-15 by 34 min; MCM-41 also delayed the onset of glucose-supported respiration. Neither SBA-15 nor MCM-41 affected cellular glutathione. Both nanoparticles inhibited respiration of isolated mitochondria and submitochondrial particles.

  12. Role of galactose in cellular senescence.

    PubMed

    Elzi, David J; Song, Meihua; Shiio, Yuzuru

    2016-01-01

    Cellular senescence has been proposed to play critical roles in tumor suppression and organismal aging, but the molecular mechanism of senescence remains incompletely understood. Here we report that a putative lysosomal carbohydrate efflux transporter, Spinster, induces cellular senescence in human primary fibroblasts. Administration of d-galactose synergistically enhanced Spinster-induced senescence and this synergism required the transporter activity of Spinster. Intracellular d-galactose is metabolized to galactose-1-phosphate by galactokinase. Galactokinase-deficient fibroblasts, which accumulate intracellular d-galactose, displayed increased baseline senescence. Senescence of galactokinase-deficient fibroblasts was further enhanced by d-galactose administration and was diminished by restoration of wild-type galactokinase expression. Silencing galactokinase in normal fibroblasts also induced senescence. These results suggest a role for intracellular galactose in the induction of cellular senescence.

  13. Crack propagation in bamboo's hierarchical cellular structure.

    PubMed

    Habibi, Meisam K; Lu, Yang

    2014-07-07

    Bamboo, as a natural hierarchical cellular material, exhibits remarkable mechanical properties including excellent flexibility and fracture toughness. As far as bamboo as a functionally graded bio-composite is concerned, the interactions of different constituents (bamboo fibers; parenchyma cells; and vessels.) alongside their corresponding interfacial areas with a developed crack should be of high significance. Here, by using multi-scale mechanical characterizations coupled with advanced environmental electron microscopy (ESEM), we unambiguously show that fibers' interfacial areas along with parenchyma cells' boundaries were preferred routes for crack growth in both radial and longitudinal directions. Irrespective of the honeycomb structure of fibers along with cellular configuration of parenchyma ground, the hollow vessels within bamboo culm affected the crack propagation too, by crack deflection or crack-tip energy dissipation. It is expected that the tortuous crack propagation mode exhibited in the present study could be applicable to other cellular natural materials as well.

  14. Cellular therapies for type 1 diabetes.

    PubMed

    Lee, D D; Grossman, E; Chong, A S

    2008-02-01

    Type 1 diabetes mellitus (T1DM) is a disease that results from the selective autoimmune destruction of insulin-producing beta-cells. This disease process lends itself to cellular therapy because of the single cell nature of insulin production. Murine models have provided opportunities for the study of cellular therapies for the treatment of diabetes, including the investigation of islet transplantation, and also the possibility of stem cell therapies and islet regeneration. Studies in islet transplantation have included both allo- and xeno-transplantation and have allowed for the study of new approaches for the reversal of autoimmunity and achieving immune tolerance. Stem cells from hematopoietic sources such as bone marrow and fetal cord blood, as well as from the pancreas, intestine, liver, and spleen promise either new sources of islets or may function as stimulators of islet regeneration. This review will summarize the various cellular interventions investigated as potential treatments of T1DM.

  15. Cellular complexity captured in durable silica biocomposites

    PubMed Central

    Kaehr, Bryan; Townson, Jason L.; Kalinich, Robin M.; Awad, Yasmine H.; Swartzentruber, B. S.; Dunphy, Darren R.; Brinker, C. Jeffrey

    2012-01-01

    Tissue-derived cultured cells exhibit a remarkable range of morphological features in vitro, depending on phenotypic expression and environmental interactions. Translation of these cellular architectures into inorganic materials would provide routes to generate hierarchical nanomaterials with stabilized structures and functions. Here, we describe the fabrication of cell/silica composites (CSCs) and their conversion to silica replicas using mammalian cells as scaffolds to direct complex structure formation. Under mildly acidic solution conditions, silica deposition is restricted to the molecularly crowded cellular template. Inter- and intracellular heterogeneity from the nano- to macroscale is captured and dimensionally preserved in CSCs following drying and subjection to extreme temperatures allowing, for instance, size and shape preserving pyrolysis of cellular architectures to form conductive carbon replicas. The structural and behavioral malleability of the starting material (cultured cells) provides opportunities to develop robust and economical biocomposites with programmed structures and functions. PMID:23045634

  16. Cellular immunity to Bacteroides fragilis capsular polysaccharide

    PubMed Central

    1982-01-01

    The polysaccharide capsule of Bacteroides fragilis has been shown to be important in the virulence of the organism. The capsular polysaccharide (CP) of B. fragilis has been extensively purified. Using a murine model of intraabdominal abscess formation, we have been able to demonstrate cellular immunity to the capsular polysaccharide of B. fragilis. Immunization of C57BL/10J mice with the CP over 5 wk prevents abscess formation when the mice are challenged with B. fragilis intraperitoneally. This immunity can be transferred to naive mice with spleen cells from immune animals. The immune cells bear Thy-1.2 and Ly- 2.2 antigens. The immune response has been shown to be antigen specific, but not H-2 restricted. The possibility that these immune cells are suppressor T cells is discussed. The experimental system presented provides a model for the examination of the cellular interactions responsible for abscess formation and the cellular response to bacterial pathogens. PMID:6174672

  17. Modelling of the cellular automata space deformation within the RCAFE framework

    NASA Astrophysics Data System (ADS)

    Sitko, Mateusz; Madej, Łukasz

    2016-10-01

    Development of the innovative approach to micro scale cellular automata (CA) space deformation during dynamic recrystallization process (DRX) is the main goal of the present paper. Major assumptions of the developed CA DRX model as well as novel space deformation algorithm, which is based on the random cellular automata concept and FE method, are described. Algorithms and methods to transfer input/output data between FE and CA are presented in detail. Visualization tool to analyze progress of deformation in the irregular CA space is also highlighted. Finally, initial results in the form of deformed and recrystallized microstructures are presented and discussed.

  18. Three-dimensional microscopic deformation measurements on cellular solids.

    PubMed

    Genovese, K

    2016-07-01

    The increasing interest in small-scale problems demands novel experimental protocols providing dense sets of 3D deformation data of complex shaped microstructures. Obtaining such information is particularly significant for the study of natural and engineered cellular solids for which experimental data collected at macro scale and describing the global mechanical response provide only limited information on their function/structure relationship. Cellular solids, in fact, due their superior mechanical performances to a unique arrangement of the bulk material properties (i.e. anisotropy and heterogeneity) and cell structural features (i.e. pores shape, size and distribution) at the micro- and nano-scales. To address the need for full-field experimental data down to the cell level, this paper proposes a single-camera stereo-Digital Image Correlation (DIC) system that makes use of a wedge prism in series to a telecentric lens for performing surface shape and deformation measurements on microstructures in three dimensions. Although the system possesses a limited measurement volume (FOV~2.8×4.3mm(2), error-free DOF ~1mm), large surface areas of cellular samples can be accurately covered by employing a sequential image capturing scheme followed by an optimization-based mosaicing procedure. The basic principles of the proposed method together with the results of the benchmarking of its metrological performances and error analysis are here reported and discussed in detail. Finally, the potential utility of this method is illustrated with micro-resolution three-dimensional measurements on a 3D printed honeycomb and on a block sample of a Luffa sponge under compression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Cellular reprogramming through mitogen-activated protein kinases

    PubMed Central

    Lee, Justin; Eschen-Lippold, Lennart; Lassowskat, Ines; Böttcher, Christoph; Scheel, Dierk

    2015-01-01

    Mitogen-activated protein kinase (MAPK) cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554) in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins) as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression—including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding, and degradation) steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes. PMID:26579181

  20. Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

    EPA Science Inventory

    CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...